# Prenatal Screening Pathology > Prenatal screening in MBBS Pathology: NT scan, double, triple and quadruple tests, NIPT, diagnostic CVS and amniocentesis, and the PCPNDT Act. - Canonical URL: https://prepelephant.com/topics/mbbs/pathology/prenatal-screening-pathology - Exam / course: MBBS · Subject: Pathology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Prenatal Screening Pathology", PrepElephant, https://prepelephant.com/topics/mbbs/pathology/prenatal-screening-pathology ## Direct answer Screening tests estimate risk; diagnostic tests establish it — the first sentence of every antenatal-testing answer. First-trimester combined screening pairs nuchal translucency on ultrasound (11-13 weeks 6 days, crown-rump 45-84 millimetres) with serum PAPP-A (low) and free beta-hCG (high) — the double marker — detecting most Down syndrome pregnancies; the second-trimester triple test (AFP, unconjugated oestriol, hCG) and the quadruple (adding inhibin A) cover those who book late. Cell-free fetal DNA (NIPT) screens at above 99 per cent sensitivity for trisomy 21 from ten weeks but remains a screening test; definitive diagnosis requires chorionic villus sampling at 11-14 weeks or amniocentesis after 15 weeks with karyotype or chromosomal microarray. In India, all of it operates under the PCPNDT Act, 1994, which prohibits determination and disclosure of fetal sex. ## What you must remember - **Marker patterns for trisomy 21:** low AFP, low unconjugated oestriol, high hCG, high inhibin A — a four-analyte melody worth memorising; trisomy 18 shows all four analytes low. - **First-trimester package:** nuchal translucency above 3.5 millimetres raises aneuploidy risk and, if karyotype is normal, congenital heart disease risk justifying fetal echocardiography; nasal bone, ductus venosus flow and tricuspid regurgitation add discrimination. - **Open neural tube defect:** maternal serum AFP high, with acetylcholinesterase in amniotic fluid confirming an open defect; the anomaly scan closes the loop. - **Diagnostic tests with their windows and risks:** chorionic villus sampling at 11-14 weeks (placental karyotype, earlier result, small fetoplacental mosaicism risk, procedure-related loss around 1-2 per cent); amniocentesis after 15 weeks (fetal cells from amniotic fluid, loss under 1 per cent); both now often coupled with rapid FISH or QF-PCR and chromosomal microarray, which also detects submicroscopic copy-number changes. - **NIPT caveats:** a screening test needing diagnostic confirmation; results are confounded by placental mosaicism, vanishing twin, maternal malignancy and low fetal fraction (high BMI, early sampling); it screens 21, 18, 13 and sex-chromosome aneuploidy best. - **Thalassaemia screening — the Indian dimension:** in a country with a large beta-thalassaemia burden, carrier screening by HPLC (haemoglobin A2 of 3.5 per cent or more) for couples, with prenatal diagnosis by CVS for at-risk pairs, is routine genetic-prevention practice — more relevant to Indian exams than any Western panel. - **The PCPNDT Act, 1994:** regulates genetic clinics and prohibits sex determination and disclosure to combat female foeticide — the legal frame within which every Indian prenatal test is performed; a favoured medico-social viva point. ## Interpreting a screen-positive triple test A 27-year-old at 17 weeks has a triple test reporting a Down syndrome risk of 1 in 150; she is anxious and eight weeks from her anomaly scan. Step one is validation: was the sample dated correctly, and does the dating scan agree with her dates? A misdated pregnancy is the commonest source of false positives. Step two interprets the pattern, not the ratio: low AFP and oestriol with high hCG raise trisomy 21 risk; a very high AFP redirects the search to open neural tube defects or abdominal wall defects, with acetylcholinesterase in amniotic fluid as the discriminator. Step three offers choice — NIPT as a secondary screen, or straight to amniocentesis for a definitive karyotype with microarray. Step four supports the result whatever it is: a negative NIPT reduces risk substantially but does not remove the need for the anomaly scan; a positive report makes diagnostic testing mandatory. The architecture — validate, interpret pattern, offer tiered testing, counsel — is the same for every antenatal screen. ## Where students slip Calling NIPT diagnostic loses the mark every time; it is a highly sensitive screen on placental DNA, and discordance with the fetus, though rare, is real. The second error is reading the triple test as one number: the pattern of its four (or three) analytes points to different conditions, and pattern-reading is the examiner's actual question. Remember timing windows — CVS before amniocentesis in the calendar, both with FISH for rapid aneuploidy. And the PCPNDT answer must be precise: the Act prohibits sex determination and disclosure; it does not prohibit legitimate aneuploidy or metabolic testing. ## Frequently asked questions ### What constitutes first-trimester combined screening? Nuchal translucency ultrasound at 11-13 weeks 6 days plus serum PAPP-A and free beta-hCG — the double marker — with detection of most trisomy 21 pregnancies. ### Which marker pattern suggests open neural tube defect? Elevated maternal serum alpha-fetoprotein, with acetylcholinesterase in amniotic fluid supporting an open lesion on confirmative testing. ### Why is NIPT not diagnostic? It analyses placental cell-free DNA, which can disagree with the fetal genome through confined placental mosaicism or maternal factors; abnormal results need CVS or amniocentesis. ### When are chorionic villus sampling and amniocentesis performed? CVS at 11-14 weeks on placental tissue; amniocentesis after 15 weeks on amniotic-fluid fetal cells — both with procedure-related miscarriage risk around or below 1-2 per cent. ### What does the PCPNDT Act regulate? It prohibits prenatal sex determination and disclosure in India, registering and monitoring genetic laboratories to counter female foeticide.