he screening performance of cell-free DNA is excellent. In a metaanalysis of 37 studies of largely high-risk pregnancies, the pooled sensitivity to detect Down syndrome was 99 percent, and for trisomies 18 and 13, 96 percent and 91 percent, respectively. For each of these autosomal trisomies, the speciicity was 99.9 percent. Thus, most unafected pregnancies received a norml screening result. Cell-free DNA also detects 90 percent with Turner syndrome (45,X) and 93 percent with sex chromosome aneuploidies other than 45,X (Gil, 2015). The false-positive rate is cumulative for each aneuploidy for which screening is performed, but it is usually only 0.5 to 1 percent. s a result, cell-free DNA screening is recommended as a screening option in those at increased risk for fetal autosomal trisomy (American College of Obstetricians and Gynecologists, 2017c; Society for MaternalFetal Medicine, 2015). This includes the following categories: 1.
2.
3.
Sonogram with a minor aneuploidy marker 4.
Prior pregnancy with autosomal trisomy 5.
Known carriage (patient or partner) of a balanced robertsonian translocation involving chromosome 21 or 13.
If cell-free DNA screening is performed as a seconday screen following a positive irst-or second-trimester analyte-based test result, a normal result is not quite as reassuring. The residual risk for chromosomal abnormality is estimated to be 2 percent (Norton, 2014). Compared with amniocentesis, use of cellfree DNA screening after an initial abnormal analyte-based test result is estimated to yield a 20-percent reduction in aneuploidy diagnoses. his takes into consideration false-negative diagnoses and aneuploidies not detectable with cell-free DNA screening (Davis, 2014; Norton, 2014). In addition, definitive diagnosis may be delayed, potentially afecting management. Concurrent or parallel screening is not recommended, and if an aneuploidy screening test of any type yields a negative result, additional screening is not indicated (American College of Obstetricians and Gynecologists, 2016b, 2017c).
he association between increased NT values and fetal structural and genetic abnormalities has raised questions about the role of a NT measurements following cell-free DNA screening. he College (20 16b) has stated that NT measurement is not necessary at the time of cell-free DNA screening but that sonography may help to conirm fetal number and viability and to assign gestational age. he Society for Maternal-Fetal Medicine (20i15) states that after a negative cell-free DNA screening test result, the additional clinical utility of NT measurement to detect other chromosomal or structural abnormalities is unknown but appears to be limited.
Most studies of cell-free DNA have been conducted in highrisk pregnancies. Pragmatically, chromosomal abnormalities are individually so rare that even large studies of low-risk pregnancies contain few afected cases. Available data suggest that the high sensitivity and speciicity for Down syndrome detection are preserved in low-risk pregnancies (Norton, 2015; Pergament, 2014; Zhang, 2015). Importantly, the positive-predictive value of cell-free DNA screening still depends greatly on maternal age and the specific aneuploidy in question (see Table 14-5). For a woman in her early 20s, the positive-predictive value is approximately 50 percent for fetal trisomy 21, 15 percent for trisomy 18, and < 10 percent for trisomy 13. Hence, decisions for irreversible medical intervention should not be based on the results of this or other screening test alone.
Important caveats are considered with selection of cell-free