🧒 Fetal Growth

• Fetal birthweight matters for immediate neonatal health AND long-term adult health (even into the next generation)
• Barker (Thrifty Phenotype) Hypothesis: Reduced fetal growth → chronic conditions later in life (coronary heart disease, stroke, diabetes, hypertension)
• Fetal size assessed two ways:
  • Externally: Symphysis-fundal height (SFH) tape measure
  • Ultrasound: Estimated fetal weight (EFW) using Hadlock equations
• Fetal size presented on centile charts for gestational age
• Customized centile charts adjust for maternal height, weight, parity, ethnicity, fetal sex
• Fetus < 10th centile = Small for Gestational Age (SGA) - statistical concept, not necessarily pathological
• Fetal Growth Restriction (FGR): Failure to reach growth potential - high risk of perinatal morbidity/mortality
• FGR complications:
  • Acute: Intrauterine hypoxia/asphyxia, stillbirth, HIE (seizures, multiorgan damage)
  • Neonatal: Hypothermia, hypoglycaemia, infection, necrotizing enterocolitis, cerebral palsy
  • Long-term: Hypertension, cardiovascular disease, diabetes in adult life

❤️ Fetal Circulation

• Oxygenation occurs in the placenta, not the lungs
• Right and left ventricles work in parallel (not in series)
• Heart, brain, upper body get blood from left ventricle; placenta and lower body from both ventricles

• Ductus venosus: Umbilical vein → IVC (bypasses liver)
• Foramen ovale: Right atrium → left atrium (bypasses lungs)
• Ductus arteriosus: Pulmonary artery → descending aorta (bypasses lungs); kept open by prostaglandin E2 and prostacyclin; premature closure caused by cyclooxygenase inhibitors

• Umbilical blood flow ceases → ductus venosus closes
• Lungs inflate → pulmonary vascular resistance falls → foramen ovale closes
• Ductus arteriosus closes functionally within a few days

🧠 Central Nervous System

• One of the earliest to begin, last to complete development
• CNS starts as neural plate → groove → tube
• Failure of neural tube to close = Neural Tube Defects (NTDs)
• Rapid increase in grey matter in last trimester (fourfold increase in cortical grey matter)

🫁 Respiratory System

• Lung begins as foregut outgrowth at 3-4 weeks
• By 4-7 weeks: epithelial tubes branching
• By 20 weeks: conductive airway tree established
• By 26 weeks: Type I and II epithelial cells differentiating
• Surfactant produced by Type II cells from ~30 weeks
  • Main phospholipid = phosphatidylcholine (lecithin) - 80%
  • Production enhanced by cortisol, growth restriction, prolonged membrane rupture
  • Production delayed in maternal diabetes
• RDS (Respiratory Distress Syndrome):
  • Due to surfactant deficiency in preterm infants
  • Occurs in >80% of infants born 23-27 weeks, falls to 10% at 34-36 weeks
  • Presents with tachypnoea, cyanosis within first hours of life
  • Antenatal steroids given to mothers at risk of preterm delivery → stimulate early surfactant release
• Fetal Breathing Movements (FBM): Maintain lung expansion; apnoeic periods with laryngeal constriction resist lung fluid escape
• Oligohydramnios or reduced intrathoracic space → pulmonary hypoplasia

🍽️ Alimentary System

• Foregut → oesophagus, stomach, proximal duodenum, liver, pancreas
• Midgut → distal duodenum, jejunum, ileum, caecum, appendix, ascending + transverse colon
• Hindgut → descending colon, sigmoid colon, rectum
• 5-6 weeks: Midgut herniates into umbilical cord (physiological hernia)
• Returns to abdominal cavity by 12 weeks
• Failure to return = Omphalocele/Exomphalos (associated with chromosomal anomaly)
• Malrotation → volvulus, bowel obstruction
• Tracheo-oesophageal fistula (TOF): Connection between distal oesophagus and trachea
  • Part of VACTERL association (Vertebral, Anal, Cardiac, Tracheal, (O)esophageal, Renal, Limb)
  • Obstruction of fetal swallowing → polyhydramnios
• Meconium in amniotic fluid = associated with post-term pregnancy or fetal hypoxia; aspiration → meconium aspiration syndrome

🫀 Liver, Pancreas & Gall Bladder

• Liver appears in 3rd week as hepatic diverticulum
• By 6th week: fetal liver performs haematopoiesis (peaks 12-16 weeks, continues to ~36 weeks)
• Fetal liver has reduced ability to conjugate bilirubin (deficient glucuronyl transferase)
• After birth, loss of placental bilirubin excretion → physiological jaundice (especially in preterm)
• Glycogen storage: Starts 1st trimester, maximal in 3rd trimester
• Growth-restricted and premature infants → deficient glycogen stores → prone to neonatal hypoglycaemia

🫘 Kidney & Urinary Tract

• Pronephros: ~3 weeks, non-functional in mammals
• Ureteric bud: Develops at 5th week from Wolffian duct → forms collecting system (ureter, pelvis, calyces, collecting ducts) + induces renal secretory system (glomeruli, convoluted tubules, loops of Henle)
• All nephrons formed by 32-36 weeks
• Failure of kidney migration → pelvic kidney
• Renal agenesis → oligohydramnios/anhydramnios
• Potter's syndrome: Bilateral renal agenesis → widely spaced eyes, small jaw, low set ears, oligohydramnios → die from renal failure or pulmonary hypoplasia
• Posterior urethral valves = most common obstructive uropathy → hydronephrosis + renal interstitial fibrosis

🧴 Skin & Homeostasis

• Epidermis from surface ectoderm; dermis/hypodermis from mesenchymal cells (mesoderm)
• By 4th week: single ectodermal layer surrounds embryo
• At 6 weeks: differentiates into periderm (→ vernix) and basal layer (→ epidermis, glands, nails, hair)
• By 16-20 weeks: all epidermal layers developed
• Preterm babies: no vernix, thin skin → high insensible water loss; poor thermal regulation
• Heat generated by brown fat catabolism (deficient in preterm/FGR)
• Lanugo: Fine fetal hair, first appears on head at 24 weeks, usually shed before birth

🩸 Blood & Immune System

• Haematopoietic cells: yolk sac (early) → liver at 8 weeks → bone marrow by 20 weeks
• Fetal haemoglobin (HbF): Has 2 gamma-chains; higher O₂ affinity than HbA → enhances O₂ transfer across placenta
• HbF switches to HbA between 28-34 weeks; at term ratio HbF:HbA = 80:20
• Beta-thalassaemia: Absent/reduced beta-globin → severe anaemia, FGR, musculoskeletal problems
• Alpha-thalassaemia (severe): No alpha-globin → severe fetal anaemia, cardiac failure, hepatosplenomegaly, generalised oedema → stillbirth
• T-cell precursors in thymus by 9 weeks; mature T cells in blood by 12-14 weeks
• Lymphocytes present by 16 weeks; by mid-2nd trimester all immune cells (phagocytes, T, B cells, complement) available
• IgG crosses placenta (passive immunity); IgM and IgA do not → IgM/IgA in newborn = fetal infection

⚗️ Endocrine System

• Hypothalamic-pituitary axis: In place by 12 weeks
• TRH and GnRH identified in fetal hypothalamus by end of first trimester
• Testosterone: Synthesized in 1st trimester by testis → increases 17-21 weeks (male urogenital tract differentiation)
• Growth hormone: Present from early pregnancy, detectable from 12 weeks
• Thyroid: Produces T4 from 10-12 weeks
• FGR fetuses exist in relative hypothyroidism (to decrease metabolic rate and O₂ consumption)

🏃 Behavioural States

• Fetal heart beats first → movements from 7-8 weeks
• By 12 weeks: yawning, sucking, swallowing
• 4 fetal behavioural states:
  • 1F = Quiescence (like quiet/non-REM sleep)
  • 2F = Frequent periodic gross body movements WITH eye movements (like REM sleep)
  • 3F = No gross body movements, eye movements present (quiet wakefulness)
  • 4F = Vigorous continual activity with eye movements (active wakefulness)

💧 Amniotic Fluid

• Amnion contacts chorion by 12 weeks (never fuse)
• Initially secreted by amnion; by 10th week = transudate of fetal serum via skin + umbilical cord
• From 16 weeks: fetal skin becomes impermeable → fluid volume regulated by fetal kidneys (urine) and lungs, removed by fetal swallowing
• Contains growth factors and multipotent stem cells
• Volume progression: 10 wks: 30ml → 20 wks: 300ml → 30 wks: 600ml → 38 wks: 1,000ml (peak) → 40 wks: 800ml → 42 wks: 350ml
• Amniotic fluid index (AFI): Sum of deepest pools in 4 uterine quadrants on ultrasound

1. Protect fetus from mechanical injury
2. Permit fetal movement, prevent limb contracture
3. Prevent fetal-amnion adhesions
4. Permit fetal lung development (absence in 2nd trimester → pulmonary hypoplasia)

• Oligohydramnios: Reduced fluid - caused by renal agenesis, cystic kidneys, FGR
• Polyhydramnios: Excess fluid - caused by neuromuscular disorders, anencephaly, oesophageal/duodenal atresia (prevent swallowing)