Early pregnancy placental biomarkers as predictors of preeclampsia with severe features.

Introduction: Multiple studies have evaluated late second and third trimester values for soluble Fms-like tyrosine kinase 1 (sFlt-1), placental-like growth factor (PlGF), and sFlt-1:PlGF ratio for preeclampsia risk stratification, but few studies have assessed sFlt-1:PlGF ratio earlier in pregnancy. Objective: To investigate the utility of early pregnancy sFlt-1:PlGF ratio for predicting preeclampsia with severe features, and to compare its predictive ability with that of the United States Preventive Services Task Force (USPSTF) risk assessment algorithm. Methods: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). Of 10,038 participants, 1977 (enriched for adverse outcomes) had blood, which had been drawn at the first (6w0d-13w6d) and second (16w0d-21w6d) visits, assayed for sFlt-1 and PlGF, allowing for the calculation of sFlt-1:PlGF ratios from both visits as well as the change between visits. The primary outcome for this analysis was preeclampsia with severe features. The predictive ability of the sFlt-1:PlGF ratio was compared to that of the USPSTF risk assessment algorithm using area under the receiver operating characteristic curves (AUROC). Youden indexes were used to identify optimal sFlt-1:PlGF ratio cut-points. The predictive characteristics of these cut-points were compared to those of a positive USPSTF risk assessment result. Results: Preeclampsia with severe features was diagnosed in 240 (12.1%) eligible participants, among whom the mean gestational age at delivery was 36w0d. The optimal sFlt-1:PlGF ratio for predicting this outcome was 19.1 at visit 1, 6.2 at visit 2, and a decrease of 15.0 between visits. The sFlt-1:PlGF ratio was inferior to the USPSTF risk assessment algorithm in predicting this diagnosis (AUROC: 0.51-0.60 vs. 0.60, Conclusions: Early pregnancy sFLt-1:PlGF ratio is a poor risk assessment tool for preeclampsia with severe features.