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Preterm Labor - Comprehensive Exam Notes

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1. DEFINITION

• Preterm birth: Delivery between 20 0/7 and 36 6/7 weeks of gestation (< 259 days)
• Preterm labor: Regular uterine contractions with progressive cervical change before 37 completed weeks
• Subcategories by gestational age:

• Subcategories by birth weight:
  • LBW: < 2500 g
  • VLBW: < 1500 g
  • ELBW: < 1000 g

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2. EPIDEMIOLOGY

• Preterm birth rate in the USA: ~10.23% (2019), rising since 2015
• Most common underlying cause of perinatal and infant morbidity and mortality in developed nations
• Consequences extend across the life course: neurodevelopmental, respiratory, gastrointestinal morbidities
• Spontaneous preterm labor accounts for ~50% of all preterm births; the rest are indicated (medically initiated) for maternal or fetal compromise

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3. CLASSIFICATION

1. Spontaneous preterm birth
   • Spontaneous onset of labor (with intact membranes)
   • Preterm prelabor rupture of membranes (pPROM)
   • Preterm cervical insufficiency
   • Uterine bleeding of uncertain origin (including abruption)
2. Provider-initiated (indicated) preterm birth
   • Induction of labor or elective cesarean before 37 weeks for maternal/fetal indications

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4. PATHOPHYSIOLOGY

1. Cervical ripening - premature softening, effacement, dilation
2. Membrane and decidual activation - cytokine release, prostaglandin production
3. Coordinated uterine contractility - shift from quiescence to active contractions

• Proinflammatory agents (LPS, IL-1β) can stimulate preterm labor in animal models
• Infection/inflammation is identified in up to 25-40% of preterm births, especially at very early gestational ages

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5. RISK FACTORS

A. Maternal Characteristics

B. Infections/Medical Conditions

• Urinary tract infection, malaria, HIV, syphilis, bacterial vaginosis
• Diabetes, hypertension, anaemia, asthma, thyroid disease

C. Lifestyle/Environmental

• Smoking, excess alcohol, recreational drugs
• Nutritional: undernutrition, obesity, micronutrient deficiencies
• Excess physical work/activity

D. Obstetric Factors

• Polyhydramnios, placenta previa, abruption
• Uterine fibroids, prior uterine surgery
• ART-conceived pregnancies (increased multiple gestation risk)

E. Genetic Factors

• Familial risk: if a woman's mother had a preterm delivery, her risk increases
• Polymorphisms in EBF1, EEFSEC, AGTR2 genes (uterine development, vascular control)
• Collagen disorders (Ehlers-Danlos) - associated with cervical insufficiency

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6. DIAGNOSIS

Clinical Criteria

• Persistent uterine contractions (≥ 6/hour) + cervical dilation ≥ 3 cm or effacement ≥ 80%
• Or: membrane rupture/bleeding
• Problem: overdiagnosis in 40-70% of women diagnosed with preterm labor clinically
• Contractions may be painful or painless depending on cervical resistance

• Pelvic pressure, increased vaginal discharge, backache, menstrual-like cramps (more by persistence than severity)

Diagnostic Tests

1. Fetal Fibronectin (fFN)

• Extracellular matrix protein normally found at choriodecidual junction
• Sampled from cervicovaginal fluid between 22-34 weeks
• Negative fFN (< 50 ng/mL): High negative predictive value (~99%) - delivery within 7 days very unlikely
• Positive fFN: lower predictive value but warrants further management
• Do NOT swab after digital exam, intercourse, or if membranes ruptured

2. Transvaginal Ultrasound (TVU) Cervical Length

• Transabdominal measurement has poor reproducibility - always confirm with TVU
• Combining cervical length + fFN improves NPV to ~99%

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7. MANAGEMENT

Step 1 - Confirm Preterm Labor and Assess Gestational Age

• Detailed US for fetal presentation, weight, anomalies
• GBS culture, cervicovaginal fFN, TVU cervical length
• Rule out contraindications to tocolysis

Step 2 - Antenatal Corticosteroids (ACS)

• Indicated: 24 0/7 to 33 6/7 weeks (also consider 34-36 6/7 weeks in select cases)
• Betamethasone 12 mg IM x2 doses 24 hours apart OR
• Dexamethasone 6 mg IM x4 doses 12 hours apart
• Benefits:
  • Reduces neonatal mortality, RDS, IVH, NEC, patent ductus arteriosus
  • Promotes surfactant synthesis, increases lung compliance, reduces vascular permeability
  • Maturational effects on brain, kidneys, gut

Step 3 - Tocolysis

Contraindications to Tocolysis

• Absolute: Severe preeclampsia/gestational hypertension, hemorrhage/abruption, intrauterine infection, maternal cardiac disease
• Fetal: Non-reassuring fetal status, lethal anomaly, IUGR with reverse diastolic flow

First-Line Tocolytic Agents

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Key exam point: MgSO₄ is NOT recommended as a tocolytic (ACOG) but IS recommended for fetal neuroprotection when delivery is anticipated < 32 weeks.

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• Blocks oxytocin receptors → decreased uterine contractions
• Not available in the USA; used in Europe
• Cochrane: inferior to calcium channel blockers and β-agonists for tocolysis
• Advantage: minimal maternal/fetal side effects

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Summary Table: Tocolytics

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Step 4 - Neuroprotection with MgSO₄

• All women at risk of delivery before 32 weeks
• Regimen: 4-6 g IV bolus over 30 min, then 1-2 g/hr for up to 24 hr
• Reduces moderate-severe cerebral palsy significantly
• Rescue dosing if >12 hours from last dose and delivery imminent

Step 5 - GBS Prophylaxis

• Antibiotics for GBS prophylaxis only (penicillin or ampicillin IV)
• Antibiotics for other specific pathogens (e.g., UTI)
• Routine broad-spectrum antibiotics for preterm labor with intact membranes have NOT been effective in prolonging pregnancy or reducing morbidity

Step 6 - Regionalized Care

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8. MAINTENANCE TOCOLYSIS

• Cochrane reviews of oral β-mimetics, terbutaline pump, oxytocin antagonists, and calcium channel blockers show no decline in preterm birth frequency with maintenance therapy
• Some evidence of nifedipine prolonging pregnancy (mean 5.35 days) but no reduction in preterm birth at various cutoffs
• Outpatient uterine contraction monitoring also NOT beneficial

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9. PREVENTION

Primary Prevention

• Public education about avoidable risk factors (smoking, ART, short inter-pregnancy interval)
• Policies to reduce higher-order multiple gestations
• Nutritional support, treatment of infections (UTI, BV)

Secondary Prevention (Screening)

• Cervical length screening at 18-24 weeks in singleton pregnancies with prior PTB
  • CL < 25 mm: offer vaginal progesterone (17-hydroxyprogesterone caproate or micronized progesterone)
  • Reduces PTB risk by ~30-40%
• Fetal fibronectin screening in high-risk women
• Cerclage: Indicated for cervical insufficiency with prior PTB and short cervix; NOT beneficial for multiple gestations

Tertiary Prevention (Management of Active Preterm Labor)

• Tocolysis + ACS + neuroprotection + regionalized care (as above)

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10. COMPLICATIONS / NEONATAL OUTCOMES

Directly Related to Prematurity

• Consequences extend across life course: NCDs (hypertension, diabetes) in later life
• Morbidity and mortality inversely proportional to gestational age

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11. QUICK EXAM MNEMONICS

• Prior PTB
• Uterine anomalies
• Multiple gestation
• Placental problems (previa, abruption)
• Extremes of age
• Distension (polyhydramnios)
• Medical conditions (DM, HTN)
• Obesity/nutrition
• Microbial infections (BV, UTI)

• Preterm = < 37 weeks (20-36+6)
• Fetal fibronectin: positive if > 50 ng/mL
• Cervical length reassuring: ≥ 30 mm; high risk: < 15 mm
• Indomethacin: use ONLY < 32 weeks, max 48 hours
• MgSO₄ neuroprotection: < 32 weeks
• ACS: 24-33+6 weeks (consider 34-36+6)
• Respiratory depression from MgSO₄: at 14 mg/dL
• DTR loss from MgSO₄: at 9-13 mg/dL

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12. HIGH-YIELD EXAM POINTS

1. Preterm birth is the #1 cause of perinatal and infant morbidity/mortality in developed nations
2. Antenatal corticosteroids are the most important single intervention; reduce RDS, IVH, NEC, mortality
3. Nifedipine is the preferred first-line tocolytic (Cochrane evidence)
4. MgSO₄ is NOT a tocolytic but is the agent for neuroprotection < 32 weeks
5. Indomethacin: limit to < 32 weeks, max 48 hours (ductal constriction risk)
6. Maintenance tocolysis is ineffective - do not use
7. fFN negative = very high NPV (~99%) for PTB within 7 days; useful for ruling OUT true preterm labor
8. Antibiotics: only for GBS prophylaxis in preterm labor with intact membranes; NOT for prolonging pregnancy
9. Cerclage: beneficial for cervical insufficiency in singletons; NOT beneficial in multiple gestations
10. Atosiban not available in USA but widely used in Europe
11. Overdiagnosis of preterm labor occurs in 40-70% with clinical criteria alone
12. Prior PTB is the single strongest clinical risk factor for recurrence

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