Prenatal screening & diagnosis of congenital abnormalities

Maternal serum screening · Ultrasound · First trimester · Second trimester · Combined test · Integrated test · Contingent screening · Safety of ultrasound · Forfar & Arneil’s Textbook (Chapter 11)
📌 Core principles: Prenatal screening aims to identify pregnancies at increased risk for congenital anomalies (chromosomal, structural). First‑trimester combined test (NT + β‑hCG + PAPP‑A) detects ~85% of Down syndrome. Second‑trimester quadruple screen (AFP, β‑hCG, uE3, inhibin A). Integrated and contingent strategies optimize detection and reduce false positives. Ultrasound is safe and central to anomaly detection.

📖 Core Summary: Prenatal screening & diagnosis

🧪 Maternal serum screening
First trimester: PAPP‑A, free β‑hCG. Second trimester: AFP, β‑hCG, uE3, inhibin A (quadruple). Low PAPP‑A + high β‑hCG → trisomy 21; both low → trisomy 18.
📊 First trimester ultrasound (11–13⁺⁶ wk)
Nuchal translucency (NT) measurement. NT ≥95th centile increases risk for trisomy 21, 18, 13, Turner, Noonan, CHD. Nasal bone assessment adds sensitivity.
🔬 Second trimester ultrasound (18–22 wk)
Detailed anomaly scan: CNS, cardiac (4‑chamber + outflow tracts), abdomen, renal, skeletal, placenta. Detects structural defects, soft markers (echogenic bowel, choroid plexus cyst, renal pyelectasis).
⚙️ Combined test (1st trimester)
NT + PAPP‑A + β‑hCG. Detection rate for Down syndrome ~85% at 5% FPR. Widely used for early aneuploidy risk assessment.
📈 Integrated & contingent screening
Integrated: 1st trimester NT + PAPP‑A + 2nd trimester quadruple → DR ~95%. Contingent: risk‑based stratification (high‑risk → invasive testing, intermediate → further screening, low‑risk → routine care).
🛡️ Safety of ultrasound
No confirmed adverse biological effects. ALARA principle (lowest possible power, shortest exposure). B‑mode and Doppler used judiciously. Essential tool with excellent safety record.
📌 Invasive diagnostic tests: Chorionic villus sampling (CVS) 11–14 wk (karyotype, microarray). Amniocentesis ≥15 wk (fetal cells in amniotic fluid). Fetal blood sampling (cordocentesis) for rapid karyotype, anemia evaluation.

🔍 Approach: abnormal prenatal screening results

1
Increased nuchal translucency (≥3.5 mm or ≥95th centile) – Offer CVS (karyotype + microarray), detailed early anatomy scan, fetal echocardiography at 18–22 weeks. NT 3.5–4.4 mm: ~40% anomaly risk.
2
Low PAPP‑A (<5th centile) in first trimester – Associated with placental dysfunction, IUGR, pre‑eclampsia, stillbirth. Serial growth scans, uterine artery Doppler, low‑dose aspirin for pre‑eclampsia prevention.
3
Elevated maternal serum AFP (2nd trimester) – Suspect open neural tube defect (spina bifida, anencephaly), ventral wall defect (gastroschisis, omphalocele), multiple gestation. Targeted ultrasound with high‑frequency transducer.
4
Ultrasound soft markers (echogenic intracardiac focus, choroid plexus cyst, mild pyelectasis) – Isolated markers in low‑risk population often benign. If multiple markers or high‑risk maternal age, offer NIPT or invasive testing.
5
Contingent screening strategy – Step 1: combined test (NT + biochemistry). High risk (>1/50) → CVS. Moderate risk (1/51–1/1500) → second‑trimester quadruple screen. Low risk (<1/1500) → routine care.

📋 Stepwise prenatal screening algorithm (first & second trimester)

1
First trimester (11–13⁺⁶ weeks) – Offer combined test (NT + PAPP‑A + free β‑hCG). Calculate risk for trisomy 21, 18, 13. Provide pre‑test counseling.
2
Risk stratification (combined test) – High‑risk cut‑off (e.g., 1:100 – 1:250) → offer CVS or NIPT. Low‑risk → proceed to standard care.
3
Second trimester (15–20 weeks) – Quadruple screen (AFP, β‑hCG, uE3, inhibin A) for those who missed first‑trimester screening or integrated protocol. Uterine artery Doppler for pre‑eclampsia risk.
4
Integrated screening – Combine first‑trimester NT + PAPP‑A with second‑trimester quadruple → detection rate 94–96%, false positive ~5%. Single result after second trimester.
5
Contingent screening pathway – (a) Immediate high‑risk → invasive testing. (b) Intermediate‑risk → second‑trimester markers. (c) Very low‑risk → reassurance. Efficient and reduces unnecessary amniocentesis.
6
Detailed anomaly scan (18–22 weeks) – Mandatory regardless of prior screening. Evaluate CNS, heart (4‑chamber, outflow tracts), abdomen, kidneys, spine, extremities.
⚡ Key reminder: Nuchal translucency must be measured by certified sonographers; quality control essential. Negative screening does not guarantee normal fetus.

🧠 Reflex prompts – prenatal screening high‑yield

🤰 34yo G2P0, 12 weeks: NT 4.8 mm, nasal bone present. Next step?
Offer CVS for karyotype and CMA. Detailed echocardiography. Risk for CHD ~20%, aneuploidy ~30%.
🧪 First‑trimester: PAPP‑A 0.25 MoM, β‑hCG 0.30 MoM, NT normal. Most likely aneuploidy?
Trisomy 18 (both markers low). Edwards syndrome. Often associated with structural anomalies, growth restriction.
⚠️ Integrated screening: low risk but 2nd trimester AFP 3.5 MoM. What is the concern?
Open neural tube defect (spina bifida, anencephaly). Also ventral wall defect, multiple gestation. Targeted ultrasound with spinal and cranial views.
📊 Combined test risk for Down syndrome 1:180 (cut‑off 1:250). Your recommendation?
Offer NIPT (cell‑free DNA) or CVS. Discuss advantages: NIPT higher specificity, less invasive. CVS provides diagnostic karyotype.
💡 What are the major components of the integrated test?
First trimester: NT + PAPP‑A. Second trimester: AFP, β‑hCG, uE3, inhibin A (quadruple). Result not given until 2nd trimester, but DR ~95%.
🛡️ Is diagnostic ultrasound safe for the fetus?
Yes, no confirmed harmful effects. Thermal and mechanical indices (MI/TI) kept low (ALARA). Doppler is used only when clinically indicated.