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WILLIAMS OBSTETRICS - COMPREHENSIVE REVIEW

Resident-Level Study Guide

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TOPIC 1: MATERNAL ANATOMY AND PHYSIOLOGY

Bony Pelvis

• Gynecoid - round inlet, wide forepelvis, straight sidewalls; most favorable for vaginal delivery (~50% of women)
• Android - heart-shaped inlet, narrow forepelvis, convergent sidewalls; associated with arrest disorders
• Anthropoid - oval inlet (AP > transverse), long AP diameter; occiput posterior presentations common
• Platypelloid - flat/oval inlet (transverse > AP); rare; transverse arrest common

• Obstetric conjugate (true conjugate): 10 cm minimum - distance from sacral promontory to posterior pubic symphysis
• Diagonal conjugate: ~12.5 cm (clinically measurable; subtract 1.5 cm to estimate obstetric conjugate)
• Transverse diameter of inlet: ~13 cm
• Interspinous diameter (midpelvis): 10 cm minimum - most commonly contracted diameter
• Intertuberous diameter (outlet): >8 cm

Uterus

• Non-pregnant: 7-8 cm long, 4-5 cm wide, 2-3 cm thick; ~60 g
• At term: ~1000 g, accommodates 5 L total volume
• Three layers: perimetrium (serosa), myometrium (smooth muscle), endometrium
• Blood supply: uterine artery (branch of internal iliac) anastomoses with ovarian artery
• The lower uterine segment (LUS) forms from the isthmus in the third trimester - site of Cesarean incision

Physiological Changes in Pregnancy

• Cardiac output increases 30-50% (peaks at 28-32 weeks)
• Heart rate increases ~15-20 bpm
• Blood pressure decreases in first two trimesters (due to reduced SVR from progesterone and placental vasodilation), returns to baseline in third trimester
• Plasma volume increases ~50%; RBC mass increases ~25% → dilutional anemia ("physiologic anemia of pregnancy")
• Supine hypotension syndrome: aortocaval compression by gravid uterus; treat by left lateral decubitus positioning

• Tidal volume increases 40% (most important change)
• Respiratory rate unchanged or slightly increased
• Functional residual capacity (FRC) decreases 20-25% (diaphragm elevation)
• Mild respiratory alkalosis: PaCO2 ~30 mmHg (normal ~40 mmHg); compensated by renal HCO3 excretion
• Oxygen consumption increases ~20%

• GFR increases 50% by first trimester → lower serum creatinine (normal in pregnancy: ~0.5-0.7 mg/dL)
• Glucosuria can be normal in pregnancy
• Ureteral dilation (right > left) due to progesterone and uterine compression
• Increased risk of pyelonephritis from bacteriuria

• WBC: increases to 12,000-15,000/mm³ (can reach 25,000 in labor - normal)
• Platelets: mildly decrease; <150,000 requires investigation
• Coagulation: hypercoagulable state; factors I, VII, VIII, IX, X increase; protein S decreases
• ESR: dramatically elevated (not useful in pregnancy)

• Decreased lower esophageal sphincter tone → GERD common
• Decreased gastric motility → constipation
• Hemorrhoids common from venous congestion

• hCG: produced by syncytiotrophoblast; peaks at 10-12 weeks, then declines
• Progesterone: from corpus luteum until 8-10 weeks, then placenta takes over ("luteal-placental shift")
• Estrogen: from placenta (requires fetal adrenal DHEAS and fetal liver)
• Thyroid: TBG increases → total T3/T4 increase, but free T3/T4 remain normal; TSH briefly decreases in first trimester (hCG stimulation)

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TOPIC 2: OBSTETRIC HISTORY AND EXAMINATION

Obstetric History

• Gravida: total number of pregnancies (including current)
• Para: deliveries after 20 weeks (each multiple gestation = 1 para)
• GTPAL: Gravida / Term births / Preterm births / Abortions / Living children

• LMP and EDD (Naegele's rule: LMP + 9 months + 7 days)
• Menstrual history, cycle regularity, contraceptive use
• Prior pregnancy outcomes: mode of delivery, complications, birth weights, gestational ages
• Medical/surgical history: hypertension, diabetes, thyroid, cardiac, renal, autoimmune
• Family history: genetic conditions, twins, congenital anomalies
• Social history: smoking (placental abruption, IUGR, preterm), alcohol (FAS), illicit drugs
• Occupational and environmental exposures

Estimation of Gestational Age

• Naegele's rule: assumes 28-day cycle; first day of LMP + 280 days
• Ultrasound dating: most accurate in first trimester (CRL measurement; ±5-7 days accuracy at 6-11 weeks)
• After 20 weeks, fundal height in cm ≈ gestational age in weeks (±2-3 cm)

Physical Examination

• 12 weeks: just above pubic symphysis
• 16 weeks: midway between symphysis and umbilicus
• 20 weeks: at umbilicus
• 36 weeks: at xiphoid process
• 38-40 weeks: may decrease as head engages ("lightening")

1. Fundal grip - identifies fetal part in fundus (breech = irregular, soft; head = hard, round, ballottable)
2. Umbilical grip - locates fetal back and small parts
3. Pawlik's grip - identifies presenting part above symphysis
4. Pelvic grip - determines engagement and attitude of presenting part

• Components: dilation, effacement, station, consistency, position
• Score ≥8: favorable cervix; Score <6: cervical ripening recommended before induction

• Station: level of presenting part relative to ischial spines (-5 to +5 or -3 to +3 cm scale)
• Engagement: when widest diameter of presenting part passes through pelvic inlet (0 station)

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TOPIC 3: CONGENITAL GENITOURINARY ABNORMALITIES

Uterine Anomalies (Mullerian Duct Anomalies)

• Class I - Hypoplasia/Agenesis: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome - absent uterus and upper vagina; normal ovaries; primary amenorrhea
• Class II - Unicornuate: one functioning horn; associated with renal anomalies (always check kidneys); highest risk of preterm delivery and malpresentation
• Class III - Didelphys: complete non-fusion; two separate uteri, two cervices, often longitudinal vaginal septum; surprisingly good obstetric outcomes
• Class IV - Bicornuate: partial non-fusion at fundus; may be complete or partial; associated with preterm birth
• Class V - Septate: most common anomaly; resorption failure; septum is fibrous/avascular; highest risk of first trimester loss; treated by hysteroscopic resection
• Class VI - Arcuate: slight fundal indentation; considered normal variant
• Class VII - DES-related: T-shaped uterus from in utero diethylstilbestrol exposure

• Increased risk: miscarriage, preterm birth, malpresentation, cesarean delivery, placenta previa/abruption
• Cervical incompetence particularly associated with unicornuate and bicornuate uteri

Vaginal Anomalies

• Transverse vaginal septum: partial/complete obstruction; can cause cryptomenorrhea or dystocia
• Longitudinal vaginal septum: commonly associated with uterine didelphys; usually asymptomatic
• Imperforate hymen: primary amenorrhea, cyclic pelvic pain, hematocolpos; treat by cruciate incision

Ovarian Anomalies

• Supernumerary ovaries, accessory ovary - rare
• Ovarian torsion risk increased in pregnancy (especially with stimulated ovaries)

Renal Anomalies Associated with Genital Anomalies

• Renal agenesis (unilateral) is common with unicornuate uterus - always image kidneys
• Horseshoe kidney, pelvic kidney may complicate labor and delivery

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TOPIC 4: PRECONCEPTIONAL COUNSELING

Goals

Key Components

• 400-800 mcg/day for all women planning pregnancy (start at least 1 month before conception)
• 4 mg/day for women with prior NTD-affected pregnancy, on anticonvulsants, or with diabetes
• Reduces neural tube defect (NTD) risk by 50-70%

• Diabetes: optimize glycemic control before conception; HbA1c <6.5% target; elevated HbA1c associated with congenital anomalies (cardiac, neural tube)
• Hypertension: switch to pregnancy-safe antihypertensives (methyldopa, labetalol, nifedipine); stop ACE inhibitors/ARBs (teratogenic)
• Epilepsy: valproate has highest teratogenic risk; consider switching to safer agent (lamotrigine, levetiracetam); continue folic acid
• Thyroid disease: achieve euthyroid state; hypothyroidism associated with miscarriage, impaired fetal neurodevelopment
• Autoimmune disease (SLE, APS): assess disease activity; hydroxychloroquine is safe and protective; optimize before conception
• Thrombophilia: counsel on anticoagulation if indicated

• MMR, varicella: live vaccines - give preconception, not during pregnancy
• Influenza, Tdap: safe in pregnancy (give at appropriate times)
• COVID-19: safe in pregnancy; recommended

• Stop: ACE inhibitors, ARBs, statins, warfarin, isotretinoin, methotrexate, mycophenolate
• Continue/adjust: antihypertensives, thyroid medications, anticoagulation

• Smoking cessation: reduces risk of miscarriage, IUGR, preterm labor, placental complications
• Alcohol: complete abstinence recommended
• Weight optimization: obesity increases risk of GDM, pre-eclampsia, cesarean delivery, fetal anomalies

• Carrier screening: cystic fibrosis, spinal muscular atrophy (offered to all); hemoglobinopathies, Tay-Sachs (ethnicity-based)
• Family history of genetic conditions: refer to genetic counseling
• Advanced maternal age (≥35 at delivery): discuss aneuploidy screening options

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TOPIC 5: PRENATAL CARE

Initial Visit (First Trimester)

• Urine or serum hCG confirmation
• Transvaginal ultrasound for dating (CRL)
• Confirm intrauterine location

• CBC (anemia, thrombocytopenia)
• Blood type and Rh factor; antibody screen
• Rubella immunity
• Hepatitis B surface antigen
• Syphilis (RPR or VDRL)
• HIV testing (opt-out; universal)
• Urinalysis and urine culture
• Cervical cytology (Pap smear) if due
• Gonorrhea/chlamydia screen
• TB screening if at risk
• Thyroid function (controversial; screen if symptomatic or risk factors)
• Hemoglobin electrophoresis if indicated

• Nuchal translucency (NT) ultrasound: 11-14 weeks
• Cell-free fetal DNA (cfDNA/NIPT): from 10 weeks; screens for trisomies 21, 18, 13, sex chromosome abnormalities
• First trimester combined screen: NT + PAPP-A + free beta-hCG

Subsequent Visits

• Every 4 weeks until 28 weeks
• Every 2 weeks from 28-36 weeks
• Weekly from 36 weeks onward

• Quad screen (AFP, hCG, estriol, inhibin A): 15-20 weeks
• Anatomy ultrasound: 18-22 weeks
• Cervical length if risk factors for preterm birth

• Repeat CBC
• Glucose challenge test (GCT/1-hour, 50g): screen for GDM
• Repeat Rh antibody screen; Rh-negative women receive Rho(D) immunoglobulin (RhoGAM) 300 mcg
• Group B Streptococcus (GBS) vaginal-rectal culture: 36-37 weeks

• Fundal height
• Fetal heart tones (FHT) - Doppler from 10-12 weeks
• Blood pressure, weight, edema
• Fetal movement (from ~24 weeks)
• Review symptoms: contractions, bleeding, leaking fluid, dysuria

Weight Gain Recommendations (IOM guidelines)

• Underweight (BMI <18.5): 28-40 lb
• Normal weight (BMI 18.5-24.9): 25-35 lb
• Overweight (BMI 25-29.9): 15-25 lb
• Obese (BMI ≥30): 11-20 lb

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TOPIC 6: PLACENTATION

Development

• Implantation occurs ~6-10 days post-fertilization (blastocyst stage)
• Trophoblast differentiates into:
  • Cytotrophoblast: inner layer; mononuclear; proliferative
  • Syncytiotrophoblast: outer layer; multinuclear; invasive; produces hCG, progesterone, estrogen, hPL
• Extravillous trophoblast (EVT): invades decidua and myometrium; remodels spiral arteries (converts them from high-resistance to low-resistance vessels by 18-20 weeks)
• Failure of spiral artery remodeling → pre-eclampsia, IUGR, placental abruption

Placental Structure

• Chorionic villi: functional unit; surrounded by intervillous space where maternal blood circulates
• Cotyledons: 15-30 maternal-facing lobules
• Mature placenta: 15-20 cm diameter, 2-3 cm thick, ~500 g
• Umbilical cord: 2 arteries, 1 vein (single umbilical artery associated with renal and cardiac anomalies)

Placental Functions

1. Gas exchange: O2 and CO2 transfer by simple diffusion
2. Nutrient transfer: glucose (facilitated diffusion), amino acids (active transport), fatty acids
3. Hormone production: hCG, progesterone, estrogen, hPL (human placental lactogen)
4. Immunological barrier: IgG crosses placenta (active transport via FcRn receptors); protective in neonate
5. Drug/substance transfer: most drugs, alcohol, nicotine, most viruses can cross

Placental Abnormalities

• Placenta overlying or within 2 cm of internal cervical os
• Complete previa: os completely covered
• Partial/marginal previa: edge at or within 2 cm of os
• Risk factors: prior cesarean, uterine surgery, multiparity, advanced age, smoking
• Presentation: painless bright red vaginal bleeding (especially third trimester)
• Management: no digital vaginal exam; ultrasound diagnosis; delivery by cesarean (usually at 36-37 weeks for complete previa)

• Abnormal placental attachment to myometrium
• Accreta: villi attach to myometrium (no decidua)
• Increta: villi invade into myometrium
• Percreta: villi penetrate through myometrium to serosa (or beyond)
• Risk factors: prior cesarean + placenta previa (risk ~25% with 1 prior CS + previa; ~50% with 2; >60% with ≥3)
• Management: planned cesarean-hysterectomy at 34-35 weeks; multidisciplinary team; blood bank preparation

• Premature separation of normally implanted placenta
• Incidence: ~1%
• Risk factors: hypertension (most common), prior abruption (10x risk), cocaine use, smoking, trauma, preterm PROM
• Classic presentation: painful vaginal bleeding with uterine tenderness and increased tone ("woody" uterus)
• Concealed abruption: no external bleeding (retroplacental clot)
• Complications: DIC (from thromboplastin release), fetal distress/death, Couvelaire uterus
• Management: depends on gestational age and maternal/fetal status; delivery if severe or fetal compromise

• Fetal vessels traverse the membranes over the internal os
• Risk factors: velamentous cord insertion, succenturiate lobe, low-lying placenta
• Presents with painless bright bleeding at rupture of membranes + fetal bradycardia
• Kleihauer-Betke or APT test confirms fetal blood
• Catastrophic if undiagnosed; prenatal diagnosis allows planned cesarean before rupture (at 34-36 weeks)

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TOPIC 7: EMBRYOGENESIS AND FETAL DEVELOPMENT

Fertilization and Early Development

• Fertilization: in ampulla of fallopian tube; sperm penetrates zona pellucida
• Zygote → cleavage → morula (day 4) → blastocyst (day 5-6) → implantation (day 6-10)
• Inner cell mass → embryo; trophoblast → placenta and membranes

Embryonic Period (Weeks 3-8)

• Week 3: gastrulation; three germ layers formed (ectoderm, mesoderm, endoderm); neural plate formation
• Week 4: neural tube closes (anterior by day 25, posterior by day 27); heart begins beating; arm/leg buds appear
• Week 5-6: limb development; hand and foot plates; lens vesicle
• Week 7-8: fingers separate; major features recognizable; CRL ~1-2 cm

Germ Layer Derivatives

• Ectoderm: skin, nervous system, sensory organs, anterior pituitary
• Mesoderm: muscle, bone, cartilage, connective tissue, cardiovascular system, urogenital system, adrenal cortex
• Endoderm: GI tract lining, respiratory tract, thyroid, parathyroid, liver, pancreas, bladder

Fetal Development by Trimester

• 10 weeks: all organs formed; CRL ~3 cm; external genitalia still undifferentiated
• 12 weeks: kidneys begin urine production; sucking reflex develops; sex distinguishable on ultrasound

• 16 weeks: gender determination by ultrasound; lanugo appears; meconium formation begins
• 18-20 weeks: quickening (fetal movements perceived by mother); vernix caseosa develops
• 20 weeks: fetus weighs ~300 g; viability threshold approaching
• 24 weeks: viability threshold (~50% survival with NICU care); surfactant production begins (Type II pneumocytes)
• 28 weeks: eyelids open; weight ~1000 g; survival ~90% with NICU

• 32 weeks: subcutaneous fat deposition; sleep-wake cycles
• 36 weeks: lung maturity usually achieved; weight ~2500 g
• 40 weeks (term): weight ~3400 g; lanugo shed; vernix present in folds

Fetal Organ Development

• Surfactant (phosphatidylcholine/lecithin) produced from ~24 weeks; L/S ratio ≥2.0 indicates maturity
• Phosphatidylglycerol (PG) appears at ~36 weeks; additional maturity marker

• Begin urine production at ~10-12 weeks; urine is the main source of amniotic fluid after 16 weeks
• Renal agenesis → oligohydramnios → Potter sequence (pulmonary hypoplasia, limb deformities, facial features)

• Oxygenated blood from placenta via umbilical vein → ductus venosus → IVC → right heart
• Foramen ovale: shunts blood from right to left atrium (bypasses lungs)
• Ductus arteriosus: shunts blood from pulmonary artery to aorta (bypasses lungs)
• At birth: cord clamping → increased SVR → decreased pulmonary resistance → foramen ovale closes; ductus arteriosus closes (prostaglandin levels fall with air breathing)

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TOPIC 8: FETAL IMAGING

Ultrasound in Obstetrics

• Confirm intrauterine pregnancy
• Assess viability (cardiac activity)
• Number of embryos; chorionicity in multiple gestations
• CRL measurement for dating (most accurate before 14 weeks)
• Nuchal translucency (NT) at 11-14 weeks: >3.5 mm associated with aneuploidy, cardiac defects
• Detect early anomalies: anencephaly, major cardiac defects

• Head: BPD, HC, cerebellum, cavum septum pellucidum, ventricular width
• Face: lips, palate, orbits, nasal bone
• Neck: nuchal fold thickness (>6 mm at 16-22 weeks associated with Down syndrome)
• Chest: heart (4-chamber, outflow tracts, situs), lungs
• Abdomen: stomach, kidneys, bladder, cord insertion, abdominal circumference
• Spine: neural tube defects
• Limbs: length, structure
• Placenta: location, cord insertion
• Cervical length (transvaginal)
• Amniotic fluid (AFI or MVP)
• Fetal weight estimation (Hadlock formula using BPD, HC, AC, FL)

• Fetal growth (EFW)
• Amniotic fluid assessment
• Placental location
• Fetal presentation
• Biophysical profile (BPP)
• Doppler studies

Doppler Ultrasound

• Umbilical artery Doppler: assesses placental resistance; S/D ratio, pulsatility index, resistance index
  • Absent end-diastolic flow (AEDF): severe uteroplacental insufficiency
  • Reversed end-diastolic flow (REDF): imminent fetal compromise
• Middle cerebral artery (MCA) Doppler: peak systolic velocity (PSV) >1.5 MoM suggests fetal anemia
• Ductus venosus Doppler: absent or reversed 'a' wave indicates cardiac decompensation

MRI in Obstetrics

• Used when ultrasound inconclusive (especially CNS anomalies, placenta accreta)
• Gadolinium contrast: avoid in first trimester; use only if clearly necessary
• No known radiation risk; can be performed at any gestational age

Radiation Safety

• X-ray, CT, fluoroscopy: ionizing radiation; avoid unless medically necessary
• Fetal radiation dose threshold for deterministic effects: >100-200 mGy (most diagnostic studies deliver <10 mGy)
• No justification to terminate pregnancy if fetal exposure <50 mGy

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TOPIC 9: AMNIOTIC FLUID DISORDERS

Amniotic Fluid Physiology

• Composition: early pregnancy - transudate from fetal skin; after 16-20 weeks - primarily fetal urine
• Also contributed by: fetal lung fluid (secreted), fetal oral/nasal secretions
• Removed by: fetal swallowing (500-700 mL/day), intramembranous absorption
• Volume: increases through pregnancy; peaks at ~34 weeks (~800-1000 mL); decreases after 40 weeks

Assessment

• AFI (Amniotic Fluid Index): sum of deepest vertical pockets in four quadrants; normal 5-25 cm
• Maximum Vertical Pocket (MVP): single deepest pocket without cord; normal 2-8 cm
• Oligohydramnios: AFI <5 cm or MVP <2 cm
• Polyhydramnios: AFI >24-25 cm or MVP >8 cm

Oligohydramnios

• Uteroplacental insufficiency (most common in late pregnancy) → decreased fetal renal perfusion → decreased urine output
• Renal anomalies: bilateral renal agenesis (Potter sequence), obstructive uropathies, multicystic kidneys
• PROM (premature rupture of membranes) - leakage
• Post-term pregnancy
• ACE inhibitors/NSAIDs (reduce fetal renal perfusion)
• Chromosomal abnormalities

• Pulmonary hypoplasia (if early onset, prolonged)
• Limb contractures
• Cord compression during labor → variable decelerations
• Potter sequence with bilateral renal agenesis

• Identify cause (ultrasound for structural anomalies, fetal karyotype if indicated)
• Serial ultrasound for growth and fluid
• NST/BPP for fetal wellbeing
• Amnioinfusion for cord compression in labor

Polyhydramnios

• Fetal causes (~30%): decreased swallowing - esophageal/duodenal atresia, anencephaly, facial clefts, neuromuscular disorders; increased urine output - macrosomia/GDM, hydrops fetalis, twin-twin transfusion
• Maternal causes: gestational diabetes (most common identifiable cause), diabetes mellitus
• Idiopathic: ~50-60%

• Preterm labor/birth (uterine overdistension)
• PROM
• Cord prolapse (malpresentation, unstable lie)
• Placental abruption (sudden decompression)
• Maternal discomfort, respiratory compromise

• Identify cause: detailed ultrasound, OGTT, fetal karyotype if structural anomaly
• Symptomatic/severe: therapeutic amnioreduction or indomethacin (reduces fetal urine output; avoid >32 weeks due to premature ductus arteriosus closure risk)
• Monitor for preterm labor

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TOPIC 10: TERATOLOGY AND TERATOGENS

Principles of Teratology (Wilson's Principles)

1. Susceptibility depends on genotype of the conceptus
2. Susceptibility varies with developmental stage at time of exposure
3. Teratogenic agents act by specific mechanisms
4. Teratogens reach the conceptus in certain ways
5. Four manifestations of abnormal development: death, malformation, growth restriction, functional defects
6. Manifestations increase with dose
7. Agent must reach susceptible embryonic tissue

Critical Periods

• Preimplantation (0-2 weeks): "all-or-nothing" effect; exposure leads to either death or no effect
• Embryonic period (3-8 weeks): organogenesis; highest susceptibility to structural malformations
• Fetal period (9 weeks onward): growth and functional maturation; teratogens cause growth restriction, organ function defects, behavioral effects

Known Human Teratogens

• Alcohol: fetal alcohol spectrum disorder (FASD); fetal alcohol syndrome (FAS): IUGR, facial features (smooth philtrum, thin upper lip, small palpebral fissures), cognitive impairment; no safe dose
• Cocaine: IUGR, placental abruption, fetal cerebrovascular events
• Smoking: IUGR, preterm birth, SIDS, placental complications

• Rubella: cataracts, cardiac defects (PDA, pulmonary stenosis), sensorineural deafness; especially first trimester
• CMV: most common congenital infection; hearing loss, IUGR, microcephaly, periventricular calcifications
• Toxoplasma: chorioretinitis, intracranial calcifications (diffuse), hydrocephalus
• Syphilis: stillbirth, hydrops, bone changes, saddle nose, Hutchinson triad
• Varicella: limb hypoplasia, skin scarring, eye defects (first/second trimester infection)
• Zika virus: microcephaly, brain malformations; transmitted by Aedes mosquito

• Ionizing radiation >100 mGy: microcephaly, intellectual disability, organ malformations
• Most diagnostic imaging: well below this threshold

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TOPIC 11: GENETICS

Basic Concepts

• Karyotype: 46,XX or 46,XY (normal human); analysis requires dividing cells (chorionic villi, amniocytes, fetal blood)
• Autosome: chromosomes 1-22; Sex chromosomes: X and Y
• Allele: alternative form of a gene at a locus

Patterns of Inheritance

• One mutant allele sufficient for phenotype
• 50% transmission to offspring
• Variable expressivity and penetrance common
• Examples: Marfan syndrome, neurofibromatosis, Huntington disease, achondroplasia, BRCA1/2

• Both alleles must be mutant
• 25% recurrence risk if both parents are carriers
• Examples: cystic fibrosis, sickle cell disease, PKU, Tay-Sachs, spinal muscular atrophy

• Gene on X chromosome; males affected, females are carriers
• 50% of sons affected, 50% of daughters are carriers
• Examples: Duchenne muscular dystrophy, hemophilia A and B, G6PD deficiency

• One mutant X allele causes phenotype in females and males
• Often lethal in males
• Example: Rett syndrome, incontinentia pigmenti

• Maternally inherited
• All offspring of affected mother at risk
• Variable expression (heteroplasmy)
• Examples: MELAS, Leber hereditary optic neuropathy

Chromosomal Abnormalities

• Trisomy 21 (Down syndrome): most common; intellectual disability, hypotonia, upward slanting palpebral fissures, endocardial cushion defects (AV canal), duodenal atresia; risk increases with maternal age
• Trisomy 18 (Edwards): severe defects; overlapping fingers, rocker-bottom feet, AVSD, micrognathia; usually fatal within first year
• Trisomy 13 (Patau): holoprosencephaly, midline defects, polydactyly, cardiac defects; usually fatal

• Turner (45,X): short stature, webbed neck, coarctation of aorta, primary amenorrhea, streak gonads; most common cause of primary amenorrhea
• Klinefelter (47,XXY): tall, hypogonadism, infertility, gynecomastia, mild intellectual disability
• 47,XXX: usually normal; mild learning difficulties
• 47,XYY: tall; usually normal intelligence

• Deletions, duplications, inversions, translocations
• Microdeletions: 22q11.2 deletion (DiGeorge/velocardiofacial: cardiac, thymus, parathyroid, palatal defects); 15q11-q13 (Prader-Willi if paternal deletion; Angelman if maternal deletion)
• Translocations: Robertsonian translocation of chromosome 14/21 → familial Down syndrome risk

Genetic Testing Options

• NIPT/cfDNA: screening test; highly sensitive for common trisomies; not diagnostic
• Chorionic villus sampling (CVS): 10-13 weeks; diagnostic; 1% procedure-related loss
• Amniocentesis: 15-20 weeks; diagnostic; 0.1-0.3% procedure-related loss
• Microarray (chromosomal microarray analysis, CMA): detects microdeletions/duplications; recommended when structural anomaly found on ultrasound

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TOPIC 12: PRENATAL DIAGNOSIS

Screening vs. Diagnostic Testing

• Screening: identifies risk (sensitivity/specificity tradeoff); no false-positive free; includes serum markers, ultrasound, cfDNA
• Diagnostic: definitive answer; invasive (CVS, amniocentesis)

Serum Screening

• PAPP-A (low in trisomy 21) + free beta-hCG (high in trisomy 21) + NT
• Detection rate: ~85-90% for trisomy 21 (5% FPR)

• AFP, hCG, estriol, inhibin A
• Trisomy 21: low AFP, high hCG, low estriol, high inhibin A
• Trisomy 18: all four markers low
• NTD: elevated AFP
• Detection rate: ~80% for Down syndrome (5% FPR)

• From 10 weeks; analyzes fetal DNA fragments in maternal plasma
• Screens for: trisomies 21, 18, 13; sex chromosome abnormalities; some microdeletions (22q11.2)
• Detection rate: >99% for trisomy 21; >98% for trisomy 18; 91-99% for trisomy 13
• Positive predictive value varies with prevalence (lower PPV in low-risk population)
• Not a diagnostic test - positive result requires confirmatory invasive testing

Maternal Serum AFP (MSAFP)

• Elevated: open NTDs (anencephaly, open spina bifida), open abdominal wall defects (omphalocele, gastroschisis), multiple gestation, incorrect dates, fetal demise, placental bleeding
• Decreased: trisomy 21 and 18, gestational diabetes

Invasive Diagnostic Procedures

• 10-13 weeks
• Transcervical or transabdominal
• Provides chorionic villi for karyotype, microarray, enzymatic, molecular testing
• Advantage: earlier diagnosis, earlier termination if desired
• Risk: ~0.5-1% procedure-related pregnancy loss
• Limitation: cannot diagnose NTDs (no AFP); confined placental mosaicism possible (found in 1-2%, requires amniocentesis confirmation)

• 15-20 weeks (standard); can be done later
• Transabdominal; 20-22 gauge needle; 20-30 mL fluid removed
• Tests: karyotype, microarray, AFP, AChE (for NTDs), viral PCR, metabolic studies
• Procedure risk: ~0.1-0.3% pregnancy loss
• Complications: leaking fluid, chorioamnionitis, needle injury (rare)

Fetal Anatomy Survey (Anomaly Scan)

• 18-22 weeks; identifies major structural anomalies
• Sensitivity: ~50-70% for all anomalies; higher for severe anomalies

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TOPIC 13: FETAL DISORDERS

Fetal Growth Restriction (FGR) / Intrauterine Growth Restriction (IUGR)

• Symmetric: all parameters reduced equally; early onset; often genetic or infectious etiology
• Asymmetric: head sparing; AC and EFW reduced more than HC; late onset; usually uteroplacental insufficiency

• Placental: uteroplacental insufficiency (most common), placental abruption, preeclampsia
• Fetal: aneuploidy, congenital anomalies, infections (CMV, rubella, toxoplasma)
• Maternal: hypertension, diabetes with vascular disease, smoking, malnutrition, SLE, APS

• Serial growth ultrasounds every 2-4 weeks
• Doppler (umbilical artery, MCA, ductus venosus)
• NST and BPP
• Deliver based on gestational age + Doppler status

Fetal Anemia

Hydrops Fetalis

• Cardiovascular anomalies (most common)
• Chromosomal (Turner syndrome, trisomies)
• Infections (parvovirus B19, syphilis, CMV)
• Twin-twin transfusion syndrome (TTTS)
• Thoracic lesions (CCAM, diaphragmatic hernia)
• Metabolic disorders

Alloimmunization

• Rh(D) is most clinically significant
• Prevention: RhoGAM (anti-D immunoglobulin) given to Rh-negative women at 28 weeks, after sensitizing events (bleeding, amniocentesis, trauma, delivery)
• Once sensitized: no prevention possible; monitor with maternal titers; MCA Doppler surveillance; IUT if fetal anemia develops

Twin-Twin Transfusion Syndrome (TTTS)

• Occurs in monochorionic-diamniotic (MCDA) twins (~15% incidence)
• Unbalanced placental vascular anastomoses → blood shunted from donor to recipient
• Donor: oligohydramnios, IUGR, "stuck twin"
• Recipient: polyhydramnios, cardiac overload, hydrops
• Quintero staging: I-V
• Treatment: fetoscopic laser photocoagulation of anastomoses (preferred for stages II-IV at 16-26 weeks); amnioreduction
• Selective fetal reduction, delivery, or expectant management depending on stage/gestational age

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TOPIC 14: FETAL THERAPY

Intrauterine Transfusion (IUT)

• Indication: fetal anemia (alloimmunization, parvovirus B19)
• Route: intravascular (umbilical vein at cordocentesis) - preferred; or intraperitoneal
• Target post-transfusion hematocrit: 45-55%
• Repeat every 2-4 weeks

Fetoscopic Laser Photocoagulation

• For TTTS: laser ablation of inter-twin placental anastomoses
• Performed at 16-26 weeks
• Reduces mortality and neurodevelopmental morbidity vs. amnioreduction alone

Fetal Shunt Procedures

• Vesicoamniotic shunt: lower urinary tract obstruction (posterior urethral valves) → bladder drainage to amniotic space; preserves renal function and prevents pulmonary hypoplasia
• Thoracoamniotic shunt: large pleural effusion or CCAM with hydrops

Open Fetal Surgery

• Myelomeningocele (MMC) repair: MOMS trial showed intrauterine repair at 19-25 weeks improved neurological outcomes (reduced need for VP shunt, improved leg function) vs. postnatal repair; but increased preterm birth risk
• Ex utero intrapartum treatment (EXIT procedure): for large fetal airway masses (CCAM, cervical teratoma); maintain uteroplacental circulation while airway is secured before cord clamping

Medical Fetal Therapy

• Congenital adrenal hyperplasia (CAH): maternal dexamethasone to suppress fetal adrenal androgen → prevent virilization of female fetus (started before sex determination; stopped if fetus is male or unaffected)
• Fetal arrhythmia: maternal digoxin, flecainide, sotalol for SVT/hydrops
• Fetal thyroid disorders: propylthiouracil or levothyroxine injected into amniotic fluid
• Betamethasone: given to mother for fetal lung maturation (24-34 weeks, or up to 36-6/7 weeks per recent ALPS trial data)

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TOPIC 15: FETAL ASSESSMENT

Kick Counts (Fetal Movement Counting)

• Maternal perception of fetal movements from ~24 weeks
• "Count-to-10": patient counts movements until 10 felt; should occur within 2 hours
• Decreased fetal movement warrants NST/BPP evaluation

Non-Stress Test (NST)

• Cardiotocography (CTG) without uterine contractions
• Reactive (normal): ≥2 accelerations (heart rate increase ≥15 bpm for ≥15 seconds) in 20-40 minutes
• Non-reactive: insufficient accelerations; requires further evaluation (acoustic stimulation, BPP)
• High sensitivity for fetal wellbeing when reactive; non-reactive has high false-positive rate

Biophysical Profile (BPP)

• 5 components, each scored 0 or 2 (maximum 10/10):
  1. NST (reactive = 2; non-reactive = 0)
  2. Fetal breathing movements (≥1 episode ≥30 seconds in 30 min)
  3. Fetal movement (≥3 discrete movements in 30 min)
  4. Fetal tone (≥1 extension/flexion of limb or trunk)
  5. Amniotic fluid (MVP ≥2 cm)
• Score 8-10/10: reassuring; routine management
• Score 6/10: equivocal; repeat in 24 hours (or deliver if term)
• Score 4/10 or less: consider delivery

Contraction Stress Test (CST) / Oxytocin Challenge Test (OCT)

• Assess fetal heart rate response to uterine contractions (3 in 10 min)
• Negative (normal): no late decelerations - fetal reserve adequate
• Positive (abnormal): persistent late decelerations - placental reserve inadequate; delivery may be needed
• Largely replaced by BPP and Doppler

Umbilical Artery Doppler

• Measures placental vascular resistance
• Used in growth-restricted fetuses
• AEDF or REDF: high risk of perinatal mortality; hospitalization and delivery planning indicated

Indications for Antenatal Surveillance

• IUGR, oligohydramnios, post-term pregnancy, preeclampsia, diabetes with vascular disease, SLE, prior stillbirth, alloimmunization, multiple gestations with growth discordance

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TOPIC 16: ABORTION

Definitions

• Spontaneous abortion (miscarriage): pregnancy loss <20 weeks (some definitions use <500 g)
• Occurs in ~15-20% of recognized pregnancies; up to 50% of all conceptions

Types of Spontaneous Abortion

• Expectant: await natural expulsion; 80% complete in 2 weeks
• Medical: misoprostol (vaginal/sublingual/buccal); highly effective (80-95% complete)
• Surgical: manual vacuum aspiration (MVA) or suction curettage; most rapid, nearly 100% effective

Recurrent Pregnancy Loss (RPL)

• Defined as ≥3 (or ≥2 by ASRM 2012) consecutive losses <20 weeks
• Causes and workup:
  • Anatomic: uterine anomalies, fibroids, polyps, intrauterine adhesions (hysteroscopy/SIS)
  • Genetic: parental karyotype; products of conception karyotype
  • Thrombophilia: antiphospholipid syndrome (APS) - most important treatable cause; test: anticardiolipin Ab, anti-beta2-glycoprotein I Ab, lupus anticoagulant
  • Hormonal: poorly controlled thyroid, hyperprolactinemia, poorly controlled diabetes
  • ~50% unexplained

Septic Abortion

• Infection of products of conception/uterus
• Signs: fever, uterine tenderness, purulent discharge, systemic illness
• Serious complication: endotoxic shock, DIC
• Management: broad-spectrum IV antibiotics + uterine evacuation (do NOT delay evacuation)

Elective Termination of Pregnancy

• Medical (up to 10 weeks): mifepristone (antiprogesterone) + misoprostol (prostaglandin); 95-98% effective
• Surgical: suction curettage (first trimester); D&E (dilation and evacuation) second trimester; intact D&X (partial birth, rarely performed)

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TOPIC 17: ECTOPIC PREGNANCY

Definition

• Tubal: 95-97% (ampulla most common ~70%; isthmus ~12%; fimbria ~11%)
• Non-tubal: cornual/interstitial (2%), ovarian (3%), cervical (<1%), abdominal (<1%), cesarean scar (<1%)
• Heterotopic: simultaneous intrauterine + ectopic (rare spontaneously; 1:100 with IVF)

Risk Factors

• Prior ectopic pregnancy (most significant; 10-15% recurrence)
• Prior PID/salpingitis
• Tubal surgery or sterilization
• IUD use (not causative; if pregnant with IUD, higher proportion is ectopic)
• Assisted reproduction (IVF)
• Smoking
• Previous cesarean or abdominal surgery
• Endometriosis

Diagnosis

• Serial quantitative serum beta-hCG every 48 hours
• Normal viable IUP: hCG rises ≥66% every 48 hours
• Ectopic/non-viable: hCG plateaus, rises suboptimally, or falls (but not diagnostic alone)
• Discriminatory zone: hCG level at which IUP should be visible on TVS (~1500-3500 IU/L depending on institution); if above discriminatory zone and no IUP seen on TVS → concern for ectopic

• Definitive if extrauterine gestational sac seen (with yolk sac or embryo)
• Empty uterus + adnexal mass + free fluid = high suspicion
• "Pseudogestational sac" in uterus: decidual reaction, not a true GS

Management

• Very select criteria: hCG <200 IU/L and falling, small unruptured ectopic, asymptomatic

• Mechanism: folate antagonist; inhibits trophoblast cell division
• Single-dose protocol: MTX 50 mg/m²; monitor hCG days 4 and 7; successful if >15% drop
• Criteria: hemodynamically stable, unruptured, hCG <5000 IU/L (relative), no fetal cardiac activity, no contraindications, compliant patient, no immunodeficiency/liver/renal disease
• After MTX: avoid NSAIDs, folic acid supplements, alcohol; avoid sun exposure; use contraception for 3 months

• Salpingostomy (tube preserved) vs. salpingectomy (tube removed)
• Salpingectomy preferred for: ruptured ectopic, recurrent ectopic in same tube, severely damaged tube, patient wishes
• Laparoscopy preferred over laparotomy if stable
• Emergency laparotomy/laparoscopy for ruptured/hemodynamically unstable

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TOPIC 18: GESTATIONAL TROPHOBLASTIC DISEASE (GTD)

Classification

Hydatidiform Mole (Molar Pregnancy)

• Karyotype: 46,XX (diploid) - all paternal origin (androgenetic); 46,XY less common
• No fetal/embryonic tissue
• All villi are hydropic
• Risk of malignant transformation: 15-20%
• Very high hCG

• Karyotype: 69,XXX or 69,XXY (triploid) - two paternal + one maternal haploid sets
• Fetal/embryonic tissue present (usually non-viable)
• Risk of malignant transformation: 1-5%
• Moderate hCG elevation

• Vaginal bleeding, uterine size > dates, hyperemesis (from high hCG), early preeclampsia (<20 weeks), hyperthyroidism (hCG cross-reacts with TSH receptor)
• Ultrasound: "snowstorm" appearance (complete mole); no fetal heart tones (complete mole)

• Suction curettage; send tissue for histology
• Serial hCG monitoring weekly until 3 consecutive normal values, then monthly x 6 months
• Contraception during monitoring (avoid pregnancy, which confounds hCG interpretation; OCP is fine)
• Prophylactic chemotherapy: not routinely recommended; may be considered in high-risk patients without reliable follow-up

Gestational Trophoblastic Neoplasia (GTN)

• Highly malignant; can follow mole, normal pregnancy, ectopic, abortion
• Hematogenous spread to lungs (most common), brain, liver
• Extremely chemosensitive; cure rates >90%

• Rare; arises from intermediate trophoblast
• Secretes hPL more than hCG
• Less chemosensitive; hysterectomy preferred

• WHO scoring system (0-6 low risk; 7+ high risk)
• Variables: age, prior pregnancy type, interval from index pregnancy, hCG level, tumor size, metastasis sites, number of metastases, prior chemotherapy

• Low-risk GTN: single-agent MTX or actinomycin D; >90% cure rate
• High-risk GTN: multi-agent chemotherapy (EMA-CO regimen); 80-90% cure rate
• Hysterectomy: for PSTT or chemotherapy-resistant disease; fertility-sparing usually possible in low-risk

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TOPIC 19: GENERAL ASSESSMENT OF THE PREGNANT WOMAN

Obstetric Triage Assessment

• Gestational age; presenting complaint
• Vital signs, fetal heart rate, uterine activity
• Vaginal bleeding, discharge, fluid leakage
• Fetal movement assessment
• Cervical examination (if appropriate)

Prenatal Labs and Normal Ranges in Pregnancy

Gestational Diabetes Mellitus (GDM) Screening and Diagnosis

• Screen (1-hr GCT): 50 g glucose; positive if ≥140 mg/dL (some use ≥130 mg/dL)
• Diagnose (3-hr GTT): 100 g glucose; Carpenter-Coustan criteria: fasting ≥95, 1hr ≥180, 2hr ≥155, 3hr ≥140 mg/dL; ≥2 values elevated = GDM
• IADPSG criteria (2-hr 75g OGTT; fasting ≥92, 1hr ≥180, 2hr ≥153 mg/dL; any 1 value = GDM)

Hypertensive Disorders Screening and Assessment

• BP at every visit; defined hypertension in pregnancy ≥140/90 mmHg on two occasions ≥4 hours apart
• Preeclampsia added features (after 20 weeks): proteinuria (≥300 mg/24h, or protein:creatinine ≥0.3), or severe features without proteinuria (thrombocytopenia, renal insufficiency, liver dysfunction, pulmonary edema, new headache)

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TOPIC 20: MEDICAL DISORDERS IN PREGNANCY

Hypertensive Disorders

1. Chronic hypertension: pre-existing or diagnosed <20 weeks
2. Gestational hypertension: new-onset ≥20 weeks; no proteinuria/severe features; resolves by 12 weeks postpartum
3. Preeclampsia: new-onset hypertension ≥20 weeks + proteinuria OR severe features
4. Preeclampsia with severe features (any one): SBP ≥160 or DBP ≥110, thrombocytopenia <100,000, creatinine >1.1 mg/dL, doubled creatinine, impaired liver function (2x ULN), pulmonary edema, new-onset headache, visual disturbances
5. HELLP syndrome: Hemolysis, Elevated Liver enzymes, Low Platelets
6. Eclampsia: new-onset seizures in preeclampsia patient
7. Superimposed preeclampsia: preeclampsia in patient with chronic hypertension

• Abnormal trophoblast invasion → impaired spiral artery remodeling → placental ischemia → maternal systemic endothelial dysfunction → hypertension, proteinuria, multi-organ injury

• Low-dose aspirin (81 mg/day) from 12-28 weeks (optimally before 16 weeks) to delivery in high-risk patients
• High-risk: prior preeclampsia, multifetal gestation, chronic hypertension, diabetes, renal disease, autoimmune disease

• Antihypertensives for severe range BP (≥160/110): labetalol IV, hydralazine IV, oral nifedipine (immediate release); goal: BP 140-155/90-105 mmHg
• Seizure prophylaxis: magnesium sulfate (4g IV bolus, 2g/hour maintenance) for preeclampsia with severe features; prevention AND treatment of eclampsia
• Eclampsia seizure: magnesium 4-6g IV; secure airway; lateral decubitus; deliver after stabilization
• Definitive treatment: delivery
  • ≥37 weeks: deliver
  • <37 weeks with severe features: deliver at ≥34 weeks (hospitalize and stabilize)
  • Expectant management <34 weeks without severe features with close monitoring

• More severe form; triad: microangiopathic hemolytic anemia (LDH >600, low haptoglobin), elevated liver enzymes (>2x ULN), platelets <100,000
• Management: magnesium, antihypertensives, steroids for fetal maturity, delivery ≥34 weeks (immediate if unstable)

Diabetes in Pregnancy

• Risks: congenital anomalies (cardiac, NTDs - related to first trimester glycemia), miscarriage, macrosomia, preeclampsia, IUGR (with vascular disease), polyhydramnios, shoulder dystocia, stillbirth
• Management: tight glycemic control (HbA1c <6-6.5%); folic acid 4 mg/day; anatomy scan at 18-20 weeks; fetal echo at 20-22 weeks; growth US every 4 weeks from 28 weeks; NST from 32-36 weeks; delivery by 39-40 weeks

• Screen 24-28 weeks (see Topic 19)
• Management: dietary modification first; if targets not met (fasting <95 mg/dL; 1-hr post-meal <140 mg/dL; 2-hr <120 mg/dL): insulin (first-line); metformin and glyburide are alternatives
• Delivery: well-controlled GDM, no other complications → 39-40 weeks; macrosomia or poor control → earlier

Cardiac Disease in Pregnancy

• 1-4% of pregnancies; leading cause of indirect maternal death in developed countries
• High-risk lesions (pregnancy contraindicated or high risk): severe pulmonary hypertension (Eisenmenger syndrome - mortality 30-50%), severe systolic dysfunction (EF <30%), severe left heart obstruction (AS, MS)

• Heart failure from last month of pregnancy to 5 months postpartum; no other cause
• EF <45%; dilated cardiomyopathy
• Treatment: standard HF therapy (diuretics, beta-blockers, ACEI postpartum); bromocriptine (prolactin inhibitor) shows benefit in some studies
• Prognosis: ~50% fully recover EF; recurrence risk in subsequent pregnancies

Thyroid Disease

• Associated with: miscarriage, preterm birth, gestational hypertension, impaired fetal neurodevelopment
• Management: levothyroxine; increase dose by 25-30% as soon as pregnancy confirmed; monitor TSH every 4-6 weeks; target TSH <2.5 mIU/L in first trimester

• Most common cause: Graves disease
• Fetal risks: IUGR, preterm birth, fetal hyperthyroidism (from TSI crossing placenta)
• Treatment: PTU (propylthiouracil) first trimester; methimazole (second/third trimester; PTU associated with hepatotoxicity; methimazole associated with aplasia cutis if used in first trimester); thyroidectomy if refractory
• Thyroid storm: rare; managed with PTU, beta-blockers, iodine, dexamethasone, supportive care

Venous Thromboembolism (VTE)

• Pregnancy is hypercoagulable state; VTE risk 5x that of non-pregnant women
• DVT most common in left leg (iliac vein compression by right iliac artery)
• Diagnosis: compression ultrasound for DVT; V/Q scan or CT pulmonary angiography for PE
• Treatment: LMWH throughout pregnancy (warfarin crosses placenta - teratogenic in first trimester, hemorrhagic fetal risk throughout)
• Prophylaxis: LMWH for prior VTE, high-risk thrombophilias

Infections in Pregnancy

• Screened at 36-37 weeks (vaginal-rectal swab)
• Intrapartum antibiotic prophylaxis (IAP) for GBS-positive, prior GBS infant, GBS bacteriuria in current pregnancy, unknown status with risk factors (preterm labor, prolonged ROM, fever in labor)
• IAP: penicillin G IV (first-line); ampicillin; clindamycin or cefazolin if penicillin-allergic
• Prevents early-onset neonatal GBS disease

• Foodborne (raw milk, soft cheeses, deli meats); disproportionately affects pregnant women
• Causes: flu-like illness, amnionitis, preterm labor, fetal infection
• Treatment: ampicillin ± gentamicin

• Asymptomatic bacteriuria: treat in pregnancy (increases risk of pyelonephritis, preterm birth if untreated)
• Pyelonephritis: most common serious infection in pregnancy; IV ampicillin + gentamicin or cephalosporins; hospitalization; may trigger preterm labor

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TOPIC 21: PHYSIOLOGY OF LABOR

Definition of Labor

Uterine Activity

• Smooth muscle; actin-myosin interaction regulated by myosin light-chain kinase (MLCK)
• Resting potential maintained by progesterone throughout pregnancy (progesterone maintains uterine quiescence)
• Oxytocin receptors increase dramatically near term
• Gap junctions form between myometrial cells near term (allows synchronized contractions)

• Remodeling of extracellular matrix: collagen breakdown, increased hydration, prostaglandin (PGE2) activity
• Cervix softens, effaces, dilates
• Progesterone withdrawal (functional in humans - progesterone receptor isoform shift) is key initiating event

Prostaglandins in Labor

• PGE2 (from amnion, chorion, decidua): cervical ripening, stimulates uterine contractions
• PGF2α (from decidua): potent uterotonic
• Key role in initiation of labor at term

Oxytocin

• Released from posterior pituitary; pulsatile pattern
• Stimulates uterine contractions via Gq-coupled oxytocin receptors
• Levels increase in labor, especially in second stage
• Exogenous oxytocin widely used for induction/augmentation

Stages of Labor

1. First stage: onset of active labor to full cervical dilation (10 cm)
   • Latent phase: to 6 cm; irregular, mild contractions; cervical effacement predominates
   • Active phase: 6-10 cm; regular, stronger contractions; rapid dilation
2. Second stage: full dilation to delivery of infant
3. Third stage: delivery of infant to delivery of placenta

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TOPIC 22: NORMAL LABOR

Diagnosis of Labor

Active Labor (ACOG 2014 definition)

• Active phase begins at 6 cm (previously 4 cm)
• Minimum acceptable rate of cervical change in active phase: 1 cm/hour (older); ACOG 2014: active labor does not require 1.2 cm/hr; labor abnormal if no progress over 4 hours with adequate contractions, or 6 hours with inadequate contractions

Cardinal Movements of Labor

1. Engagement: biparietal diameter passes through pelvic inlet
2. Descent: progressive downward movement
3. Flexion: head flexes, presenting smaller suboccipitobregmatic diameter
4. Internal rotation: occiput rotates anteriorly (from transverse to AP)
5. Extension: head extends under pubic symphysis and delivers
6. External rotation (restitution): head rotates to align with fetal shoulders
7. Expulsion: anterior then posterior shoulder delivered

Normal Labor Duration (ACOG/SMFM 2014 guidelines)

• Latent phase: can be prolonged (>20 hours nullipara, >14 hours multipara) before declaring abnormal labor
• Active phase: at least 1 cm/2 hours before cesarian for failure to progress (not 1 cm/hr as previously)
• Second stage: no intervention before:
  • Nullipara: 3 hours without epidural, 4 hours with epidural
  • Multipara: 2 hours without epidural, 3 hours with epidural

Third Stage Management

• Active management: oxytocin 10 units IM (or IV) immediately after delivery → reduces PPH risk by 40%
• Controlled cord traction + uterine massage
• Normal third stage: <30 minutes; placenta delivered by 30-45 minutes in most cases
• Signs of placental separation: gush of blood, lengthening of cord, uterus becomes globular and rises in abdomen

Episiotomy

• Mediolateral: reduced risk of third/fourth degree laceration
• Midline: easier to repair, more comfortable; higher risk of extension to sphincter
• Routine episiotomy: NOT recommended (increases lacerations, blood loss, pain)
• Selective episiotomy for: operative vaginal delivery, malpresentation, imminent severe lacerations

Perineal Lacerations

• 1st degree: mucosa and skin only
• 2nd degree: into perineal muscles
• 3rd degree: into/through external anal sphincter (3a: <50% sphincter; 3b: >50%; 3c: internal sphincter)
• 4th degree: through rectal mucosa

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TOPIC 23: ABNORMAL LABOR

Dystocia (Failure to Progress)

1. Powers: inadequate uterine contractions or maternal expulsive effort
2. Passenger: fetal macrosomia, malpresentation, asynclitism, hydrocephalus
3. Passageway: pelvic inadequacy, contracted pelvis, soft tissue obstruction

Abnormalities of the First Stage

• Nullipara: >20 hours; multipara: >14 hours
• Management: therapeutic rest (morphine), amniotomy, oxytocin augmentation

• Dilation <1 cm/2 hr despite adequate contractions
• Management: amniotomy + oxytocin; reassess passenger and passageway

• No cervical change for ≥4 hours with adequate contractions (Montevideo units ≥200) or ≥6 hours with inadequate contractions
• Management: augment oxytocin; if adequate contractions + no progress → cesarean

Abnormalities of the Second Stage

• Arrest in second stage (as per normal labor duration thresholds above)
• Management: operative vaginal delivery (if criteria met) or cesarean

Malpresentation

• Head is flexed but occiput faces posteriorly
• Associated with: android pelvis, anthropoid pelvis, poor head flexion
• Long labors, increased operative delivery
• Management: rotation (manual or forceps); can deliver face-to-pubes (persistent OP) if large enough outlet

• Head arrested in transverse position at midpelvis
• Common with platypelloid pelvis, inadequate contractions
• Management: oxytocin augmentation, manual rotation, rotational forceps (Kielland), vacuum, cesarean

• Partial extension; mentum-vertical diameter presents (largest possible diameter)
• Almost never delivers vaginally; usually requires cesarean

• Full extension; face presents
• Chin anterior (mento-anterior) may deliver vaginally
• Chin posterior (mento-posterior) cannot deliver vaginally → cesarean

Cephalopelvic Disproportion (CPD)

• True CPD: head too large for pelvis
• Relative CPD: malpresentation or asynclitism causes apparent disproportion
• Diagnosed retrospectively after adequate trial of labor

Uterine Rupture

• Catastrophic; complete: involves full thickness including serosa
• Risk factors: prior uterine surgery (prior CS most common), uterine anomaly, high parity, obstructed labor, oxytocin misuse, prior classical cesarean incision
• Symptoms: sudden severe pain, loss of fetal station, abnormal FHR (bradycardia, late decelerations), vaginal bleeding, maternal hemodynamic instability
• Management: immediate laparotomy; repair if possible; hysterectomy if necessary; aggressive resuscitation

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TOPIC 24: INTRAPARTUM ASSESSMENT

Electronic Fetal Monitoring (EFM/CTG)

Terminology (NICHD 2008)

• Absent: undetectable amplitude
• Minimal: >0 but ≤5 bpm
• Moderate (normal): 6-25 bpm
• Marked: >25 bpm

• ≥32 weeks: peak ≥15 bpm above baseline, ≥15 seconds duration
• <32 weeks: peak ≥10 bpm, ≥10 seconds

• Early: gradual onset, nadir with peak of contraction; head compression (vagal); benign
• Late: gradual onset, nadir after peak of contraction; uteroplacental insufficiency; significant if persistent
• Variable: abrupt onset, V-shaped; cord compression; significance depends on severity and persistence
• Prolonged: ≥15 bpm below baseline for ≥2 minutes but <10 minutes; significant

Three-Tier Classification

• Baseline 110-160 bpm, moderate variability, late/variable decelerations absent, early decelerations present/absent, accelerations present/absent
• No intervention required

• Does not meet Category I or III criteria
• Requires evaluation, surveillance, and reevaluation; correct reversible causes

• Sinusoidal pattern, OR
• Absent baseline variability with: recurrent late decelerations, recurrent variable decelerations, or bradycardia
• Requires expeditious delivery after failed resuscitative efforts

Intrauterine Resuscitation

1. Left lateral decubitus (relieve aortocaval compression)
2. IV fluid bolus
3. Discontinue or reduce oxytocin
4. Supplemental oxygen
5. Correct hypotension (especially post-epidural): IV ephedrine or phenylephrine
6. Amnioinfusion for variable decelerations (cord compression)
7. Tocolysis (terbutaline 0.25 mg SQ) for tachysystole
8. If unresolving Category III: expedite delivery

Fetal Scalp Stimulation

• Compression or pinching of fetal scalp; if acceleration results → strongly associated with fetal pH >7.20
• Negative stimulation does not confirm acidosis but warrants further evaluation

Intrauterine Pressure Catheter (IUPC)

• Invasive; measures contraction intensity in mmHg; allows MVU calculation
• Indicated when external monitoring insufficient or need to assess uterine activity objectively

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TOPIC 25: INDUCTION AND AUGMENTATION OF LABOR

Indications for Induction

• Post-term pregnancy (≥41 weeks; ARRIVE trial: elective induction at 39 weeks reduces CS rate and perinatal mortality)
• Preeclampsia/eclampsia
• PROM at term
• Fetal compromise (IUGR, oligohydramnios, abnormal Doppler)
• Diabetes mellitus (type 1/2: 39 weeks; GDM with insulin: 39-40 weeks)
• Placental abruption (without maternal/fetal compromise)
• Maternal medical conditions (hypertension, cardiac disease)
• Logistical reasons (remote from hospital, rapid laborer) - elective induction only at ≥39 weeks

Cervical Ripening (Unfavorable Cervix, Bishop Score <6)

• Dinoprostone (PGE2): Cervidil (slow-release vaginal insert, 10 mg; remove after 12 hours or onset of active labor); Prepidil (gel, 0.5 mg intracervically every 6 hours x3)
• Misoprostol (PGE1 analogue): 25 mcg vaginally or 25 mcg orally every 4 hours; off-label but widely used; inexpensive; contraindicated with prior uterine scar (higher uterine rupture risk)
• Prostaglandins contraindicated in: prior cesarean/uterine scar (use with caution), active asthma (PGF2α), placenta previa, non-reassuring FHR

• Foley catheter balloon: 30-80 mL inflated in cervix; mechanical ripening; safe with prior cesarean
• Osmotic cervical dilators (laminaria): hygroscopic; placed in cervical canal night before

Amniotomy (AROM)

• Artificial rupture of membranes
• Shortens labor by ~1-2 hours
• Requires engaged presenting part to avoid cord prolapse
• Irreversible; increases risk of cord prolapse, chorioamnionitis with prolonged ROM

Oxytocin

• Synthetic peptide; IV administration
• Low-dose vs. high-dose protocols (various; most start at 0.5-2 mU/min, increase by 1-2 mU/min every 15-40 minutes)
• Maximum dose: 20-40 mU/min (institution dependent)
• Tachysystole: >5 contractions in 10 minutes in any 20-minute window; reduce/stop oxytocin
• Complications: uterine hyperstimulation (→ fetal distress), water intoxication at high doses (oxytocin has ADH-like activity), hypotension if rapid IV bolus
• Antidote for hyperstimulation: stop oxytocin; terbutaline 0.25 mg SQ

Contraindications to Labor Induction

• Placenta previa
• Prior classical cesarean
• Active genital herpes (primary outbreak)
• Transverse lie
• Umbilical cord prolapse
• Certain fetal conditions (e.g., severe hydrocephalus with planned cesarean)

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TOPIC 26: OBSTETRIC ANALGESIA AND ANESTHESIA

Labor Pain Pathways

• First stage: visceral pain via T10-L1 (cervical dilation, uterine contractions)
• Second stage: somatic pain via S2-S4 (perineal distension, pudendal nerve)

Non-Pharmacological Methods

• Hydrotherapy, TENS, acupuncture, sterile water injections, breathing techniques
• Modest efficacy; no fetal risk

Systemic Opioids

• IV or IM narcotics: fentanyl (IV, short duration), morphine, meperidine (Demerol)
• Cross placenta; neonatal respiratory depression if given close to delivery
• Naloxone for neonatal reversal
• Patient-controlled analgesia (PCA): IV fentanyl commonly used

Nitrous Oxide

• 50:50 nitrous oxide/oxygen (Entonox); inhaled by patient
• Moderate pain relief; patient-controlled; safe for fetus
• Common in Europe; increasing use in USA

Neuraxial Anesthesia (Epidural/Spinal)

• Catheter in epidural space (lumbar); most common form of labor analgesia
• Agents: local anesthetic (bupivacaine, ropivacaine) ± opioid (fentanyl)
• Combined spinal-epidural (CSE): spinal for rapid onset + epidural catheter for maintenance
• Advantages: superior pain relief, can be extended for operative delivery, no neonatal respiratory depression
• Complications: hypotension (most common; treat with IV fluids, ephedrine/phenylephrine); dural puncture headache (~1%); high spinal (intrathecal injection → respiratory arrest); epidural hematoma/abscess (rare)

• Patient refusal
• Coagulopathy (platelets <80,000 or abnormal coagulation)
• Anticoagulation within therapeutic window
• Local infection at injection site
• Hemodynamic instability
• Increased ICP

• Slows labor slightly and increases instrumental delivery rate (but high-quality evidence suggests does not increase cesarean rate)

Spinal Anesthesia

• Single injection into subarachnoid space; used for cesarean delivery
• Fast onset, dense block
• Agents: hyperbaric bupivacaine + fentanyl + morphine (for postoperative analgesia)
• Most common form of anesthesia for elective cesarean

General Anesthesia (GA)

• Reserved for: epidural failure, contraindications to neuraxial, emergency cesarean requiring rapid induction
• Risks: difficult/failed airway (more common in obstetric patients), aspiration (Mendelson syndrome)
• Rapid sequence induction (RSI) mandatory: cricoid pressure (Sellick maneuver), thiopental or ketamine + succinylcholine
• Avoid gastric aspiration: NPO guidelines, sodium citrate antacid, metoclopramide pre-op

Postpartum Analgesia

• NSAIDs: highly effective; first-line after vaginal delivery (ibuprofen, ketorolac)
• Acetaminophen: effective, safe in breastfeeding
• Opioids: reserve for severe pain; short course; monitor for sedation in breastfed neonate

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TOPIC 27: VAGINAL DELIVERY

Preparation

• Verify gestational age, presentation (vertex), fetal wellbeing (continuous or intermittent monitoring)
• IV access, maternal consent, analgesia
• Bladder emptied; positioning: lithotomy or semi-recumbent

Mechanism of Normal Delivery (Recap)

Delivery of the Head

• Allow gradual crowning; controlled expulsion prevents perineal lacerations
• Check for nuchal cord: if present, attempt to reduce (slip over head); if tight, double-clamp and cut ("somersault maneuver" alternative)
• Bulb suction of mouth/nose: only if meconium-stained fluid and not crying

Delivery of the Shoulders

• After external rotation, gentle downward traction on head for anterior shoulder under pubic symphysis
• Then upward traction for posterior shoulder
• Risk: shoulder dystocia

Shoulder Dystocia

• McRoberts maneuver: hyperflexion of maternal thighs onto abdomen (most effective first step; flattens lumbar lordosis, rotates pubic symphysis superiorly)
• Suprapubic pressure: by assistant (NOT fundal pressure); dislodges anterior shoulder
• H - Call for Help
• E - Evaluate for Episiotomy (if needed for access)
• L - Legs (McRoberts)
• P - Suprapubic Pressure
• E - Enter (internal rotational maneuvers):
  • Rubin II: pressure on posterior aspect of anterior shoulder (inward)
  • Woods screw: pressure on anterior aspect of posterior shoulder (outward)
  • Zavanelli: considered last resort (cephalic replacement then cesarean)
• R - Remove posterior arm: sweep posterior arm across chest
• R - Roll patient to all-fours (Gaskin maneuver): often effective, especially for birthing centers

Third Stage

• Active management: oxytocin + controlled cord traction + uterine massage
• Signs of separation: gush of blood, cord lengthens, uterus contracts and rises
• Inspect placenta for completeness; inspect membranes

Repair of Lacerations

• Continuous suture; adequate analgesia; restore anatomy
• Fourth-degree lacerations require sphincter repair (overlapping or end-to-end) + bowel prep/stool softener

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TOPIC 28: BREECH DELIVERY

Types of Breech Presentation

• Frank breech (~65%): hips flexed, knees extended (legs alongside trunk); most common; most favorable for vaginal delivery
• Complete breech (~10%): hips and knees flexed (fetus in "cannonball" position)
• Incomplete/Footling breech (~25%): one or both feet below the buttocks; highest risk for cord prolapse

Incidence and Risk Factors

• 3-4% at term (25% at 28 weeks; spontaneous version common before term)
• Risk factors: uterine anomalies, fibroids, placenta previa, prior breech, fetal anomalies (hydrocephalus), multiple gestation, oligohydramnios, polyhydramnios

External Cephalic Version (ECV)

• Manual external rotation of fetus to vertex presentation
• Performed at 36-37+ weeks
• Success rate: ~50-60% (lower with anterior placenta, nulliparity, normal AFI, engaged breech)
• Requires: reactive NST before, continuous FHR monitoring, IV access, O-negative blood available
• Tocolysis (terbutaline 0.25 mg SQ) commonly used; neuraxial anesthesia may improve success
• Complications: placental abruption, cord prolapse, fetal bradycardia, PROM (rare, ~0.5-1%)
• Contraindications: PROM, placenta previa, non-reactive NST, uterine scar (relative), fetal anomaly incompatible with survival

Planned Cesarean for Breech

• Standard of care since Term Breech Trial (Hannah 2000): significantly reduced neonatal morbidity/mortality vs. planned vaginal delivery
• Planned at 38-39 weeks

Vaginal Breech Delivery

• Still performed in select circumstances (premature breech, second twin, precipitous delivery, patient preference, experienced provider)
• Requires: frank or complete breech, adequate pelvis, no fetal anomalies, EFW 2000-3500g, experienced provider

1. Allow spontaneous descent to umbilicus; avoid temptation to pull
2. Loop of cord pulled down after umbilicus delivered
3. Lovset maneuver: rotate trunk 180° to deliver arms
4. Delivery of after-coming head:
   • Mauriceau-Smellie-Veit (MSV): infant straddles forearm; finger in mouth for flexion; two fingers on shoulders for traction
   • Piper forceps: applied to after-coming head for controlled delivery
5. Maintain head flexion throughout

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TOPIC 29: OPERATIVE VAGINAL DELIVERY

Definition

Indications

• Prolonged second stage (meeting ACOG time thresholds)
• Non-reassuring fetal status in second stage
• Maternal condition requiring shortened second stage (severe cardiac disease, exhaustion)

Prerequisites (ACOG)

• Fully dilated cervix
• Ruptured membranes
• Known fetal presentation and position
• Engaged fetal head (0 station or below)
• Adequate maternal pelvis
• Empty bladder
• Adequate analgesia
• Provider trained and willing to perform cesarean if needed

Vacuum Extractor

• Soft silicone cup or rigid metal cup applied to fetal occiput (over posterior fontanelle)
• Traction applied with contractions + maternal pushing
• Maximum: 3 pop-offs, 3 pulls without descent, total duration <30 minutes
• Complications: cephalohematoma (subperiosteal - most common), caput succedaneum, subgaleal hematoma (most serious - can cause severe hemorrhage), scalp lacerations, intracranial hemorrhage
• Contraindications: prematurity (<34 weeks), face or brow presentation, unengaged head

Forceps

• Two interlocking blades: cephalic curve matches fetal head; pelvic curve matches pelvis
• Outlet forceps, low forceps, mid-forceps (based on station)
• Types: Simpson (elongated head), Tucker-McLane, Elliott (round head), Kielland (rotational)
• Application: left blade first (posterior position, then rotate to left side of pelvis); right blade second; lock; check application (sagittal suture perpendicular to shanks)
• Traction: Pajot's maneuver (downward + outward); with contractions
• Complications: 3rd/4th degree lacerations, facial nerve injury, skull fracture, intracranial hemorrhage

Sequential Use (Vacuum then Forceps)

• Strongly discouraged: significantly increases risk of intracranial hemorrhage; if vacuum fails, proceed to cesarean

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TOPIC 30: CESAREAN DELIVERY

Indications

• Placenta previa (complete or near-complete)
• Prior classical/T-incision cesarean
• Vasa previa
• Obstructed labor (CPD)
• Active genital herpes (primary outbreak)
• Placenta accreta spectrum (planned)

• Non-reassuring fetal status not responding to resuscitation
• Failure to progress in labor
• Malpresentation at term (breech, transverse lie)
• Umbilical cord prolapse
• Uterine rupture
• Macrosomia with prior shoulder dystocia
• Multiple gestation (first twin non-vertex)

Incision Types

• Low transverse (LSCS/Kerr): most common; transverse incision in lower uterine segment; lowest risk of rupture in subsequent pregnancy (~0.5-0.9%)
• Low vertical: occasionally needed for poorly formed LUS, preterm, transverse lie; slightly higher rupture risk
• Classical (vertical in upper segment): reserved for: extreme prematurity (LUS not formed), anterior placenta previa/accreta, transverse lie with ruptured membranes, cervical cancer; highest rupture risk (~4-9%); precludes TOLAC

• Pfannenstiel: most common; transverse, below hairline; cosmetically superior
• Midline vertical: faster access; used in emergencies

Procedure

1. Abdominal entry (Pfannenstiel or midline)
2. Bladder flap dissection; bladder retracted inferiorly
3. Low transverse uterine incision
4. Delivery of fetus; neonatal resuscitation team present
5. Delivery of placenta (manual or spontaneous)
6. Uterine repair (single vs. double layer closure)
7. Abdominal closure in layers

Complications

• Hemorrhage: most common indication for peripartum hysterectomy
• Bladder/ureter injury (increased with prior surgeries, accreta)
• Bowel injury
• Infection: endometritis, wound infection, UTI
• VTE (higher risk than vaginal delivery)
• Anesthesia complications
• Future placentation complications: accreta spectrum, previa

Pre-operative Considerations

• NPO 6-8 hours (or per anesthesia protocol)
• Antacid prophylaxis (sodium citrate) + H2 blocker
• Foley catheter
• Antibiotic prophylaxis: cefazolin 2g IV within 60 minutes (single dose) - reduces endometritis and wound infection significantly
• DVT prophylaxis: sequential compression devices; LMWH in high-risk patients

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TOPIC 31: PRIOR CESAREAN DELIVERY

Trial of Labor After Cesarean (TOLAC)

• One or two prior low transverse uterine incisions
• Clinically adequate pelvis
• No other uterine scars
• Continuous EFM in labor
• Facility capable of emergency cesarean within 30 minutes (ACOG)

• Success rate: ~60-80% overall; higher with: prior vaginal delivery, favorable cervix, spontaneous labor, non-recurrent indication for prior CS
• VBAC calculator (Grobman calculator): predicts individual success probability

• Prior classical cesarean or T-incision
• Prior uterine rupture
• Prior myomectomy entering endometrial cavity
• Placenta previa or accreta

• Prior low transverse: 0.5-0.9%
• Prior low vertical: ~1-2%
• Prior classical: 4-9%
• Two prior low transverse: ~0.9% (similar to one)

• Oxytocin for augmentation: acceptable (slightly increased rupture risk)
• Induction with oxytocin: acceptable but increases rupture risk (~1.5x)
• Misoprostol: contraindicated (high uterine rupture risk)
• Foley balloon ripening: acceptable

• Sudden severe pain (often felt even with epidural)
• Fetal bradycardia or prolonged deceleration (most common sign)
• Loss of fetal station
• Maternal tachycardia, hypotension
• Hematuria

Planned Repeat Cesarean

• Offered as alternative to TOLAC
• Reduced risk of uterine rupture
• Increased risks: placenta accreta spectrum with subsequent pregnancies, surgical complications, longer recovery
• Timing: elective repeat cesarean at 39 0/7 weeks (reduces neonatal respiratory morbidity)

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TOPIC 32: THE NEWBORN

Immediate Assessment and Care

• 7-10: Normal
• 4-6: Moderate depression; stimulate
• 0-3: Severe depression; resuscitation needed

Neonatal Resuscitation (NRP)

• Initial steps: warm, dry, stimulate; clear airway (suction if needed; not routine for clear fluid)
• HR <100 bpm: positive pressure ventilation (PPV) with room air or 21% O2
• HR <60 bpm after PPV x 30 sec: chest compressions (3:1 ratio); increase O2 to 100%
• HR still <60: epinephrine (IV via umbilical vein; 0.01-0.03 mg/kg)
• No meconium and vigorous infant: routine care at mother's side; no routine suctioning

Routine Newborn Care

• Vitamin K 1 mg IM (prevents hemorrhagic disease of newborn)
• Erythromycin eye ointment (prevents gonorrheal ophthalmia neonatorum)
• Hepatitis B vaccine within 12-24 hours of birth (if HBsAg-negative mother)
• Newborn screening (metabolic, hemoglobin, hearing, pulse oximetry for CCHD)

Newborn Physical Exam

• Weight, length, head circumference; gestational age assessment (Ballard/Dubowitz)
• General: tone, color, activity, cry
• Head: fontanelles, sutures, caput/cephalohematoma
• Clavicles: fracture (Moro asymmetry)
• Cardiac: murmurs, pulses
• Abdomen: hepatosplenomegaly, umbilical vessels
• Genitalia, anus
• Extremities, hips (Ortolani/Barlow for DDH)
• Neurologic: Moro, grasp, root, suck, stepping reflexes

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TOPIC 33: PRETERM NEWBORN

Definitions

• Preterm: <37 completed weeks
• Very preterm: <32 weeks
• Extremely preterm: <28 weeks
• Late preterm: 34 0/7 - 36 6/7 weeks (largest subgroup; often undertreated)

Complications of Prematurity

• Respiratory Distress Syndrome (RDS/HMD): surfactant deficiency; ground-glass appearance on CXR; treatment: exogenous surfactant (beractant, calfactant) + CPAP or mechanical ventilation
• Antenatal corticosteroids (betamethasone 12 mg IM x2 doses, 24 hours apart) reduce RDS, IVH, NEC, and mortality
• Bronchopulmonary Dysplasia (BPD): chronic lung disease; O2 dependence at 36 weeks PMA

• Intraventricular hemorrhage (IVH): bleeding into germinal matrix; grades I-IV
  • Grade I: germinal matrix only
  • Grade II: IVH without ventricular dilation
  • Grade III: IVH with ventricular dilation
  • Grade IV: periventricular hemorrhagic infarction (severe, poor prognosis)
• Periventricular leukomalacia (PVL): white matter damage; cerebral palsy risk
• Magnesium sulfate given to mothers with preterm birth <32 weeks reduces risk of cerebral palsy

• Necrotizing enterocolitis (NEC): ischemic/inflammatory bowel necrosis; presents with feeding intolerance, bloody stools, abdominal distension; pneumatosis intestinalis on XR; treatment: NPO, antibiotics, TPN; surgery for perforation

• Patent ductus arteriosus (PDA): failure of ductus arteriosus to close; bounding pulses, wide pulse pressure, systolic murmur; treatment: indomethacin or ibuprofen (prostaglandin inhibitors) or surgical ligation; may require no treatment

• Retinopathy of prematurity (ROP): abnormal retinal vascular development; screen all infants <30 weeks or <1500g; treatment: laser photocoagulation, anti-VEGF

• Hypoglycemia, hypocalcemia, hypothermia, anemia of prematurity, jaundice

Late Preterm Infants (34-36 weeks)

• Higher rates of: feeding difficulties, hypoglycemia, jaundice, temperature instability, apnea, readmission
• Not as "near-term" as often assumed; require close monitoring

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TOPIC 34: DISEASES OF THE TERM NEWBORN

Neonatal Jaundice (Hyperbilirubinemia)

• Appears day 2-3; peaks day 3-5; resolves by day 1-2 weeks
• Due to high RBC turnover + immature hepatic conjugation

• ABO incompatibility (most common hemolytic cause)
• Rh hemolytic disease
• G6PD deficiency
• Polycythemia
• Infection (sepsis)
• Hypothyroidism
• Biliary atresia (conjugated hyperbilirubinemia; acholic stools, dark urine)

• Phototherapy: converts unconjugated bilirubin to water-soluble isomers excreted without conjugation
• Exchange transfusion: for severe hyperbilirubinemia or signs of kernicterus (bilirubin encephalopathy)
• Kernicterus: bilirubin deposition in basal ganglia; hypertonia/hypotonia, seizures, opisthotonos, hearing loss

Neonatal Infection

• Organisms: GBS (most common), E. coli, Listeria
• Risk factors: maternal GBS+ without IAP, PROM >18h, chorioamnionitis, prematurity
• Treatment: ampicillin + gentamicin

• CONS (coagulase-negative staph) most common in NICU; MRSA, Candida
• Often nosocomial

Meconium Aspiration Syndrome (MAS)

• Aspiration of meconium-stained amniotic fluid
• Causes: chemical pneumonitis, airway obstruction, secondary infection
• Treatment: supportive; surfactant; inhaled nitric oxide (iNO) for pulmonary hypertension; ECMO if refractory

Persistent Pulmonary Hypertension of Newborn (PPHN)

• Failure of normal postnatal decrease in pulmonary vascular resistance
• Right-to-left shunting through PDA/PFO
• Causes: MAS, asphyxia, sepsis, diaphragmatic hernia
• Treatment: optimize oxygenation/ventilation, iNO, sildenafil, ECMO

Neonatal Hypoglycemia

• Definition: glucose <40-45 mg/dL in first 4 hours; <45 mg/dL thereafter
• Risk groups: IDMs, SGA, LGA, preterm, hypoxic-ischemic injury
• Treatment: early feeding; IV dextrose if symptomatic or not correcting with feeds

Hypoxic-Ischemic Encephalopathy (HIE)

• Peripartum asphyxia → brain injury
• Sarnat grading: mild (I), moderate (II), severe (III)
• Therapeutic hypothermia: whole-body cooling to 33-34°C for 72 hours; initiated within 6 hours of birth; reduces death and disability in moderate-severe HIE
• EEG monitoring; MRI at 5-7 days for prognosis

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TOPIC 35: STILLBIRTH

Definition

• Fetal death at ≥20 weeks or ≥500 g birth weight (USA)
• WHO: ≥28 weeks for international comparisons

Incidence

• ~6 per 1000 births in USA; much higher in low-income countries

Causes (Stillbirth Collaborative Research Network, SCRN)

• Placental disease: abruption, placental insufficiency (~29%)
• Obstetric complications: prematurity, hemorrhage (~14%)
• Fetal anomalies: chromosomal, structural (~13%)
• Infection: primarily in low-resource settings (~14%)
• Umbilical cord abnormalities: prolapse, true knot (~10%)
• Hypertensive disorders
• Diabetes
• Unexplained: ~25%

Evaluation of Stillbirth

• Fetal autopsy (consent required; most informative investigation)
• Placental pathology (mandatory)
• Fetal karyotype or microarray (amniocentesis or fetal tissue)
• Cord blood: infection workup
• Maternal labs: Kleihauer-Betke (fetomaternal hemorrhage), toxicology screen, thrombophilia workup (APS), OGTT, viral titers (CMV, parvovirus, syphilis), thyroid function
• Complete documentation of clinical history

Management

• Timing of delivery: stillbirth labor induction; most women can wait for spontaneous labor (safe for 2-3 weeks with monitoring), but most elect induction promptly
• Methods: vaginal delivery preferred; misoprostol, dinoprostone, oxytocin induction; cervical ripening agents
• Emotional support: bereavement care, photography (Now I Lay Me Down to Sleep), chaplaincy, grief counseling, support groups
• Preterm stillbirth (<28 weeks): high-dose misoprostol or mifepristone + misoprostol

Recurrence and Subsequent Pregnancy

• Depends on cause
• Unexplained stillbirth: ~1-2% recurrence risk
• Subsequent pregnancy: increased surveillance from 32 weeks (or 2 weeks before gestational age of prior stillbirth); consider delivery at 39-40 weeks

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TOPIC 36: PUERPERIUM

Definition

Uterine Involution

• Uterus shrinks from ~1000g to ~60g over 6 weeks
• Fundus: immediately postpartum at umbilicus; decreases ~1 cm/day; non-palpable by 2 weeks
• Lochia: uterine discharge
  • Lochia rubra: days 1-4; red/bloody
  • Lochia serosa: days 4-8; pink/brown
  • Lochia alba: days 10+; yellow-white
• Foul-smelling or heavy lochia → endometritis

Lactation

• Colostrum: first 2-5 days; high protein, IgA, growth factors; lower fat/lactose
• Mature milk: from day 5-14
• Prolactin drives milk production; oxytocin drives let-down reflex
• Breastfeeding benefits: antibody transfer (IgA), reduced SIDS risk, lower obesity/allergy risk, uterine involution, maternal weight loss, lactational amenorrhea (contraception)
• Contraindications: HIV (in high-income countries), active tuberculosis, chemotherapy, certain medications, galactosemia

Return of Menstruation

• Non-breastfeeding: typically 6-8 weeks
• Breastfeeding: variable; may be 6 months or longer

Postpartum Depression Screening

• Edinburgh Postnatal Depression Scale (EPDS): ≥10-13 requires evaluation
• Postpartum depression (PPD): 10-15% of women; onset within 4 weeks to 12 months
• Treatment: therapy, SSRIs (sertraline, paroxetine preferred in breastfeeding), support
• Postpartum psychosis: rare (1-2/1000); onset within 2 weeks; hallucinations, disorganized behavior; psychiatric emergency

Immunizations Postpartum

• Rubella vaccine (if not immune): give before discharge
• Varicella (if not immune): give before discharge
• Tdap: give to mother and household contacts if not received in pregnancy
• Influenza: if not received in pregnancy
• Rh-negative women: anti-D immunoglobulin within 72 hours if Rh-positive infant

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TOPIC 37: PUERPERAL COMPLICATIONS

Postpartum Hemorrhage (PPH)

1. Tone (70-80%): uterine atony - failure of uterine contraction
2. Trauma (10-20%): lacerations, hematomas, uterine rupture, uterine inversion
3. Tissue (5-10%): retained placenta or products
4. Thrombin (<5%): coagulopathy (DIC, pre-existing bleeding disorder, anticoagulation)

1. Bimanual uterine massage + compression
2. Oxytocin: 10-40 units in 1L NS infusion; or 10 units IM
3. Methylergonovine (Methergine): 0.2 mg IM; contraindicated in hypertension
4. Carboprost (Hemabate, PGF2α): 0.25 mg IM every 15-90 min (max 8 doses); avoid in asthma
5. Misoprostol: 800-1000 mcg rectally or sublingually; when other uterotonics unavailable
6. Tranexamic acid (TXA): IV 1g; antifibrinolytic; improves survival if given within 3 hours of PPH onset (WOMAN trial)
7. Surgical: uterine compression sutures (B-Lynch), intrauterine balloon tamponade (Bakri balloon), uterine artery ligation (O'Leary sutures), internal iliac artery ligation, hysterectomy (definitive)
8. Interventional radiology: uterine artery embolization (if stable)
9. Massive transfusion protocol: 1:1:1 ratio packed RBCs:FFP:platelets; fibrinogen replacement (cryoprecipitate)

Endometritis

• Infection of uterine lining postpartum
• More common after cesarean (3-10x more than vaginal)
• Polymicrobial: GBS, E. coli, Bacteroides, Enterococcus
• Signs: fever (>38.0°C), uterine tenderness, foul lochia, leukocytosis
• Treatment: IV clindamycin + gentamicin (gold standard); 24 hours of afebrile before switch to oral (no oral step-down needed for mild cases)
• Prevention: cefazolin prophylaxis before cesarean skin incision

Wound Complications

• Wound dehiscence: open wound; superficial infections
• Necrotizing fasciitis: rare but life-threatening; requires broad-spectrum antibiotics + aggressive surgical debridement

Puerperal Fever Workup ("Wind, Water, Walking, Wound, Wonder drugs, Womb")

• Day 1-2: atelectasis (Wind), UTI
• Day 3-5: UTI (Water), DVT (Walking)
• Day 5-7: wound infection (Wound), drug reaction
• Endometritis (Womb): any time; most common cause of sustained fever

Deep Vein Thrombosis and Pulmonary Embolism

• Highest risk period: first week postpartum
• Early ambulation, hydration, sequential compression devices, LMWH in high-risk
• Diagnosis: compression US (DVT); CT pulmonary angiography (PE)
• Treatment: therapeutic LMWH; switch to warfarin or continued LMWH for 3-6 months

Bladder Dysfunction

• Urinary retention common (especially after epidural, prolonged second stage)
• Overdistension injury → long-term dysfunction if untreated
• Management: straight catheterization or indwelling Foley until bladder function returns

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TOPIC 38: CONTRACEPTION

Effectiveness Categories

• Copper IUD (Paragard): 10+ year use; also most effective emergency contraception (up to 5 days post-intercourse)
• Levonorgestrel IUD (Mirena 5y; Kyleena 5y; Liletta 6y; Skyla 3y): highly effective; reduces menorrhagia; amenorrhea common
• Subdermal implant (Nexplanon): 68 mg etonogestrel; 3 years; highly effective

• Depot medroxyprogesterone acetate (Depo-Provera): 150 mg IM every 3 months; amenorrhea; delayed return of fertility 9-18 months
• Combined oral contraceptives (COCs): estrogen + progestin; various formulations; reduce dysmenorrhea, endometriosis, acne, ovarian/endometrial cancer risk
• Progestin-only pills (POP/"mini-pill"): for breastfeeding or estrogen contraindications
• Patch (Xulane), vaginal ring (NuvaRing): similar efficacy to COCs

• Condoms: only method with STI protection
• Diaphragm + spermicide
• Spermicide alone
• Fertility awareness methods (FAM): calendar, BBT, cervical mucus (sympto-thermal)

Postpartum Contraception

• IUD: can be placed immediately postpartum (within 10 minutes of placental delivery) or at 4-6 week visit
• Implant: immediately postpartum
• Progestin-only methods: immediately postpartum (safe in breastfeeding)
• Combined hormonal (estrogen-containing): avoid for 6 weeks postpartum if breastfeeding (suppresses milk); avoid for 3 weeks in non-breastfeeding (VTE risk)
• DMPA: first visit postpartum or before hospital discharge

Emergency Contraception

1. Copper IUD: most effective (>99%); up to 5 days post-intercourse
2. Ulipristal acetate (ella): selective progesterone receptor modulator; 30 mg orally; up to 5 days; more effective than Plan B
3. Levonorgestrel (Plan B): 1.5 mg orally; up to 72 hours (up to 120h with decreasing efficacy); OTC; least effective of above; not effective for BMI >75th %ile
4. Yuzpe method: high-dose COCs; rarely used; significant nausea

Special Considerations

• COC absolute contraindications (USMEC Cat 4): personal history of DVT/PE, current breast cancer, migraines with aura, age ≥35 + smoking ≥15 cigarettes/day, severe hypertension, active liver disease, within 21 days postpartum

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TOPIC 39: STERILIZATION

Female Sterilization

• Postpartum tubal ligation (PPTL): most common; performed within 24-48 hours after vaginal delivery or at time of cesarean; modified Pomeroy or Parkland technique (partial salpingectomy)
• Interval sterilization: 6+ weeks from delivery; laparoscopic approach
• Hysteroscopic sterilization (Essure): transcervical placement of microinserts; no incision; FDA restricted in 2018 due to complications; largely discontinued

• Modified Pomeroy: elevate tube into knuckle; ligate with absorbable suture; excise knuckle; most common PPTL method
• Parkland: ligate and excise segment
• Irving: bury proximal stump in myometrium; lowest failure rate
• Partial salpingectomy: removal of midportion; also reduces ovarian cancer risk
• Salpingectomy (bilateral): complete removal; most effective; recommended by ACOG for cancer risk reduction

• Intended to be permanent
• Failure rate (including ectopic risk)
• Alternatives
• Reversibility is not guaranteed
• Regret rates higher in younger women and those who have pregnancy-related sterilization (postpartum emotional decision)

Male Sterilization (Vasectomy)

• Outpatient; local anesthesia; bilateral vas deferens occlusion
• More effective, safer, less costly than female sterilization
• Requires semen analysis 3 months post-procedure to confirm azoospermia

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TOPIC 40: OBSTETRIC EMERGENCIES

Eclampsia

• Grand mal seizures in setting of preeclampsia
• Management: (1) lateral decubitus, protect airway; (2) magnesium sulfate 4-6g IV bolus → 2g/hour maintenance; (3) antihypertensives for severe BP; (4) fetal monitoring; (5) delivery after stabilization
• Magnesium toxicity: loss of DTRs (first sign), respiratory depression, cardiac arrest
  • Treat with: calcium gluconate 1g IV

Uterine Rupture

Cord Prolapse

• Umbilical cord descends ahead of presenting part after ROM
• Incidence: 0.1-0.6%; higher with footling breech, polyhydramnios, preterm, multiparity
• Immediate fetal bradycardia
• Management:
  1. Call for immediate cesarean
  2. Replace cord into vagina (keep warm and moist)
  3. Manual elevation of presenting part (examiner's hand in vagina) to relieve cord compression - maintain until cesarean
  4. Knee-chest or Trendelenburg position
  5. Bladder filling with 500-700 mL saline: lifts presenting part off cord
  6. Do NOT reduce cord above presenting part

Placental Abruption

• PPH, DIC: treat with blood products (1:1:1 massive transfusion), TXA, address underlying coagulopathy

Amniotic Fluid Embolism (AFE)

• Catastrophic; amniotic fluid/fetal cells enter maternal circulation → cardiopulmonary collapse + coagulopathy
• Incidence: 1-12/100,000; mortality: 20-60%
• Presents: sudden cardiorespiratory collapse, DIC, fetal distress
• No specific treatment; 100% supportive: CPR, hemodynamic resuscitation, mechanical ventilation, correct DIC with massive transfusion protocol
• Perimortem cesarean: if no ROSC within 4-5 minutes of CPR; improves maternal and fetal outcomes

Uterine Inversion

• Fundus inverts through cervix (partial or complete)
• Usually from excessive cord traction or fundal pressure
• Presents: acute hemorrhage, severe pelvic pain, inability to palpate fundus, shock
• Management:
  1. Call for help
  2. Do NOT remove placenta (increases hemorrhage)
  3. Johnson maneuver: push uterus back through cervix with palm of hand (inside out correction)
  4. Tocolysis (terbutaline, magnesium, nitroglycerin) to relax cervical ring if manual replacement fails
  5. Oxytocin AFTER replacement to contract uterus
  6. Surgical correction if manual fails (Huntington or Haultain procedure)

Perimortem Cesarean

• If cardiac arrest in gravid patient ≥20 weeks
• Begin within 4 minutes of arrest; deliver within 5 minutes ("4 and 5 minute rule")
• Improves maternal cardiac output (removes aortocaval compression)
• Improves neonatal outcome (decreases time to delivery)
• Performed at bedside; do not transport to OR

Massive Obstetric Hemorrhage Protocol

• Activate massive hemorrhage protocol
• Two large-bore IVs + blood type and crossmatch
• Labs: CBC, coagulation, fibrinogen, TEG if available
• 1:1:1 pRBC:FFP:platelets; cryoprecipitate for fibrinogen <200 mg/dL
• Tranexamic acid 1g IV within 3 hours
• Address underlying cause (atony, laceration, accreta)
• Cell salvage, interventional radiology, hysterectomy as escalating measures

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TOPIC 41: NEONATOLOGY

Overview

NICU Levels of Care

• Level I: basic newborn care; ≥35 weeks, low-risk
• Level II: special care nursery; ≥32 weeks
• Level III: NICU; <32 weeks or complex care
• Level IV: regional NICU with surgical capabilities; most complex

Respiratory Support

• CPAP (Continuous Positive Airway Pressure): prevents alveolar collapse; first-line for RDS in viable preterm; avoids intubation (INSURE: INtubate-SURfactant-Extubate to CPAP)
• Mechanical ventilation: pressure-limited, volume-targeted; minimize barotrauma
• High-frequency oscillatory ventilation (HFOV): for refractory respiratory failure
• Inhaled nitric oxide (iNO): pulmonary vasodilator; for PPHN and term/near-term hypoxemia
• ECMO: extracorporeal membrane oxygenation; last resort for reversible cardiorespiratory failure (CDH, MAS, PPHN)

Surfactant Therapy

• Indication: RDS (FiO2 requirement in intubated infant)
• Natural surfactants preferred (calfactant, beractant, poractant alfa)
• Less invasive surfactant administration (LISA/MIST): surfactant via thin catheter while infant breathes spontaneously on CPAP; avoids intubation

Nutrition in NICU

• Early enteral nutrition preferred (breast milk > formula)
• Parenteral nutrition (TPN): for extremely preterm or when enteral feeds not tolerated
• Donor breast milk: reduces NEC risk in extremely preterm
• Fortification of breast milk: for very preterm infants requiring higher caloric density

Congenital Diaphragmatic Hernia (CDH)

• Herniation of abdominal organs into chest through diaphragmatic defect (usually left)
• Causes: pulmonary hypoplasia, PPHN
• Prenatal: bowel/liver/stomach in chest on US; polyhydramnios; lung-to-head ratio (LHR) predicts severity
• Treatment: stabilize first (do NOT bag-mask); gentle ventilation; iNO; ECMO if needed; surgical repair after stabilization

Neonatal Abstinence Syndrome (NAS) / NEONATAL OPIOID WITHDRAWAL

• Withdrawal from opioids (heroin, methadone, buprenorphine) in neonates of exposed mothers
• Symptoms: irritability, high-pitched cry, poor feeding, tremors, vomiting, diarrhea, seizures
• Assessment: Finnegan Neonatal Abstinence Scoring System
• Management: non-pharmacological first (swaddling, low stimulation, frequent small feeds); pharmacological: oral morphine or methadone; clonidine adjunct
• Breastfeeding: encouraged (small amounts of methadone/buprenorphine in milk but beneficial bonding outweighs risk)

Selected Congenital Heart Defects

• Hypoplastic left heart syndrome (HLHS): ductal flow maintains systemic circulation
• Pulmonary atresia, critical pulmonary stenosis: ductal flow maintains pulmonary circulation
• Transposition of great arteries (d-TGA): ductal/PFO mixing required for oxygenation; balloon atrial septostomy + arterial switch operation

Ethics in Neonatology

• 22 weeks: most centers offer comfort care; some offer resuscitation with family decision
• 23 weeks: active intervention generally offered; 50-60% survival with significant morbidity
• 24 weeks: standard resuscitation; ~70-80% survival
• 25 weeks: ~85-90% survival
• Parental involvement in decision-making at periviable gestations is standard practice
• Palliative care/comfort care: appropriate when death is inevitable or interventions offer no meaningful benefit

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EXTENDED CLINICAL PEARLS & DEEPER DETAIL

Continuation - All 41 Topics

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TOPIC 1 EXTENDED: MATERNAL ANATOMY & PHYSIOLOGY

Detailed Cardiovascular Changes

• Uterus: increases from 2% (non-pregnant) to 17% at term (~700-900 mL/min)
• Kidneys: 20% increase in blood flow
• Skin: increased for thermoregulation
• Breasts: increased in preparation for lactation

• Systemic vascular resistance (SVR): decreases 20%
• Pulmonary vascular resistance (PVR): decreases 30%
• Mean arterial pressure: slightly decreases in mid-pregnancy
• Central venous pressure: unchanged
• Colloid oncotic pressure: decreases (from reduced albumin) → increased susceptibility to pulmonary edema

• S1: louder with exaggerated splitting
• S3: common and normal
• Grade 1-2/6 systolic murmur: normal (increased flow)
• Diastolic murmurs: NEVER normal; always investigate

Respiratory Changes - Detailed

• Tidal volume: increases 40% (from 500 to 700 mL)
• Inspiratory reserve volume: increases slightly
• Expiratory reserve volume: decreases 20%
• Residual volume: decreases 20%
• FRC = ERV + RV: decreases 20-25%
• Total lung capacity: decreases slightly
• Inspiratory capacity: increases

• Affects 60-70% of pregnant women
• Begins first/second trimester; often before mechanical compression
• Related to increased respiratory drive from progesterone (CO2 sensitivity)
• Distinguish from pathological dyspnea (cardiac, pulmonary embolism)

Renal Changes - Detailed

• Renal plasma flow increases 75-80% in first trimester, then decreases to 50% above baseline at term
• GFR increases 50% → lower creatinine, BUN, uric acid
• Uric acid: decreased early pregnancy; rises with preeclampsia (>5.5 mg/dL concerning; >6 mg/dL strongly associated)
• Glycosuria: 1-10g/day normal in pregnancy (lowered tubular threshold); not a reliable GDM screen
• Proteinuria: up to 300 mg/24h normal

Hematological Changes - Detailed

• First trimester: minimal (menstruation stops)
• Second/third trimester and delivery: ~5-6 mg/day absorbed
• Total: ~1000 mg iron required (300 mg fetus/placenta; 500 mg expanded RBC mass; 200 mg losses)
• Supplemental iron: 30-60 mg elemental iron/day recommended

Gastrointestinal - Detailed

• Nausea and vomiting of pregnancy (NVP): affects 70-80%; peaks 8-12 weeks
• Hyperemesis gravidarum: <2% of pregnancies; >5% weight loss, ketonuria, electrolyte disturbances; treatment: IV fluids, thiamine (B1) supplementation first (prevents Wernicke encephalopathy), antiemetics (ondansetron, promethazine, metoclopramide), vitamin B6 + doxylamine (Diclegis - first-line per ACOG)
• GERD: treat with antacids (calcium carbonate), H2 blockers (famotidine), PPI if needed (omeprazole - safe)
• Constipation: increased progesterone → decreased motility; treat with increased fiber, hydration, docusate

Skin Changes

• Chloasma (melasma): hyperpigmentation of face from MSH/estrogen; "mask of pregnancy"
• Linea nigra: darkening of linea alba
• Striae gravidarum (stretch marks): mid-dermal collagen breakdown
• Vascular changes: spider angiomata, palmar erythema (from increased estrogen)
• All usually resolve postpartum

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TOPIC 2 EXTENDED: OBSTETRIC HISTORY AND EXAMINATION

Detailed Cervical Assessment

• Score ≥8: very favorable; labor likely to proceed well with induction
• Score <6: cervical ripening recommended before induction
• Modified Bishop Score variants used in some institutions

Fetal Presentation and Position Nomenclature

• Vertex (cephalic): occiput is denominator
• Breech: sacrum is denominator
• Face: mentum (chin) is denominator
• Shoulder: acromion is denominator

• LOT: Left Occiput Transverse (most common engagement position)
• LOA: Left Occiput Anterior
• LOP: Left Occiput Posterior
• ROT: Right Occiput Transverse
• ROA: Right Occiput Anterior
• ROP: Right Occiput Posterior
• OA: Occiput Anterior (delivery position)
• OP: Occiput Posterior

Dating the Pregnancy

• CRL (6-13+6 weeks): >7 days → redateusing ultrasound
• BPD/HC/AC/FL (14-15+6 weeks): >7 days → redate
• BPD/HC/AC/FL (16-21+6 weeks): >10 days → redate
• BPD/HC/AC/FL (22-27+6 weeks): >14 days → redate
• BPD/HC/AC/FL (≥28 weeks): >21 days → redate (least accurate; avoid redating late)

Pelvic Assessment Details

• Diagonal conjugate <11.5 cm: contracted inlet
• Interspinous diameter <10 cm: contracted midpelvis
• Intertuberous diameter <8 cm: contracted outlet
• Subpubic angle <90°: narrow forepelvis (android features)
• Prominent/converging ischial spines: android/anthropoid features

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TOPIC 3 EXTENDED: CONGENITAL GENITOURINARY ABNORMALITIES

Detailed Mullerian Anomaly Obstetric Management

• Functional horn: highest risk of ectopic pregnancy if contralateral rudimentary horn has patent tube
• Rudimentary horn pregnancies: can rupture (catastrophic); treat with surgical removal
• Cervical cerclage: often placed prophylactically at 12-14 weeks for incompetent cervix

• Untreated: recurrent pregnancy loss ~25-65%
• After hysteroscopic metroplasty: pregnancy loss rate reduces to ~5-10%
• Recommend surgery before conception in women with RPL and septate uterus

• Historical relevance: DES used 1940s-1970s
• T-shaped uterus, hypoplastic uterus, cervical hood
• "DES daughters": increased risk of clear cell adenocarcinoma vagina/cervix (rare), ectopic pregnancy, miscarriage, preterm birth
• No longer a common clinical problem with generational passage

Urinary Tract Anomalies

• Located in pelvis; may obstruct labor
• May be mistaken for soft tissue tumor
• Vaginal delivery usually possible; cesarean if obstructed
• Manage with planned cesarean if pelvic mass anticipated to obstruct

• Fused lower poles; crosses midline anteriorly
• Usually does not obstruct labor
• Monitor for UTI (increased risk with any renal anomaly)

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TOPIC 4 EXTENDED: PRECONCEPTIONAL COUNSELING

Risk Stratification for Pregnancy

• Class I (no additional risk): small uncomplicated VSD, PDA, mitral valve prolapse
• Class II (small increased risk): repaired tetralogy, uncomplicated AS/PS
• Class III (significant risk, specialist care required): moderate mitral stenosis, mechanical heart valves
• Class IV (extremely high risk, pregnancy contraindicated)**: severe pulmonary hypertension, severe systolic dysfunction (EF <30%), severe aortic stenosis, Marfan syndrome with aortic root >45mm, prior peripartum cardiomyopathy with residual dysfunction

Medications to Review

• Thyroid medications (levothyroxine, PTU in first trimester)
• Most antihypertensives except ACE/ARB
• Insulin, metformin (for diabetes)
• Low-dose aspirin (for at-risk women)
• Most antibiotics (penicillin, cephalosporins, azithromycin, nitrofurantoin except near term)

• ACE inhibitors/ARBs → switch to methyldopa, labetalol, nifedipine
• Statins → discontinue (Category X)
• Warfarin → switch to LMWH (especially first trimester)
• Valproate → consider switch to lamotrigine or levetiracetam
• Isotretinoin → stop ≥1 month before conception; pregnancy test before each prescription
• Methotrexate → stop ≥3 months before conception
• Mycophenolate mofetil → stop ≥6 weeks before conception

Preconception Genetic Screening Updates

• Pan-ethnic panel (same panel for all ethnicities) now preferred over ethnicity-based
• Common panel includes: SMA, CF, fragile X (females), hemoglobinopathies, spinal muscular atrophy
• If both parents are carriers of same AR condition: 25% risk to offspring; refer to genetic counselor; offer PGT-M (preimplantation genetic testing for monogenic disease) or prenatal diagnosis

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TOPIC 5 EXTENDED: PRENATAL CARE

Laboratory Abnormalities and Management

• Iron deficiency anemia (most common): MCV low, ferritin low, TIBC high; treat with oral iron 325 mg TID (or IV iron if GI intolerance)
• Folate deficiency: macrocytic; supplemental folate
• B12 deficiency: macrocytic; common in vegetarians; supplement
• Thalassemia trait: microcytic, normal ferritin; identify and offer partner testing

• Any GBS bacteriuria (even <100,000 CFU/mL) in pregnancy = automatic indication for IAP in labor
• Treat at time of discovery with appropriate antibiotic; AND give IAP at delivery regardless

• ASCUS: HPV reflex testing; if high-risk HPV positive → colposcopy
• LSIL: colposcopy (unless <25 years → manage conservatively)
• HSIL: colposcopy required
• Colposcopy: safe in pregnancy; biopsy only if invasive cancer suspected
• LEEP/excision: generally deferred to postpartum unless invasive cancer confirmed

Group Prenatal Care

• Models like CenteringPregnancy: group of 8-12 women; evidence shows improved outcomes for low-income and Black women; reduces preterm birth, improves breastfeeding rates

Nutrition Guidelines

• Iron: 27 mg/day (prenatal vitamin)
• Calcium: 1000 mg/day
• Folic acid: 400-800 mcg (4 mg if high-risk)
• DHA/omega-3: 200-300 mg/day (brain development)
• Vitamin D: 600 IU/day (some recommend higher)
• Iodine: 220 mcg/day (from prenatal vitamin or iodized salt)

• Raw/undercooked meats (Toxoplasma, Salmonella)
• High-mercury fish (swordfish, shark, king mackerel, tilefish, bigeye tuna): limit to 2 servings/week; avoid high-mercury species
• Raw shellfish (Vibrio)
• Unpasteurized dairy (Listeria)
• Raw sprouts (Salmonella, E. coli)
• Deli meats/hot dogs (Listeria): heat until steaming

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TOPIC 6 EXTENDED: PLACENTATION

Placental Development - Detailed

• Two waves of invasion:
  • First wave: 8-10 weeks; cytotrophoblasts invade decidua
  • Second wave: 14-18 weeks; cytotrophoblasts invade inner third of myometrium and spiral arteries
• Spiral artery transformation: maternal spiral arteries converted from narrow, high-resistance vessels to wide, low-resistance uteroplacental vessels
• In preeclampsia: only first wave occurs; spiral arteries retain smooth muscle and vasoconstrict

• Simple diffusion: O2, CO2, water, fatty acids, most drugs, alcohol, nicotine
• Facilitated diffusion: glucose (GLUT1 transporter)
• Active transport: amino acids, iron, calcium, folate, IgG (FcRn receptor)
• Pinocytosis: large molecules
• Independent transport: fetal red cells (small numbers cross even normally - basis of Kleihauer-Betke test)

Cord Blood Gas Interpretation

• pH: 7.25-7.35
• PO2: 15-25 mmHg
• PCO2: 45-55 mmHg
• Base excess: -2 to -8 mEq/L

• Respiratory acidosis: elevated PCO2, normal base excess → acute (cord compression)
• Metabolic acidosis: normal PCO2, base excess more negative than -8 → prolonged asphyxia
• Mixed: both abnormal

• pH <7.0 + base deficit >12 mEq/L: significant risk for HIE, organ damage
• pH <7.0 alone: not sufficient; combined with neurological signs defines birth asphyxia

Vasa Previa - Detailed

• Type I: velamentous cord insertion (cord inserts into membranes rather than placenta)
• Type II: between two lobes of succenturiate placenta

• Color Doppler TVS at 18-22 weeks: vessels crossing os
• If diagnosed prenatally: hospitalize at 30-32 weeks; cesarean at 34-35 weeks
• Undiagnosed: rupture of membranes → fetal bradycardia within minutes → fetal exsanguination (fetal blood volume ~80 mL/kg; even small bleed fatal)
• APT test: distinguish fetal vs. maternal blood (alkali denaturation; fetal hemoglobin resistant)

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TOPIC 7 EXTENDED: EMBRYOGENESIS AND FETAL DEVELOPMENT

Neural Tube Defects (NTD) - Detailed

• Anencephaly: failure of anterior neuropore to close; absent cerebral hemispheres; incompatible with extrauterine life; delivery/termination; obstetric risks: polyhydramnios, malpresentation
• Open spina bifida (myelomeningocele): posterior neuropore failure; spinal cord exposed; lower limb paralysis, bowel/bladder dysfunction, Arnold-Chiari II malformation (hindbrain herniation → hydrocephalus)
• Spina bifida occulta: bony defect without neural tissue exposure; often asymptomatic; tethered cord possible
• Encephalocele: herniation of brain through cranial defect

• Open NTDs (not skin-covered): elevated MSAFP
• Closed NTDs (skin-covered): normal MSAFP
• Acetylcholinesterase (AChE) in amniotic fluid: elevated in open NTD (more specific than AFP)

• Lemon sign: scalloping of frontal bones (Arnold-Chiari)
• Banana sign: curved cerebellum from posterior fossa compression

Fetal Sex Development

• 6-7 weeks: undifferentiated gonads (bipotential)
• 7 weeks: SRY gene on Y chromosome activates → testis-determining factor → testes differentiate
• 8-9 weeks: Sertoli cells produce AMH (anti-Mullerian hormone) → Mullerian duct regression
• Leydig cells produce testosterone → Wolffian duct develops → vas deferens, epididymis, seminal vesicles
• Without SRY: ovarian differentiation; Mullerian ducts form uterus, tubes, upper vagina; Wolffian ducts regress
• External genitalia differentiation: 9-12 weeks under DHT (testosterone converted by 5α-reductase)

• Congenital adrenal hyperplasia (21-hydroxylase deficiency): excess androgens → virilization of XX fetus
• Androgen insensitivity syndrome (AIS): XY with non-functional androgen receptor → female external genitalia; blind vagina; absent uterus; testes (intra-abdominal)

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TOPIC 8 EXTENDED: FETAL IMAGING

Detailed Ultrasound Biometry

• BPD (Biparietal diameter): measured at level of thalami, falx, and cavum septum pellucidum; outer to inner
• HC (Head circumference): same axial plane as BPD
• Cerebellum: used for dating (cerebellar diameter in mm ≈ weeks GA up to ~20 weeks); posterior fossa anomalies

• AC (Abdominal circumference): at level of stomach, portal/umbilical vein junction; most sensitive for growth restriction

• Long axis; most reproducible after 20 weeks
• Short FL: skeletal dysplasia, Down syndrome

• Hadlock formula (most widely used): uses BPD, HC, AC, FL
• EFW 10th percentile: SGA; 90th percentile: LGA (macrosomia)
• EFW accuracy: ±15-20% at term; less accurate at extremes of size

Anomalies Detected at 18-22 Week Scan

• Anencephaly, ventriculomegaly (lateral ventricle ≥10 mm), Dandy-Walker malformation, holoprosencephaly, agenesis of corpus callosum, spina bifida (lemon and banana signs)

• Hypoplastic left heart, VSD, AV canal defect (Down syndrome), transposition of great arteries (outflow view critical), tetralogy of Fallot, double outlet RV

• Omphalocele (contains liver; associated with aneuploidy), gastroschisis (no sac; to right of cord; usually isolated), duodenal atresia (double bubble; ~30% Down syndrome), renal agenesis, multicystic kidneys, echogenic bowel (CF, Down syndrome, infection, FMH)

• Echogenic cardiac focus, choroid plexus cysts (trisomy 18 association), nuchal fold ≥6 mm, short femur, pyelectasis
• Isolated soft markers in low-risk patients: reassure; not indication for invasive testing alone (especially in era of cfDNA)

Cervical Length Measurement

• Transvaginal (TVS) cervical length at 18-24 weeks
• Normal: ≥25 mm
• Short cervix: <25 mm → increased preterm birth risk
• ≤15 mm: very high risk; same risk as PPROM
• Management: vaginal progesterone (200 mg nightly) for singleton pregnancies with short cervix reduces preterm birth by 25-45%
• Cerclage: for prior preterm birth + short cervix (history-indicated or ultrasound-indicated)

Fetal Echocardiography

• Indications: family history CHD, prior CHD infant, maternal diabetes, maternal SSA/SSB antibodies (fetal heart block), suspected fetal cardiac anomaly on anatomy scan, nuchal translucency ≥3.5 mm, fetal arrhythmia
• Timing: 20-24 weeks
• Views: four-chamber, LVOT, RVOT, three-vessel, ductal arch, aortic arch, systemic veins

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TOPIC 9 EXTENDED: AMNIOTIC FLUID DISORDERS

Oligohydramnios - Detailed Management

• AFI <5 cm with normal fetal anatomy, normal Doppler, normal growth
• Controversial: some evidence of increased adverse outcomes (cord compression, meconium aspiration, cesarean for FHR abnormalities); others dispute
• Management debate: delivery at 36-37 weeks vs. continued surveillance
• ACOG: reasonable to offer delivery from 36-37 weeks with isolated oligohydramnios

• High-risk combination; Doppler abnormalities often accompany
• Management guided by Doppler and gestational age

• Latency period shorter; infection risk higher
• Deliver at 34 weeks in uncomplicated cases (expedite if chorioamnionitis develops)

• Bilateral renal agenesis (Potter sequence): oligohydramnios detected by 16-18 weeks; lethal condition
• Posterior urethral valves: male fetus; dilated posterior urethra ("keyhole sign"), bladder distension, bilateral hydronephrosis, oligohydramnios; fetal intervention (vesicoamniotic shunt) to preserve kidneys and prevent pulmonary hypoplasia

Polyhydramnios - Detailed

• Mild: AFI 25-30 cm
• Moderate: AFI 30-35 cm
• Severe: AFI >35 cm

• Mechanism: reduces fetal urine output via prostaglandin inhibition on renal vasculature
• Dose: 25-50 mg orally every 6 hours
• Use before 32 weeks to avoid premature ductal closure
• Monitor ductus arteriosus (weekly echocardiogram if used >48 hours); monitor fetal renal function (serial AFI)
• Maximum use: 48-72 hours; reassess after

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TOPIC 10 EXTENDED: TERATOLOGY

Drug Safety Categories - FDA Labeling

• Category A: no fetal risk in human studies
• Category B: no animal risk; no adequate human studies
• Category C: adverse animal effects; no adequate human studies
• Category D: evidence of fetal risk; benefit may outweigh risk
• Category X: fetal risk outweighs benefit; contraindicated

Commonly Tested Drug Safety

• Penicillins, cephalosporins, azithromycin
• Acetaminophen (first-line analgesic)
• Metformin, insulin
• Heparin/LMWH
• Labetalol, methyldopa, nifedipine
• Levothyroxine
• Hydroxychloroquine
• Most antihistamines (diphenhydramine, loratadine)
• Ondansetron (some debate about cardiac defects at very high doses in first trimester; small absolute risk)
• Proton pump inhibitors

• NSAIDs: first trimester (gastroschisis debate), after 32 weeks (premature ductal closure, oligohydramnios)
• Fluconazole: high doses teratogenic (skeletal abnormalities); single-dose 150 mg likely safe
• Trimethoprim: folate antagonist; avoid first trimester if possible
• Sulfonamides: avoid in third trimester/near term (neonatal hyperbilirubinemia, kernicterus)
• Ciprofloxacin: cartilage effects in animals; avoid if alternatives available
• Chloramphenicol: gray baby syndrome in neonate

Radiation Exposure Guide

• No single diagnostic study exceeds the threshold for deterministic effects (100 mGy)
• Cumulative exposure counseling important if multiple studies needed

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TOPIC 11 EXTENDED: GENETICS

Chromosomal Microarray Analysis (CMA)

• Comparative genomic hybridization (CGH) array: detects copy number variants (CNVs) - deletions and duplications >50-100 kb
• SNP array: detects CNVs + uniparental disomy (UPD) + regions of homozygosity
• Cannot detect: balanced translocations, low-level mosaicism, point mutations, trinucleotide repeats

• Structural anomaly on ultrasound: CMA detects additional abnormalities in 6-7% of cases with normal karyotype
• Replaces karyotype in many prenatal settings
• Limitation: variants of uncertain significance (VUS); requires genetic counseling

Trinucleotide Repeat Disorders

• Most common inherited intellectual disability
• FMR1 gene on X chromosome; CGG repeats: normal <45, premutation 55-200, full mutation >200
• Full mutation: gene silenced (methylation) → no FMRP protein
• Male carriers: intellectual disability, macroorchidism, large ears, prominent jaw
• Premutation females: premature ovarian insufficiency (POI); FXTAS in older males
• Anticipation: premutation expands to full mutation when passed by female carrier (NOT by male carrier)

• CAG repeats in HTT gene; >36 repeats = disease
• AD; 50% risk; 100% penetrance if repeat length >39
• Age of onset inversely related to repeat length
• Anticipation with paternal transmission (paternal repeat instability)

• CTG repeats; AD
• Congenital form: severe; caused by large maternal expansions
• Features: myotonia, cataracts, cardiac conduction, diabetes, infertility

Imprinting and Uniparental Disomy

• Prader-Willi syndrome: deletion/UPD of paternal chromosome 15q11-q13; or maternal disomy 15
  • Features: neonatal hypotonia, poor suck, then childhood hyperphagia, obesity, intellectual disability, hypogonadism
• Angelman syndrome: deletion/UPD of maternal chromosome 15q11-q13; or paternal disomy 15
  • Features: severe intellectual disability, seizures, inappropriate laughter, ataxia, absent speech
• Beckwith-Wiedemann: overgrowth, macroglossia, omphalocele, hemihypertrophy, hypoglycemia; paternal disomy 11 or loss of maternal imprinting at 11p15

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TOPIC 12 EXTENDED: PRENATAL DIAGNOSIS

cfDNA (NIPT) - Detailed

• Cell-free DNA (cfDNA) in maternal plasma: ~10-15% is fetal (placental) origin
• Fetal fraction increases with gestational age; decreases with obesity
• Low fetal fraction (<4%): test failure or uninterpretable result; associated with maternal obesity, early gestational age
• Sequencing/counting: identifies relative excess of chromosomal segments

• Diagnose structural anomalies
• Detect all chromosomal abnormalities (only those screened for)
• Identify all microdeletions reliably (expanding panels have lower performance)
• Replace anatomy scan

• Confined placental mosaicism (false positive): placenta is aneuploid, fetus is not
• True fetal mosaicism
• Vanishing twin
• Maternal malignancy (maternal chromosomal abnormalities detected)
• Low fetal fraction

Amniocentesis - Detailed Protocol

• Performed under continuous ultrasound guidance
• 20-22 gauge needle; no-pass technique (minimize membrane puncture attempts)
• 20-30 mL amniotic fluid removed
• Complications:
  • Pregnancy loss: 0.1-0.3% (modern data; older 0.5% estimate now considered high)
  • Fluid leaking: 1-2%; usually seals within 1 week
  • Chorioamnionitis: <0.1%
  • Fetal injury: extremely rare with ultrasound guidance
  • Rh sensitization: give RhoGAM to Rh-negative women within 72 hours

Preimplantation Genetic Testing (PGT)

• Testing of embryos created via IVF before uterine transfer
• PGT-A (aneuploidy): screens for chromosomal aneuploidies; improves implantation rates in IVF
• PGT-M (monogenic): for specific single gene disorders (CF, Huntington, BRCA); customized per family
• PGT-SR (structural rearrangements): for balanced translocations; selects unbalanced/balanced/normal embryos
• Controversial in some contexts; genetic counseling essential

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TOPIC 13 EXTENDED: FETAL DISORDERS

Fetal Growth Restriction (FGR) - Delphi Consensus Classification (2020)

• Stage 1: AC or EFW <3rd percentile OR umbilical artery PI >95th percentile; low risk of immediate compromise; surveillance twice weekly
• Stage 2: Absent end-diastolic flow (AEDF) in umbilical artery; hospital admission; steroids if <34 weeks; delivery 34-37 weeks
• Stage 3: Reversed end-diastolic flow (REDF) OR MCA PI <5th percentile OR ductus venosus PI >95th percentile; high risk; steroids; deliver 30-34 weeks
• Stage 4: Abnormal CTG (reduced variability, late decelerations) OR ductus venosus reversed a-wave; immediate delivery regardless of gestational age

Parvovirus B19 in Pregnancy

• Transmission: respiratory droplets; 30-50% seropositive adults
• Fetal infection: transplacental; tropism for erythroid precursors
• Manifestations: fetal anemia, hydrops fetalis (non-immune), fetal death
• Risk of hydrops: ~3% if exposure; 5-10% if maternal infection confirmed
• Highest risk: 9-20 weeks (most active fetal erythropoiesis)
• Diagnosis: maternal serology (IgG/IgM); fetal US for hydrops; MCA PSV for anemia
• Management: if hydrops/anemia → IUT; most cases resolve spontaneously without hydrops
• No specific antiviral treatment; no vaccine

Congenital Cytomegalovirus (CMV)

• Most common congenital infection: ~0.6-0.7% of all births
• Primary maternal infection in pregnancy: 30-40% transmission
• Recurrent infection: lower transmission (1-2%) but still causes disease
• Ultrasound findings: ventriculomegaly, periventricular calcifications, IUGR, hepatosplenomegaly, ascites
• Diagnosis: amniocentesis + CMV PCR in amniotic fluid (>after 20 weeks)
• Postnatal: CMV PCR from saliva/urine in first 3 weeks of life
• Sequelae: hearing loss (most common), intellectual disability, cerebral palsy, vision loss
• Treatment: postnatal valganciclovir for symptomatic congenital CMV improves hearing outcomes; valacyclovir in pregnancy under investigation

Toxoplasmosis in Pregnancy

• Primary infection only (not reactivation in immunocompetent) causes fetal disease
• Source: undercooked meat, cat litter (oocysts)
• Classic triad (congenital toxoplasmosis): chorioretinitis, intracranial calcifications (diffuse, throughout parenchyma), hydrocephalus
• Diagnosis: maternal serology; amniocentesis + Toxoplasma PCR if maternal infection confirmed
• Treatment: spiramycin (reduces maternal-to-fetal transmission; does not treat established fetal infection); pyrimethamine + sulfadiazine + leucovorin (if fetal infection confirmed)
• Prevention: cook meat well, avoid cat litter box, wear gloves gardening

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TOPIC 14 EXTENDED: FETAL THERAPY

Antenatal Corticosteroids - Evidence and Protocols

• 12 mg IM x2 doses, 24 hours apart (preferred)
• Alternative: dexamethasone 6 mg IM x4 doses, 12 hours apart
• Benefits: reduced RDS, IVH, NEC, periventricular leukomalacia, neonatal death

• Optimal benefit: 24 hours to 7 days after second dose
• Standard: give when delivery expected within 7 days at 24 0/7 - 34 6/7 weeks
• Late preterm (34 0/7 - 36 6/7 weeks): single course (ALPS trial); reduces respiratory morbidity; slight increase in neonatal hypoglycemia
• Repeat courses: previously controversial; single rescue course if:
  • First course given >14 days earlier
  • <34 weeks gestation
  • Expected to deliver within 7 days
  • Multiple courses: reduced birth weight and head circumference; avoid routine repeated courses

Magnesium Sulfate for Neuroprotection

• 4g IV bolus over 20-30 minutes; 1-2g/hour maintenance
• For women with anticipated preterm delivery <32 weeks
• Goal: reduces cerebral palsy and gross motor dysfunction in surviving preterm infants
• Stop if delivery not imminent after 12-24 hours; can restart if delivery again expected
• Monitor: urine output (≥30 mL/hr), respiratory rate (≥12/min), DTRs (must be present), serum Mg if renal impairment
• Toxicity: therapeutic 4-7 mEq/L; DTR loss at 7-10 mEq/L; respiratory arrest at 10-13 mEq/L; cardiac arrest >15 mEq/L
• Antidote: calcium gluconate 1g IV over 3 minutes

Tocolysis

1. Corticosteroid administration
2. Transfer to appropriate level facility
3. GBS prophylaxis

• Nifedipine (calcium channel blocker): first-line at most centers; oral; 20-30 mg loading, 10-20 mg every 4-6 hours; contraindicated with magnesium (potentiates hypotension)
• Indomethacin (NSAIDs): 50-100 mg rectal/oral loading; 25-50 mg q6h; use <32 weeks; monitor ductus arteriosus and AFI
• Terbutaline (beta-2 agonist): SQ 0.25 mg; mainly for acute tocolysis; oral terbutaline no longer recommended (FDA black box warning for maintenance tocolysis - cardiac events in mother)
• Magnesium sulfate: tocolytic effect weak; most beneficial for neuroprotection and management of severe preeclampsia

• Oral terbutaline: removed from market for this indication
• Bed rest alone: no proven benefit

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TOPIC 15 EXTENDED: FETAL ASSESSMENT

Antepartum Testing Protocols

Fetal Movement and Kick Counts

• "Count to 10": count until 10 movements felt; should occur within 2 hours in most pregnancies
• "Daily fetal movement count": compare to baseline movement; decreasing trend is concerning
• Action for decreased movement: NST; if non-reactive → BPP or modified BPP

• 55% of women who had a stillbirth noticed decreased movement beforehand and did not report it
• Education: normalize reporting decreased movement; reduces delay in evaluation

Interpretation of CTG in Antenatal Setting

• ≥2 accelerations (≥15 bpm x ≥15 seconds) in 20 minutes (extend to 40 minutes before declaring non-reactive)
• <32 weeks: use criteria of ≥10 bpm x ≥10 seconds

• Apply artificial larynx to maternal abdomen; fetal response (acceleration) is reassuring
• Negative test (no acceleration): further evaluation; may indicate fetal sleep cycle; re-evaluate in 30 minutes

BPP Scoring Nuances

• Each component reflects different aspects of CNS function:
  • NST: cortical arousal (most sensitive to acute asphyxia)
  • Breathing: cortical phrenic center (inhibited early in hypoxia)
  • Movement: cortical motor center
  • Tone: deepest cortical function (last to be lost)
  • Fluid (AFI): chronic uteroplacental function (decreased with oliguria from renal hypoperfusion)

• 10/10 or 8/10 with normal fluid: reassuring; repeat per risk factor
• 8/10 with oligohydramnios: deliver if ≥36 weeks or high risk
• 6/10: equivocal; if ≥36 weeks → deliver; if <36 weeks → repeat in 24 hours; if still 6 → consider delivery
• 4/10: deliver regardless of gestational age (except extreme prematurity with shared decision-making)
• 0-2/10: deliver

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TOPIC 16 EXTENDED: ABORTION

Medical Management - Detailed

• Mifepristone 200 mg orally; followed by misoprostol 800 mcg vaginally, buccally, or sublingually 24-48 hours later
• Up to 10 weeks: complete abortion rate ~95-98%
• 10-12 weeks: efficacy decreases slightly
• Side effects of misoprostol: cramping, nausea, vomiting, diarrhea, low-grade fever, chills
• Follow-up: confirm complete abortion (clinical symptoms + ultrasound OR serum hCG)

• Less effective (~80-85%)
• Multiple doses may be needed

• Serum hCG should decrease >50% at 1 week; >80% at 4 weeks
• Persistent hCG elevation → incomplete abortion OR gestational trophoblastic disease (if rising)

Surgical Methods - Detailed

• Handheld 60 mL syringe; safe, effective; first trimester
• Can be performed in office setting
• Complication rate <1%

• Electric suction; operating room or procedure room
• Most common surgical method; first trimester; 5-15 minutes

• Second trimester (13-24+ weeks)
• Requires cervical preparation (laminaria placed 1-3 days before for dilation, or misoprostol)
• Forceps used to remove fetal parts
• More technically demanding; specialist required
• Safest second trimester method when performed by trained provider

• Uterine perforation: 0.1%; higher risk with uterine anomalies, cervical stenosis, inexperienced provider; may require laparoscopy
• Incomplete evacuation: <1%; requires repeat aspiration
• Infection: 0.5-1%; prophylactic doxycycline given
• Cervical laceration: rare with gentle technique
• Asherman syndrome: intrauterine adhesions from vigorous curettage (avoid sharp curettage)
• Failed abortion (continuing pregnancy): 1:300 first trimester; must confirm cessation of pregnancy

Post-Abortion Contraception

• Can start any hormonal contraceptive on day of surgical abortion
• IUD can be placed immediately after aspiration
• Ovulation can resume within 2 weeks → contraception essential

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TOPIC 17 EXTENDED: ECTOPIC PREGNANCY

Cornual/Interstitial Ectopic Pregnancy

• Located in intramural portion of fallopian tube (within uterine wall)
• Accounts for 2-4% of ectopics
• Rupture occurs later (10-16 weeks) because surrounded by myometrium
• Rupture is catastrophic → massive hemorrhage
• Ultrasound: gestational sac surrounded by myometrium, eccentrically placed, <5 mm of myometrium around sac
• Management: methotrexate (systemic or local injection); or surgical (cornual resection via laparoscopy or hysteroscopy)

Cesarean Scar Ectopic Pregnancy (CSP)

• Implantation in prior cesarean scar niche
• Increasing incidence with rising CS rates
• High risk of placenta accreta if not identified and treated early
• Ultrasound: GS in anterior lower uterine segment, within scar, with minimal myometrium between GS and bladder
• Management: MTX (local + systemic), suction curettage + Foley balloon, or surgical excision; UAE + curettage (uterine artery embolization)
• Expectant management NOT recommended (very high risk of massive hemorrhage)

Methotrexate Protocol Details

• MTX 50 mg/m² IM on day 1
• Check hCG day 4 and day 7
• If day 4 to day 7 hCG falls ≥15%: success; check weekly until undetectable
• If fall <15%: second dose of MTX OR surgery

• MTX day 1; repeat day 4 regardless; check hCG day 4 and day 7; similar monitoring
• Slightly higher efficacy than single-dose; similar side effects

• MTX days 1, 3, 5, 7; leucovorin rescue days 2, 4, 6, 8
• For cornual or CSP; highest efficacy; most side effects

• Intrauterine pregnancy (absolute)
• Immunodeficiency
• Active pulmonary disease
• Hepatic or renal disease
• Peptic ulcer disease
• Blood dyscrasias
• Breastfeeding
• Hemodynamic instability (surgery required)
• Fetal cardiac activity (relative; higher failure rate)

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TOPIC 18 EXTENDED: GESTATIONAL TROPHOBLASTIC DISEASE

Complete vs Partial Mole - Key Distinctions

• Bilateral; from overstimulation by high hCG
• Usually regress spontaneously after mole evacuation
• Risk of ovarian torsion
• Do NOT surgically drain unless torsion occurs

GTN FIGO Scoring System

• Score 0-6: low-risk; single-agent chemotherapy (MTX or actinomycin D)
• Score ≥7: high-risk; multi-agent chemotherapy (EMA-CO)

• Etoposide, Methotrexate, Actinomycin D (days 1-2); Cyclophosphamide, Oncovine (vincristine) (day 8)
• 80-90% cure rate for high-risk GTN

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TOPIC 19 EXTENDED: GENERAL ASSESSMENT

Common Symptoms and Differential in Pregnancy

• Round ligament pain: sharp, unilateral, groin area; worsens with movement; normal; reassurance
• Uterine fibroids (degeneration): acute severe pain; fever; elevated WBC; rest, NSAIDs, IV fluids
• Ovarian torsion: sudden severe unilateral pain; adnexal mass; Doppler may show decreased/absent flow (but normal flow does NOT rule out torsion)
• Appendicitis: right lower quadrant but appendix displaced superiorly by gravid uterus; diagnosis difficult; MRI preferred for diagnosis in pregnancy; don't delay surgery
• Placental abruption: constant severe pain with uterine rigidity

• Tension/migraine: most common
• Preeclampsia: severe, frontal, unrelenting; rule out with BP assessment
• Post-dural puncture headache: positional; after epidural/spinal; onset 24-48 hours; treat with caffeine, hydration, blood patch
• Intracranial venous thrombosis: seizures, focal neurological signs; MRI/MRV for diagnosis; anticoagulation

• First trimester: threatened/incomplete/missed abortion, ectopic pregnancy, implantation bleeding, subchorionic hematoma
• Second trimester: placenta previa, cervical incompetence (with ROM), abruption
• Third trimester: placenta previa (painless), abruption (painful), vasa previa, labor (bloody show), cervical lesions

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TOPIC 20 EXTENDED: MEDICAL DISORDERS

Preeclampsia - New Diagnostic Criteria (ACOG 2019/2020)

• Platelet count <100,000/µL
• Creatinine >1.1 mg/dL OR doubling of creatinine
• Liver transaminases ≥2x upper limit of normal
• Pulmonary edema
• New-onset headache unresponsive to medication AND not accounted for by other diagnoses
• Visual disturbances

• Prior preeclampsia (most important single factor)
• Multifetal gestation
• Chronic hypertension
• Type 1 or 2 diabetes
• Renal disease
• Autoimmune disease (SLE, antiphospholipid syndrome)

• Nulliparity
• Obesity (BMI >30)
• Family history of preeclampsia
• Sociodemographic characteristics (African American race, low socioeconomic status)
• Age ≥35
• Personal history: prior adverse outcome, prior low birth weight/SGA

HELLP Syndrome - Classification

• Class 1 (severe): platelets ≤50,000; LDH ≥600 IU/L; AST/ALT ≥70 IU/L
• Class 2 (moderate): platelets 50,000-100,000; LDH ≥600; AST/ALT ≥70
• Class 3 (mild): platelets 100,000-150,000; LDH ≥600; AST/ALT ≥40

• Hepatic hematoma/rupture (rare, life-threatening): severe RUQ/epigastric pain; hepatic rupture → hemorrhagic shock; manage with surgical packing ± TAE
• Placental abruption: 10-20% of HELLP cases
• Acute renal failure
• Pulmonary edema
• DIC: occurs in 4-38%

Cardiac Disease - Detailed by Lesion

• Most common rheumatic heart disease in pregnancy
• Poorly tolerated in pregnancy due to increased HR (reduces diastolic filling time) and increased CO
• Symptoms worsen at 20-28 weeks (peak hemodynamic stress)
• Management: heart rate control (beta-blockers: metoprolol); diuretics for pulmonary congestion; percutaneous balloon mitral valvuloplasty (safe in pregnancy for severe MS); delivery with HR control

• Aortic root dilation; risk of dissection increases in pregnancy (estrogen-related aortic changes)
• Aortic root >40 mm: increased risk; >45 mm: pregnancy contraindicated (relative)
• Management: beta-blockers throughout; serial echocardiography every trimester; cesarean if root >40-45 mm

• Anticoagulation dilemma: warfarin is teratogenic in first trimester but most effective for valve protection; heparin less effective
• ACOG/AHA options:
  • High-dose LMWH (anti-Xa monitoring) throughout pregnancy
  • UFH after 6-12 weeks switch to warfarin; switch to LMWH/UFH at 36 weeks
  • Warfarin throughout pregnancy with LMWH near delivery (if warfarin dose ≤5 mg/day, embryopathy risk lower)

Seizure Disorders in Pregnancy

• Continue antiepileptic drug (AED) at lowest effective dose
• Valproate: highest teratogenic risk (spina bifida 1-2%, IQ reduction); avoid if possible
• Lamotrigine and levetiracetam: best safety profiles; note lamotrigine levels drop significantly in pregnancy (increased metabolism) → dose often must be increased; monitor levels
• Folic acid 4-5 mg/day
• Vitamin K supplementation in late pregnancy for enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital)
• Breastfeeding: generally safe with most AEDs

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TOPIC 21 EXTENDED: PHYSIOLOGY OF LABOR

Biochemistry of Uterine Quiescence and Activation

• Progesterone: maintains quiescence by:
  • Promoting synthesis of cAMP (reduces intracellular calcium)
  • Opposing estrogen-induced gap junction formation
  • Suppressing oxytocin receptor expression
  • Suppressing prostaglandin production
• Nitric oxide (NO): potent myometrial relaxant; from decidua
• CRH: paradoxically, placental CRH early in pregnancy promotes quiescence; at term, receptor shifts to promote contraction
• Progesterone receptor (PR) isoforms: PR-B (quiescence) → PR-A (pro-labor) shift near term

• Estrogen increases: enhances prostaglandin synthesis, increases oxytocin receptors, promotes gap junctions
• Functional progesterone withdrawal: PR-A predominance
• Fetal cortisol: fetal lung maturity signal; triggers placental prostaglandin production
• CRH rise: exponentially rises near term; stimulates ACTH, fetal cortisol, prostaglandins

Pain Pathways in Labor - Detail

• First stage (latent and early active): uterine contractions and cervical dilation stimulate visceral afferents via T10-L1
• Active first stage and second stage: somatic pain via S2-S4 (pudendal nerve) from perineal descent and stretching
• This is why paracervical blocks work in early labor but are inadequate in second stage; pudendal blocks address second-stage perineal pain

Fetal Lung Maturity Tests (Mostly historical, rarely used now)

• L/S ratio: lecithin/sphingomyelin; ≥2.0 indicates maturity; unreliable in diabetes
• Phosphatidylglycerol (PG): appears at 36 weeks; most specific marker; unaffected by blood/meconium contamination
• TDx-FLM II: lamellar body count: >50,000/µL = mature; >15,000 = transition
• Currently: routine fetal lung maturity testing before 39 weeks not recommended (ACOG); deliver at ≥39 weeks without testing in uncomplicated pregnancies

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TOPIC 22 EXTENDED: NORMAL LABOR

Friedman Curve vs. Contemporary Labor Curves

• Active phase began at 4 cm
• Minimum active phase rate: 1.2 cm/hr (nullipara), 1.5 cm/hr (multipara)
• Modern ACOG guidelines (2014) based on Zhang et al. data (>62,000 singleton term labors):
  • Active phase begins at 6 cm
  • Median labor: 5.5 hours (nullipara active phase) but normal range wide
  • Even arrest at 6-10 cm not abnormal until ≥4 hours of adequate contractions without progress

• Do NOT call arrest of active phase before 6 cm dilation
• Do NOT diagnose active phase arrest without ≥4 hours of adequate contractions (≥200 MVU) or ≥6 hours with inadequate contractions
• This change has potentially reduced cesarean rates for labor dystocia

Placental Delivery - Third Stage

• Calkin's sign: uterus becomes globular and firm
• Brandt's sign: cord lengthens
• Gush of blood

• Brandt-Andrews maneuver: controlled cord traction with suprapubic counterpressure
• Never pull cord without fundal stabilization (uterine inversion risk)

• Manual removal: with analgesia; insert hand into uterus; cleave plane between placenta and uterine wall
• If placenta accreta suspected: do NOT attempt manual removal; prepare for hemorrhage management

Episiotomy - Current Evidence

• Selective use preferred over routine episiotomy
• Midline episiotomy: increases 3rd/4th degree laceration risk 3-4x
• Mediolateral: less extension but more blood loss and longer healing time
• Warm compresses and perineal massage in second stage: reduce severe lacerations

• Shoulder dystocia (to allow obstetric maneuvers)
• Operative vaginal delivery (forceps)
• Tight perineum threatening 3rd/4th degree tear
• Fetal compromise requiring expedited delivery

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TOPIC 23 EXTENDED: ABNORMAL LABOR

Classification of Uterine Activity

• Uterine resting tone >15-20 mmHg
• Coordinated contractions but abnormal pressure
• Cause: oxytocin hyperstimulation, placental abruption, cocaine
• Treatment: stop oxytocin; tocolysis; left lateral position

• Normal resting tone but insufficient contraction strength (MVU <200)
• Most common cause of active phase arrest
• Treatment: oxytocin augmentation; amniotomy

• 5 contractions in 10 minutes (averaged over 30 minutes)

• Regardless of FHR pattern
• Hyperstimulation (old term) = tachysystole WITH FHR changes
• Management: reduce/stop oxytocin; tocolysis if needed

Deep Transverse Arrest

• Head arrested in transverse position at midpelvis
• Ischial spines prominent
• May respond to: oxytocin augmentation, maternal position changes (hands-and-knees), pushing technique changes, manual rotation by provider
• Operative options: Kielland rotational forceps (high skill required), vacuum with rotation, cesarean

Obstructed Labor

• Progressive labor without descent despite adequate uterine activity
• Causes: CPD, hydrocephalus, conjoined twins, fetal abdomen enlargement (hydrops, large sacrococcygeal teratoma)
• Risk in resource-limited settings: obstetric fistula (vesicovaginal or rectovaginal) from prolonged obstructed labor
• Management: cesarean; hydrocephalus may require transvaginal cephalocentesis to reduce head size before delivery

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TOPIC 24 EXTENDED: INTRAPARTUM ASSESSMENT

Sinusoidal FHR Pattern

• Regular sine wave oscillation: 3-5 cycles per minute; amplitude 5-15 bpm; persists ≥20 minutes
• Smooth undulating pattern WITHOUT accelerations or variability
• Cause: severe fetal anemia (Rh disease, massive FMH, parvovirus), hydrops; brain damage
• Must distinguish from "pseudosinusoidal" (medications: meperidine, betamethasone; transient; accelerations present)
• Sinusoidal pattern = Category III = emergent delivery

Umbilical Cord Prolapse vs. Cord Presentation

• Cord presentation: cord below presenting part with intact membranes; risk of prolapse; reposition patient; emergency cesarean
• Cord prolapse: cord below presenting part with ruptured membranes; Category III (immediate bradycardia likely)

Scalp pH Sampling (Fetal Blood Sampling)

• Largely replaced by fetal scalp stimulation and acoustic stimulation in USA
• More widely used in UK/Europe
• Normal scalp pH: ≥7.25; reassuring, continue labor
• pH 7.20-7.24: borderline; repeat in 30 minutes
• pH <7.20: significant acidosis; expedite delivery

Intrauterine Resuscitation - Detailed Steps

• S - Stop oxytocin
• T - Turn patient (left lateral)
• O - Oxygen 10 L/min by non-rebreather mask
• P - Position change
• L - IV Fluid bolus (500-1000 mL LR)
• A - Assess for hypotension (treat with phenylephrine or ephedrine)
• C - Consider tocolysis (terbutaline) for tachysystole

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TOPIC 25 EXTENDED: INDUCTION AND AUGMENTATION

ARRIVE Trial (2018) - Key Evidence

• Randomized trial of elective labor induction at 39 0/7 weeks vs. expectant management
• Results: induction group had LOWER cesarean rate (18.6% vs. 22.2%)
• Lower rates of: NICU admission, perinatal death, meconium aspiration
• No increase in perinatal morbidity
• Conclusion: elective induction at 39 weeks is safe and may reduce cesarean rates; shifted practice significantly

Failed Induction

• Definition: failure to achieve active labor (6 cm) after:
  • Adequate uterine activity (MVU ≥200 over 4 hours) for at least 4 hours, OR
  • 6 hours of oxytocin with inadequate contractions AND ruptured membranes
• Important: patient should not be called "failed induction" prematurely; allow adequate latent phase time (up to 12-24 hours)

Prostaglandin E1 (Misoprostol) - Detailed

• Highly effective cervical ripening and induction
• Low cost; stable at room temperature
• Contraindication: prior uterine scar (ABSOLUTE - high risk of uterine rupture)
• Tachysystole: more common than with PGE2; can use IV fluid flush or tocolysis

• Similar efficacy; may have fewer hyperstimulation episodes
• Some protocols use 50 mcg orally; higher dose = more tachysystole

Special Induction Situations

• Prolonged SROM (>18 hours) increases neonatal GBS risk
• If GBS-positive (or unknown) and ROM occurs: start IAP immediately; proceed with labor induction to minimize duration of ROM

• <28 weeks: misoprostol 200 mcg vaginally/sublingually every 4-6 hours; or mifepristone 200 mg + misoprostol
• ≥28 weeks with prior uterine scar: D&E preferred by some centers, or oxytocin induction (lower misoprostol doses)
• Cervical ripening important; intracervical foley safe

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TOPIC 26 EXTENDED: OBSTETRIC ANALGESIA

Neuraxial Block Complications - Detailed

• Incidence: 1-2% of epidurals (inadvertent dural puncture)
• Onset: 24-48 hours; positional (worse sitting/standing; better lying flat)
• Mechanism: CSF leak → low ICP → traction on pain-sensitive intracranial structures
• Conservative: caffeine (300-500 mg), hydration, bed rest, analgesics
• Definitive: epidural blood patch (15-20 mL autologous blood injected into epidural space; clot seals dural hole); 70-90% effective; repeat if needed

• Intrathecal injection of epidural dose
• Symptoms: rapid ascending block, respiratory distress/arrest, hypotension, unconsciousness
• Management: airway support, vasopressors, left lateral tilt, CPR if needed

• Rare (<1:150,000); more common with coagulopathy or difficult insertion
• Symptoms: back pain + neurological deterioration (weakness, bowel/bladder dysfunction) within 24-48 hours
• Emergency MRI → surgical decompression within 8 hours to prevent permanent deficit

Regional vs. General Anesthesia for Cesarean

• Avoids difficult airway (maternal anatomic changes: large breasts, edematous airway, short neck)
• Mother awake for birth
• Lower aspiration risk
• Neonatal depression minimal
• Superior postoperative analgesia (intrathecal morphine)

• True emergency (no time for regional)
• Contraindication to regional
• Failed regional (4-level block failure)
• Patient refusal

• Higher incidence than general population (1:250 vs. 1:2000)
• Airway management plan essential (video laryngoscope, supraglottic airway)
• If cannot intubate + cannot oxygenate: emergent surgical airway (cricothyrotomy)

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TOPIC 27 EXTENDED: VAGINAL DELIVERY

Perineal Protection Techniques

• Both acceptable
• "Hands-on": apply pressure to fetal head to control speed of delivery; support perineum
• Studies mixed on superiority; individual provider preference
• Ritgen maneuver: applying upward pressure under chin through perineum + pressure on occiput = controlled extension; reduces lacerations in some studies

• Applied to perineum in second stage
• Reduces risk of 3rd/4th degree lacerations (RCT evidence)
• Easy, cheap, effective; widely underused

Immediate Cord Clamping vs. Delayed Cord Clamping (DCC)

• Term infants: higher Hgb, improved iron stores at 3-6 months, possible improved neurodevelopmental outcomes
• Preterm infants: reduced IVH, NEC, RDS, blood transfusion need
• Mechanism: placental-to-infant transfusion of blood (~80 mL) occurs in first 60-180 seconds

• Term: delay ≥30-60 seconds for all vigorous infants
• Preterm: delay 30-60+ seconds for infants not requiring immediate resuscitation
• If resuscitation needed: can milk (strip) cord toward infant 3-4x as alternative

Water Birth

• Laboring in water (hydrotherapy): well-tolerated; reduces pain perception; no increased risk
• Delivering in water (water birth): more controversial; risk of neonatal respiratory distress, infection if water contaminated; cord snapping
• ACOG position: insufficient evidence for routine recommendation; perform in research or protocol settings only

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TOPIC 28 EXTENDED: BREECH DELIVERY

ECV - Detailed Protocol

• Confirm breech presentation (ultrasound)
• Reactive NST
• Rh status (give RhoGAM before procedure if Rh-negative)
• Consent for emergency cesarean
• NPO (if emergency cesarean needed)
• IV access
• Tocolytic: terbutaline 0.25 mg SQ or nitroglycerin IV

• Patient supine or slight Trendelenburg
• Assistant on opposite side
• Operator: disengage breech from pelvis with upward pressure on lower pole
• Forward roll (most common): move head toward right flank; buttocks leftward and upward
• Backward roll (alternative): if forward roll fails
• Steady continuous pressure; stop if fetal distress, pain, or resistance
• Post-ECV: NST ≥20 minutes; confirm cephalic presentation on ultrasound

Management of Unavoidable Vaginal Breech Delivery

• Frank or complete breech (NOT footling)
• Normal pelvic dimensions (or confirmed adequate pelvis)
• EFW: 2500-4000 g (relative)
• Flexed head (not hyperextended - risk of cord/head entrapment; hyperextension on X-ray indicates cesarean)
• Skilled, experienced provider
• Continuous EFM
• Anesthesia available
• OR available for emergency cesarean

• Fetal arms wrapped around neck; can occur with breech delivery
• Lovset maneuver: rotate body 180° keeping back uppermost; brings posterior arm to anterior where it can be swept across face and delivered; repeat for other arm

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TOPIC 29 EXTENDED: OPERATIVE VAGINAL DELIVERY

Forceps Classification by Station

• High forceps: contraindicated (risk outweighs benefit)
• Mid-forceps: acceptable in specific circumstances by experienced operators

Vacuum Application

• Cup center over posterior fontanelle (occiput)
• "Flexion point": 3 cm anterior to posterior fontanelle; over sagittal suture
• Misapplication over anterior fontanelle → asynclitism → failure + scalp injury

• With each contraction + maternal push
• Traction axis: J-shaped (downward, then outward, then upward as head follows pelvic curve)
• No torque/twisting motion with vacuum (unlike forceps where rotation is possible)

Subgaleal Hematoma (Subaponeurotic)

• Bleeding into subgaleal space (between galea aponeurosis and periosteum)
• Can expand to entire calvarium
• Neonatal blood volume: 80-90 mL/kg; scalp can accommodate ENTIRE blood volume
• Signs: head growing, fluctuant swelling that crosses suture lines (distinguishes from cephalohematoma which does NOT cross sutures), pallor, tachycardia, shock
• Management: recognize early (immediately post-delivery), IV access, transfusion, monitoring; ICU care
• Associated with: vacuum delivery (especially prolonged or multiple attempts)

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TOPIC 30 EXTENDED: CESAREAN DELIVERY

Surgical Technique Details

• Straight, horizontal incision 3 cm above pubic symphysis (higher than Pfannenstiel)
• Blunt tissue entry (reduced blood loss, shorter operating time)
• Some evidence of reduced febrile morbidity vs. Pfannenstiel

• Single-layer vs. double-layer closure: double-layer associated with thicker LUS scar; lower risk of uterine dehiscence in subsequent pregnancy; most providers use double-layer
• Locking vs. non-locking suture: some evidence non-locking single-layer has worse outcomes for subsequent TOLAC

• Exteriorizing (lifting uterus out of abdomen for repair): allows better hemostasis visualization; may reduce febrile morbidity
• No clear difference in outcomes; individual surgeon preference

• Subcuticular suture: cosmetically superior
• Staples: faster; equivalent healing; more patient-reported discomfort

Enhanced Recovery After Cesarean (ERAC)

• Preoperative: carbohydrate loading, antacid prophylaxis, compression stockings
• Intraoperative: spinal anesthesia preferred; intrathecal morphine; warming; minimize fluids unless indicated
• Postoperative: early feeding (within 2 hours), early ambulation (6-8 hours), scheduled multimodal analgesia (ibuprofen + acetaminophen scheduled), early Foley removal (≤12 hours), limit opioid use

Peripartum Hysterectomy

• Last resort for uncontrolled hemorrhage (usually accreta or atony)
• Total vs. subtotal hysterectomy: subtotal (supracervical) faster, less blood loss, lower ureter injury risk; adequate if hemorrhage controlled
• Blood loss often massive: activate massive hemorrhage protocol
• Ovaries usually preserved in young women

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TOPIC 31 EXTENDED: PRIOR CESAREAN DELIVERY

VBAC Success Prediction - Grobman Calculator

• Prior vaginal delivery (most powerful predictor): 86-90% success
• Prior VBAC: highest success probability
• Non-recurrent indication for CS
• Spontaneous labor onset
• Low BMI

• Prior CS for failure to progress
• No prior vaginal delivery
• High BMI
• Induction of labor
• High Bishop score needed
• Increased maternal age

Uterine Rupture - Detailed

• Scar thinning or separation of old uterine incision but peritoneum intact
• Usually asymptomatic; discovered at cesarean
• Less associated with fetal compromise than complete rupture

• Peritoneum disrupted; extrusion of fetus/placenta possible
• Catastrophic; requires immediate intervention

• Variable decelerations first (cord compression as fetal head retracts)
• Then bradycardia (catastrophic or prolonged deceleration >5 minutes)
• Loss of station on vaginal exam
• The most common sign: sudden prolonged FHR deceleration in patient undergoing TOLAC

1. Immediately call for cesarean
2. Massive hemorrhage protocol
3. General anesthesia (fastest)
4. Laparotomy: extract fetus, clamp broad ligament, assess uterus
5. Repair vs. hysterectomy based on extent and patient's desire for future fertility

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TOPIC 32 EXTENDED: THE NEWBORN

Ballard Score (Neuromuscular and Physical Maturity)

• Posture, square window (wrist), arm recoil, popliteal angle, scarf sign, heel-to-ear

• Skin, lanugo, plantar surface, breast, eye/ear, genitals

Neonatal Physical Exam - Detailed

• Caput succedaneum: edema of scalp (above periosteum, crosses sutures); present at birth; resolves in days
• Cephalohematoma: subperiosteal hematoma; does NOT cross sutures; appears after birth; resolves in weeks to months; risk of hyperbilirubinemia
• Subgaleal hematoma: emergency (see Topic 29)

• Subconjunctival hemorrhage: benign; from delivery trauma; resolves weeks
• Unequal pupils: neurological concern
• Red reflex: absent → possible cataract, retinoblastoma

• Ortolani maneuver: adduct and lift thigh → "clunk" of femoral head entering acetabulum = positive (dislocated hip being reduced)
• Barlow maneuver: adduct and push posteriorly → "clunk" of femoral head exiting acetabulum = positive (dislocatable hip)
• Risk factors for DDH: female sex, breech presentation, family history, oligohydramnios
• Screening ultrasound: at 6 weeks (or earlier if high risk); X-ray after 4-6 months (ossification)

Newborn Screening (Expanded Panel - US)

• Metabolic: PKU, galactosemia, MSUD (maple syrup urine disease), organic acidemias, fatty acid oxidation disorders (MCAD deficiency most common)
• Endocrine: congenital hypothyroidism (most common endocrine disorder detected), congenital adrenal hyperplasia
• Hematologic: sickle cell disease, hemoglobinopathies
• Other: cystic fibrosis (IRT + DNA), severe combined immunodeficiency (SCID)
• CCHD pulse oximetry screen: screen for critical congenital heart disease at 24-48 hours

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TOPIC 33 EXTENDED: PRETERM NEWBORN

Respiratory Distress Syndrome (RDS) - Detailed

• Surfactant deficiency → increased surface tension → alveolar collapse at end-expiration → atelectasis → V/Q mismatch → hypoxemia → acidosis → pulmonary vasoconstriction → worsening V/Q
• "Vicious cycle" of progressive respiratory failure

• Indications: intubated infant with RDS requiring supplemental O2 (FiO2 ≥30%)
• Agents: poractant alfa (Curosurf), beractant (Survanta), calfactant (Infasurf)
• Natural surfactants > synthetic for reducing mortality and pneumothorax
• Administer into trachea via endotracheal tube
• INSURE protocol: intubate → surfactant → extubate to CPAP (avoids prolonged ventilation)
• LISA/MIST: less invasive; surfactant via thin catheter while infant breathes on CPAP

Chronic Lung Disease (BPD) - New Definition

• Grade I: room air; ≥4 nasal cannula
• Grade II: >21% O2 via NC or noninvasive PPV
• Grade III: invasive mechanical ventilation

Necrotizing Enterocolitis (NEC) - Detailed

• Stage I (suspected): apnea, temperature instability, gastric residuals; non-specific
• Stage II (definite): Stage I + pneumatosis intestinalis on abdominal X-ray ± portal venous gas
• Stage III (advanced): Stage II + deterioration, peritonitis, acidosis, DIC, perforation

• NPO; nasogastric decompression; TPN
• Broad-spectrum antibiotics: ampicillin + gentamicin + metronidazole (or piperacillin-tazobactam)
• Serial abdominal X-rays
• Surgical consultation (Stage III or clinical deterioration)
• Surgery: bowel resection ± ostomy; peritoneal drain (very unstable infants)

• Breast milk (most effective); avoid formula in ELBW infants
• Probiotic supplementation (Lactobacillus species): reduces NEC (evidence supports use in resource-limited settings; caution in immunocompromised)

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TOPIC 34 EXTENDED: DISEASES OF THE TERM NEWBORN

Jaundice - Phototherapy Thresholds

• Phototherapy based on: total serum bilirubin, age (hours), gestational age at birth, risk factors (isoimmune hemolytic disease, G6PD, asphyxia, significant lethargy, temperature instability, sepsis, acidosis)
• Nomogram used (Bhutani hour-specific bilirubin nomogram)
• Risk zones: low-risk, low-intermediate, high-intermediate, high-risk

• Blue-green light (430-490 nm) most effective
• Converts unconjugated bilirubin to water-soluble geometric and structural isomers
• "Bronze baby syndrome": if conjugated bilirubin elevated + phototherapy → bronze skin discoloration (benign)

ABO Incompatibility vs. Rh Disease

Hypoxic-Ischemic Encephalopathy (HIE) - Detailed

• ≥36 weeks gestation
• ≥1 of: Apgar ≤5 at 10 min, prolonged resuscitation ≥10 min, pH ≤7.0 or BD ≥16 (cord or 1-hour gas), or clinical encephalopathy
• AND: abnormal neurological exam (seizures, abnormal tone, impaired reflexes)
• Initiate within 6 hours of birth

• Grade I (mild): hyperalertness, hyperreflexia, normal tone, no seizures, EEG normal; full recovery expected
• Grade II (moderate): lethargy, hypotonia, seizures, abnormal EEG; 20-30% die or have disability
• Grade III (severe): coma, flaccid tone, absent brainstem reflexes, continuous seizures; >70% die or profound disability

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TOPIC 35 EXTENDED: STILLBIRTH

Perinatal Autopsy Components

• Provides diagnosis in 20-30% of cases where cause unknown clinically
• Identifies recurrence risk (critical for counseling)
• May identify familial conditions

• External examination (photographs, measurements)
• Internal examination (organ weights, histology)
• Placental examination (ALWAYS send separately; examines morphology, cord, membranes)
• Karyotype (from fetal tissue: fascia, lung, skin)
• Microarray preferred over karyotype (higher diagnostic yield)

• Partial autopsy (specific systems only)
• External exam + photographs only
• Placental pathology (can consent to this alone)
• Genetic testing from placenta (does not require fetal autopsy)

Fetomaternal Hemorrhage (FMH)

• Acid elution of fetal hemoglobin from maternal blood; fetal RBCs retain Hgb F (red); maternal RBCs ghost out
• Percentage of fetal cells in maternal circulation × maternal blood volume (5000 mL) = estimate of fetal bleeding
• Indication: unexplained stillbirth, suspected FMH (sinusoidal FHR, fetal hydrops, decreased fetal movement)
• Massive FMH (>30-50 mL): rare cause of stillbirth; risk in otherwise unexplained cases

Grief and Bereavement

• Memory making: photos, footprints, locks of hair; greatly valued by bereaved parents even if initially reluctant
• Funeral: hospital can assist with arrangements
• Support groups: "Share" organization, "STILL Standing" magazine
• Psychiatric referral: if complicated grief, PTSD, antenatal depression in subsequent pregnancy
• Timeline for conception: no absolute contraindication; some recommend waiting 6-12 months for emotional preparation; no evidence early conception worsens outcomes

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TOPIC 36 EXTENDED: PUERPERIUM

Postpartum Fever Definition

• Temperature ≥38.0°C (100.4°F) on any 2 of first 10 postpartum days (excluding first 24 hours)
• First 24 hours: fever common from dehydration, physiologic; evaluate if >38.5°C or persistent
• Note: day 0 = delivery day

Postpartum Thyroiditis

• Autoimmune thyroiditis occurring in first year postpartum
• Affects 5-10% of women
• Phase 1 (thyrotoxic): 1-4 months postpartum; from stored thyroid hormone release; palpitations, anxiety, weight loss; TSH suppressed; do NOT use ATDs (not synthesis-related)
• Phase 2 (hypothyroid): 4-8 months; anti-TPO antibodies destroy thyroid; fatigue, depression, cognitive difficulty; treat with levothyroxine
• Resolution: 80% return to normal thyroid function by 12 months; 20% remain permanently hypothyroid

Breastfeeding - Clinical Details

• Days 3-5; full, firm, warm breasts; distinguish from mastitis (fever, systemic symptoms)
• Management: frequent feeding, warm compresses before feeding, cold compresses after

• Usually unilateral; Staphylococcus aureus most common (including MRSA)
• Wedge-shaped erythema + fever + flu-like symptoms
• Management: continue breastfeeding (empties breast, reduces progression); dicloxacillin or cephalexin 10-14 days; MRSA → TMP-SMX or clindamycin
• Progression: if not improving in 48-72 hours → breast abscess (ultrasound; surgical drainage or aspiration)

• HIV positive (in high-income countries); exclusive formula feeding recommended
• Active tuberculosis (until treated ≥2 weeks)
• HTLV-1 or HTLV-2 infection
• Active herpes simplex lesions on breast
• Chemotherapy (antimetabolites)
• Radioactive isotopes (temporary cessation)
• Galactosemia in infant (complete contraindication)
• Phenylketonuria: can breastfeed with careful monitoring

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TOPIC 37 EXTENDED: PUERPERAL COMPLICATIONS

Postpartum Hemorrhage - Risk Stratification

• No previous uterine surgery
• Singleton pregnancy
• ≤4 prior deliveries
• No history of PPH
• No known coagulopathy
• No chorioamnionitis

• Prior uterine surgery
• Multiple gestation
• ≥4 prior vaginal deliveries
• Previous PPH
• Large uterine fibroids
• Magnesium sulfate in labor
• BMI >40

• Placenta previa, low-lying placenta
• Suspected accreta spectrum
• ≥3 prior cesareans
• Platelet count <100,000
• Active bleeding on admission
• Known coagulopathy

Surgical Management of PPH - Stepwise

• B-Lynch suture: large absorbable suture compresses uterus vertically + horizontally; effective for diffuse atony
• Square sutures (Cho technique): multiple interrupted sutures; for atony + suspected accreta
• Uterovaginal packing: Bakri balloon, Sengstaken-Blakemore tube, condom catheter; 200-500 mL saline fill; tamponade; leave 24 hours

• Uterine artery ligation (O'Leary sutures): medial to uterine vessels at uterine isthmus; effective; preserves uterus
• Utero-ovarian ligament ligation
• Internal iliac (hypogastric) artery ligation: complex; requires vascular knowledge; reduces pulse pressure; preserves uterus; 50% failure rate for PPH control
• Uterine artery embolization (UAE): requires stable patient and IR; coils or gelatin sponge; 85-90% success; preserves fertility; risk: postembolization syndrome

Wound Hematoma

• Expanding hematoma in abdominal wall after cesarean
• If small and stable: observe; if enlarging or infected: open and evacuate; packing or drain
• Risk: coagulopathy, inadequate hemostasis, anticoagulation

Ovarian Vein Thrombosis

• Occurs postpartum (usually right ovarian vein)
• Presents: fever (unresponsive to antibiotics), right lower quadrant pain, tender rope-like structure on exam
• Diagnosis: CT scan
• Treatment: anticoagulation (LMWH or warfarin) + antibiotics 10-14 days

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TOPIC 38 EXTENDED: CONTRACEPTION

LARC Insertion Techniques

• Best timing: immediately postpartum (before hospital discharge), at interval visit (≥4 weeks postpartum), or any time if not pregnant
• Postplacental insertion: within 10 minutes of placental delivery; higher expulsion rate (~10-15%) vs. interval insertion (2-5%) but vastly increases uptake
• Expulsion most common in first month; women should be taught string check
• Hormonal IUD in breastfeeding: safe; does not affect milk supply; can be started immediately postpartum

Emergency Contraception - Detailed Mechanism

• Mechanism: primarily inhibits/delays ovulation by suppressing LH surge; may thicken cervical mucus
• Does NOT prevent implantation of an established fertilized egg
• Not effective if ovulation already occurred (limited to pre-ovulatory use)

• Mechanism: copper ions spermicidal; also impairs fertilization; may have post-fertilization effects
• Most effective EC (>99%); works regardless of timing in cycle
• Added benefit: ongoing highly effective contraception for 10+ years

Contraception and Medical Conditions (US MEC)

• Migraines with aura
• Personal history VTE
• Active DVT/PE
• Ischemic heart disease
• Stroke history
• Hypertension with vascular disease
• Diabetes with nephropathy/retinopathy/neuropathy
• Current breast cancer
• Cirrhosis (severe), hepatocellular adenoma, hepatoma
• Lactating and <21 days postpartum
• Age ≥35 + smoking ≥15 cigarettes/day

• Current breast cancer (Category 4)
• Otherwise much safer than COCs for cardiovascular conditions

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TOPIC 39 EXTENDED: STERILIZATION

Counseling Requirements

• Federal regulations: signed consent ≥30 days before procedure (or ≥72 hours for emergency procedures, premature delivery, or abdominal delivery)
• Consent must be signed when NOT in labor or under influence of alcohol/drugs
• Must be ≥21 years old
• Purpose: prevent coerced sterilization (historically performed on marginalized women without consent)

Regret After Sterilization

• Age ≤30 at time of sterilization
• Sterilization done postpartum (emotional vulnerability)
• Childless at time of sterilization
• Relationship status changes after procedure
• Overall regret rate: ~6-12% at 14 years (CREST study)

• Strongly advise younger women to consider LARCs (equivalent efficacy; reversible)
• Document counseling thoroughly
• Explore reasons for sterilization decision without pressure in either direction
• Discuss vasectomy option (safer, cheaper, more effective)

Salpingectomy for Ovarian Cancer Risk Reduction

• Recommendation: bilateral salpingectomy at time of cesarean or gynecologic surgery (instead of tubal ligation) for desired permanent sterilization
• Evidence: majority of high-grade serous ovarian carcinomas originate from fallopian tube epithelium (BRCA1/2 mutation, sporadic)
• Salpingectomy reduces ovarian cancer risk by 42-65%
• No negative effect on ovarian reserve or menopause timing (preserved ovarian blood supply)
• ACOG and SGO recommend counseling all patients about this option

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TOPIC 40 EXTENDED: OBSTETRIC EMERGENCIES

Amniotic Fluid Embolism - Pathophysiology

• Not a simple "embolism" but an anaphylactoid response to fetal antigens entering maternal circulation
• Fetal squamous cells, mucin, lanugo enter maternal vascular system through open myometrial venous sinuses
• Phase 1: initial vasospasm → right heart failure → hypoxia
• Phase 2: left heart failure; pulmonary edema
• Phase 3: DIC (thought to be from fetal thromboplastin, activating extrinsic coagulation cascade)

• Autopsy finding of squamous cells in pulmonary vasculature confirms but is not necessary for clinical diagnosis

• 100% oxygen / intubation
• Resuscitation (CPR if arrest)
• Massive transfusion (1:1:1 + cryoprecipitate for DIC)
• Vasopressors (norepinephrine or phenylephrine)
• Extracorporeal support (ECMO) at specialized centers
• No proven specific treatment; hydroxyprogesterone, ondansetron, atropine, plasma exchange studied in case reports

Eclampsia - Management Detail

• CNS: blocks NMDA receptors; reduces neuronal excitability
• Vascular: calcium antagonism → vasodilatation
• Does NOT lower blood pressure significantly; not an antihypertensive

• Assess and stabilize airway
• Load MgSO4 if not already on it
• Give bolus if seizing despite maintenance dose (2g IV push)
• Diazepam (10 mg IV) only if refractory to magnesium
• After seizure: fetal monitoring for bradycardia (expected transient bradycardia; usually recovers); delivery after maternal stabilization
• Do NOT rush to emergency cesarean during or immediately after seizure unless fetal status non-recoverable

Massive Obstetric Hemorrhage - Resuscitation Targets

• pH >7.35
• Temperature ≥36°C (warm patient)
• Ionized calcium ≥1.1 mEq/L (calcium for every 4 units of pRBC)
• Fibrinogen ≥200 mg/dL (primary target in obstetric hemorrhage; often drops precipitously)
• Platelets ≥50,000/µL (ideally >100,000 with ongoing bleeding)
• PT/PTT <1.5x normal

• TXA 1g IV within 3 hours of PPH diagnosis (second dose 0.5g if still bleeding at 30 minutes)
• Reduced maternal death from bleeding (1.5% vs. 1.9%; RR 0.81)
• No benefit after 3 hours
• No increased thromboembolic events
• Now standard of care: give within 3 hours of PPH recognition

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TOPIC 41 EXTENDED: NEONATOLOGY

Congenital Diaphragmatic Hernia (CDH) - Extended

• Lung-to-head ratio (LHR): <1.0 = severe pulmonary hypoplasia; 1.0-1.6 = intermediate
• Liver herniation: liver in chest = poor prognosis
• Contralateral lung volume (TFLV by MRI): best predictor
• Survival: right-sided CDH worse prognosis than left-sided

1. Intubate immediately (avoid bag-mask ventilation → gastric distension)
2. Nasogastric tube for decompression
3. Gentle ventilation (low PIP, permissive hypercapnia)
4. iNO for pulmonary hypertension
5. High-frequency oscillatory ventilation if conventional fails
6. ECMO if refractory (survival 50-80% with ECMO support)
7. Surgery: AFTER pulmonary hypertension resolves and patient stabilized (delayed repair improves outcomes vs. immediate)

Total Body Cooling (Therapeutic Hypothermia) - Protocol

• Servo-controlled cooling blanket (whole-body cooling) or head cooling + mild systemic hypothermia
• Target core temperature: 33.0-34.0°C
• Duration: 72 hours
• Rewarm: 0.5°C per hour over 6-8 hours
• Monitoring during cooling: continuous EEG (detect seizures), ECHO (assess cardiac function), serial metabolic panels, renal function
• Maintain glucose ≥50 mg/dL, ionized calcium normal
• Seizure management: phenobarbital first-line; levetiracetam second

• Number needed to treat (NNT) to prevent death or major disability: ~7-8
• Works by: reducing cerebral metabolic demand, limiting secondary injury cascade

Retinopathy of Prematurity (ROP) - Screening and Staging

• Birth weight <1500 g OR gestational age ≤30 weeks
• Birth weight 1500-2000 g with unstable clinical course at discretion of neonatologist
• First exam: 31 weeks PMA OR at 4-6 weeks postnatal age (whichever is later)
• Performed by ophthalmologist with indirect ophthalmoscope

• Zone: I (posterior), II (middle), III (peripheral)
• Stage 1: demarcation line
• Stage 2: ridge
• Stage 3: extraretinal fibrovascular proliferation
• Stage 4: partial retinal detachment
• Stage 5: total retinal detachment

• Laser photocoagulation: ablates avascular peripheral retina; gold standard
• Anti-VEGF (bevacizumab): intravitreal injection; newer; may be superior in Zone I disease; concerns about systemic VEGF suppression in developing organs
• Stage 4-5: vitreoretinal surgery; poor visual prognosis

Persistent Pulmonary Hypertension - Extended

• Echo: elevated RV pressure, bidirectional or right-to-left shunting at PDA/PFO, poor RV function
• Pre-ductal (right hand) and post-ductal (foot) SpO2 difference >10% = right-to-left ductal shunting

• Inhaled nitric oxide → smooth muscle relaxation in pulmonary vasculature → selective pulmonary vasodilation
• Does NOT affect systemic vasculature (inactivated by hemoglobin in pulmonary capillaries)
• Start: 20 ppm; may wean over days

• Abrupt discontinuation of iNO → rebound pulmonary vasoconstriction
• Wean gradually: 20 → 10 → 5 → 1 → off

NICU Family-Centered Care

• Parents as primary caregivers (not visitors)
• Open visiting hours
• Kangaroo care (skin-to-skin): improves temperature stability, breastfeeding, bonding, weight gain, reduces sepsis rates in preterm
• Family-integrated care models: parents perform routine caregiving under NICU nurse guidance
• Communication: daily family rounds; written communication supplements verbal
• Palliative care consultation early in course of severe conditions

Metabolic Screening - Action for Positive Results

• Phenylalanine hydroxylase deficiency → phenylalanine accumulation → neurotoxicity
• Treatment: phenylalanine-restricted diet starting within 7-10 days of birth
• Maternal PKU: high phenylalanine crosses placenta → intellectual disability, congenital anomalies in infant; must maintain low Phe diet in pregnancy

• Most common preventable cause of intellectual disability
• Causes: thyroid agenesis/dysgenesis, dyshormonogenesis, iodine deficiency
• Treatment: levothyroxine within 2 weeks of birth; maintain normal T4 for neurodevelopment
• Outcomes: normal intellect with early treatment

• Medium-chain acyl-CoA dehydrogenase deficiency (fatty acid oxidation disorder)
• Crisis triggered by fasting or illness
• Presents: hypoglycemia, elevated acylcarnitines
• Treatment: avoid fasting; carnitine supplementation; emergency glucose during illness

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SUMMARY OF CRITICAL DRUG DOSAGES (Resident Quick Reference)

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KEY MNEMONICS SUMMARY

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TOPICS 20 TO 27 - ULTRA-DETAILED CLINICAL GUIDE

Williams Obstetrics - Resident Level

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TOPIC 20: MEDICAL DISORDERS IN PREGNANCY

HYPERTENSIVE DISORDERS OF PREGNANCY

Classification and Definitions

• Pre-existing hypertension diagnosed BEFORE pregnancy OR before 20 weeks gestation
• OR hypertension that persists >12 weeks postpartum
• Affects 1-5% of pregnancies
• Higher prevalence in African American women, obese women, advanced maternal age
• Subtypes:
  • Primary (essential): >90% of cases
  • Secondary: renal disease, renovascular hypertension, primary aldosteronism, Cushing syndrome, pheochromocytoma, coarctation of aorta, sleep apnea

• New-onset hypertension at ≥20 weeks WITHOUT proteinuria or severe features
• Resolves by 12 weeks postpartum (if persists = chronic hypertension diagnosed postpartum)
• 15-25% will progress to preeclampsia
• Diagnosis of exclusion - must rule out preeclampsia

• New-onset hypertension (SBP ≥140 OR DBP ≥90 on two occasions ≥4 hours apart) at ≥20 weeks PLUS:
  • Proteinuria ≥300 mg/24h, OR protein:creatinine ratio ≥0.3, OR urine dipstick ≥2+ (use only if other methods unavailable)
  • OR in ABSENCE of proteinuria: any one severe feature (see below)
• Affects 3-5% of pregnancies
• Leading cause of maternal and perinatal morbidity/mortality worldwide

• SBP ≥160 mmHg OR DBP ≥110 mmHg on two occasions ≥4 hours apart while patient is on bed rest (or immediately if antihypertensives to be administered)
• Thrombocytopenia: platelets <100,000/µL
• Renal insufficiency: creatinine >1.1 mg/dL OR doubling of creatinine in absence of other renal disease
• Impaired liver function: elevated liver transaminases to ≥2x upper limit of normal AND/OR severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses
• Pulmonary edema
• New-onset headache unresponsive to medication and not accounted for by alternative diagnoses
• Visual disturbances (scotomata, blurring, diplopia, photopsia)

• Hemolysis + Elevated Liver enzymes + Low Platelets
• Variant of severe preeclampsia; may occur WITHOUT hypertension or proteinuria in 15-20% of cases
• Incidence: 0.5-0.9% of all pregnancies; 10-20% of severe preeclampsia

• New-onset generalized tonic-clonic seizures in woman with preeclampsia
• No other cause of seizures identified
• 40% occur before delivery; 16% occur >48h postpartum (up to 4 weeks postpartum reported)
• Mortality: 0-1.8% in developed countries; much higher in low-resource settings

• Sudden worsening of hypertension requiring additional medications
• New-onset proteinuria in woman with chronic hypertension without prior proteinuria
• Sudden increase in proteinuria if already present
• New-onset thrombocytopenia or abnormal liver enzymes
• Signs/symptoms of severe preeclampsia

Pathophysiology of Preeclampsia - Detailed

• Stage 1 (Placental): Impaired trophoblast invasion → failure of spiral artery remodeling → placental ischemia/hypoperfusion → placental release of antiangiogenic factors
• Stage 2 (Maternal): Circulating factors cause systemic maternal endothelial dysfunction → clinical syndrome

• sFlt-1 (soluble FMS-like tyrosine kinase 1): Anti-angiogenic; binds and neutralizes free VEGF and PlGF → endothelial dysfunction; elevated WEEKS before clinical symptoms
• PlGF (placental growth factor): Pro-angiogenic; decreased in preeclampsia; low PlGF ratio (sFlt-1:PlGF >38) predicts development of preeclampsia within 4 weeks
• Endoglin: Anti-angiogenic; inhibits TGF-β signaling; elevated in preeclampsia
• VEGF (vascular endothelial growth factor): Reduced bioavailability → glomerular endotheliosis (pathognomonic renal lesion)

• Glomerular endotheliosis: swollen glomerular endothelial cells occlude capillary lumen; pathognomonic on biopsy
• Reduced GFR → elevated creatinine, uric acid, BUN
• Proteinuria from loss of glomerular charge barrier
• Oliguria: <500 mL/24h in severe disease

• Periportal hemorrhagic necrosis
• Fibrin deposits in sinusoids
• Subcapsular hematoma (rare but catastrophic)
• Hepatic rupture: mortality >50%; presents with sudden severe RUQ pain + hemodynamic collapse

• Cerebral vasospasm → ischemia → focal neurological signs
• Loss of cerebral autoregulation → hypertensive encephalopathy
• Cerebral edema → herniation (rare)
• Petechiae, microinfarcts

• Microangiopathic hemolytic anemia (MAHA): fibrin strands shear RBCs → schistocytes on smear, elevated LDH, decreased haptoglobin, elevated indirect bilirubin
• Thrombocytopenia: platelet activation and consumption at sites of endothelial damage
• DIC: in severe HELLP (5-10%)

• Elevated SVR
• Reduced cardiac output (in some patients)
• Reduced plasma volume (opposite of normal pregnancy)
• Pulmonary edema: from low colloid oncotic pressure + increased capillary permeability + iatrogenic fluid overload

Prevention of Preeclampsia

• Mechanism: suppresses thromboxane A2 > prostacyclin → improves placental blood flow; reduces platelet aggregation
• Dose: 81 mg/day (some European guidelines use 150 mg/day)
• Timing: START at 12-16 weeks (ideally ≤16 weeks); continue until delivery
• Reduces preeclampsia risk by ~10-24% overall; up to 62% reduction in high-risk women when started before 16 weeks (ASPRE trial with 150 mg dose)
• HIGH-RISK criteria (ACOG - any ONE):
  • Prior preeclampsia
  • Multifetal gestation
  • Chronic hypertension
  • Type 1 or 2 diabetes
  • Renal disease
  • Autoimmune (SLE, APS)
• MODERATE-RISK criteria (ACOG - aspirin if ≥2):
  • Nulliparity, obesity (BMI>30), family history, Black race, age ≥35, prior adverse outcome (SGA, preterm), interval >10 years

• Mean uterine artery pulsatility index (UtAPI) + MAP + PlGF + PAPP-A + patient factors
• FMF algorithm (Fetal Medicine Foundation): predicts preterm preeclampsia (<37 weeks) with 75% detection at 10% FPR
• Allows targeted aspirin use
• sFlt-1:PlGF ratio at 11-13 weeks: powerful predictive tool

• 1.5-2g/day in women with low dietary calcium intake (<600 mg/day)
• Reduces preeclampsia risk by ~55% in low-calcium populations (WHO recommendation)
• Less benefit in populations with adequate calcium intake

Antihypertensive Management in Pregnancy

• Chronic hypertension: treat if BP ≥150/100 mmHg (or lower if end-organ damage)
• Acute severe hypertension (≥160/110): TREAT WITHIN 30-60 MINUTES to reduce maternal stroke risk

• 20 mg IV over 2 min; if inadequate response after 10 min → 40 mg IV; then 80 mg q10 min; max 300 mg/episode
• Combined alpha and beta blockade; safe; no fetal effects
• Avoid in asthma, heart block, decompensated heart failure

• 5 mg IV or 10 mg IM over 2 min; repeat 5-10 mg every 20 min; max 20 mg IV or 30 mg IM
• Direct arteriolar vasodilator
• Side effects: tachycardia, headache, nausea, lupus-like syndrome with prolonged use
• Unpredictable response; more side effects than labetalol in some studies

• 10-20 mg orally; repeat 20 mg after 20 min if needed; then 10-20 mg q2-6h; max 180 mg/day
• Do NOT give sublingually (precipitous BP drop → fetal distress)
• Safe; effective; widely available
• Theoretical concern with concurrent magnesium (potentiation) - clinical significance minimal at recommended doses

• ACE inhibitors: fetal renal tubular dysplasia, oligohydramnios, skull ossification defects (Category D)
• ARBs: same mechanism; contraindicated second/third trimester
• Atenolol: IUGR; avoid throughout pregnancy
• Nitroprusside: cyanide toxicity to fetus; last resort only

Seizure Prophylaxis and Treatment

• Drug of choice for prevention AND treatment of eclamptic seizures
• Superior to phenytoin, diazepam, and other anticonvulsants for eclampsia (Magpie Trial, 2002)
• Mechanism: blocks NMDA receptors; peripheral vasodilation; reduces cerebral ischemia

• Urine output: ≥25-30 mL/hour (Mg is renally excreted; toxicity with oliguria)
• Respiratory rate: ≥12/minute before each dose/hourly
• Deep tendon reflexes: must be present (patellar reflex first to disappear with toxicity)
• Serum Mg level if concerned: therapeutic 4-7 mEq/L
• Pulse oximetry: continuous

• 4-7 mEq/L: therapeutic range
• 7-10 mEq/L: loss of patellar reflexes
• 10-13 mEq/L: respiratory paralysis

• 15 mEq/L: cardiac arrest

• Antidote: Calcium gluconate 1g (10 mL of 10% solution) IV over 3 minutes; repeat every hour as needed until toxicity resolved

1. Call for HELP; do not leave patient alone
2. Left lateral decubitus position; protect from injury
3. Secure airway; supplemental O2; pulse oximetry
4. IV access (if not already present)
5. MgSO4 4-6g IV bolus; 2g/hr maintenance
6. If seizing despite Mg: additional 2g bolus IV; consider IV lorazepam/diazepam
7. Control severe hypertension with IV labetalol or hydralazine
8. Fetal monitoring (transient bradycardia expected after seizure - usually recovers in 3-10 minutes; do NOT rush to cesarean during or immediately after seizure)
9. Delivery after maternal stabilization (route depends on cervical status, fetal presentation, urgency)
10. Postpartum: continue MgSO4 ≥24 hours; monitor closely (40% of eclampsia is postpartum)

HELLP Syndrome - Detailed

• Hemolysis: abnormal peripheral smear (schistocytes, burr cells), serum bilirubin >1.2 mg/dL, LDH >600 U/L
• Elevated liver enzymes: AST ≥70 U/L, LDH ≥600 U/L
• Low platelets: <100,000/µL

• Class 1: Platelets ≤50,000; LDH ≥600; AST/ALT ≥70
• Class 2: Platelets 50,001-100,000; LDH ≥600; AST/ALT ≥70
• Class 3: Platelets 100,001-150,000; LDH ≥600; AST/ALT ≥40

• 90% present between 27-37 weeks; 10% <27 weeks
• 30% occur within 48 hours POSTPARTUM
• Presenting symptoms: RUQ/epigastric pain (65%), nausea/vomiting (36%), headache (31%)
• Hypertension absent in 15-20%; proteinuria absent in 5-15% → can be missed
• Malaise, flu-like symptoms may precede diagnosis by days

• DIC: 4-38%
• Placental abruption: 9-20%
• Acute renal failure: 7-36%
• Pulmonary edema: 8%
• Hepatic hematoma/rupture: 1-2%
• Maternal death: 1-3%
• Perinatal mortality: 7-60% (varies with gestational age)

• MgSO4 for seizure prophylaxis
• Antihypertensives for severe BP
• Corticosteroids: dexamethasone 10 mg IV q12h (controversial for HELLP itself; some evidence of platelet improvement, reduced blood product transfusion; evidence inconsistent)
• Transfuse platelets: if <20,000, or <50,000 with active bleeding, or <50,000 before cesarean
• Fresh frozen plasma: for DIC with active bleeding
• Delivery:
  • ≥34 weeks: deliver promptly after stabilization
  • <34 weeks: individual decision; if Class 1 or clinical deterioration → deliver; some advocate for 24-48 hours of stabilization/steroids if <34 weeks in Class 2-3 with stable patient
  • <24 weeks: high maternal morbidity risk; delivery often recommended
• Route: vaginal delivery preferred if cervix favorable; cesarean for standard obstetric indications

• Presents with acute severe RUQ pain, hemodynamic instability
• Imaging: CT/US shows subcapsular hematoma
• Intact hematoma: conservative management (ICU, correct coagulopathy, monitor)
• Rupture: immediate surgery (packing ± hepatic artery ligation ± hepatectomy); interventional radiology (embolization); liver transplant for massive necrosis
• Mortality: 50-75% for rupture

Delivery in Preeclampsia

• Preeclampsia WITHOUT severe features:
  • ≥37 0/7 weeks: DELIVER (HYPITAT trial showed induction not inferior to expectant; reduces maternal morbidity)
  • 34 0/7 - 36 6/7 weeks: deliver vs. expectant management; ACOG recommends delivery at ≥37 weeks; earlier if maternal/fetal compromise
  • <34 weeks: expectant management in tertiary center with careful monitoring (if stable)
• Preeclampsia WITH severe features:
  • ≥34 0/7 weeks: DELIVER after stabilization
  • <34 weeks: admit to tertiary care; corticosteroids; MgSO4; antihypertensives; deliver if deterioration, renal failure, pulmonary edema, abruption, abnormal fetal testing, DIC, eclampsia
  • <24 weeks: individualized; delivery vs. pregnancy termination (very high maternal risk)

• Avoid excessive IV fluids (pulmonary edema risk; colloid oncotic pressure low)
• Monitor urine output continuously (oliguria concerning)
• Continuous FHR monitoring (uteroplacental insufficiency common)
• Anesthesia: epidural preferred (avoids hypertensive response to intubation); regional safe if platelets ≥70,000-80,000
• Third stage: use oxytocin (NOT ergot alkaloids - methylergonovine causes vasoconstriction, worsens hypertension)

• BP often WORSENS in first 3-6 days postpartum
• New-onset severe range BP or severe features in first 4-6 weeks = postpartum preeclampsia
• Treat with oral antihypertensives: nifedipine XL, labetalol
• MgSO4 ≥24 hours postpartum for severe features
• Discharge BP criteria: stable BP <150/100 with or without medication; follow-up within 3-7 days

• 2x lifetime risk of cardiovascular disease
• 4x risk of hypertension
• 2x risk of stroke and ischemic heart disease
• Increased risk of renal disease
• Counseling about lifestyle modification, BP monitoring, statin consideration

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DIABETES IN PREGNANCY

Pre-gestational Diabetes

• Type 1 (absolute insulin deficiency): 0.5% of pregnancies; all complications + increased DKA risk in pregnancy
• Type 2 (insulin resistance + relative deficiency): increasing prevalence with obesity epidemic; 1-2% of pregnancies

• Diabetic ketoacidosis (DKA): can occur at lower glucose levels in pregnancy (euglycemic DKA); triggered by: infection, emesis, insulin pump failure, stress
• Hypoglycemia: increased sensitivity; unawareness common; particularly dangerous for fetus
• Worsening retinopathy: first trimester laser treatment if needed; avoid pregnancy with active proliferative retinopathy until treated
• Worsening nephropathy: increased proteinuria; preeclampsia risk very high (up to 30-40% with nephropathy)
• Preeclampsia: 10-20% overall; much higher with nephropathy or poor control
• Infection: UTI, candidiasis, wound infection
• Cesarean: 2-3x higher rate
• PPH: macrosomia increases risk

• Congenital anomalies (related to FIRST TRIMESTER glycemic control):
  • Cardiac (most common): VSD, ASD, HLHS, TGA (50% of anomalies are cardiac)
  • CNS: NTDs (3x increased risk)
  • Sacral agenesis/caudal regression (pathognomonic of DM; 200x increased risk)
  • Skeletal, genitourinary, gastrointestinal anomalies
  • Risk proportional to HbA1c: HbA1c 6-7% → 2-4% anomaly risk; HbA1c >10% → 15-20% risk
• Macrosomia (LGA, EFW >4000-4500g): from fetal hyperinsulinemia (Pedersen hypothesis)
• IUGR: with diabetic vasculopathy and nephropathy
• Polyhydramnios: from fetal hyperglycemia → osmotic diuresis → increased urine output
• Preterm birth: both spontaneous and iatrogenic
• Stillbirth: 3-5x increased risk (especially third trimester); from chronic hypoxia, acidosis
• Neonatal hypoglycemia: after birth, hyperinsulinism persists without maternal glucose supply; check glucose at 30-60 minutes after birth
• Neonatal hypocalcemia, hypomagnesemia, polycythemia, hyperbilirubinemia
• Respiratory distress: surfactant maturation delayed with poor glycemic control
• Long-term: increased obesity, metabolic syndrome, type 2 diabetes in offspring

• Target HbA1c <6.5% (ideally <7% before conception)
• Folic acid 4 mg/day
• Ophthalmology, nephrology, cardiology evaluation
• Switch to insulin if on oral agents (except metformin which some continue)
• Optimize BP control (switch from ACEI/ARB)

• Confirm dates, viability
• HbA1c
• 24-hour urine protein or protein:creatinine ratio
• Thyroid function (frequent association with autoimmune thyroid disease in Type 1)
• BUN, creatinine
• Ophthalmology visit
• Start folic acid if not already taking

• Anatomy scan 18-20 weeks
• Fetal echocardiogram 20-22 weeks
• Growth ultrasound q4 weeks from 28 weeks
• HbA1c each trimester

• Growth ultrasounds every 4 weeks
• Antenatal surveillance: NST/BPP twice weekly from 32-36 weeks
• Consider delivery:
  • Type 1 or 2, well-controlled, no complications: 39-40 weeks
  • Poor control or complications: individualize; may deliver earlier

• Fasting: <95 mg/dL
• 1-hour postprandial: <140 mg/dL
• 2-hour postprandial: <120 mg/dL
• Bedtime: 100-140 mg/dL
• 3 AM: >60 mg/dL (prevent nocturnal hypoglycemia)
• HbA1c: <6-6.5% (lower target than non-pregnancy; <6% if achievable without hypoglycemia)

• Insulin requirements change dramatically through pregnancy:
  • First trimester: may DECREASE (nausea, vomiting reduces intake; early insulin sensitivity)
  • Second/third trimester: INCREASES significantly (hormonal insulin resistance from hPL, cortisol, estrogen, progesterone); may need 2-3x preconception dose by third trimester
  • Postpartum: plummets (remove placenta → remove insulin-antagonizing hormones); often 50% reduction immediately
• Insulin analogs safe: lispro, aspart (short-acting); detemir, glargine (long-acting; Category B/C data)
• Continuous glucose monitoring (CGM): significantly improves outcomes; recommended for Type 1 in pregnancy (CONCEPTT trial)
• Insulin pump (CSII): allows precise dosing; preferred for Type 1 with brittle control

Gestational Diabetes Mellitus (GDM)

• Normal pregnancy: progressive insulin resistance from mid-pregnancy (due to hPL, progesterone, cortisol, prolactin)
• GDM: insufficient beta-cell compensation for increased insulin resistance
• Often represents underlying Type 2 predisposition unmasked by pregnancy

1. 1-hour GCT (50g oral glucose, non-fasting): Positive threshold ≥140 mg/dL (some use ≥130 mg/dL; increases sensitivity, more false positives)
2. If positive GCT: 3-hour GTT (100g oral glucose, fasting)
   • Values (Carpenter-Coustan criteria): Fasting ≥95, 1h ≥180, 2h ≥155, 3h ≥140 mg/dL
   • ≥2 abnormal values = GDM
   • ≥1 abnormal value = "impaired" (some centers treat as GDM)

• 2-hour 75g OGTT (fasting)
• Any ONE value: Fasting ≥92, 1h ≥180, 2h ≥153 mg/dL = GDM
• More sensitive; diagnoses more women; controversial whether all benefit from treatment

• Goals: glucose targets (fasting <95, 1h pp <140, 2h pp <120) without ketones
• Carbohydrate: 33-40% of calories; distributed throughout day (3 meals + 2-3 snacks)
• Avoid concentrated sweets; limit refined carbohydrates
• Complex carbohydrates preferred (lower glycemic index)
• Adequate calories to avoid ketosis: 30-35 kcal/kg ideal body weight (25 kcal/kg if obese)
• Registered dietitian counseling

• 30 minutes moderate exercise after meals reduces postprandial glucose
• Walking after meals most practical
• Reduces pharmacologic treatment need

• Gold standard; safest; does not cross placenta; rapidly titratable
• Start with NPH at bedtime + short-acting with meals (or basal-bolus with analogs)
• Typical starting dose: 0.7-1.0 units/kg/day (total); adjust based on glucose logs

• Increasingly used; oral; cheaper; less hypoglycemia than insulin
• Crosses placenta: fetal exposure; long-term safety data largely reassuring (MiG trial, follow-up studies)
• 30-40% of women will still need supplemental insulin
• Avoid in renal insufficiency, hepatic disease, contrast exposure
• ACOG: acceptable alternative to insulin with patient counseling about placental transfer

• Previously popular alternative; NOW less favored
• Crosses placenta (detected in cord blood at significant levels)
• Higher rates of neonatal hypoglycemia, macrosomia than insulin in meta-analyses
• ACOG: may use if insulin and metformin not acceptable but should be with awareness of higher failure rate

• Self-monitoring of blood glucose (SMBG): fasting + 1-2h after meals
• HbA1c: not ideal for GDM monitoring (normal lower in pregnancy due to increased RBC turnover)
• Ketone testing: if glucose high or caloric restriction; ketones cross placenta and impair fetal neurological development

• Well-controlled GDM on diet alone (A1GDM): NST starting at 40 weeks; deliver by 40-41 weeks
• GDM requiring medication (A2GDM): NST twice weekly from 32-34 weeks; deliver 39-40 weeks
• Growth ultrasound at 28-32 weeks; additional at 36 weeks if macrosomia suspected

• Well-controlled A1GDM: deliver at 40-41 weeks (no earlier without indication)
• A2GDM: deliver at 39 0/7 - 39 6/7 weeks
• Macrosomia: consider cesarean if EFW ≥4500g (Type 1/2 DM) or ≥5000g (GDM) to prevent shoulder dystocia
• Intrapartum glucose monitoring: glucose every 1-2 hours; target 70-120 mg/dL; insulin drip if needed
• Discontinue all glucose-lowering therapy after placental delivery

• GDM resolves after delivery in most cases
• OGTT at 6-12 weeks postpartum (75g, 2-hour): diagnose overt diabetes or prediabetes
• 50% lifetime risk of developing Type 2 diabetes
• Annual fasting glucose or HbA1c; lifestyle modification; metformin for high-risk women
• Breastfeeding: lowers GDM recurrence and reduces offspring metabolic risk

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CARDIAC DISEASE IN PREGNANCY - DETAILED

Peripartum Cardiomyopathy (PPCM) - Extended

• Heart failure secondary to left ventricular dysfunction
• Occurs toward END of pregnancy or WITHIN 5 MONTHS of delivery
• No other identifiable cause
• EF <45%

• Incidence: 1 in 1000-4000 deliveries
• Higher incidence in: African American women (3-4x), multiparity, multiple gestation, advanced maternal age, preeclampsia, malnutrition, prolonged tocolysis with beta-agonists, cocaine use

• Prolactin hypothesis (leading theory): Oxidative stress in the peripartum period → cathepsin D cleaves 23-kDa prolactin → vasoinhibin (anti-angiogenic) → cardiomyocyte apoptosis and dysfunction
• Autoimmune mechanisms: cross-reactive antibodies against cardiac proteins
• Viral myocarditis: trigger in some cases
• Genetic predisposition: peripartum PPCM may be a stress-unmasked familial cardiomyopathy (TTN mutations, FLNC, etc.)

• Symptoms: dyspnea, orthopnea, PND, edema, fatigue, palpitations, hemoptysis
• Physical exam: displaced PMI, S3, mitral regurgitation murmur, JVD, bilateral crackles, peripheral edema
• Must distinguish from normal pregnancy (dyspnea is common) → echo is key
• Thromboembolism risk very high (dilated LV, AF, hypercoagulability of pregnancy)

• Echocardiography: dilated LV, reduced EF, +/- RV involvement, mitral regurgitation
• BNP/NT-proBNP: elevated; useful for monitoring
• MRI: characterizes fibrosis, inflammation; predicts recovery
• Troponin: elevated in severe disease; indicates myocardial injury

• Standard HF therapy (modified for pregnancy/lactation):
  • Diuretics: furosemide (safe postpartum; with caution antepartum)
  • Beta-blockers: carvedilol, metoprolol (safe postpartum; metoprololsuccinate during pregnancy)
  • ACE inhibitors/ARBs: POSTPARTUM ONLY (contraindicated in pregnancy); enalapril, captopril
  • Hydralazine + nitrates: antepartum vasodilator alternative (instead of ACEI)
  • Digoxin: for symptomatic HF; safe in pregnancy
  • Anticoagulation: full anticoagulation recommended with EF <35% (LMWH in pregnancy; warfarin postpartum)
• Bromocriptine (dopamine agonist):
  • Inhibits prolactin secretion → interrupts vasoinhibin pathway
  • Two trials (REBIRTH, BOARD) show improved EF recovery and outcomes vs. standard care alone
  • Dose: 2.5 mg BID x2 weeks then 2.5 mg daily x6 weeks (varies by protocol)
  • Suppresses lactation (inform patient)
  • ESC 2018: IIb recommendation (consider in PPCM)
• Cardiac resynchronization therapy (CRT): if EF <35% with LBBB; can implant during pregnancy with shielding
• LVAD/transplant: for refractory cases

• Hemodynamically stable: await spontaneous labor or induce at 37-38 weeks
• Hemodynamically unstable: stabilize then deliver; mode by obstetric indications
• Anesthesia: epidural preferred (reduces afterload, preload); avoid spinal if hypotensive
• Postpartum: intensify treatment (ACEI can now be started); monitor closely first week (highest risk period)

• Recovery of EF (>50%): 30-50% by 6 months; up to 72% with bromocriptine
• EF normalization predicts survival
• Persistent dysfunction: chronic cardiomyopathy; heart failure mortality
• Subsequent pregnancy: HIGH RISK even if EF recovered
  • Recurrence: 21-44%
  • If EF not recovered: mortality up to 25% with subsequent pregnancy
  • If EF fully recovered: recurrence risk 11-21%; counsel extensively

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THYROID DISEASE IN PREGNANCY - DETAILED

Physiology of Thyroid in Pregnancy

• TBG (thyroid-binding globulin): increases 2-3x (from estrogen stimulation) → increased total T3/T4; free levels unchanged
• hCG cross-reacts with TSH receptor (structural similarity): TSH decreases in first trimester (5-15% women have TSH <0.1 mIU/L normally in first trimester)
• Iodine requirements increase: 250 mcg/day (vs. 150 mcg non-pregnant); increased renal clearance + fetal use

• First trimester TSH: 0.1-2.5 mIU/L
• Second trimester TSH: 0.2-3.0 mIU/L
• Third trimester TSH: 0.3-3.5 mIU/L
• Free T4: generally normal (use trimester-specific lab ranges)

Hypothyroidism in Pregnancy

• Hashimoto thyroiditis (most common): autoimmune; anti-TPO antibodies
• Prior radioactive iodine or thyroidectomy
• Iodine deficiency (global leading cause)
• Drugs: amiodarone, lithium, interferon-alpha

• Maternal: preeclampsia, placental abruption, anemia, preterm birth, postpartum hemorrhage, cardiac dysfunction
• Fetal: miscarriage, IUGR, preterm birth, stillbirth
• Neonatal: impaired neurological development, lower IQ (ESPECIALLY with free T4 deficiency in FIRST TRIMESTER - critical window for brain development before fetal thyroid functional at 18-20 weeks)
• CATS trial: treatment of subclinical hypothyroidism did NOT improve child cognitive outcomes (if started at 8-20 weeks); suggests very early identification and treatment critical

• Levothyroxine (T4): drug of choice; start immediately on confirmation of pregnancy
• Typical dose increase: 25-30% as soon as pregnancy confirmed (increased T4 demand)
• Titrate to TSH: first trimester goal TSH 0.1-2.5 mIU/L; second trimester 0.2-3.0 mIU/L
• Monitor TSH every 4-6 weeks in first half of pregnancy; every 6-8 weeks second half
• Timing: take on empty stomach; 30-60 min before food/coffee
• Avoid taking with: iron supplements, calcium, antacids (decrease absorption)
• Postpartum: return to preconception dose; recheck at 6 weeks postpartum

• ACOG: targeted case finding (screen women with symptoms, risk factors, history) rather than universal
• ATA/Endocrine Society: some recommend universal screening
• Risk factors for screening: prior thyroid disease, family history, goiter, symptoms, autoimmune disease, prior preterm birth/miscarriage, residing in iodine-deficient area, prior head/neck irradiation

Hyperthyroidism in Pregnancy

1. Graves disease (85%): autoimmune; TSH receptor-stimulating antibodies (TRAb/TSI); most common cause
2. Gestational transient thyrotoxicosis: hCG-mediated; first trimester; no TRAb; mild; resolves spontaneously; treat symptomatically (hydration, beta-blockers if severe); NO antithyroid drugs needed
3. Toxic multinodular goiter
4. Toxic adenoma
5. Thyroiditis (subacute, postpartum)
6. Struma ovarii
7. Molar pregnancy (very high hCG → thyrotoxicosis)

• Maternal: thyroid storm, cardiac arrhythmias, HF, preeclampsia
• Fetal/neonatal:
  • Fetal hyperthyroidism: TRAb crosses placenta → fetal goiter, tachycardia, IUGR, hydrops, bone age advancement, craniosynostosis
  • Neonatal thyrotoxicosis: TRAb in neonatal circulation at birth → neonatal Graves (lasts until TRAb cleared); affects 2-5% of neonatal Graves mothers; can be life-threatening
  • Neonatal hypothyroidism: if mother on antithyroid drugs (crosses placenta)
  • Monitor: TRAb levels at 18-20 weeks and 30-36 weeks; if elevated → fetal monitoring for signs of fetal hyper/hypothyroidism

• FIRST TRIMESTER: preferred (MMI associated with aplasia cutis, MMI/CBZ embryopathy in first trimester)
• Mechanism: blocks thyroid peroxidase + blocks peripheral conversion T4→T3
• Dose: 100-150 mg every 8 hours; titrate to free T4 in upper normal range
• Side effects: hepatotoxicity (rare but serious; black box warning - 1 in 10,000); agranulocytosis (<0.5%)
• SWITCH to MMI after first trimester (MMI preferred in second/third trimester due to PTU hepatotoxicity risk)

• SECOND AND THIRD TRIMESTER: preferred after first trimester
• Mechanism: blocks thyroid peroxidase only (no peripheral conversion effect)
• Dose: 5-30 mg/day divided
• MMI embryopathy (if used first trimester): aplasia cutis, choanal atresia, esophageal atresia, MMI syndrome (facial features)
• Side effects: agranulocytosis (<0.5%); rash; arthralgias

• Propranolol or atenolol for symptomatic control (palpitations, tremor, heat intolerance)
• Short-term use; avoid chronic use (IUGR, bradycardia, neonatal hypoglycemia)

• Reserved for: non-compliance, drug reaction, very large goiter with obstruction, refractory disease
• Best performed in second trimester
• Risk: hypoparathyroidism, recurrent laryngeal nerve damage, fetal loss (~4.5%)

• Life-threatening; mortality 10-25%
• Triggers: infection, surgery, labor, abrupt medication discontinuation
• Diagnosis: clinical (Burch-Wartofsky score >45 = likely storm)
• Features: fever >38.5°C, tachycardia >140 bpm, CNS dysfunction (agitation, psychosis, coma), GI symptoms, cardiac arrhythmia/HF

1. PTU 500-1000 mg oral/NG loading → 250 mg q4h (preferred over MMI due to peripheral conversion blockade)
2. Iodine (AFTER PTU by 1 hour to prevent organification): Lugol solution 8 drops q6h OR potassium iodide (SSKI) 5 drops TID; blocks thyroid hormone release (Wolff-Chaikoff effect)
3. Propranolol: 60-80 mg oral q4h OR 1-2 mg IV slowly; controls adrenergic symptoms + blocks T4→T3 conversion
4. Hydrocortisone: 300 mg IV then 100 mg q8h (reduces hormone release; blocks peripheral conversion; treats possible adrenal insufficiency)
5. ICU admission; aggressive cooling; treat precipitating cause
6. Cholestyramine: if resistant; binds thyroid hormones in GI tract
7. Plasmapheresis: last resort

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VENOUS THROMBOEMBOLISM IN PREGNANCY - DETAILED

Risk Assessment

• Hypercoagulability: increased procoagulant factors (I, VII, VIII, X, XII, vWF), decreased protein S, decreased fibrinolysis → 4-5x increased clotting risk
• Venous stasis: uterine compression of inferior vena cava; decreased venous tone (progesterone)
• Endothelial injury: especially during delivery (especially cesarean)

• Previous unprovoked VTE or VTE on estrogen
• VTE + thrombophilia
• Antiphospholipid syndrome + prior VTE
• High-risk thrombophilia (antithrombin deficiency, combined defects)

• Hospital admission for >3 days
• Active systemic illness
• Surgical procedure in pregnancy
• Hyperemesis requiring hospitalization

• BMI >30, age >35, multiparity ≥3, smoking, varicose veins, pre-eclampsia, multiple gestation, PPH

Deep Vein Thrombosis in Pregnancy

• Unilateral leg swelling, warmth, erythema, tenderness
• Preferentially LEFT leg (right iliac artery compresses left iliac vein - May-Thurner syndrome exaggerated in pregnancy)
• Iliac vein thrombosis: back/flank/abdominal pain without classical leg findings → easy to miss
• Superficial thrombophlebitis: distinguish from DVT; usually self-limited; NSAIDs; low VTE risk unless near sapheno-femoral junction

• Compression ultrasound: first-line; high sensitivity (95%) for symptomatic proximal DVT; lower for distal DVT; safe (no radiation)
• D-dimer: markedly elevated in normal pregnancy; NOT useful for excluding DVT in pregnancy (cannot use PERC rule or Wells criteria as in non-pregnant)
• MR venography: for iliac vein thrombosis (pelvic DVT not seen on lower extremity US); no radiation; excellent visualization
• CT venography: higher radiation; second choice

Pulmonary Embolism in Pregnancy

• Dyspnea (most common), pleuritic chest pain, hemoptysis, tachycardia, hypoxia
• Massive PE: hemodynamic collapse, cardiac arrest
• May be clinically silent

• Chest X-ray: first-line (normal in most; Westermark sign, Hampton hump rarely seen); guides V/Q interpretation
• V/Q scan: preferred in pregnancy (lower radiation to maternal breast vs. CTPA); order if CXR normal
  • Normal: essentially excludes PE
  • High probability: treat as PE
  • Non-diagnostic: proceed to CTPA
  • Fetal dose: 0.1-0.5 mGy (very low)
• CT pulmonary angiography (CTPA): high sensitivity and specificity; may be preferred with abnormal CXR; fetal dose 0.01-0.66 mGy; maternal breast dose higher (increased cancer risk concern)
• Leg compression US: if positive → treat without CTPA (no additional benefit of confirming PE)
• Echocardiography: RV dilation, TR, D-septum → suggests massive PE; guides resuscitation; not diagnostic

• LMWH (first-line):
  • Enoxaparin: 1 mg/kg SQ every 12 hours (therapeutic dose) OR 1.5 mg/kg once daily
  • Monitor: anti-Xa level 4 hours after dose; target 0.6-1.0 IU/mL (BID dosing) or 1.0-2.0 IU/mL (OD dosing)
  • Does NOT cross placenta; safe for fetus
  • Does NOT prevent epidural - hold 12-24h before epidural placement
• Unfractionated heparin (UFH):
  • IV continuous infusion: used near term or in situations requiring rapid reversal
  • Weight-based dosing: 80 units/kg bolus + 18 units/kg/hour; titrate to aPTT 60-100 sec
  • Reversal: protamine sulfate
  • Switch from LMWH to UFH at 36-37 weeks (UFH cleared faster; better for operative delivery)
• Warfarin: AVOID in first trimester (warfarin embryopathy: nasal hypoplasia, stippled epiphyses, chondrodysplasia); safe second trimester (crosses placenta → fetal anticoagulation → hemorrhage risk at delivery); avoid throughout; OK to use postpartum
• Direct oral anticoagulants (DOACs): cross placenta; NO data in pregnancy; contraindicated; switch if patient taking before pregnancy
• Systemic thrombolysis (tPA): reserved for MASSIVE PE with hemodynamic collapse; risk of maternal hemorrhage (especially postpartum); life-threatening situation only
• Catheter-directed thrombolysis: lower systemic dose; for submassive/massive PE
• Surgical embolectomy: rare; for refractory massive PE

• Acute VTE in pregnancy: treat for minimum 3 months AND at least until 6 weeks postpartum
• Total minimum duration: 6 months

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INFECTIONS IN PREGNANCY - DETAILED

Group B Streptococcus (GBS) - Extended

• Colonization rate: 10-30% of pregnant women
• Without prophylaxis: 1-2% of colonized women transmit to neonate
• Vertical transmission occurs: during labor, after ROM, or rarely ascending through intact membranes

• 36 0/7 - 37 6/7 weeks: vaginal-rectal swab (NOT cervical swab)
• Technique: single swab to vaginal introitus first, then same swab to anorectum (or separate swabs)
• Enrichment culture (Todd-Hewitt broth): standard; 24-48 hours; highest sensitivity
• Rapid GBS tests (PCR): high sensitivity/specificity; 30-45 min turnaround; useful when culture status unknown; not yet standard

• GBS positive on current culture
• GBS bacteriuria in current pregnancy (any count)
• Prior GBS-positive infant
• Unknown status WITH any of: delivery <37 weeks, intrapartum fever ≥38°C, ROM ≥18 hours
• Previous GBS-positive culture in this pregnancy even if current culture not available

• Prior GBS positive history but negative culture in current pregnancy
• Elective cesarean with intact membranes (regardless of GBS status)
• Planned cesarean before labor onset with intact membranes

• Penicillin G: 5 million units IV loading → 2.5-3 million units IV every 4 hours until delivery

• Cefazolin: 2g IV loading → 1g IV every 8 hours until delivery

• Must have susceptibility testing performed on GBS isolate
• If susceptible to clindamycin: clindamycin 900 mg IV every 8 hours
• If resistant to clindamycin OR susceptibility unknown: vancomycin 20 mg/kg IV every 8 hours (max 3g/dose)

• Most common presentation: sepsis, pneumonia, meningitis
• From maternal vertical transmission
• IAP reduces incidence by 80%

• From environmental/hospital/community acquisition
• Meningitis most common
• Not preventable by IAP

Urinary Tract Infections in Pregnancy - Detailed

• Definition: ≥100,000 CFU/mL of single organism in CLEAN CATCH specimen without symptoms (OR any growth of GBS)
• Prevalence: 2-7% of pregnant women
• Must treat (UNLIKE non-pregnant adults): 25-40% will develop pyelonephritis if untreated; associated with preterm birth and low birth weight
• Treatment: 3-7 day course based on organism and sensitivity:
  • Nitrofurantoin 100 mg ER BID x5 days (avoid at ≥36 weeks - neonatal hemolysis; avoid in G6PD deficiency)
  • Amoxicillin-clavulanate 875/125 mg BID x3-7 days
  • Cephalexin 500 mg QID x3-7 days
  • Fosfomycin 3g single dose (effective; useful for MDR organisms)
  • Avoid: fluoroquinolones, tetracyclines, TMP (first trimester), sulfonamides (near term)
• Repeat urine culture 1-2 weeks after treatment (test of cure)
• Monthly cultures for remainder of pregnancy after treated ASB (25-30% recurrence)

• Symptoms: frequency, urgency, dysuria, suprapubic pain
• No fever, no flank pain, no CVA tenderness
• Treatment: same agents as ASB x 7 days
• Urine culture essential for diagnosis and sensitivity

• MOST COMMON serious medical complication of pregnancy
• Incidence: 1-2% (if ASB untreated, higher)
• Onset: usually second or third trimester; more common right side
• Presentation: fever ≥38°C, shaking chills, flank pain/CVA tenderness, nausea/vomiting, bacteriuria/pyuria
• Organisms: E. coli (70-80%), Klebsiella, Enterobacter, GBS
• Complications in pregnancy: septic shock, ARDS (from endotoxin-induced pulmonary injury), preterm labor, anemia (from endotoxin-mediated RBC hemolysis)

• HOSPITALIZATION (in pregnancy, due to preterm labor risk and complications)
• IV antibiotics until afebrile ≥48 hours + clinically improved:
  • Ceftriaxone 1g IV q24h (first-line)
  • Cefazolin 1g IV q8h
  • Ampicillin 2g IV q6h + gentamicin 1.5 mg/kg q8h (if resistant or septic; avoid prolonged gentamicin)
  • Aztreonam: if penicillin-allergic with severe allergy
• Switch to oral antibiotics after fever resolution (usually 4-7 days total course)
• Blood cultures: obtain if septic
• Urine culture (repeat after treatment)
• Monitor for preterm contractions; tocolysis if needed
• Maintenance prophylaxis: nitrofurantoin 50-100 mg nightly OR cephalexin 250-500 mg nightly for remainder of pregnancy (monthly cultures if prophylaxis not chosen)

HIV in Pregnancy - Detailed

1. Maternal health (prevent AIDS progression)
2. Prevention of mother-to-child transmission (PMTCT)
3. Safe delivery

• Without any intervention: 15-45%
• With full PMTCT program: <1%

• Start as early as possible (ideally preconception or immediately upon diagnosis in pregnancy)
• Preferred regimens (DHHS 2023):
  • Tenofovir DF (TDF) + emtricitabine (FTC) + dolutegravir (DTG) - first-line
  • TDF/FTC + atazanavir/ritonavir - alternative
  • TDF/FTC + lopinavir/ritonavir - available
  • DTG: previously avoided in first trimester due to neural tube defect signal; more recent data shows risk is very small (<0.3%); now recommended throughout pregnancy
• Goal: viral load (VL) <50 copies/mL by delivery

• Viral load <50 copies/mL at ≥36 weeks: vaginal delivery acceptable; no additional benefit of cesarean
• Viral load ≥1000 copies/mL at ≥36 weeks: scheduled cesarean at 38 weeks (before labor and ROM); reduces MTCT by ~87%
• Viral load 50-999 copies/mL: individualized; discuss with ID specialist
• Intrapartum IV zidovudine: for VL >400 copies/mL or unknown VL at delivery
• Avoid amniotomy, fetal scalp electrode, scalp sampling if avoidable (increase transmission)

• ALL infants born to HIV-positive mothers: zidovudine 4 mg/kg/dose BID x4 weeks
• High-risk infants (VL >400 or unknown; no antenatal ART): 3-drug prophylaxis
• HIV testing: at birth, 14-21 days, 1-2 months, 4-6 months; HIV RNA PCR (not antibody - passive maternal antibody persists 18 months)

• HIGH-INCOME COUNTRIES: formula feeding recommended (eliminates postnatal transmission risk)
• LOW-RESOURCE SETTINGS (WHO): exclusive breastfeeding with maternal ART for first 6 months, then weaning; formula unavailable or unsafe water makes formula risky

Herpes Simplex Virus (HSV) in Pregnancy

• More severe; prolonged viremia; risk of HSV hepatitis, encephalitis
• Highest risk of neonatal transmission (30-50%) during delivery if primary lesions present at time of delivery

• Lower viral load; shorter shedding; risk of neonatal transmission at delivery: 0-3%

• Devastating: skin/eye/mouth disease (SEM), CNS disease, disseminated disease
• Mortality: SEM low; CNS 15%; disseminated 50%

• Acyclovir/valacyclovir: safe in pregnancy (Pregnancy Registry data reassuring)
• Primary infection: treat with acyclovir 400 mg TID or valacyclovir 1g BID x7-10 days
• Suppressive therapy from 36 weeks: valacyclovir 500 mg BID OR acyclovir 400 mg TID → reduces recurrences at delivery; reduces need for cesarean; reduces (but does not eliminate) neonatal transmission
• Cesarean indication: active genital lesions OR prodromal symptoms AT TIME OF DELIVERY (in woman with primary infection or known recurrent HSV)
• If ROM with active lesions: weigh risks; most advise cesarean regardless of duration ROM
• Asymptomatic woman with prior HSV: no lesion = vaginal delivery acceptable with suppression therapy

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TOPIC 21: PHYSIOLOGY OF LABOR - MAXIMUM DETAIL

Uterine Quiescence - Molecular Biology

cAMP Pathway (Pro-quiescence)

• Beta-2 adrenergic receptor activation → Gs protein → adenylyl cyclase → cAMP ↑ → protein kinase A → phosphorylation of myosin light-chain kinase (MLCK) → MLCK inactivated → NO cross-bridge cycling → relaxation
• Progesterone enhances this pathway
• Basis of beta-agonist tocolysis (terbutaline, ritodrine)

Calcium Signaling (Pro-contraction)

• Oxytocin receptor activation → Gq protein → phospholipase C → IP3 + DAG → IP3 opens SR calcium channels → cytosolic Ca2+ rises → Ca2+-calmodulin complex → activates MLCK → phosphorylates myosin light chain → cross-bridge formation → contraction
• Depolarization → voltage-gated Ca channels open (additional Ca influx)

Gap Junctions

• Connexin 43 (Cx43) is major uterine gap junction protein
• Allow electrical and chemical communication between myometrial cells → synchronized contractions
• Expression dramatically increases near term (estrogen upregulates; progesterone suppresses)
• Functionally critical for coordinated labor contractions

Stretch-Activation

• Uterine distension (by growing fetus, multiple gestation, polyhydramnios) → mechanical stretch → upregulation of:
  • CAPs (contraction-associated proteins): Cx43, OTR (oxytocin receptor), PGH synthase-2
  • Explains why multiple gestation and polyhydramnios increase preterm labor risk
  • Distension alone can initiate parturition (cervical dilation from Foley balloon works partly through stretch-signaling)

Cervical Ripening - Biochemistry

Extracellular Matrix Remodeling

• Cervix is mainly collagen (type I and III) with proteoglycans and water
• Ripening: collagen fibers disperse and disorganize → softer cervix
• Key enzymes: matrix metalloproteinases (MMP-8, MMP-1) degrade collagen
• Hyaluronic acid replaces dermatan sulfate → binds water → hydrated, softer cervix
• Prostaglandins (PGE2 from chorion/amnion) drive this process

Inflammatory Model of Parturition

• Near-term parturition resembles controlled inflammatory response
• Infiltration of macrophages and neutrophils into myometrium and cervix
• Cytokines (IL-1β, IL-8, TNF-α) activate MMPs, prostaglandin synthesis, upregulate OTR
• Infection/inflammation causes PRETERM parturition via same pathway (premature activation)

Oxytocin - Detailed Pharmacology

• G-protein coupled receptor (Gq); predominantly in myometrium and decidua
• Upregulated by estrogen (dramatically increases near term)
• Downregulated by progesterone
• Reaches maximum expression at 32-34 weeks in decidua; 37-38 weeks in myometrium

• Posterior pituitary releases oxytocin in pulses
• Frequency increases during labor
• Ferguson reflex: fetal head pressure on cervix → stretch receptors → reflex OT release from posterior pituitary → positive feedback loop → increasing contraction frequency/intensity

• Prolonged exogenous oxytocin exposure → receptor desensitization/downregulation
• Basis of "oxytocin holiday": if oxytocin running for >12-18 hours with poor progress → consider stopping for 30-60 min to allow receptor upregulation → restart

Mechanisms Initiating Labor at Term

• Produced by placenta from 8 weeks
• Exponential rise in last 6-8 weeks of pregnancy
• In early pregnancy: CRH binds CRH-binding protein (inactive)
• Near term: CRH-BP decreases → free CRH bioavailable
• CRH stimulates: fetal pituitary ACTH → fetal adrenal cortisol and DHEAS
• Fetal cortisol: feeds back to placenta → placental enzyme shift → more estrogen from DHEAS
• Fetal DHEAS → placental estrogen production ↑

• In animals: luteal progesterone withdrawal precedes labor
• In humans: no systemic progesterone drop
• FUNCTIONAL withdrawal: PR-A isoform (anti-progesterone action) increases relative to PR-B (pro-progesterone action) near term
• Progesterone metabolites: allopregnanolone (inhibitory) → isopregnanolone (pro-labor) shift

• Fetal lung surfactant released into amniotic fluid → triggers maternal cervical macrophage activation
• Platelet-activating factor (PAF) from fetal urine → stimulates prostaglandin synthesis
• Fetal cortisol: key driver of "fetal readiness" signal

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TOPIC 22: NORMAL LABOR - MAXIMUM DETAIL

Labor Diagnosis and Admission Criteria

• Active labor: regular contractions with cervical dilation ≥3-6 cm
• PROM (any gestational age)
• Medical complications requiring monitoring
• Equivocal cases (cervical change on repeat exam in 1-2h = admission)

Detailed Partogram Description

• X-axis: time in hours
• Y-axis: cervical dilation (cm)
• Alert line: expected minimum progress (WHO partogram: 1 cm/hr from 4 cm)
• Action line: 4 hours to right of alert line; if progress behind action line → intervention

• Fetal head descent plotted alongside dilation
• S-shaped curve: plateau in active first stage, accelerated descent in second stage

First Stage - Detailed Analysis

Latent Phase

• Highly variable; mean 8.6 hours (nullipara), 5.3 hours (multipara)
• Prolonged latent phase: >20 hours (nullipara), >14 hours (multipara)
• Prolonged latent phase does NOT increase perinatal morbidity if fetal status reassuring

• Therapeutic rest: morphine sulfate 10-15 mg IM + promethazine 25 mg IM
  • If true labor: woman will sleep 4-6 hours then wake in active labor
  • If false labor: contractions stop; woman sleeps; re-evaluate
• Ambulation
• Amniotomy + oxytocin: if ready to commit to delivery; enters active labor in most
• Expectant management: acceptable if maternal/fetal status reassuring

Active Phase

• "Active" from 6 cm: contractions more regular, stronger
• Rapid progressive dilation: typically 1-1.5 cm/hour (nullipara), 1.5-2 cm/hour (multipara) - but normal variation is wide
• Fetal head flexes further; internal rotation begins as head meets pelvic floor resistance

• Based on Consortium on Safe Labor (Zhang et al., 228,668 vaginal deliveries)
• Progress is NOT linear; initially slow at 6-7 cm, then accelerates
• 50th percentile for dilation 6→10 cm: 2.2 hours (multipara) to 3.8 hours (nullipara)
• 95th percentile: 13.7 hours (nullipara) - so some nulliparas take this long and still deliver vaginally
• Key point: DON'T call arrest of active phase without:
  • 4 hours of adequate contractions (≥200 MVU on IUPC) with no progress, OR
  • 6 hours if contractions inadequate AND membranes ruptured

Second Stage - Detailed

• From full dilation to delivery
• Ferguson reflex: fetal head on pelvic floor + rectum → reflex urge to push (Ferguson reflex)
• Voluntary "pushing" augments expulsive contractions
• "Passive descent": allow passive fetal descent before active pushing (reduces fatigue; may reduce operative delivery)

• Allow fetal descent for up to 60-90 minutes before active pushing (if FHR reassuring)
• Passive descent occurs via contractions alone + gravity
• Laboring down: evidence shows reduced operative vaginal delivery, fewer decelerations with delayed pushing, BUT slightly longer total labor

• Valsalva (closed glottis): traditional; increase intraabdominal pressure; most effective per push
• Physiologic/open-glottis pushing: shorter pushes with breathing; less effect per push; may reduce fetal hypoxia; preferred by some
• Upright vs. supine positions: upright/lateral may increase pelvic dimensions, reduce episiotomy, reduce pain; maternal preference

• No intervention before:
  • Nullipara without epidural: 3 hours
  • Nullipara with epidural: 4 hours
  • Multipara without epidural: 2 hours
  • Multipara with epidural: 3 hours
• ACOG: may allow additional time if progress documented, maternal/fetal status reassuring

Third Stage - Maximum Detail

• Uterine myometrium contracts after fetal delivery → placental site shrinks → placenta cannot shrink → shearing forces → retroplacental clot forms → Baudelocque-Schultze mechanism (central separation, fetal surface delivers first) OR Duncan mechanism (marginal separation, maternal surface first)
• Schultze: 80% of placental deliveries; folded on itself; cord lengthens then gush of blood
• Duncan: rolls out sideways; bleeding precedes full separation

• Components (WHO AMTSL):
  1. Uterotonic within 1 minute of delivery (oxytocin 10 IU IM PREFERRED)
  2. Controlled cord traction (Brandt-Andrews maneuver)
  3. Uterine massage after placenta delivered
• Reduces PPH >500 mL by 40%; >1000 mL by 50%
• Most effective component: oxytocin (alone nearly as effective as full AMTSL)
• Controlled cord traction: when uterus contracted, one hand suprapubic (guards against inversion), other hand applies steady downward traction on cord

• WHO WOMAN-2 trial: carbetocin 100 mcg IM superior to oxytocin 10 IU IM in low-resource settings; longer lasting; room-temperature stable

• Completeness of membranes and cotyledons (15-30 cotyledons)
• Cord insertion: central, eccentric, velamentous (onto membranes - risk of vasa previa)
• Number of cord vessels: 2 arteries + 1 vein (single umbilical artery: 1% of deliveries; association with renal anomalies, cardiac, IUGR)
• Accessory (succenturiate) lobe: connected by vessels through membranes; may be retained → PPH; may be associated with vasa previa

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TOPIC 23: ABNORMAL LABOR - MAXIMUM DETAIL

Montevideo Units (MVU) - Detailed

• IUPC required
• MVU = sum of all contraction amplitudes (peak - baseline) in a 10-minute window
• Example: 3 contractions in 10 min, each with amplitude of 70 mmHg above baseline = 210 MVU

• ≥200 MVU = adequate uterine activity
• <200 MVU = inadequate; augmentation indicated before declaring arrest
• Some sources: ≥200-250 MVU over 10 minutes required for active phase progress

• Requires amniotomy and IUPC
• External tocometry cannot measure MVU
• Absolute values debated; progression more important than single value

Shoulder Dystocia - Complete Management

• NO reliable way to predict shoulder dystocia
• 50% of shoulder dystocia occurs in normal-weight infants
• Risk factors are poor predictors individually
• EFW by ultrasound: ±15-20% error; cannot reliably identify at-risk fetus

• Fetal head delivers but retracts against perineum ("turtle sign")
• Anterior shoulder fails to deliver with gentle downward traction
• Call for help IMMEDIATELY

• Brain injury: begins at 4-5 minutes of head-to-body delivery interval
• Goal: deliver body within 5 minutes of head delivery
• Do NOT panic; methodical management more effective than forceful traction

• Additional OB, pediatrics, anesthesia, nurses
• Start clock; document time of head delivery, each maneuver, body delivery time

• Does NOT resolve bony dystocia
• Only if more room needed for rotational maneuvers
• Mediolateral or generously cut midline

• Hyperflex both thighs against abdomen (requires assistants on each leg)
• Flattens lumbar lordosis
• Rotates pubic symphysis superiorly ~2 cm
• Increases relative AP diameter of pelvic outlet
• Alone resolves 42% of cases; with suprapubic pressure resolves further 26%

• Assistant places heel of hand above pubic symphysis
• Direction: push fetal shoulder DOWN and LATERALLY (toward fetal face) to dislodge from behind symphysis
• NOT fundal pressure (compresses shoulder further into symphysis)
• Continuous or rocking pressure

• Insert fingers behind posterior aspect of anterior shoulder
• Push forward (toward fetal face) → adducts shoulder → reduces shoulder diameter

• Insert fingers on anterior aspect of posterior shoulder
• Push backward (toward fetal back)
• Combined with Rubin II = Woods screw effect → rotates shoulders from AP to oblique diameter

• Push posterior shoulder anteriorly while simultaneously pushing anterior shoulder posteriorly

• Most effective when rotational maneuvers fail
• Insert hand along hollow of maternal sacrum to posterior fetal arm
• Flex arm at elbow, sweep arm across fetal chest and face
• Deliver posterior arm (shortens shoulder diameter by one arm's diameter)
• Risk: humeral fracture (acceptable)

• Turn patient to all-fours position (hands and knees)
• May dislodge anterior shoulder or convert it to posterior
• Particularly effective in birthing centers; requires mobile patient
• Creates relative extra space in sacral promontory direction

• Cephalic replacement into vagina and uterus
• Preceded by tocolysis (nitroglycerin or terbutaline)
• Return head to occiput anterior, flex and slowly reinsert into vagina
• Cesarean delivery after replacement
• High morbidity; fetal survival variable; rarely performed

• Intentional fracture of fetal clavicle to shorten shoulder diameter
• Technically difficult to do intentionally
• Clavicle fractures often occur naturally (acceptable delivery complication)

• Surgical division of fibrocartilage of pubic symphysis under local anesthesia
• Increases pelvic diameter by 2-3 cm
• Still performed in low-resource settings
• Significant maternal morbidity (chronic pelvic pain, gait instability)

• Time of head delivery and body delivery
• Each maneuver performed and sequence
• Time clock running
• Personnel present
• Fetal position and complications
• Neonatal outcome: Apgar, pH, injuries (fracture, nerve palsy)

• Maternal: 4th degree laceration, uterine rupture (rare), symphyseal separation, hemorrhage
• Neonatal:
  • Brachial plexus injury: Erb palsy (C5-C6: waiter's tip deformity); Klumpke (C8-T1: intrinsic hand muscles; rare); Horner syndrome if T1
  • Clavicle fracture: usually heals well; cry with arm movement is clue
  • Humeral fracture
  • Hypoxic brain injury (if prolonged delay)
  • Most Erb palsy resolves; permanent: 5-22%

Face and Brow Presentation - Detailed

• Complete extension of fetal head; face is presenting part
• Denominator: mentum (chin)
• Mento-anterior (MA) positions: can deliver vaginally as chin sweeps under symphysis with further extension
• Mento-posterior (MP) positions: cannot deliver vaginally (further extension impossible with chin against sacrum); require cesarean

• Anencephaly (most common cause), pelvic contraction, multiparity, polyhydramnios, cord around neck
• Idiopathic in many cases

• Confirm presentation (ultrasound + vaginal exam: orbital ridges, nasal bridge, mouth, chin palpable)
• Mento-anterior: allow labor to proceed; spontaneous vaginal delivery possible
• Mento-posterior: cesarean (persistent MP) or observe if early (may convert to MA with descent)
• Do NOT apply vacuum to face; forceps only if mento-anterior and criteria met

• Partial extension; sinciput presents
• Largest possible head diameter (occipito-mental: ~13.5 cm)
• Cannot deliver vaginally in almost all cases
• Often unstable; may convert to face or vertex with labor

• If early labor: observe; may convert spontaneously
• Persistent brow: cesarean

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TOPIC 24: INTRAPARTUM ASSESSMENT - MAXIMUM DETAIL

EFM - Physiology of Heart Rate Control

• Sympathetic: increases HR; functional from ~26 weeks
• Parasympathetic (vagus nerve): decreases HR; becomes dominant near term (explains decreasing baseline HR as gestation advances)
• Balance between SNS and PNS creates normal variability

• Peripheral chemoreceptors (carotid, aortic bodies): respond to hypoxemia → tachycardia (initial response) then bradycardia (prolonged hypoxemia)
• Central chemoreceptors: respond to PCO2

• In carotid sinus and aortic arch: respond to BP changes
• Cord compression → brief BP rise in fetus → baroreceptor reflex → vagal slowing → variable deceleration

• Maternal uterine blood flow: determined by uterine arterial pressure - venous pressure / uterine vascular resistance
• During contractions: intrauterine pressure rises → diminished arteriovenous gradient → reduced blood flow → intermittent fetal hypoxia (tolerated if fetoplacental reserve adequate)
• Normal fetus: PO2 drops ~5-10 mmHg with contraction; recovers between contractions
• Compromised fetus: cannot tolerate normal oxygen reduction with contractions → late decelerations

Detailed CTG Pattern Analysis

Baseline FHR

• Mild: 160-180 bpm
• Severe: >180 bpm
• Causes:
  • Maternal fever/infection (most common)
  • Chorioamnionitis → fetal tachycardia (early sign)
  • Fetal hypoxia (early response - catecholamine surge)
  • Medications: terbutaline, cocaine, atropine
  • Fetal anemia
  • Fetal SVT (FHR may be 220-280 bpm - sustained tachyarrhythmia)
  • Maternal hyperthyroidism (TRAb → fetal tachycardia)
  • Prematurity (higher baseline)
• Significance: tachycardia WITH absent variability + late/variable decelerations = serious

• Mild: 100-110 bpm
• Severe: <80 bpm
• Causes:
  • Fetal heart block (maternal SSA/SSB antibodies → 3rd degree block: 50-80 bpm)
  • Cord prolapse (acute severe compression)
  • Uterine rupture
  • Placental abruption
  • Maternal hypotension (epidural, supine aortocaval)
  • Vagal stimulation during transition (brief, benign if normal variability returns)
  • Medications: beta-blockers, magnesium
  • Terminal bradycardia: preceding fetal death (ominous if prolonged without recovery)

Variability - Detailed

• Short-term variability (beat-to-beat): direct ANS regulation of each heartbeat
• Long-term variability: oscillation of HR at 2-6 cycles/minute
• Electronic monitors: measure long-term variability primarily
• Beat-to-beat assessment: requires internal scalp electrode (FSE)

• Severe acidosis/asphyxia (OMINOUS)
• CNS suppression: opioids (meperidine, fentanyl), MgSO4, phenobarbital (transient; 30-90 minutes)
• Fetal sleep cycle (transient; maximum 40 minutes before next sleep cycle; acoustic stimulation can arouse)
• Extreme prematurity (<28 weeks: limited ANS maturation)
• CNS anomalies
• Cardiac arrhythmia

• Regular smooth wave: 3-5 cycles/min; amplitude 5-15 bpm; NO variability
• Duration: ≥20 minutes
• OMINOUS: severe fetal anemia; brain damage; severe acidosis
• Pseudo-sinusoidal: medications (meperidine most common); has brief accelerations; shorter duration

Decelerations - Complete Analysis

• Onset to nadir: gradual (>30 seconds)
• Nadir coincides with PEAK of contraction
• Mirror image of contraction
• Cause: head compression → vagal stimulation → slowing
• Characteristics: shape mirrors contraction; uniform; return to baseline by end of contraction
• Significance: BENIGN; no fetal acidosis; no intervention required

• Onset to nadir: gradual (>30 seconds)
• Nadir AFTER peak of contraction; begins ≥30 seconds after contraction onset
• Returns to baseline after contraction ends
• Cause: uteroplacental insufficiency → reflex (mild, with variability preserved) OR direct myocardial depression (severe, absent variability)
• Classification:
  • Reflex late decelerations (with variability): baroreceptor/chemoreceptor mediated; better fetal reserve; respond to resuscitation
  • Non-reflex late decelerations (absent variability): direct myocardial and CNS depression; severe metabolic acidosis
• SIGNIFICANCE: persistent late decelerations with absent variability = Category III; emergent delivery

• Onset to nadir: ABRUPT (<30 seconds)
• Variable shape, timing, duration
• Cause: umbilical cord compression → brief venous occlusion → fetal hypotension → tachycardia (initial) → arterial occlusion → HTN → baroreceptor → vagal slowing → severe bradycardia
• Characteristics: sudden drop; V-shaped; rapid recovery; often with shoulders (initial acceleration then deceleration then final acceleration)
• "Shoulders" indicate adequate fetal reserve
• Significance: depends on severity and persistence
  • Mild: amplitude <80 bpm, duration <30 sec → benign
  • Moderate: amplitude 70-80 bpm drop from baseline, duration 30-60 sec
  • Severe: amplitude drop >80 bpm, duration >60 sec, slow recovery, loss of shoulders, variable baseline → concerning

• Loss of initial acceleration (shoulder)
• Loss of secondary acceleration (shoulder)
• Slow return to baseline (>30 seconds)
• Prolonged secondary tachycardia
• Continued baseline changes
• Biphasic shape

• 15 bpm below baseline for ≥2 minutes and <10 minutes

• Causes: maternal hypotension, cord prolapse, uterine rupture, abruption, head engagement, tetanic contraction, epidural placement, position change, vaginal exam
• Management: identify and correct cause; intrauterine resuscitation; if ≥10 minutes = bradycardia

NICHD Category System - Clinical Application

• Baseline 110-160 bpm
• Moderate variability (6-25 bpm)
• No late/variable decelerations
• Early decelerations: present or absent
• Accelerations: present or absent
• Action: routine monitoring; no intervention

• EVERYTHING that is not Category I or III
• Includes:
  • Tachycardia
  • Minimal variability
  • Absent variability WITHOUT decelerations
  • Marked variability
  • Absent accelerations after vibroacoustic stimulation (in specific contexts)
  • Recurrent variable decelerations with minimal or moderate variability
  • Prolonged decelerations (2-10 min)
  • Recurrent late decelerations with moderate variability
• Action: evaluate, determine cause, consider maternal repositioning, IV fluid, oxygen, discontinue oxytocin, scalp stimulation; escalate if worsens or does not improve

• Sinusoidal pattern OR
• Absent variability WITH: recurrent late decelerations, recurrent variable decelerations, or bradycardia
• Action: identify cause; intrauterine resuscitation; if no improvement → EXPEDITE DELIVERY
• If cannot promptly improve → cesarean or operative vaginal delivery

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TOPIC 25: INDUCTION AND AUGMENTATION - MAXIMUM DETAIL

Evidence Base for Induction Timing

• 6,106 low-risk nulliparous women
• 39 weeks induction vs. expectant management
• Results:
  • Cesarean: 18.6% (induction) vs. 22.2% (expectant); OR 0.80, p=0.004
  • NICU admission: 24.3% vs. 27.6%; OR 0.87, p=0.03
  • Perinatal death: 0 vs. 7 events (too few to analyze statistically)
  • Severe maternal complications: no significant difference
  • Epidural use: no difference
• Practice change: many centers now routinely offer elective induction at 39 0/7 weeks to all low-risk nulliparous patients

• Induction at 41 weeks significantly reduces perinatal mortality vs. awaiting spontaneous labor or induction at 42 weeks
• SWEPIS trial: stopped early due to 6 perinatal deaths in expectant arm vs. 0 in induction arm
• Most centers: induce all women at ≥41 weeks; many at 40-41 weeks depending on patient preference and risk factors

Bishop Score in Clinical Practice

• ≥8: highly favorable; induction likely successful; as good as spontaneous labor for CS rate
• 6-7: moderately favorable; proceed with induction but ripening may be needed
• <6: unfavorable; cervical ripening recommended before oxytocin

Prostaglandins - Detailed Mechanisms

• Mechanism: binds EP receptors on cervical stroma → activates collagenases, hyaluronidase → collagen breakdown, water retention → cervical ripening; also stimulates myometrium via EP1/EP3 receptors
• Cervidil: 10 mg vaginal insert (slow release 0.3 mg/hr); leave in 12 hours; remove with ribbon (advantage: can remove if tachysystole); monitor FHR ≥2 hours after removal before proceeding with oxytocin
• Prepidil: 0.5 mg intracervical gel; 6-hourly; max 3 doses in 24 hours; 6-hour interval before oxytocin

• More potent receptor binding than PGE2
• Stable at room temperature; cheap; tablet form
• Vaginal: 25 mcg every 4-6 hours; 50 mcg q6h studied (more effective, more tachysystole)
• Buccal: 25 mcg q4h; similar efficacy to vaginal
• Oral: 25 mcg q2h OR 50 mcg q4h; lower uterotonic effect but very effective for ripening
• CONTRAINDICATION: ANY uterine scar (prior cesarean, myomectomy entering cavity) → 5-15x increased uterine rupture risk vs. unscarred uterus

Amniotomy (AROM) - Detailed

• Adjunct to labor augmentation (shorten labor by 1-2 hours)
• Allow IUPC or FSE placement
• Assess amniotic fluid (meconium, volume)
• Before oxytocin augmentation (synergistic effect)

• Confirm presenting part well applied to cervix (prevents cord prolapse)
• Station ≥-1 recommended
• Use amniohook or Amnihook
• Avoid umbilical cord palpation before breaking
• After AROM: reconfirm FHR (rule out cord prolapse)
• Document: time, fluid color/amount/odor, FHR before and after

• Cord prolapse: most feared; risk 0.6% (higher with high station, multiparity, abnormal presentation)
• Chorioamnionitis: risk increases with duration from AROM to delivery; >18 hours: significant GBS transmission risk
• Fetal injury: rare with correct technique
• Irreversible: cannot "unrupture" membranes

Oxytocin Protocols - Detailed

• Start: 0.5-1 mU/min
• Increase: 1-2 mU/min every 30-40 minutes
• Maximum: 20 mU/min (some protocols 40 mU/min)

• Start: 6 mU/min
• Increase: 6 mU/min every 15 minutes
• Maximum: 40 mU/min
• Evidence: faster labor, less chorioamnionitis, no increase in CS rate; more tachysystole in some studies

• 10 units in 1000 mL NS = 10 mU/mL
• 20 units in 1000 mL NS = 20 mU/mL
• Always on infusion pump; labeled clearly

• Half-life: 3-5 minutes
• Steady state: 40 minutes after dose change
• Uterine response: 3-5 minutes
• This is why dosage changes every ≥15-40 minutes (allow steady state)

• Tachysystole (>5 ctx/10 min)
• Category II or III FHR
• Tetanic contraction
• Placental abruption suspicion
• Uterine rupture suspicion
• Patient declines

• Prolonged oxytocin (>12-18 hours) → receptor desensitization
• Consider 30-60 minute "holiday" then restart
• Use with amniotomy (if not already done) for synergistic effect on restart

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TOPIC 26: OBSTETRIC ANALGESIA AND ANESTHESIA - MAXIMUM DETAIL

Pain Pathways - Complete Neuroanatomy

First Stage Pain

• Uterine body contractions → visceral afferents → sympathetic chain at T10-L1
• Cervical dilation → cervical afferents → T10, T11, T12, L1
• Route: through uterovaginal plexus → superior hypogastric plexus → lumbar/lower thoracic sympathetic chain → dorsal horn of spinal cord → thalamus → cortex

Second Stage Pain

• Distension of lower vagina, vulva, perineum → somatic afferents → pudendal nerve (S2, S3, S4)
• Pressure on bladder, urethra, rectum → pelvic splanchnic nerves (S2-S4)

Implications for analgesia:

• Epidural at L3-L4 must spread to T10 for complete first stage relief
• Second stage: must cover S2-S4 (pudendal distribution)
• Paracervical block: covers T10-L1 (first stage only); risk of fetal bradycardia from direct fetal injection or uterine artery spasm → largely abandoned

Non-pharmacological Pain Management

• Electrodes on lower back (paraspinal L1 and S2 level)
• Gate control theory: large fiber stimulation inhibits small pain fiber transmission
• Evidence: modest benefit; helps in early labor
• No fetal risk; no sedation

• 0.1 mL sterile water intradermally at four points over sacral rhomboid (Michaelis rhomboid)
• For back labor (OP position)
• Intense initial sting then relief for 45-90 minutes
• Mechanism: counter-irritation; hyperosmolar injection activates large fibers
• Evidence: RCT data shows effective for back pain relief; does not affect labor progress

• Limited evidence; some RCTs show modest pain reduction
• Specific points: ST36, SP6, LI4, BL32
• Safety profile excellent; no neonatal effects

• Cochrane review: continuous support reduces epidural use by 8-9%; reduces cesarean by 25-26%; increases spontaneous vaginal delivery by 7-8%; reduces negative birth experience
• Most cost-effective pain management intervention

Epidural Analgesia - Complete Detail

Anatomy of Epidural Space

• Posterior to posterior longitudinal ligament
• Anterior to ligamentum flavum
• Contains: epidural veins (Batson's plexus), epidural fat, nerve roots (dural sleeves)
• Pressure: slightly negative (helps confirm placement by loss of resistance)
• Depth from skin: average 5 cm (range 3-8 cm; deeper in obese patients)

Placement Technique

• Sitting (preferred): widens interspinous space; better for obese patients; better landmark identification
• Left lateral decubitus: good for patients who cannot sit

• Palpate L3-L4 or L4-L5 interspace (Tuffier's line: connects iliac crests = L4)
• Sterile technique; local anesthetic infiltration of skin and interspinous ligament
• Tuohy needle (17-18G curved tip): insert through skin, supraspinous ligament, interspinous ligament, ligamentum flavum
• Loss of resistance (LOR): with saline or air through syringe → sudden loss of pressure as needle enters epidural space
• Negative aspiration: for blood (intravascular) or CSF (intrathecal)
• Test dose: 3 mL of 1.5% lidocaine + 1:200,000 epinephrine:
  • Tachycardia within 60 seconds: intravascular placement (epinephrine sign)
  • Motor block: intrathecal placement (spinal dose)
• Thread catheter 3-5 cm into epidural space
• Aspirate catheter (for blood or CSF)
• Initial loading dose: dilute local anesthetic + opioid

• Local anesthetic: bupivacaine 0.0625-0.125% (low concentration preserves sensory > motor block; allows ambulation); ropivacaine 0.1-0.2% (slightly less motor block)
• Opioid adjunct: fentanyl 1-3 mcg/mL OR sufentanil 0.2-0.5 mcg/mL (reduces LA concentration needed; improves quality; fast onset)
• Combined: bupivacaine 0.0625-0.1% + fentanyl 2 mcg/mL → "walking epidural"

• Continuous infusion: 10-15 mL/hr
• PCEA (patient-controlled epidural analgesia): continuous 5 mL/hr + demand 5 mL every 15-20 min; preferred (less total drug, better satisfaction)
• Programmed intermittent epidural bolus (PIEB): automated bolus every 30-60 min; better distribution, better pain control

CSE (Combined Spinal-Epidural)

• Needle-through-needle: 25-27G spinal needle through Tuohy needle
• Spinal component: intrathecal opioid (± small dose local anesthetic):
  • Fentanyl 15-25 mcg intrathecal: onset 2-3 minutes; duration 60-90 min; no motor block
  • Sufentanil 5-10 mcg: similar
  • Bupivacaine 1.25-2.5 mg + fentanyl: faster, denser initial block
• Benefits: fastest onset (2-3 min vs. 15-20 min for epidural alone); better sacral coverage for second stage; useful for precipitous labors; ambulatory

Effect of Epidural on Labor

• Does NOT increase cesarean rate (Cochrane review 2023: clear evidence)
• DOES increase instrumental vaginal delivery rate (RR ~1.4-1.5)
• Does prolong first stage by ~40-90 minutes; second stage by ~15-20 minutes
• May increase oxytocin augmentation use
• Associated with maternal fever (mechanism unclear: inflammatory response, inhibited hyperventilation-thermoregulation; treated with antipyretics; may lead to neonatal workup)

• Incidence: 20-30% of laboring women with epidural (vs. <10% without)
• Mean temperature rise: 0.4-0.5°C per hour with epidural
• Mechanism: inflammatory cytokines; reduced hyperventilatory heat loss
• Clinical problem: maternal fever → neonatal sepsis workup (CBC, blood cultures, antibiotics)
• Management: acetaminophen; cooling; blood cultures if other infection signs present

Spinal Anesthesia for Cesarean - Detailed

• 0.5% bupivacaine + glucose (heavy bupivacaine)
• Dose: 10-12 mg (2.0-2.4 mL) for cesarean
• Position-dependent distribution (denser solutions settle dependent)
• Target: T4-T6 bilateral sensory block (nipple line) for cesarean

• Hyperbaric bupivacaine 10-12 mg + fentanyl 20-25 mcg + morphine 100-200 mcg (intrathecal)
• Morphine: provides excellent 12-24 hour postoperative analgesia; pruritus common (nalbuphine or low-dose naloxone treats); rare delayed respiratory depression (monitor ≥24h)

• Most common complication (80% without prophylaxis)
• Mechanism: sympathectomy → reduced SVR → venous pooling
• Prevention:
  • Left uterine displacement
  • IV preload: crystalloid 1-1.5 L (modest effect; colloid more effective)
  • Vasopressors (most effective): phenylephrine (alpha-1 agonist; preferred; maintains uteroplacental blood flow) vs. ephedrine (mixed alpha/beta; crosses placenta; fetal acidosis)
  • Phenylephrine infusion: 25-100 mcg/min started at spinal; titrate to maternal HR/BP; GOLD STANDARD
  • Sequential compression stockings

• Excessive cephalad spread of spinal block
• Symptoms: severe hypotension, difficulty breathing, arm weakness, loss of consciousness
• Risk factors: obesity, short stature, hyperbaric bupivacaine position error, high volume
• Management: immediate vasopressors (epinephrine if arrest), airway management, RSI and intubation, uterine displacement

Airway Management - Maximum Detail

• Enlarged breasts: interfere with laryngoscope handle manipulation
• Weight gain: fat deposition in pharynx/neck
• Edema: from preeclampsia, fluid administration; airway tissues engorged
• Decreased FRC (from diaphragm elevation): faster desaturation on induction
• Delayed gastric emptying: aspiration risk
• Increased oxygen consumption: less apnea tolerance

• Failed intubation: 1:250 (general population: 1:2000)
• Failed intubation AND failed oxygenation: rare but catastrophic

• Mendelson syndrome: aspiration of acidic gastric contents → chemical pneumonitis → ARDS
• Prevention:
  • NPO guidelines: clear liquids up to 2 hours before elective procedures; solids 6-8 hours
  • Antacid prophylaxis: sodium citrate 30 mL orally 15-30 min before GA (neutralizes gastric acid)
  • H2 blocker: ranitidine 150 mg oral 2h before OR 50 mg IV (reduces gastric acid production)
  • PPI: omeprazole 40 mg oral night before + morning of surgery
  • Metoclopramide: 10 mg IV (prokinetic; reduces gastric volume)
  • RSI with cricoid pressure (Sellick maneuver)

1. Preoxygenate: 100% O2 via non-rebreather mask 3-5 min (OR 4 vital capacity breaths of 100% O2)
2. Sodium citrate PO, ranitidine IV, metoclopramide IV given
3. Positioning: 30° head up OR ear-to-sternal notch alignment (improves laryngoscopy)
4. Induction agent:
   • Propofol 2-3 mg/kg IV (fastest; most common currently)
   • Ketamine 1-2 mg/kg IV (if hypotensive, asthmatic; maintains BP)
   • Thiopental 4-6 mg/kg (historical; still used in some countries)
5. Cricoid pressure applied when patient drowsy
6. Succinylcholine 1.5 mg/kg IV (fastest onset/offset; allows quick assessment of airway)
   • Alternative: rocuronium 1.2 mg/kg IV (reversed by sugammadex 16 mg/kg)
7. Laryngoscopy: direct (Miller blade - straight; Macintosh blade - curved) OR video laryngoscopy (increasing use)
8. Tube placement confirmed: direct visualization, ETCO2 (gold standard), bilateral breath sounds
9. Release cricoid pressure after confirmation

• Maintain oxygenation with face mask or supraglottic airway (LMA or i-gel)
• Continue with anesthesia via LMA (if emergency) or wake patient, establish neuraxial anesthesia

• Declare emergency
• Attempt front-of-neck airway (FONA) - emergency cricothyrotomy
• Scalpel technique (rapidly effective): transverse stab incision through cricothyroid membrane; dilate; cuffed tube; ventilate
• Needle cricothyrotomy: temporizing only (inadequate ventilation; CO2 accumulates)

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TOPIC 27: VAGINAL DELIVERY - MAXIMUM DETAIL

Preparation for Delivery

• Delivery table: adjustable; stirrups (candy-cane or boot-type)
• Lighting: adequate; overhead focused light
• Delivery table (sterile field): instruments, sutures, bulb syringe, cord clamp x2, scissors, warm blankets, towels
• Neonatal warmer: pre-warmed; suction available; PPV equipment ready
• Anesthesia provider present
• Pediatrics/neonatal team for: preterm, meconium, anticipated complications

• Perineal prep with antiseptic solution (betadine or chlorhexidine)
• Sterile drapes
• Sterile gloves

Cardinal Movements - Maximum Detail

Engagement

• Definition: largest diameter of fetal head (biparietal diameter, BPD) passes through pelvic inlet
• Clinically: presenting part at 0 station (ischial spine level)
• Descends into inlet in occiput transverse (most often) or slight oblique position (LOT most common - 40%)
• In nulliparas: often occurs before labor (lightening)
• In multiparas: often occurs during labor

Descent

• Continues throughout labor and delivery
• Active descent begins in active first stage; accelerates in second stage
• Measured by station (-5 to +5 cm system from ischial spines)
• Factors promoting descent: uterine contractions, maternal pushing, gravity, fetal weight

Flexion

• Fetal head flexes on neck as it encounters pelvic floor resistance
• Converts presentation from occipito-frontal (11.5 cm) to suboccipitobregmatic (9.5 cm) diameter
• Most critical movement for reducing diameter
• Reduced by:
  • Short umbilical cord (pulls head back)
  • Excessive abdominal muscle tension
  • Short fetal neck

Internal Rotation

• Occurs at level of ischial spines (0 station)
• Occiput rotates anteriorly from LOT or ROT to OA position
• Guided by: pelvic floor muscles (levator ani); shape of midpelvis (AP > transverse at outlet)
• LOT → 45° internal rotation → LOA → OA
• ROT → 45° internal rotation → ROA → OA (less common; longer rotation)
• LOP/ROP (occiput posterior): 135° rotation to OA OR 45° to direct OP (face to pubes delivery)

Extension

• After internal rotation, head is at vulvar outlet
• Occiput passes under pubic symphysis → head extends (follows pelvic curve)
• Suboccipitobregmatic diameter beneath symphysis; bregma, then face, then chin delivered over perineum
• Controlled delivery of the head (controlled extension) prevents perineal lacerations

External Rotation (Restitution)

• After head delivers, it rotates to align with fetal shoulders (which are in AP diameter)
• If shoulders are LOA, head rotates to face left thigh of mother
• Allows shoulders to descend in AP diameter (which is wider at outlet)

Expulsion

• Anterior shoulder delivered first: provider applies gentle DOWNWARD traction on head → anterior shoulder sweeps under symphysis
• Posterior shoulder: provider lifts head UPWARD → posterior shoulder delivered over perineum
• Rest of body follows with ease

Nuchal Cord Management

• Type 1: loosely around neck once
• Type 2: tightly around neck once
• Type 3: multiple loops

• Type 1 (loose): slip cord over head (most common approach)
• Type 2 (tight): double-clamp and cut before delivery of shoulders (cord clamp x2 → cut between clamps → deliver body)
• Alternative - "somersault technique": do NOT cut cord; deliver body while head is held close to maternal inner thigh; body somersaults through loop; avoids cord cutting; preserves placental circulation; ideal for cord blood banking

Meconium at Delivery

• Incidence: 10-15% of all deliveries
• Thin meconium (green-yellow, watery): lower risk
• Thick meconium (pea soup, dark green, viscous): higher risk

• Fetal gasping (from hypoxia or vagal stimulation) while meconium present → aspiration
• Also: in utero aspiration possible (not purely a delivery event)

• DISCONTINUE routine intrapartum suctioning (previously suctioned nose and mouth at perineum before shoulder delivery - no longer recommended)
• If infant born vigorous (cries, adequate muscle tone, HR >100): routine care; move to warmer; standard stimulation; suction only if material in mouth/nose impeding breathing
• If infant born NOT vigorous (depressed, HR <100, poor tone, not breathing): intubate trachea and suction below cords ONLY IF meconium seen below cords OR if expected clinical benefit (NRP 2016 update)
• No longer: routine intubation of all non-vigorous meconium babies; evidence did not support benefit of routine tracheal suctioning in multiple trials

• NOT recommended for prevention of MAS in MSAF (AMNIOINFUSION-M trial)
• Still recommended for symptomatic variable decelerations (cord compression) regardless of meconium

Immediate Newborn Resuscitation at Delivery

1. Term? Breathing/crying? Good tone? → YES all three → routine care at mother's side
2. Any NO → proceed to initial steps (30 seconds):
   • Warm; dry; stimulate (rub back/soles)
   • Suction if secretions (bulb syringe; only if airway not clear)
   • Open airway (sniffing position)
3. Assess HR and respirations at 30 seconds:
   • HR ≥100, breathing: routine care; observe
   • HR ≥100, labored breathing or cyanosis: supplemental O2; CPAP consider
   • HR <100 or apnea/gasping: positive pressure ventilation (PPV)
4. PPV with room air (21%; NOT 100% initially for term):
   • Rate: 40-60 breaths/min
   • Pressure: 20-25 cmH2O initial; 30-40 for no chest rise
   • Confirm: rising HR (most important marker), chest rise
   • Consider pulse ox monitoring and ECG
5. After 30 seconds PPV: reassess
   • HR improving (60-100): continue PPV; consider laryngeal mask or ETT
   • HR <60: check ventilation (most common reason for failure); consider ETT
6. HR <60 after 30 sec EFFECTIVE PPV:
   • Begin chest compressions (3:1; 90 compressions:30 breaths per minute)
   • Increase O2 to 100%
   • Consider umbilical venous catheter
7. HR <60 after 60 sec of compressions + PPV:
   • Epinephrine: IV preferred; 0.01-0.03 mg/kg (1:10,000) = 0.1-0.3 mL/kg IV
   • ETT dose (if IV access not yet available): 0.05-0.1 mg/kg (higher dose for ETT)
   • Repeat every 3-5 minutes if no response
   • Volume expander if hypovolemia suspected: normal saline 10 mL/kg IV over 5-10 min

• Vigorous term infant: clamp at ≥30-60 seconds
• Vigorous preterm: clamp at ≥30-60 seconds or cord milking (3-4 stripes toward infant)
• Compromised infant needing resuscitation: clamp immediately OR rapid umbilical cord milking (allow resuscitation without delaying)
• Lotus birth (no cord clamping): NOT recommended by ACOG/AAP; theoretical risks of polycythemia, hyperbilirubinemia, infection

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TOPIC 35: STILLBIRTH

Williams Obstetrics - Maximum Detail - Resident Level

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DEFINITION AND TERMINOLOGY

Official Definitions

• Fetal death at ≥20 weeks of gestation OR birth weight ≥350 g (when gestational age unknown)
• Further subdivided:
  • Early fetal death: 20-27 weeks
  • Late fetal death: 28-36 weeks
  • Term fetal death: ≥37 weeks

• Birth of a baby with no signs of life at ≥28 completed weeks of gestation
• Used for international comparisons and reporting
• Some countries use ≥22 weeks or ≥500 g for national reporting

• Stillbirths + neonatal deaths in first 7 days of life (early neonatal deaths)
• Perinatal mortality rate = (stillbirths + early neonatal deaths) / 1000 total births

• Stillbirth ≠ spontaneous abortion (miscarriage): spontaneous abortion = loss <20 weeks
• Macerated stillbirth: signs of intrauterine death >12-24 hours before delivery (skin slippage, discoloration, soft skull bones)
• Fresh stillbirth: minimal maceration; likely died within hours of delivery

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EPIDEMIOLOGY

United States Statistics

• Rate: ~5.74 per 1,000 total births (2020 CDC data)
• Absolute numbers: approximately 21,000 stillbirths per year in USA
• Stillbirth is MORE COMMON than sudden infant death syndrome (SIDS)
• Rate has declined slowly over decades but plateau since 2000

• Non-Hispanic Black women: 10.4 per 1,000 births (2x higher than White women)
• Non-Hispanic White women: 4.8 per 1,000 births
• Hispanic women: 3.9 per 1,000 births
• American Indian/Alaska Native: 7.4 per 1,000 births
• Disparity NOT fully explained by socioeconomic status, access to care, or medical comorbidities
• Structural racism, chronic stress (weathering hypothesis), implicit bias in care contribute

• 1.9 million stillbirths globally per year (WHO 2021)
• 98% occur in low- and middle-income countries
• Pakistan, Nigeria, India have highest absolute numbers
• Preventable fraction: >50% in low-resource settings

Risk Factors for Stillbirth

• Advanced maternal age (≥35 years): 2x risk; ≥40 years: 3-4x risk
• Obesity (BMI ≥30): 1.5-2.1x risk; mechanisms: increased placental dysfunction, GDM, preeclampsia, sleep apnea, reduced fetal movement perception
• Smoking: 1.4-1.8x risk; dose-dependent; mechanism: vasoconstriction, placental insufficiency, carbon monoxide
• Alcohol: dose-dependent risk
• Illicit drugs: cocaine (placental abruption), methamphetamine, heroin
• Nulliparity: independent risk factor
• Black race: 2x risk after controlling for other factors (structural racism component)
• Low socioeconomic status
• Prior stillbirth: 4-10x increased risk of recurrence

• Diabetes (pre-gestational): 3-5x increased risk; worse with poor control (HbA1c >8%)
• Chronic hypertension: 2-3x risk
• Preeclampsia: 3-5x risk
• SLE: 3-20x risk depending on disease activity
• Antiphospholipid syndrome (APS): one of most important treatable causes; thrombosis, placental infarction
• Inherited thrombophilias: Factor V Leiden, Prothrombin G20210A - moderate increased risk
• Intrahepatic cholestasis of pregnancy (ICP): risk of sudden fetal death (especially if bile acids >100 µmol/L); mechanism unclear (cardiac arrhythmia from bile acid cardiotoxicity in fetus)
• Renal disease
• Thyroid disease (poorly controlled)
• Sickle cell disease

• Multiple gestation: 2-3x higher stillbirth rate (monochorionic higher than dichorionic)
• IUGR: 5-10x risk
• Oligohydramnios: 4-5x risk
• Placental abruption: 50-fold increased risk of stillbirth in same pregnancy
• Placenta previa: 2-4x risk
• Umbilical cord abnormalities: true knot, velamentous insertion, vasa previa
• Post-term pregnancy (≥42 weeks): 2-3x risk vs. 40 weeks; risk increases each week beyond 40
• Prior preterm birth: associated with increased stillbirth risk in subsequent pregnancy
• Fetal growth restriction + abnormal Doppler: very high immediate risk

• Chromosomal abnormalities: trisomies, monosomy X, triploidy
• Congenital anomalies: major cardiac defects, CNS anomalies
• Infection: parvovirus B19, CMV, toxoplasma, syphilis, listeria
• Hydrops fetalis

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CAUSES OF STILLBIRTH

Stillbirth Collaborative Research Network (SCRN) - USA Data

1. Obstetric conditions (29.3%): placental abruption, previa, PROM, cord prolapse
2. Placental abnormalities (23.6%): placental insufficiency, infarction, chronic villitis, massive perivillous fibrin deposition
3. Fetal genetic/structural (13.7%): chromosomal abnormalities, single gene disorders, structural anomalies
4. Infection (12.9%): primarily bacterial ascending infection; viral less common in US
5. Umbilical cord abnormalities (10.4%): true knot, entanglement, stricture, velamentous insertion
6. Hypertensive disorders (9.2%): preeclampsia, HELLP, chronic hypertension
7. Other maternal conditions (7.8%): diabetes, thyroid, SLE, APS, ICP
8. Unknown/unexplained (25.5%): after full evaluation; remains a significant category

Placental Causes - Detailed

• Premature separation of normally implanted placenta
• Accounts for 10-15% of all stillbirths
• Mechanism: retroplacental hematoma → reduced gas exchange → fetal asphyxia
• Risk factors: hypertension (most common), trauma, cocaine, smoking, prior abruption
• Often complicated by DIC (thromboplastin release)

• Chronic uteroplacental insufficiency → IUGR → fetal hypoxia → stillbirth
• Pathological findings: infarcts, intervillous thrombi, perivillous fibrin deposits, accelerated villous maturation
• Final pathway: chronic hypoxia → metabolic acidosis → organ failure → death

• Also called maternal floor infarction
• Fibrin encasing villi → impaired exchange
• Recurrence risk: HIGH (25-50%) in subsequent pregnancy
• No effective treatment; monitor with serial growth ultrasounds; may need early delivery

• Thrombosis within fetal villous capillaries
• Associated with: inherited thrombophilias, fetal cardiac defects, umbilical cord abnormalities
• Placental histology: avascular villi, fibromuscular sclerosis of vessel walls

• Inflammatory infiltration of chorionic villi (lymphocytic)
• Often idiopathic
• Association with: IUGR, preeclampsia, stillbirth
• Recurrence risk: moderate
• No treatment; diagnosis made on placental pathology

Umbilical Cord Causes - Detailed

• Fetal body passes through loop of cord before cord shortens
• Incidence: 1% of deliveries; most are loose and non-lethal
• Stillbirth association: tight true knot with evidence of obstruction
• Pathological significance: only if vessel obstruction evident (thrombosis, hemorrhage, Wharton's jelly compression)
• Diagnosis: umbilical venous Doppler may show flow abnormalities (not reliable)
• Cannot be predicted or prevented

• Segmental narrowing of cord (reduced Wharton's jelly)
• Associated with: excessive fetal movement, sickle cell trait
• Pathological: if associated with thrombosis at stricture site

• Cord inserts into membranes rather than placenta
• Vessels unsupported by Wharton's jelly
• Risk: vessel compression during labor; vasa previa if vessels cross os

• After ROM; emergency; up to 50% mortality without immediate intervention
• Risk: footling breech, polyhydramnios, malpresentation, preterm

• Umbilical coiling index (UCI): coils per cm; normal 0.17-0.24
• Hypercoiled (UCI >0.3): associated with IUGR, stillbirth, perinatal distress
• Hypocoiled (UCI <0.1): associated with preterm birth, chromosomal anomalies
• Cannot be modified; surveillance if detected on prenatal ultrasound

Infection Causes - Detailed

1. Direct fetal infection: septicemia, pneumonia, meningitis, hepatitis
2. Placental infection: chorioamnionitis → placental dysfunction
3. Maternal fever + infection → fetal hyperthermia → stillbirth
4. Severe maternal illness → placental insufficiency

• Most common infectious cause in developed countries
• Organisms: Group B Streptococcus, E. coli, Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella, Fusobacterium
• Pathway: vaginal colonization → ascending into amniotic cavity → amnionitis → fetal infection
• Often associated with preterm birth (same pathway)
• Amniotic fluid culture or PCR at autopsy reveals organisms

• Hydrops fetalis → cardiac failure → stillbirth
• Risk of fetal death: 3-9% after maternal infection (highest 9-20 weeks)
• Mechanism: tropism for erythroid precursors → aplastic anemia → severe anemia → hydrops
• Diagnosis: maternal serology + fetal/placental parvovirus PCR
• Prevention: none (no vaccine); avoid exposure during epidemics

• Disproportionate impact on pregnant women (immunosuppression of pregnancy)
• Foodborne: unpasteurized dairy, deli meats, soft cheeses
• Presentation: flu-like illness in mother → amnionitis → preterm labor → stillbirth
• Fetal: microabscesses throughout organs
• Treatment: ampicillin ± gentamicin (if alive, may salvage fetus)
• Prevention: food safety counseling

• Major cause of stillbirth globally (especially low-resource settings)
• Mechanism: direct fetal infection in second/third trimester → hydrops, hepatitis, bone changes, pneumonia
• Diagnosis: maternal RPR/VDRL + FTA-ABS; fetal tissues + dark-field microscopy
• Treatment: penicillin G (maternal treatment treats fetal infection)
• Prevention: universal prenatal screening (first trimester + third trimester in high-prevalence areas)

• Can cause stillbirth, especially primary infection in pregnancy
• More commonly causes morbidity (IUGR, anomalies) than death

• Rarely causes stillbirth; more commonly causes fetal damage

Genetic and Chromosomal Causes

• Trisomy 21: most common autosomal trisomy in liveborns; less common in stillbirths (many survive to term)
• Trisomy 18 (Edwards): second most common in stillbirths; 90% die in utero or in neonatal period
• Trisomy 13 (Patau): most die in utero
• Monosomy X (Turner): 99% of 45,X conceptions end in spontaneous abortion or stillbirth
• Triploidy: 69,XXX or 69,XXY; most end in early loss; some survive to midtrimester
• Unbalanced translocations

• Hydrops-associated: storage disorders (Gaucher, Niemann-Pick), congenital myotonic dystrophy
• Cardiac arrhythmia-related: long QT syndrome (LQTS), Brugada syndrome
  • LQTS: sodium/potassium channel mutations; sudden cardiac death
  • Important: previously unexplained stillbirth may represent cardiac channelopathy → cardiac genetic evaluation indicated for the family
• Skeletal dysplasias: thanatophoric dysplasia, achondrogenesis (lethal)

• Chromosomal microarray (CMA): preferred over karyotype; higher diagnostic yield (additional 6-7% over normal karyotype)
• Karyotype: standard cytogenetics; requires dividing cells; culture may fail in macerated specimen
• Whole exome sequencing (WES): emerging; for unexplained structural anomalies; not yet standard of care
• Specimen sources (in order of preference): placental tissue (most reliable for culture), cord blood, fetal tissue (fascia, lung - away from skin which has bacteria)

Fetomaternal Hemorrhage (FMH) as Cause of Stillbirth

• Small amounts: normal (basis of alloimmunization)
• Massive FMH: >30 mL (or >80 mL by some definitions): uncommon but important cause of stillbirth

• Maternal: usually asymptomatic; anemia rare unless massive
• Fetal: decreased/absent movement; sinusoidal FHR pattern (if liveborn); hydrops
• Diagnosis: Kleihauer-Betke (KB) test or flow cytometry on maternal blood

• Acid elution: fetal RBCs (containing HbF) resist acid elution → stain red
• Maternal RBCs (HbA): ghost out → appear pale/empty
• Count percentage fetal cells → calculate volume: % fetal cells × maternal blood volume (5000 mL)
• Example: 1% fetal cells → 1% × 5000 = 50 mL fetal blood in maternal circulation
• Significant: >30 mL fetal blood (equivalent to fetal blood loss of ~50% of fetal blood volume)

• Uses anti-HbF antibody to identify and quantify fetal RBCs
• More sensitive and accurate than KB test (especially for small bleeds)
• Differentiates fetal RBCs from adult HbF-containing cells (hereditary persistence of HbF)
• Preferred test at centers where available

• Spontaneous (most common): no identifiable cause; placental villous disruption
• Trauma: motor vehicle accident, abdominal trauma, external version (ECV)
• Procedures: amniocentesis, CVS, cordocentesis
• Placental abnormalities: previa, abruption, choriocarcinoma

Intrahepatic Cholestasis of Pregnancy (ICP) and Stillbirth

• Total serum bile acids ≥10 µmol/L (fasting)
• Elevated liver enzymes (ALT/AST)
• Pruritus (primary symptom, often nocturnal)
• Diagnosis of exclusion (rule out hepatitis, gallstones, other liver disease)

• Overall: 1-2% (vs. 0.3% background risk)
• Bile acids <40 µmol/L: risk similar to background (~0.1-0.4%)
• Bile acids 40-99 µmol/L: 0.5-1.0% stillbirth risk
• Bile acids ≥100 µmol/L: 3-7% stillbirth risk; significantly elevated risk
• Risk is SUDDEN and UNPREDICTABLE; no prodrome

• Bile acids cross placenta → accumulate in fetal circulation
• Cardiotoxicity: bile acids disrupt fetal cardiac conduction (inhibit repolarization channels) → arrhythmia → sudden death
• Umbilical cord vasospasm: bile acids cause contraction of umbilical cord vessels in vitro
• NOT hypoxia-mediated (explains why BPP/NST do NOT reliably predict stillbirth in ICP)

• Ursodeoxycholic acid (UDCA): 10-15 mg/kg/day in divided doses; reduces bile acids, pruritus; may reduce fetal risk
• Rifampicin: add if UDCA insufficient; 150-300 mg/day
• Delivery timing:
  • Bile acids <100 µmol/L: deliver at 37-38 weeks
  • Bile acids ≥100 µmol/L: deliver at 35-37 weeks (individualize)
  • SMFM/RCOG: no role for routine fetal monitoring (NST/BPP) as not predictive of stillbirth in ICP
• Postpartum: ICP resolves within days to weeks; recurrence in subsequent pregnancy: 45-70%

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ANTEPARTUM FETAL SURVEILLANCE AND STILLBIRTH PREVENTION

Does Surveillance Prevent Stillbirth?

• No single surveillance modality has proven to reduce stillbirth in RCTs
• Kick counts: mixed evidence; systematic use may reduce stillbirth by raising awareness of decreased movement and triggering evaluation
• NST/BPP: high negative predictive value; false negative rate ~6-8/1000 per week
• Delivering at-risk pregnancies earlier: reduces stillbirth but increases iatrogenic prematurity

• No validated first-trimester screening test for late stillbirth
• Uterine artery Doppler pulsatility index at 11-13 weeks: elevated is associated with subsequent preeclampsia, IUGR, stillbirth
• PlGF (placental growth factor) at 11-13 weeks: low → increased risk
• Combined screening model (MAP + UtAPI + PlGF): predictive of preterm preeclampsia and potentially late stillbirth

• Movements represent intact neurological activity
• Decrease precedes other signs of fetal compromise by hours to days
• 55% of women who had stillbirths reported decreased movement beforehand and did not seek care

• Cluster-randomized trial: care package for reduced fetal movement vs. usual care
• Results: reduced stillbirth from 4.06 to 2.75 per 1,000 births (RR 0.68; 95% CI 0.49-0.94)
• Components: patient education (count to 10 method), clear clinical pathway, standardized management
• Concluded: structured FMC program with clear escalation pathway reduces stillbirth

1. Maternal education about fetal movement pattern from 26-28 weeks
2. "Count to 10": count until 10 movements perceived; should occur within 2 hours
3. Reduced movement reported → clinical assessment:
   • NST (first-line)
   • If non-reactive or additional concern → BPP or modified BPP (NST + AFI)
   • If BPP ≥8: reassure but document and monitor closely
   • If BPP ≤6 or other concerns: further evaluation and consider delivery

Post-Term Pregnancy and Stillbirth Risk

• 37-39 weeks: 0.3 per 1,000 ongoing pregnancies
• 40 weeks: 0.5 per 1,000 ongoing pregnancies
• 41 weeks: 1.0 per 1,000 ongoing pregnancies
• 42 weeks: 1.8-2.0 per 1,000 ongoing pregnancies
• 43+ weeks: 3+ per 1,000 ongoing pregnancies

• ≥41 weeks: universal induction (ACOG, RCOG, SMFM: offer induction at 41 0/7 weeks)
• ≥42 weeks: induction recommended (significant increase in stillbirth, meconium, operative delivery)
• ARRIVE trial secondary analysis: elective induction at 39 weeks reduced stillbirth numerically (0 vs. 7 deaths in expectant arm)

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DIAGNOSIS OF STILLBIRTH

Clinical Presentation

• Absent fetal movement (most common presenting complaint)
• Loss of fetal movement perceived days to weeks before formal diagnosis in some cases
• Uterus no longer growing
• Breast engorgement may decrease
• Some women: no symptoms (diagnosed at routine visit)

• No audible fetal heart tones by Doppler
• Uterus may feel less firm or tense
• In late intrauterine death: palpation may identify softer skull (Spalding sign on X-ray)

Ultrasound Diagnosis

• Absence of cardiac activity on M-mode tracing over ≥30 seconds
• B-mode: absence of fetal movement; unclear cardiac activity
• Must be confirmed by experienced operator (artifacts can mimic cardiac motion)
• SINGLE operator confirmation acceptable for obvious cases; second observer for equivocal

• Overlapping skull bones (Spalding sign): sutures overriding on X-ray; soft skull on ultrasound
• "Halo" around fetal skull: subcutaneous edema
• Absence of fetal movement and cardiac activity
• Hyperechoic fetal appearance
• Gas in fetal heart/great vessels (Robert sign): indicates advanced maceration; air in cardiovascular system visible on X-ray or ultrasound

• Oligohydramnios: may be present (fetal urine output decreased with fetal death)
• Sludge or particulate matter: with infection or advanced maceration

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MANAGEMENT OF STILLBIRTH

Initial Maternal Assessment

1. Confirm diagnosis (ultrasound by experienced provider)
2. Communicate diagnosis to patient and family (compassionate, clear, private setting)
3. Psychosocial support: chaplaincy, social work, bereavement team immediately
4. Medical assessment: history, physical, initial investigations
5. Discuss delivery options and timing

• CBC with differential
• Comprehensive metabolic panel (renal, liver function)
• Coagulation studies: PT, aPTT, fibrinogen, D-dimer → assess for DIC (can develop 3-4 weeks after fetal death from thromboplastin release into maternal circulation)
• Blood type and screen
• Kleihauer-Betke or flow cytometry (fetomaternal hemorrhage)
• Toxicology screen (if indicated)
• Bile acids (if pruritus)

• Antiphospholipid antibody panel: anticardiolipin IgG/IgM, anti-β2-glycoprotein I IgG/IgM, lupus anticoagulant
• Thrombophilia panel: Factor V Leiden, prothrombin G20210A, antithrombin III, protein C, protein S (note: protein S low in pregnancy normally; interpret cautiously)
• Fasting glucose or HbA1c (if not recently checked)
• Thyroid function (TSH, free T4)
• Parvovirus B19 IgG and IgM
• CMV IgG and IgM
• Syphilis serology (RPR or VDRL + treponemal test)
• Toxoplasma IgG and IgM (in some centers)
• Listeria culture (if fever or amnionitis signs)
• Urine drug screen
• Fetal karyotype/microarray (from placenta or fetal tissue)
• Maternal Hgb electrophoresis (if not done; screen for sickle cell, thalassemia)
• HbA1c (even without known diabetes; may detect previously undiagnosed)

Delivery Management

• Medical urgency: DIC risk increases with duration of retention (especially after 4 weeks, risk becomes clinically significant); most women choose delivery within days of diagnosis
• Safety of waiting: maternal risk from retention is LOW in first 2-3 weeks; coagulation should be checked serially if delay anticipated
• Patient choice: give adequate time for emotional preparation; do NOT rush unless maternal compromise present
• Most women: choose induction within 24-72 hours of diagnosis

• Vaginal delivery: preferred in vast majority; lower surgical risk; allows full fetopsy; better milk suppression planning
• Cesarean: only for standard obstetric indications (not for stillbirth per se); maternal preference occasionally
• Important counseling: mode of delivery affects future obstetric planning (VBAC/TOLAC considerations)

• Mifepristone 200 mg orally + misoprostol (highest efficacy combination):
  • 200 mg mifepristone 24-48 hours before misoprostol
  • Then misoprostol 800 mcg vaginally loading; 400 mcg sublingual or vaginally every 3-4 hours
  • Complete within 24-48 hours in >90% of cases
• High-dose oxytocin (not as effective as prostaglandins at previable gestations; cervix less responsive to oxytocin)
• D&E (dilation and evacuation): 13-24 weeks; most technically complete; lowest complication rate when performed by trained operator; limits perinatal autopsy

• Mifepristone + misoprostol: highly effective
• Misoprostol alone: 200-400 mcg vaginally/sublingual every 4-6 hours
• Cervical preparation with laminaria for 12-24 hours before misoprostol
• D&E: technically feasible; requires experienced operator

• Mifepristone pretreatment (if available): 200 mg oral, 24 hours before misoprostol
• Misoprostol: 100-200 mcg vaginally every 4-6 hours (lower doses than previable gestations)
• Cervical ripening: dinoprostone, laminaria, Foley balloon (all applicable)
• Oxytocin: can be used after adequate cervical ripening or ripening with prostaglandins

• Cervical ripening per standard protocols (Bishop score guides agent selection)
• Dinoprostone (Cervidil or Prepidil): for unfavorable cervix
• Misoprostol: effective; CAUTION with prior uterine scar (uterine rupture risk)
• Foley balloon: safe with prior cesarean
• Oxytocin: after cervical ripening or with favorable cervix
• Amniotomy: when head well applied; shortens labor

• Prior low transverse cesarean: Foley balloon + oxytocin preferred; avoid misoprostol (rupture risk)
• Classical cesarean: schedule cesarean for delivery of stillbirth OR very carefully managed induction with low-dose oxytocin only
• Must fully counsel patient about rupture risk; continuous monitoring of contractions

• Neuraxial analgesia (epidural, spinal): offered and encouraged
• IV opioids: for patients unable/unwilling to have epidural
• Important: adequate analgesia reduces psychological trauma of delivery experience
• Women should not be denied pain relief out of concern it is "unnecessary" for a fetal death

• Labor support person (partner, doula, support person) present and encouraged
• Private room whenever possible
• Sensitive, empathic nursing care
• Allow FHR monitoring to be turned off (parents may find continuous monitoring distressing when no heartbeat present)
• Photography offered but not mandated during labor

• Allow family time with infant (as long as desired, for hours if needed)
• Photography: professional bereavement photography (Now I Lay Me Down to Sleep; free service)
• Footprints and handprints on keepsake card
• Lock of hair (with family permission)
• ID bracelet and clothing for infant
• Baptism or religious ceremony if desired
• Memory box: many hospitals provide; contains mementos

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PERINATAL AUTOPSY AND INVESTIGATIONS

Fetal Autopsy

• External examination: body measurements (weight, crown-rump length, head circumference, foot length for gestational age estimation); photographs; dysmorphic features; skin; cord
• Internal examination: cranial (brain weight, structure, histology); thoracic (heart, lungs); abdominal (liver, kidneys, adrenals, bowel); musculoskeletal
• Histology: all major organs
• Radiographic skeletal survey: before autopsy; evaluates skeletal dysplasias, fractures, mineralization
• Photographs of all major findings

• Changes diagnosis or adds significant information in 20-76% of cases
• Most valuable when: cause unknown clinically, malformation suspected, recurrence risk counseling needed
• Least valuable when: known chromosomal anomaly, obvious external cause (trauma, abruption with small infant)

• Family refusal: 20-40% of families decline full autopsy
• Religious/cultural concerns
• Fear of disfigurement
• Lack of counseling or inadequate explanation of benefits
• Partial autopsy (specific systems) can be offered as compromise
• External examination only: still provides information

• Still obtain: placental pathology (separately; not part of "autopsy")
• Genetic samples: from placenta or other tissues
• Photography
• Skeletal survey (X-ray)
• Explain that limited information will be available for recurrence risk counseling

Placental Pathology

• Even with suspected cause
• Most informative single investigation after fetal autopsy
• Submit fresh (not fixed in formalin initially); allow pathologist to choose fixation after gross exam

• Gross: weight, dimensions, shape, disc, membranes, cord (length, diameter, coiling index, insertion site)
• Histology: villous maturation, infarcts, intervillous thrombi, perivillous fibrin, villitis, decidua
• Special stains if infection suspected: Gram stain, PAS, Warthin-Starry
• Culture: chorioamnionitis suspected

• Massive placental infarction: uteroplacental insufficiency; preeclampsia; thrombophilia
• Chronic villitis: recurrent; may have immunological basis
• Massive perivillous fibrin deposition: high recurrence; monitor closely next pregnancy
• Chorioamnionitis (acute): ascending infection cause
• Decidual vasculopathy: impaired spiral artery remodeling; suggests preeclampsia or thrombophilia
• Fetal thrombotic vasculopathy: fetal clotting disorder; check fetal/parental thrombophilias
• Meconium: meconium within macrophages = meconium at least 3 hours before delivery
• Umbilical cord: thrombosis, vasculitis, stricture, hypo/hypercoiling

Genetic Evaluation

1. Placental tissue (most reliable): Wharton's jelly, cord tissue, placenta after removing maternal decidua; culture success ~90% even with maceration
2. Fetal tissue at autopsy: fascia lata, cartilage, lung; avoid skin or organs exposed to environment
3. Fetal blood: cord blood or cardiac puncture (culture success lower)
4. Amniocentesis before delivery (if planned autopsy to be deferred): highest quality living cells

• Chromosomal microarray (CMA): FIRST-LINE; detects aneuploidies + microdeletions/duplications; superior to karyotype; success rate from macerated tissue: 50-75%
• Karyotype: if CMA unavailable; requires dividing cells; lower success in macerated tissue
• FISH for common aneuploidies: rapid (24-48 hr); useful if microarray fails
• Whole exome sequencing (WES): emerging; diagnoses single gene disorders; consider in unexplained with structural anomalies

• Normal microarray: does not exclude genetic cause (single gene disorders, low-level mosaicism)
• Variant of uncertain significance (VUS): requires genetic counseling; family studies may clarify significance
• Pathogenic variant: recurrence risk counseling; may indicate need for preconception genetic testing, PGT-M with IVF in future pregnancy

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RECURRENCE RISK AND SUBSEQUENT PREGNANCY

Recurrence Risk by Cause

Management of Subsequent Pregnancy After Stillbirth

• Complete evaluation of prior stillbirth before next conception
• Optimize modifiable risk factors: glycemic control, hypertension treatment, smoking cessation, weight loss
• Genetic counseling if chromosomal or single gene disorder identified
• Review antiphospholipid antibody results (confirm persistent positivity at ≥12 weeks apart for APS diagnosis)
• Thrombophilia treatment plan if indicated

• Most protocols: increased surveillance from 28-32 weeks OR 2 weeks before the gestational age of prior stillbirth (whichever is earlier)
• ACOG: individualize based on cause; no universal protocol

• Fetal movement counting: daily from 26-28 weeks; patient education
• NST: once or twice weekly from 32-36 weeks (or earlier if prior stillbirth was early)
• BPP or modified BPP: if NST non-reactive
• Serial growth ultrasounds: every 4 weeks from 28-32 weeks
• Umbilical artery Doppler: if growth restriction develops
• Uterine artery Doppler: 20-24 weeks (if elevated PI → increased placental insufficiency risk)

• Unexplained prior stillbirth: offer delivery at 39 weeks (or earlier if maternal/fetal compromise)
• Some experts: 37-38 weeks for prior unexplained stillbirth
• Prior stillbirth with identifiable cause: delivery timing based on underlying condition

• "Rainbow pregnancy": high anxiety is normal and expected; does NOT indicate pathology
• Screening: Edinburgh Postnatal Depression Scale in pregnancy for anxiety/depression
• Interventions:
  • Increased frequency of prenatal visits (evidence shows reduces anxiety WITHOUT increasing obstetric interventions if managed appropriately)
  • Psychologist or psychiatrist referral for significant anxiety
  • Pregnancy after loss support groups (e.g., "Pregnancy After Loss Support" - PALS)
  • Mindfulness-based interventions: evidence of benefit for perinatal anxiety
  • SSRIs: if depression/anxiety severe; risk/benefit counseling
• Partner support: male partners often less supported; paternal grief acknowledged and addressed
• Surviving siblings: age-appropriate explanation; grief support
• Healthcare provider communication: acknowledge prior loss at EVERY visit; avoid minimizing grief

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GRIEF AND BEREAVEMENT

Models of Grief

• Denial, Anger, Bargaining, Depression, Acceptance
• Non-linear; not sequential in all people
• Modern understanding: grief is non-linear; people cycle through stages

• Healthy grief involves maintaining ongoing relationship with the deceased rather than "moving on"
• Memory-making activities (photos, footprints) support healthy grief by creating continuing bonds
• Evidence: families who have memory boxes and photos report lower complicated grief rates

Complicated Grief (Prolonged Grief Disorder)

• Grief that significantly impairs functioning beyond 12 months
• Persistent yearning/longing for deceased; difficulty accepting death; inability to engage in life; social withdrawal

• 20-30% of bereaved mothers (higher than adult loss bereavement)
• Risk factors: poor social support, lack of partner support, prior mental health history, traumatic delivery experience, lack of memory-making opportunities

• Perinatal Grief Scale
• Inventory of Complicated Grief
• Edinburgh Postnatal Depression Scale (EPDS): screens for depression but not grief per se

• Complicated grief therapy (CGT): specialized psychotherapy; evidence-based
• CBT: cognitive-behavioral therapy adapted for grief
• SSRIs: for comorbid depression
• Peer support: bereaved parent groups

Evidence-Based Bereavement Care

• Professional photography: Now I Lay Me Down to Sleep (NILMDTS); volunteer photographers; families value photos even years later
• Footprints and handprints: most hospitals routinely provide
• Lock of hair: with permission; keepsake
• Clothing: dressing infant in clothing family brings
• Baptism or naming ceremony: regardless of religion; naming validates personhood

• Use infant's name (if given)
• Acknowledge the loss directly; avoid euphemisms ("passed away," "gone to sleep")
• Provide privacy during family time with infant
• Do NOT rush family out of delivery room; allow extended time (hours or overnight if culturally appropriate)
• Offer option to hold infant; some families need encouragement that this is acceptable

• SHARE Pregnancy and Infant Loss Support
• NILMDTS (Now I Lay Me Down to Sleep)
• March of Dimes: Share Your Story program
• Star Legacy Foundation (stillbirth-specific)
• Evidence: peer support groups reduce complicated grief, reduce social isolation

• Dedicated postpartum visit: 1-2 weeks (not standard 6-week visit); specifically for grief, physical recovery, and results discussion
• 6-week visit: review all autopsy/placental/genetic results; provide recurrence risk counseling
• Mental health referral: if EPDS elevated or complicated grief features
• Contraception counseling: when patient is ready (not immediately; but important for interval before next pregnancy)
• Future pregnancy planning: at separate visit when emotional readiness present

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PUBLIC HEALTH AND PREVENTION STRATEGIES

Modifiable Risk Factors and Interventions

• Population-attributable risk: ~5-7% of stillbirths
• Interventions: NRT (nicotine replacement) safe in pregnancy; behavioral counseling; bupropion (second-line); varenicline (limited pregnancy data); e-cigarettes NOT recommended
• Reduction (not cessation) also reduces risk

• Pre-pregnancy weight loss
• Gestational weight gain control within IOM guidelines
• Evidence for specific interventions modest; early nutritional counseling

• Going to Sleep on Side (GoSS) campaign:
  • Multiple case-control and cohort studies: supine position in third trimester associated with 2x increased risk of late stillbirth
  • Mechanism: aortocaval compression in supine → reduced uterine blood flow → fetal hypoxia
  • ACOG/RCOG: recommend women sleep on side (either side) in third trimester
  • Intervention: patient education at 28 weeks; falls asleep on side (waking in supine position not associated with risk)
  • AFFIRM-2 trial: sleep position education ongoing

• Low-dose aspirin from ≤16 weeks reduces preeclampsia risk by 10-62% depending on risk
• Indirect reduction in stillbirth through preeclampsia prevention

• Universal GBS screening and IAP: major reduction in GBS stillbirth and neonatal disease
• Routine syphilis screening and treatment: virtually eliminates congenital syphilis stillbirth in treated populations

• Induction at 41 weeks: most evidence-based timing to reduce post-term stillbirth
• ARRIVE trial extension: may push toward 39-week induction as acceptable to prevent very small number of stillbirths

Global Stillbirth Reduction

• Target: ≤12 stillbirths per 1,000 births in all countries by 2030
• Four pillars: skilled attendant at birth, antenatal care, newborn care, community engagement

• Skilled birth attendant: most important single intervention
• Antenatal syphilis screening and treatment
• Malaria prevention (ITNs, intermittent preventive treatment)
• GBS prophylaxis (limited implementation in low-resource settings)
• Corticosteroids for preterm (<34 weeks)
• Hypertension management (magnesium, antihypertensives)
• Fetal monitoring (Pinard stethoscope or Doppler)

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LEGAL, ETHICAL, AND DOCUMENTATION ASPECTS

Documentation Requirements

• Stillbirth requires separate fetal death certificate (NOT standard death certificate; NOT birth certificate)
• Some states: "Certificate of Birth Resulting in Stillbirth" available as keepsake (not legal document)
• Required information: gestational age, birth weight, cause of death (to extent determinable), maternal information

• Complete clinical summary
• All investigations ordered and results obtained
• Delivery summary: mode, complications, fetal position
• Placental and autopsy findings when available
• Counseling provided: recurrence risk, emotional support resources
• Follow-up plan

• Fetal deaths at ≥20 weeks: reportable in all US states (many states have specific forms)
• Reporting to local health department within specified time frame (varies by state; usually 3-10 days)
• CDC collects national fetal death data through NCHS

Autopsy Consent

• Written informed consent from parents (or next of kin) required
• Consent form should specify:
  • Full autopsy vs. limited (specific organ systems)
  • Retention of tissues for histology (required for diagnosis)
  • Retention of tissue for research (optional; separate consent)
  • Photography during autopsy
  • Disposition of infant after autopsy

• Frame positively: "This can help us understand what happened and help us care for future pregnancies"
• Acknowledge religious and cultural concerns without dismissing
• Offer partial autopsy alternatives
• Allow time for decision; do not pressure
• Document consent discussion even if declined

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CLINICAL PEARLS AND HIGH-YIELD POINTS FOR RESIDENTS

1. Stillbirth rate in USA: 5.74/1,000 births; ~21,000 per year; more common than SIDS
2. Racial disparity: Black women have 2x risk of stillbirth; not fully explained by socioeconomic factors; structural racism contributes
3. Most common identifiable cause: Placental disease (abruption + insufficiency combined = ~35-40%)
4. 25% of stillbirths remain unexplained even after full evaluation
5. Genetic testing: Chromosomal microarray PREFERRED over karyotype; higher yield especially in macerated specimens
6. Placental pathology: Always send; most informative single investigation after autopsy; submit fresh
7. APS: Always test; most important treatable cause of recurrent pregnancy loss AND stillbirth; treatment with aspirin + LMWH highly effective
8. ICP: Bile acids ≥100 µmol/L: significantly increased stillbirth risk; NST and BPP do NOT reliably predict ICP-related stillbirth; deliver at 35-37 weeks
9. MgSO4 toxicity antidote: Calcium gluconate 1g IV (important to remember in any obstetric emergency)
10. DIC risk after fetal demise: Clinically significant DIC from thromboplastin release after ≥3-4 weeks of retained fetus; check coagulation if delivery delayed; delivers usually prevent this
11. Grief: Memory-making (photos, footprints) reduces complicated grief; offer to all families; document offer and acceptance/refusal
12. Subsequent pregnancy: Begin enhanced surveillance at 28-32 weeks OR 2 weeks before prior stillbirth gestational age; offer delivery at 39 weeks
13. Sleep position: Advise side-sleeping from 28 weeks; supine position associated with 2x stillbirth risk (multiple studies); GoSS campaign
14. Fetomaternal hemorrhage: Consider in all unexplained stillbirths; KB test or flow cytometry; massive FMH (>30 mL) accounts for 3-4% of unexplained stillbirths
15. Prior stillbirth recurrence: Unexplained stillbirth carries ~1-2% recurrence risk in next pregnancy; counsel appropriately; avoid dismissing subsequent pregnancy as "high risk"
16. Partner grief: Often overlooked; paternal and partner grief is real; acknowledge; refer to support resources; couples may grieve differently (source of relationship stress)
17. When NOT to rush to cesarean: Stable patient with stillbirth diagnosis; vaginal delivery preferred in almost all cases; cesarean increases surgical risk without benefit to fetus
18. Autopsy consent rate: Only 40-60% of families consent; offer sensitively without pressure; partial alternatives exist; always obtain placental pathology even if full autopsy declined
19. Causes mnemo - STOPPED:

• S - Structural/chromosomal
• T - Thrombophilia/thrombosis
• O - Obstetric complications (abruption, preeclampsia)
• P - Placental pathology
• P - Post-term/Pre-term
• E - Environmental/Exposure (drugs, smoking)
• D - Diabetes/Disease (infection, ICP)

1. Follow-up visit: Schedule at 1-2 WEEKS (not standard 6 weeks); discuss preliminary results, address grief, assess mental health, plan for remaining investigations and return visit with full results

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