Pregnancy outcomes in nulliparous women with positive first-trimester preterm preeclampsia screening test: The Great Obstetrical Syndromes (GOS) cohort study

Background: The Fetal Medicine Foundation (FMF) proposed a competing risks model for early identification of women at high risk of preterm preeclampsia, typically associated with deep placentation disorders. The Great Obstetrical Syndromes include a spectrum of pregnancy complications (preeclampsia, intrauterine growth restriction, preterm birth, late spontaneous abortion, and abruptio placentae) that are also associated with deep placentation disorders.

Objective: To estimate the rate of placenta-mediated pregnancy complications in nulliparous women with a positive first-trimester FMF preterm preeclampsia screening test.

Study design: We conducted a prospective cohort study of nulliparous women recruited at 11-14 weeks of gestation. Maternal characteristics, mean arterial blood pressure, levels of maternal serum biomarkers [pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)] and mean uterine artery pulsatility index were obtained to calculate the risk of preterm preeclampsia according to the FMF algorithm. The predicted risks were dichotomised as a positive or negative test according to two risk cut-offs (1 in 70 and 1 in 100). The detection rate, false-positive rate, and positive and negative predictive values were calculated for placenta-mediated complications, including preeclampsia, small for gestational age (birthweight <10^th centile), fetal death, preterm birth and a composite outcome including any of the foregoing. The same analyses were computed for a composite of severe outcomes including preterm preeclampsia, severe small for gestational age (<3^rd centile), and fetal death.

Results: We included 4,575 participants with complete observations, of which 494 (10.8%) had an estimated risk of preterm preeclampsia ≥1 in 70 and 728 (15.9%) had a risk ≥1 in 100. The test based on a risk cut-off of 1 in 70 could have correctly predicted up to 27% of preeclampsia, 55% of preterm preeclampsia, 18% of small for gestational age, 24% of severe small for gestational age, and 37% of fetal deaths at a 10% false-positive rate. The test based on a cut-off of 1 in 100 could have predicted correctly up to 35% of preeclampsia, 69% of preterm preeclampsia, 25% of small for gestational age, 30% of severe small for gestational age, and 53% of fetal deaths at a 15% false-positive rate. The positive predictive value of a screening test for preterm preeclampsia ≥1 in 70, was 3% for preterm preeclampsia, 32% for the composite outcome and 9% for the severe composite outcome.

Conclusions: Nulliparous women with a first-trimester positive preterm preeclampsia FMF screening tests are at higher risk of both preterm preeclampsia, and other severe placenta-mediated pregnancy complications. Approximately 1 women out of 10 identified as high-risk by the FMF algorithm developed at least one severe placenta-mediated pregnancy complication.

Keywords: fetal death; fetal growth restriction; placenta-mediated complications; preeclampsia; preterm birth; risk assessment; screening; small for gestational age; validation.