Aneuploidy Screening: Newer Noninvasive Test Gains Traction

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Both the CARE and NEXT studies had limitations. They compared cfDNA testing with first- or second-trimester screening and did not evaluate integrated screening methods (sequential first- and second-trimester biomarkers plus first-trimester nuchal translucency), which have a slightly higher sensitivity and specificity than first-trimester screening alone.

Multiple companies offer cfDNA, and the test is not subject to FDA approval. The CARE and NEXT studies used tests from companies that provided funding for these studies and employ several of the study authors.

Although cfDNA has increased specificity compared to standard screening, there have been case reports of false-negative results. Further testing has shown that such false-negative results could be caused by mosaicism in either the fetus and/or placenta, vanishing twins, or maternal malig­nancies.8-10

In the CARE and NEXT trials, cfDNA produced no results in 0.9% and 3% of women, respectively. Patients for whom cfDNA testing yields no results have higher rates of aneuploidy, and therefore require further diagnostic testing.

Because the prevalence of aneuploidy is lower in the general obstetric population than it is among women whose pregnancies are at high risk for aneuploidy, the PPV of cfDNA testing is also lower in the general obstetric population. This means that there are more false-positive results for women at lower risk for aneuploidy. Therefore, it is imperative that women with positive cfDNA tests receive follow-up diagnostic testing, such as chorionic villus sampling or amniocentesis, before making a decision about termination.

All commercially available cfDNA tests have high sensitivity and specificity for trisomy 21, 18, and 13. Some offer testing for sex chromosome abnormalities and microdeletions. However, current cfDNA testing methods are unable to detect up to 17% of other clinically significant chromosomal abnormalities,11and cfDNA cannot detect neural tube or ventral wall defects. Therefore, ACOG and SMFM recommend that women who choose cfDNA as their ­aneuploidy screening method also be offered maternal serum alpha-fetoprotein or ultrasound evaluation.

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