Key Facts

Antenatal screening is a public health programme offering all pregnant women tests to assess risk of fetal abnormality and maternal infection. It enables early detection of conditions where intervention, treatment, or informed planning may improve outcomes. Screening is not diagnostic — it identifies individuals at higher risk who may benefit from further diagnostic testing.

Epidemiology

Down syndrome (T21) affects approximately 1 in 800-1,000 births (incidence before screening). Edwards syndrome (T18) ~1 in 6,000; Patau syndrome (T13) ~1 in 10,000. The UK FASP screens approximately 600,000+ pregnancies annually. Neural tube defects have a prevalence of approximately 1 in 1,000 pregnancies (significantly reduced by folic acid supplementation). HIV prevalence in pregnant women in the UK is approximately 1 in 500.

Aetiology

Conditions screened for have various aetiologies:

• Chromosomal (T21, T18, T13): Usually sporadic non-disjunction; risk increases with maternal age
• Structural anomalies: Multifactorial; some genetic (cardiac defects, renal anomalies)
• Neural tube defects: Folate deficiency is a major risk factor; folic acid supplementation reduces risk by ~70%
• Infections: HIV, hepatitis B, syphilis — transmission risk to fetus without intervention

Pathophysiology

Screening markers:

• Nuchal translucency: Increased subcutaneous fluid at back of fetal neck; associated with T21, T18, T13, Turner syndrome, cardiac defects
• β-hCG: Elevated in T21, reduced in T18/T13
• PAPP-A: Reduced in T21, T18, T13
• AFP: Elevated in neural tube defects, abdominal wall defects; reduced in T21
• Cell-free fetal DNA (NIPT): Fragments of fetal DNA (from placental trophoblast) circulate in maternal blood from ~10 weeks; can be analysed for chromosome copy number

Screening Schedule

• Booking bloods (by 10 weeks): Blood group, antibodies, FBC, HIV, hepatitis B, syphilis
• Combined screening (11+0 to 14+1 weeks): Nuchal translucency + serum markers
• Anomaly scan (18+0 to 20+6 weeks): Structural assessment of 11 conditions
• 28 weeks: Repeat antibody screen

Positive Screening Result Discussion

• Results expressed as probability (e.g., 1:100 for T21)
• Screen-positive threshold: ≥1:150 for combined/quadruple test (offered further testing)
• Counselling about diagnostic options (amniocentesis, CVS) including risks and implications
• Non-directive approach — support whatever decision the parents make

Conditions Screened by Anomaly Scan

• Anencephaly, open spina bifida, cleft lip, diaphragmatic hernia, exomphalos, gastroschisis, serious cardiac abnormalities, bilateral renal agenesis, lethal skeletal dysplasia, Edwards syndrome (T18), Patau syndrome (T13)

Red Flags

• Very high-risk screening result (e.g., 1:5 for T21) — urgent counselling and diagnostic testing
• Major structural anomaly on scan — fetal medicine referral
• Positive HIV, hepatitis B, or syphilis — immediate specialist management pathway
• Significantly raised AFP — consider neural tube defect, abdominal wall defect, or placental pathology

Bedside

• Nuchal translucency USS (11-14 weeks): NT ≥3.5mm is significantly increased risk; combined with maternal age and serum markers for risk calculation

Bloods

• Combined test (11-14 weeks): NT + free β-hCG + PAPP-A — T21 detection ~85%, 5% FPR
• Quadruple test (15-20 weeks): AFP + total β-hCG + uE3 + inhibin A — T21 detection ~80%, 5% FPR
• NIPT (from 10 weeks): Maternal blood sample; analyses cell-free fetal DNA; >99% sensitivity for T21, ~97% for T18/T13; FPR <0.1%
• Booking screening bloods: HIV antibody, HBsAg, syphilis (TPHA/EIA), blood group + antibodies, FBC
• Haemoglobinopathy screening: At booking — sickle cell and thalassaemia (universal or targeted based on ethnicity)

Imaging

• Dating scan (11-14 weeks): CRL measurement, viability, multiple pregnancy, NT
• Anomaly scan (18-20+6 weeks): Systematic structural assessment; sensitivity varies by condition (~50-60% for cardiac defects, >95% for anencephaly)
• Fetal echocardiography: If raised NT, family history CHD, maternal diabetes, or anomaly scan concern

Special Tests

• Amniocentesis (from 15 weeks): Aspiration of amniotic fluid — karyotype, microarray, specific gene testing; miscarriage risk ~0.5-1%
• CVS (from 11 weeks): Placental tissue sampling — earlier diagnosis; miscarriage risk ~0.5-1%
• QF-PCR (quantitative fluorescence PCR): Rapid result (24-48h) for common aneuploidies (T21, T18, T13, sex chromosomes)

Non-pharmacological

• Pre-test counselling: Explain what screening involves, what it detects, limitations, and implications of results
• Informed consent: Screening is voluntary; document consent/declination
• Post-result counselling: If screen-positive, provide balanced information; discuss diagnostic testing options
• Specialist referral: Fetal medicine for abnormal screening/scan findings
• Psychological support: Access to counselling service for parents facing difficult decisions
• Multidisciplinary planning: If fetal anomaly confirmed — paediatric surgery, neonatology, genetics, palliative care as appropriate

Pharmacological

• HIV: Start antiretroviral therapy to reduce vertical transmission to <0.5% (aim for undetectable viral load)
• Hepatitis B: HBIG + hepatitis B vaccine for neonate at birth; maternal antiviral if high viral load
• Syphilis: IM benzathine penicillin 2.4 million units (single dose for early; 3 weekly doses for late) — treats maternal infection and prevents congenital syphilis
• Anti-D: If invasive diagnostic procedure performed (amnio/CVS) in Rh-negative woman
• Folic acid: 5mg daily if increased NTD risk (previous NTD, epilepsy medication, diabetes)

Surgical/Interventional

• Amniocentesis: USS-guided transabdominal needle aspiration of amniotic fluid
• CVS: Transabdominal or transcervical biopsy of chorionic villi
• Fetal therapy: In utero repair of spina bifida (MOMS trial), laser for twin-twin transfusion syndrome, fetal blood transfusion for alloimmune anaemia
• Termination of pregnancy: Available up to 24 weeks, or beyond if substantial risk of serious handicap (Ground E, Abortion Act 1967)

Referral Criteria

• Screen-positive result — fetal medicine for counselling and diagnostic testing
• Structural anomaly on scan — fetal medicine specialist
• Positive infectious disease screen — respective specialist (HIV, hepatology, GUM)
• Previous affected pregnancy or family history — genetics/fetal medicine for preconception counselling

• Combined screening: ~85% detection rate for T21 with 5% FPR
• NIPT: >99% detection rate for T21; FPR <0.1%; reduces need for invasive testing by ~50%
• Amniocentesis/CVS: Diagnostic accuracy essentially 100% for chromosomal disorders
• Anomaly scan: Detection rates vary — ~50-60% for cardiac defects, >95% for anencephaly, ~80-90% for spina bifida
• HIV screening and treatment: Reduces vertical transmission from ~25% to <0.5%
• Hepatitis B: Neonatal vaccination + HBIG reduces transmission from ~90% to <5%
• Syphilis treatment: Prevents congenital syphilis in ~98% of treated cases
• Neural tube defects: Folic acid supplementation reduces risk by approximately 70% (MRC Vitamin Study 1991)

Comparison of Screening Tests for Chromosomal Abnormalities

11 Conditions Screened at Anomaly Scan (FASP)