The role of the first trimester screen in the face of normal cell free DNA

There is no consensus for the method of aneuploidy screening in pregnancy. Cell free DNA (cfDNA) is the most sensitive screen for trisomies 21, 13, and 18, however the first trimester screen (FTS) is a marker for other adverse outcomes, such as structural anomalies, growth restriction, and preeclampsia. In 2019, we offered FTS (nuchal translucency (NT) and analytes) with or without cfDNA. The purpose of this study was to assess clinical relevance of abnormal FTS in women with normal cfDNA.

We retrospectively reviewed women undergoing screening in our Fetal Evaluation Unit in 2019. Women included had normal cfDNA and abnormal FTS; consisting of NT >95%, PAPP-A < 0.4 MoM, beta-HCG >2.5 MoM, or overall increased risk of trisomies.

195 patients had abnormal FTS and normal cfDNA. 41 (21%) had adverse maternal outcomes including hypertension, abnormal placentation, and placental abruption. 34 (17%) had adverse fetal outcomes including growth restriction, structural anomalies, fetal demise, polyhydramnios, previable PPROM, necrotizing enterocolitis after a preterm birth, and a balanced translocation.

Abnormal FTS predicts adverse outcomes in 33% of women with normal cfDNA. Our data suggests that offering universal FTS with cfDNA may have clinical benefit.