SWARAJ HOSPITAL & RESEARCH INSTITUTE

BOLANGIR, ODISHA  •  OBSTETRICS & GYNAECOLOGY CLINICAL PATHWAY SERIES

Clinician Reference Infographic

Genetic Screening and NIPT

Genetic screening gives a chance, not a diagnosis, and non-invasive prenatal testing (NIPT) is its most accurate form for common chromosome conditions. This guide covers carrier screening, screening test options, how NIPT works, what to do with the result, and counselling and the law, using the GENES approach.

🎯 AT A GLANCE — GENETIC SCREENING AND NIPT

Genetic screening estimates the chance of a condition; diagnostic testing (chorionic villus sampling or amniocentesis) confirms it

Non-invasive prenatal testing (NIPT) measures cell-free DNA in the mother’s blood; it can be done from 10 weeks and carries no risk of miscarriage

For Down syndrome it detects over 99% with a false-positive rate under 0.1–0.5%, better than the combined test or quadruple test

NIPT is still a screening test: a positive result needs confirmation by a diagnostic test before any decision about the pregnancy

In western Odisha, screening for sickle cell disease and thalassaemia at booking, with partner testing, is the most useful genetic screening and should never be missed

NIPT is a screening test, so say “chance”, not “diagnosis”, and keep fetal sex undisclosed as the PCPNDT Act requires

🚨 DO NOT MISS

High-chance NIPT result — never advise termination on NIPT alone; offer chorionic villus sampling or amniocentesis, with a genetic counsellor

No result (low fetal fraction) — do not simply reassure; it can be linked to trisomy 13 or 18 or triploidy, so counsel and consider a diagnostic test

Abnormal anomaly scan or thick nuchal translucency (3.5 mm or more) with a low-chance NIPT — offer a diagnostic test with microarray

Both parents carriers of sickle cell, beta-thalassaemia, or the same condition — offer early prenatal diagnosis by chorionic villus sampling at 11–13 weeks

Any request to disclose or hint at fetal sex — refuse; it is prohibited by the PCPNDT Act

🗺️ THE PATHWAY AT A GLANCE

1 · Before or at bookingFamily history, consanguinity, previous affected child; carrier screening (HPLC for haemoglobinopathies) for both partners

2 · CounsellingExplain what screening can and cannot tell; written consent

3 · 10–14 weeksNIPT (from 10 weeks), or combined test (nuchal translucency, PAPP-A, free beta-hCG at 11–13+6 weeks)

4 · 15–20 weeksQuadruple test if first-trimester screening was missed

5 · 18–22 weeksDetailed anomaly scan for every woman

6 · High chanceChorionic villus sampling (11–14 weeks) or amniocentesis (from 15 weeks), then genetic counselling

STEP 1 · UNDERSTAND GENETIC SCREENING — what is offered and when

🧬 TYPES OF GENETIC SCREENING

Type	What it does
Carrier screening	Finds healthy people who carry a gene change; in India, HPLC for sickle cell and beta-thalassaemia is the key test, and the partner should be tested if the woman is a carrier
Aneuploidy screening	Estimates the chance of trisomy 21, 18, or 13 (combined test, quadruple test, or NIPT)
Structural screening	Anomaly scan at 18–22 weeks finds many major anomalies; it is offered to all
Diagnostic testing	Chorionic villus sampling or amniocentesis with karyotype or chromosomal microarray gives a definite answer for chromosome conditions
Who should be offered	Every pregnant woman should be offered screening; women with higher risk (age 35 or over, previous affected pregnancy, abnormal scan, family history) are offered diagnostic testing directly

STEP 2 · COMPARE THE SCREENING TESTS — choose with the woman

🧪 SCREENING OPTIONS FOR DOWN SYNDROME

Test	Timing	Approximate detection for trisomy 21
Combined first-trimester test	11–13+6 weeks	About 85–90% at a 5% false-positive rate; nuchal translucency, PAPP-A, free beta-hCG, and maternal age
Quadruple test	15–20 weeks	About 80% at a 5% false-positive rate; AFP, hCG, uE3, inhibin A
NIPT (cell-free DNA)	From 10 weeks	Over 99% with a false-positive rate under 0.1–0.5%
Contingent approach	Combined test first, NIPT only for the intermediate-risk group	Lower cost, with most of the benefit of NIPT
Practical point	Where NIPT is unaffordable	The combined test with a good nuchal translucency scan remains a sound choice

Detection rates are from studies of single pregnancies and vary with the laboratory; read the performance stated in your laboratory’s report

STEP 3 · KNOW NIPT IN DETAIL — how it works and what it can and cannot do

🩸 NON-INVASIVE PRENATAL TESTING

Topic	Details
How it works	Cell-free DNA in the mother’s blood comes mainly from the placenta (fetal fraction about 4–10% or more, from 10 weeks); the laboratory counts chromosome fragments to find extra or missing copies
Sample	One blood tube from the mother; no fasting; result in about 1–2 weeks
What it screens	Trisomy 21, 18, and 13; some laboratories add sex chromosome conditions and selected microdeletions, which are less reliable
What it does not find	Single gene conditions, structural anomalies, neural tube defects, most small deletions, and mosaicism that is confined to the placenta
Positive predictive value	Depends on how common the condition is: for trisomy 21 it is high in older women, but lower in young women, and lower again for trisomy 13 and 18 and sex chromosome conditions (about 50–60% at age 25 and over 90% at age 40 for Down syndrome; approximate)
Causes of a false result	Confined placental mosaicism, a vanished twin, maternal chromosome change, maternal cancer, organ transplant, recent blood transfusion, or low fetal fraction
Twins and IVF	Can be used in twins for trisomy 21 with slightly lower accuracy; not suitable after donor egg from a different woman without advice, or with a vanished twin
No result	Occurs in about 1–5%; more often with higher maternal weight or early sampling; repeat once if the fetal fraction is low, and offer other testing if it fails again

Scientific bodies (ACOG, ACMG) now support offering NIPT to all pregnant women, but a screening test must always be paired with counselling and diagnostic confirmation (recommendations differ between countries)

STEP 4 · ACT ON THE RESULT — what to do next

📋 RESULT AND ACTION

Result	What to do
Low chance	Reassure that the chance is very low but not zero; continue the anomaly scan and routine care
High chance	Counsel the same day, offer chorionic villus sampling (11–14 weeks) or amniocentesis (from 15 weeks); the woman decides whether to proceed
No result	Review dating and weight, repeat once, and offer a scan review or diagnostic test
Discordant findings	Normal NIPT with abnormal scan means diagnostic testing with microarray
Diagnostic procedure	Karyotype and, where available, chromosomal microarray; fetal loss risk is low (about 0.1–0.3% or less), done by an experienced operator under ultrasound
After a procedure	Anti-D immunoglobulin to Rh-negative women; advise rest for the day and warning signs (bleeding, fluid loss, fever)
Confirmed abnormality	Refer to a fetal medicine or genetic team; discuss outcome, options, and support

STEP 5 · COUNSEL, CONSENT AND THE LAW — do it properly

💬 COUNSELLING AND LEGAL POINTS

Topic	Advice
Counselling before testing	Explain what is tested and what is not; that the result is a chance; the possible results; cost; and the right to decline
Counselling style	Non-directive, in a language she understands, and with her partner if she wishes
Consent	Written, informed consent before NIPT and before any invasive test
PCPNDT Act	Sex determination and disclosure are prohibited; testing should be done in registered centres and laboratories, with the required forms; laboratories must not report fetal sex (check the current rules and your laboratory’s policy)
MTP Act	Termination is lawful within the limits of the Medical Termination of Pregnancy Act (as amended in 2021); beyond the usual limit, a medical board decides for substantial fetal abnormality (confirm the current provisions)
Privacy	Keep results confidential; share only with the woman unless she agrees
Support	Offer follow-up counselling, and a team for care of a child with Down syndrome if she continues

⚠️ COMMON PITFALLS

Calling NIPT a diagnostic test and advising termination on it alone

Skipping the anomaly scan because the NIPT was normal

Missing carrier screening for sickle cell and thalassaemia and not testing the partner

Sending blood too early (before 10 weeks) or without confirming dates

Reading a sex chromosome result without counselling or disclosing fetal sex

Offering the tests without pre-test counselling or without consent

Forgetting anti-D after a diagnostic procedure in an Rh-negative woman

Memory Aid

GENES

Five steps for genetic screening and NIPT.

G

Gather the history — family history, consanguinity, carrier screening for both partners

E

Explain — screening gives a chance; diagnosis gives an answer

N

NIPT or combined test — NIPT from 10 weeks; nuchal translucency at 11–13+6 weeks

E

Establish the diagnosis — chorionic villus sampling or amniocentesis if the chance is high

S

Support and stay within the law — non-directive counselling, PCPNDT and MTP Acts

Remember: NIPT screens, it does not diagnose; confirm before acting, and never disclose fetal sex.

Swaraj Hospital & Research Institute · Department of Obstetrics & Gynaecology, Bolangir, Odisha

Clinician-facing summary drawn from memory of guidance from the American College of Obstetricians and Gynecologists (ACOG), the American College of Medical Genetics and Genomics (ACMG), the International Society for Prenatal Diagnosis, the Fetal Medicine Foundation, and Indian law and practice; no source was read for this sheet. Performance figures, predictive values, and timing are approximate and vary between laboratories and studies. The PCPNDT Act and MTP Act points are from memory: check the current Acts, rules, and your laboratory’s policy. Test choice and result handling must be set by the senior obstetrician with a genetic counsellor; thresholds, intervals and regimens vary between guidelines — follow local protocol and involve a senior obstetrician in any high-risk case.