Key Facts

Human embryology describes the developmental processes from fertilisation through to birth. Understanding normal development is essential for recognising congenital anomalies and appreciating the clinical significance of developmental defects.

Epidemiology

Congenital anomalies affect approximately 2-3% of live births in the UK. Neural tube defects have declined from ~3 per 1,000 births to ~0.5 per 1,000 following folic acid supplementation programmes. Congenital heart disease is the most common group of congenital malformations (~8 per 1,000 live births).

Aetiology

Key developmental stages:

• Week 1: Fertilisation → cleavage → morula → blastocyst → implantation
• Week 2: Bilaminar disc (epiblast + hypoblast), amniotic cavity, yolk sac
• Week 3: Gastrulation (formation of three germ layers), primitive streak, neurulation begins
• Weeks 3-8: Organogenesis — all major organ systems established
• Weeks 9-38: Fetal period — growth and maturation

Pathophysiology

Germ layer derivatives:

• Ectoderm: Epidermis, CNS (brain and spinal cord), neural crest cells (melanocytes, adrenal medulla, peripheral nerves, pharyngeal arch cartilage), anterior pituitary, lens
• Mesoderm: Skeletal muscle, bone, cartilage, cardiovascular system (heart, blood vessels), kidneys, adrenal cortex, spleen, gonads
• Endoderm: GI tract epithelium, liver, pancreas, thyroid, parathyroids, lungs, bladder epithelium

Neural crest cells are particularly important — defects cause neurocristopathies (Hirschsprung disease, melanoma, neurofibromatosis, DiGeorge syndrome)

Fetal circulation adaptations at birth:

• Ductus arteriosus closes (becomes ligamentum arteriosum) — PGE2 keeps it open; indomethacin promotes closure
• Foramen ovale closes (becomes fossa ovalis) — due to increased left atrial pressure
• Ductus venosus closes (becomes ligamentum venosum)
• Umbilical vessels close (arteries → medial umbilical ligaments; vein → ligamentum teres)

Neural Tube Defects

• Anencephaly: Absence of cranial vault and cerebral hemispheres — incompatible with life
• Spina bifida occulta: Failure of vertebral arch fusion — usually asymptomatic, tuft of hair/dimple
• Meningocele: Meninges protrude through defect
• Myelomeningocele: Spinal cord and meninges protrude — motor/sensory deficit below level, hydrocephalus

Congenital Heart Defects

• VSD: Most common CHD overall — pansystolic murmur at left sternal edge
• ASD: Secundum (most common), primum — fixed split S2
• Tetralogy of Fallot: VSD + right ventricular outflow obstruction + overriding aorta + RVH — cyanotic "tet spells"
• Transposition of great arteries: Aorta from RV, PA from LV — duct-dependent circulation, cyanosis from birth

Other Congenital Anomalies

• Tracheo-oesophageal fistula: Drooling, choking with feeds, inability to pass NG tube
• Diaphragmatic hernia (Bochdalek): Respiratory distress, bowel sounds in chest, scaphoid abdomen
• Hirschsprung disease: Failure of neural crest migration → aganglionic bowel → functional obstruction

Red Flags

• Cyanosis in a newborn — consider duct-dependent cardiac lesion (start prostaglandin E1)
• Bilious vomiting in neonate — malrotation with volvulus until proven otherwise (surgical emergency)
• Failure to pass meconium within 48 hours — consider Hirschsprung disease, CF

Bedside

• Newborn examination (NIPE): Within 72 hours — eyes, heart, hips, testes
• Pulse oximetry screening: Pre- and post-ductal SpO2 for critical CHD

Bloods

• Newborn blood spot: Day 5 screening (PKU, CHT, SCD, CF, MCADD + others)
• Karyotype/genetic testing: Chromosomal abnormalities (trisomy 21, 18, 13; Turner syndrome, Klinefelter syndrome)
• FISH for 22q11.2: DiGeorge syndrome

Imaging

• Antenatal USS: Dating (12 weeks), anomaly scan (18-21 weeks)
• Echocardiogram: Congenital heart disease assessment
• MRI: Complex anomalies, brain malformations

Special Tests

• Combined first trimester screening: Nuchal translucency + PAPP-A + free β-hCG (11-14 weeks) — trisomy risk
• NIPT (non-invasive prenatal testing): Cell-free fetal DNA — high sensitivity for trisomies 21, 18, 13
• Amniocentesis: After 15 weeks — karyotype, specific genetic tests (1% miscarriage risk)
• Chorionic villus sampling (CVS): 11-14 weeks — earlier diagnosis (1-2% miscarriage risk)

Non-pharmacological

• Folic acid supplementation: 400mcg daily preconception and first 12 weeks; 5mg if high risk (previous NTD, anti-epileptic drugs, diabetes)
• Avoidance of teratogens: Alcohol, smoking, retinoids, sodium valproate (MHRA Pregnancy Prevention Programme)
• Antenatal care and screening: As per NICE NG201
• Genetic counselling: For families affected by genetic conditions

Pharmacological

• Prostaglandin E1 (alprostadil): Maintains patent ductus arteriosus in duct-dependent CHD until surgical correction
• Indomethacin/ibuprofen: Closes patent ductus arteriosus in premature infants
• Surfactant replacement: Intratracheal for neonatal RDS (surfactant deficiency in premature infants)

Surgical

• Congenital heart disease: Surgical correction or palliation (depending on anatomy)
• Tracheo-oesophageal fistula: Surgical repair — primary anastomosis of oesophageal ends, fistula ligation
• Diaphragmatic hernia repair: Stabilise, then surgical repair
• Neural tube defects: Neurosurgical closure of myelomeningocele; VP shunt for hydrocephalus

Referral Criteria

• Abnormal antenatal screening — fetal medicine
• Suspected congenital anomaly — appropriate specialist (cardiology, surgery, genetics)
• Family history of genetic condition — clinical genetics

• Anencephaly: Uniformly fatal — most die within hours to days of birth
• Myelomeningocele: ~85% survive with treatment; degree of disability depends on level (higher = more severe)
• Tetralogy of Fallot: Excellent surgical outcomes; >90% long-term survival with complete repair
• Tracheo-oesophageal fistula: Survival >95% in isolated cases; reduced if associated anomalies (VACTERL)
• Folic acid supplementation: Reduces NTD risk by approximately 70%
• Congenital heart disease: Overall surgical mortality <5% in specialist centres; lifelong follow-up required

Germ Layer Derivatives

Key Teratogens