NT Scan, Double Marker and NIPT: What the Numbers Actually Mean

Almost every woman who has an NT scan or a double marker test in India is handed a report she cannot read, containing a number like “1 in 480” and a word like “screen negative”, and is left to work out from the doctor's face whether that is good news.

These are the most misunderstood reports in pregnancy. The single most important thing about all of them — the NT scan, the double marker, the quadruple marker and NIPT — is this: they are screening tests, not diagnoses. They sort pregnancies into higher and lower chance. None of them tells you whether your baby has a condition.

What these tests are trying to find

All of them look mainly for three chromosomal conditions: trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). The second-trimester blood tests also pick up open neural tube defects such as spina bifida.

They do not look for most other conditions. A normal result on every one of these tests does not mean a normal baby — it means those specific conditions are unlikely. The anomaly scan at around 20 weeks is a different test looking at structure, and it finds things these never would.

The NT scan

The nuchal translucency is a thin layer of fluid at the back of the baby's neck, present in every fetus. It is measured on ultrasound between 11 weeks and 13 weeks 6 days, when the crown-rump length is between 45 and 84 mm. Outside that window the measurement cannot be interpreted, which is why the appointment is given for a particular week rather than “sometime in the first trimester”.

A thicker measurement is associated with a higher chance of chromosomal conditions, heart defects and some genetic syndromes. On its own it is a weak test. Its value is in being combined with the blood test and your age.

The measurement that changes the conversation is 3.5 mm and above. At that level, further testing is offered regardless of what the combined risk number says, along with a detailed scan and usually a fetal heart scan, because about a third of babies with an NT of 3.5 mm or more and normal chromosomes have a structural problem. Between 3.0 and 3.4 mm the yield is much lower but not nothing.

The same scan also checks the nasal bone, the dates, the number of babies and whether the pregnancy is developing normally — which is often the most useful part of it.

The double marker

The double marker is a blood test taken in the same window, measuring two substances made by the pregnancy: free β-hCG and PAPP-A. Your levels are compared with the expected level for your week of pregnancy and expressed as MoM — multiples of the median. A MoM of 1.0 is exactly average. Those two numbers, plus the NT measurement, plus your age, are combined by software into one risk figure. That combination is what people mean by “first-trimester combined screening”.

Low PAPP-A on its own, with a normal risk number, is worth knowing about for a different reason: it is associated with a slightly higher chance of the baby growing poorly or of pre-eclampsia later, so it usually means closer monitoring rather than more genetic testing. See high blood pressure in pregnancy.

Reading the risk number

The report gives something like 1 in 480, and labels it screen negative, low risk, or screen positive. Most Indian laboratories use a cut-off around 1 in 250, though it varies, and some report a separate cut-off for trisomy 18.

The quadruple marker

If you missed the first-trimester window — which happens constantly, because women book late or the dates turn out different — the quadruple marker is the second-trimester alternative, taken between about 15 and 20 weeks. It measures four substances: AFP, hCG, unconjugated estriol and inhibin A. It is less accurate than combined first-trimester screening for Down syndrome, but it does screen for open neural tube defects, which the first-trimester tests do not.

NIPT, and why it is different

NIPT — also sold as cell-free DNA screening, or under brand names — is a maternal blood test from 10 weeks onwards. Fragments of placental DNA circulate in your blood, and the test counts them to detect an excess of a particular chromosome.

It is substantially better than the double marker at what it does:

Three honest limitations. First, it screens well for trisomy 21, 18 and 13 and not much else reliably; screening for microdeletions and copy number variants is not recommended, because the false-positive rate is unacceptable. Second, it needs enough placental DNA in the sample — the fetal fraction — and sometimes gives no result at all, which itself needs following up rather than ignoring. Third, it is a blood test, so it tells you nothing about the baby's structure; you still need the scans.

A positive result is not an answer

This is where the most harm is done. In a large study of over 17,000 pregnancies, when NIPT reported a high chance of trisomy 21, it was right about 95% of the time overall — but in women with no other risk factor, a positive result for trisomy 18 was correct only half the time, and for trisomy 13 about 62% of the time. In other words, one woman in two told her baby had Edwards syndrome was carrying a baby who did not.

No decision about a pregnancy should ever be made on a screening result alone. That is not a cautious opinion; it is the explicit position of the obstetric guidelines.

The tests that do give an answer

Chorionic villus sampling takes a sample of placenta, usually from about 11 to 14 weeks. Amniocentesis takes a small amount of fluid from around the baby, from 15 weeks. Both are done under ultrasound guidance, take a few minutes, and give a definite result on the chromosomes.

The fear attached to them is out of date. A systematic review and meta-analysis found the procedure-related risk of miscarriage to be 0.30% for amniocentesis — and when only comparable groups of women were compared, 0.12%, which was not statistically significant. The authors concluded the risk is around 1 in 300 at most, and quite possibly no measurable increase at all. For CVS the analysis found no significant procedure-related risk. Most women in India are still quoted 1 in 100.

About the sex of the baby

Under the Pre-Conception and Pre-Natal Diagnostic Techniques Act, it is illegal in India to determine or communicate the sex of a fetus, by words, signs or any other method. This applies to ultrasound and to blood tests including NIPT, and Indian laboratories mask that information on the report. Please do not ask the sonographer, the laboratory or your doctor — the request puts them at risk of prosecution and they will say no.

What happens at the clinic

Counselling about which screening is appropriate for you, interpreting the report you have already been given, and arranging the next step all happen at the clinic. Scans are arranged by referral, as is CVS or amniocentesis at a fetal medicine unit when it is needed.

If you are holding a report you do not understand, bring it. Our Decode Your Report page explains many of the individual phrases, and what is normal in the first trimester covers the rest of these weeks.