Prenatal genetic testing has expanded rapidly, and the range of options can be confusing. The most important distinction is between screening tests, which estimate a chance, and diagnostic tests, which give a definitive answer.
Screening Tests
First-trimester combined screening uses maternal age, nuchal translucency measurement and maternal serum markers to calculate the chance of trisomy 21, 18 and 13. It detects around 85 to 90% of pregnancies with trisomy 21, with a false-positive rate of about 5%.
Non-invasive prenatal testing (NIPT) analyses cell-free DNA in maternal blood, which is derived largely from the placenta. It detects more than 99% of trisomy 21 pregnancies with a false-positive rate well below 1%, making it the most accurate screening test available.
Why Screening is not Diagnosis
Even a highly accurate screening test has a positive predictive value that depends on how common the condition is in the population being tested. In younger women, where trisomies are less common, a larger proportion of high-chance results are false positives. In addition, cell-free DNA comes from the placenta, which does not always have the same chromosomes as the fetus. This is known as confined placental mosaicism.
For these reasons, a high-chance NIPT result should always be confirmed by a diagnostic test before any decision is made about the pregnancy.
Diagnostic Tests
Diagnostic testing analyses fetal cells obtained by chorionic villus sampling or amniocentesis. QF-PCR gives a rapid result for the common aneuploidies, chromosomal microarray detects submicroscopic deletions and duplications, and karyotyping detects balanced rearrangements. Amniocentesis is preferred to confirm a high-chance NIPT result for trisomy 13 or 18, or for sex chromosome aneuploidy, because these are more often associated with placental mosaicism.
When Ultrasound Shows an Anomaly
NIPT is not the right test when ultrasound shows a fetal structural anomaly. Many of the chromosomal causes of anomalies are not detected by NIPT. In this situation, invasive testing with QF-PCR and chromosomal microarray is recommended.