Fetal Aneuploidy: Screening and Diagnostic Testing

Aneuploidy is the presence of one or more extra chromosomes or the absence of one or more chromosomes. The risk of fetal aneuploidy rises with increasing maternal age. Because fetal aneuploidy can affect any pregnancy, all pregnant women should be offered screening. First-trimester combined screening performed between 10 and 13 weeks' gestation detects 82% to 87% of trisomy 21 (Down syndrome) cases. Second-trimester serum quadruple screening performed between 15 and 22 weeks' gestation detects 81% of trisomy 21 cases. Combinations of these tests include integrated or serum integrated, stepwise sequential, and contingent sequential screenings, all of which improve detection rates compared with each test alone. Fetal cell-free DNA testing (noninvasive prenatal testing) performed at or after 10 weeks' gestation detects more than 99% of trisomy 21 cases, with a lower false-positive rate than traditional first- or second-trimester screening methods. Fetal cell-free DNA testing has similar detection rates in high- and low-risk populations but has lower positive predictive values in younger women. It may be performed as primary screening or as a follow-up test to abnormal findings on first- or second-trimester screenings. Second-trimester ultrasonography has limited utility in aneuploidy screening in women who have already been screened with a first- or second-trimester serum test. Diagnostic tests following a positive screening result include chorionic villus sampling performed between 10 and 13 weeks' gestation or amniocentesis performed after 15 weeks' gestation.