How NIPT works
During pregnancy, small fragments of DNA from the placenta circulate in the mother's blood, and NIPT measures these cell-free DNA fragments. RANZCOG's 2024 guideline states that NIPT is a highly accurate screening test for trisomies 21, 18 and 13 in singleton pregnancies from 10 weeks of gestation, and it advises an early ultrasound before NIPT to confirm dating, identify multiple pregnancy and confirm a live fetus. In the United States, the American College of Medical Genetics and Genomics (ACMG) recommends NIPT over traditional screening methods for trisomies 21, 18 and 13 in singleton and twin pregnancies.
What expanded NIPT adds
Expanded NIPT panels add other conditions: sex chromosome aneuploidies such as Turner or Klinefelter syndrome, rare autosomal trisomies involving other chromosomes, and copy number variants, which are missing or extra segments of a chromosome such as the 22q11.2 deletion. RANZCOG considers screening for sex chromosome aneuploidies accurate enough to offer with specific counselling and consent, but finds expanded NIPT for rare autosomal trisomies and copy number variants not accurate enough to be offered routinely to all women. ACMG conditionally recommends offering screening for 22q11.2 deletion syndrome. Expanded testing has a higher false positive rate and can reveal unexpected findings, including previously unknown conditions in the mother.
A screening test, not a diagnosis
NIPT reports a high chance or low chance result. Because the DNA comes mainly from the placenta, a chromosome change confined to the placenta (confined placental mosaicism) can cause a false positive result. A low chance result does not exclude all genetic conditions, and false negatives can occur. RANZCOG recommends that anyone with a high chance result is offered diagnostic confirmation before any further management decisions. Diagnostic testing uses chorionic villus sampling (CVS) or amniocentesis, which provide diagnostic testing for the targeted chromosome condition, although further interpretation is sometimes needed, and the risks of pregnancy loss after the two procedures are not substantially different.
When no result is returned
Between 1% and 6% of NIPT tests performed after 10 weeks fail to give a result, most often because the fetal fraction, the amount of placental DNA in the sample, is too low. A body mass index above 30 can increase this chance. Because women with a no-call result have a higher rate of some fetal chromosome conditions, they should have follow-up assessment including detailed ultrasound, and be offered repeat NIPT (successful in about half of cases), diagnostic testing or another form of screening.
Why regulated test quality matters
NIPT combines laboratory reagents, an analysis platform and software that calculates the result, and the platforms in use differ. RANZCOG advises health professionals to understand the scope, capabilities and limitations of the specific test they offer. In Australia, the Therapeutic Goods Administration (TGA) assesses in vitro diagnostic devices for safety and performance, and unless exempt or excluded they must be included in the Australian Register of Therapeutic Goods before they can be legally supplied. Products in the research phase are labelled for research use only and are not intended for diagnosis; United States regulations require them to carry the statement "For Research Use Only. Not for use in diagnostic procedures." Clinicians and families can ask whether a prenatal screening test is approved for clinical use in the country where it is performed.