Modified multiple marker aneuploidy screening as a primary screening test for preeclampsia: A validation study

Our previous case-controlled study indicates that the combination of maternal characteristics, serum placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) can predict early-onset and preterm preeclampsia with reasonable accuracy. This study aims to validate whether our preeclampsia screening algorithm can be applied to a large general obstetric population by using serum markers obtained from routine aneuploidy screening.

This retrospective cohort study analyzed maternal characteristics, serum markers, and pregnancy outcomes from pregnant individuals who underwent enhanced first-trimester screening and delivered at a Toronto tertiary center between December 2017 and June 2021.

Logistic regression was used to assess prediction accuracy and compare screening performance with algorithm from our previous case-control study. The multiple of the median (MoM) of serum markers were compared between cases and controls using Mann-Whitney U tests.

The study included 340 preeclampsia cases (15 delivered < 34 weeks, 77 delivered < 37 weeks and 263 delivered ≥ 37 weeks) and 10,145 controls. Preeclampsia cases had significantly lower MoM of PlGF (0.83 vs 1.02) and PAPP-A (0.89 vs 1.07) (p < 0.0001 for both). At a 20 % false-positive rate, 80 % of early-onset, 68 % of preterm, and 58 % of term preeclampsia cases could be predicted using maternal characteristics and serum markers. Applying our previously developed algorithm achieved a comparable accuracy in this population.

Our findings support expanding multiple marker aneuploidy screening to include accurate, cost-effective preeclampsia risk prediction, enabling early intervention for high-risk pregnant individuals.