Prenatal Screening Tests: Combined Test, NIPT and the Anomaly Scan

Prenatal screening is one of the most frequently discussed aspects of antenatal care. Its purpose is to estimate the probability that a baby is affected by a chromosomal or structural condition, and to guide further investigation where needed. Screening tests do not establish a diagnosis: a high-risk result does not mean the baby is affected.

Schedule of screening tests

• 6–10 weeks: confirmation of pregnancy, fetal heart activity, and baseline blood tests (blood group, full blood count, thyroid function, infection screening).
• From 10 weeks: NIPT (cell-free fetal DNA testing) — optional, with the highest detection rate of any screening test.
• 11–14 weeks: combined test with nuchal translucency (NT) measurement, nasal bone assessment and early structural review.
• 16–18 weeks: quadruple test where the combined test was not performed, and AFP for neural tube defect screening.
• 20–22 weeks: the detailed anomaly scan.
• 24–28 weeks: oral glucose tolerance test and screening for anaemia.
• 28 weeks: anti-D immunoglobulin for rhesus-negative women.
• 35–37 weeks: group B streptococcus culture and birth planning.

The combined test and nuchal translucency

Performed between 11 weeks 0 days and 13 weeks 6 days. Maternal serum PAPP-A and free beta-hCG are measured, while ultrasound assesses nuchal translucency and crown-rump length. Together with maternal age, these produce an individual risk for trisomies 21, 18 and 13, with a detection rate of approximately 90% at a 5% false-positive rate. Adding nasal bone, ductus venosus and tricuspid flow assessment improves accuracy further.

Triple and quadruple tests

Offered between 16 and 18 weeks where the first-trimester window has been missed. The triple test measures AFP, hCG and unconjugated oestriol; the quadruple test adds inhibin A, with a detection rate of around 80%. A raised AFP additionally raises the possibility of a neural tube defect such as spina bifida.

NIPT: cell-free fetal DNA testing

Non-invasive prenatal testing analyses placenta-derived cell-free DNA circulating in maternal blood and can be carried out from 10 weeks. Detection of Down syndrome exceeds 99%, with a false-positive rate below 1 in 1000. It also reports on the sex chromosomes.

NIPT nonetheless remains a screening test: a positive result must be confirmed by amniocentesis or CVS. It does not detect structural anomalies of the heart, spine or kidneys, and therefore does not replace ultrasound screening.

The anomaly scan

At 20–22 weeks the fetal brain and spine, cardiac chambers and great vessels, face and lips, stomach, kidneys, bladder, hands and feet are examined systematically, together with placental position, amniotic fluid volume and cervical length. A substantial proportion of structural anomalies are identified at this examination.

What does a “high-risk” result mean?

Risk is expressed as a ratio. A result of 1 in 150 means that one of 150 comparable pregnancies would be affected — in other words, a 99.3% probability that this baby is unaffected. Where the result exceeds the threshold (usually 1 in 250 to 1 in 300), the options are:

• NIPT as a second-line screening test in intermediate-risk results.
• Diagnostic testing by chorionic villus sampling (CVS, 11–14 weeks) or amniocentesis (16–20 weeks).
• Detailed fetal ultrasound and, where indicated, fetal echocardiography.

In experienced centres, the pregnancy loss rate attributable to invasive testing is currently reported as approximately 1 in 300 to 1 in 1000.

Common misunderstandings

• Treating a screening result as a diagnosis and acting on it in haste.
• Missing the combined test window at 13 weeks 6 days.
• Omitting the anomaly scan because NIPT was normal.
• Undergoing several screening tests and interpreting each in isolation.

When to seek advice

• As soon as a pregnancy test is positive, for the first review at 6–8 weeks.
• Before making any decision following a screening result above the threshold.
• Where there is a family history of inherited disease or a previous affected pregnancy.
• In advanced maternal age (35 and over) or recurrent pregnancy loss.

Antenatal care in Adana

The value of screening depends on performing each test in the correct window and interpreting the results as a whole. Op. Dr. Sadık Kükrer, MD provides antenatal care, nuchal translucency measurement, detailed anomaly scanning and high-risk pregnancy management in Adana, Türkiye.