In high-risk pregnant women, noninvasive prenatal testing with the use of massively parallel sequencing of maternal plasma cell-free DNA (cfDNA testing) accurately detects fetal autosomal aneuploidy. Its performance in low-risk women is unclear.

Noninvasive prenatal testing (NIPT) using massively parallel sequencing of cell-free DNA (cfDNA) in maternal plasma has recently changed the clinical paradigm of prenatal screening for the common fetal autosomal aneuploidies (abnormal numbers of whole chromosomes).^1,2 Using this technology, the sensitivities for the detection of fetal trisomies 21 and 18 are, on average, 99% and 96%, respectively, with specificities of 99% to 100%.³ Many professional societies have recommended that NIPT can be offered to pregnant women at high risk for having a fetus with autosomal aneuploidy, with follow-up diagnostic testing recommended to confirm a positive test result.^1,4-6

Advances in DNA sequencing have facilitated a change in the method used to screen for fetal chromosome trisomies. This review describes the basis and development of the method.

Maternal plasma cell-free DNA sequencing reveals rare autosomal trisomies that are associated with perinatal complications.

BACKGROUND: Over the past 2 years, noninvasive prenatal testing (NIPT), which uses massively parallel sequencing to align and count DNA fragments floating in the plasma of pregnant women, has become integrated into prenatal care. Professional societies currently recommend offering NIPT as an advanced screen to pregnant women at high risk for fetal aneuploidy, reserving invasive diagnostic procedures for those at the very highest risk.CONTENT: In this review, we summarize the available information on autosomal and sex chromosome aneuploidy detection. Clinical performance in CLIA-certified, College of American Pathology–accredited laboratories appears to be equivalent to prior clinical validation studies, with high sensitivities and specificities and very high negative predictive values. The main impact on clinical care has been a reduction in invasive procedures. Test accuracy is affected by the fetal fraction, the percentage of fetal DNA in the total amount of circulating cell-free DNA. Fetal fraction is in turn affected by maternal body mass index, gestational age, type of aneuploidy, singleton vs multiples, and mosaicism. Three studies comparing NIPT to serum or combined screening for autosomal aneuploidy all show that NIPT has significantly lower false-positive rates (approximately 0.1%), even in all-risk populations. A significant number of the discordant positive cases have underlying biological reasons, including confined placental mosaicism, maternal mosaicism, cotwin demise, or maternal malignancy.SUMMARY: NIPT performs well as an advanced screen for whole chromosome aneuploidy. Economic considerations will likely dictate whether its use can be expanded to all risk populations and whether it can be applied routinely for the detection of subchromosome abnormalities.