BACKGROUND: We aimed to evaluate the value of inhibin A and PAPP-A2 (pregnancy-associated plasma protein-A2) as novel biomarkers in the prediction of preeclampsia-related complications and how they compare with angiogenic biomarkers. METHODS AND RESULTS: Making use of a secondary analysis of a prospective, multicenter, observational study, intended to evaluate the usefulness of sFlt-1 (soluble Fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio, we measured inhibin A and PAPP-A2 levels in 524 women with suspected/confirmed preeclampsia. Women had a median gestational age of 35 weeks (range, 20–41 weeks) while preeclampsia occurred in 170 (32%) women. Levels of inhibin A and PAPP-A2 were significantly increased in women with preeclampsia and in maternal perfusate of preeclamptic placentas. Inhibin A and PAPP-A2 (C-index = 0.73 and 0.75) significantly improved the prediction of maternal complications when added on top of the traditional criteria; gestational age, parity, proteinuria, and diastolic blood pressure (C-index = 0.60). PAPP-A2 was able to improve the C-index from 0.75 to 0.77 when added on top of the sFlt-1/PlGF ratio for the prediction of maternal complications. To discriminate fetal/neonatal complications on top of traditional criteria, inhibin A and PAPP-A2 showed additive value (C-index = 0.79 to 0.80 and 0.82, respectively) but their discriminative ability remained inferior to that of sFlt-1/PlGF ratio or PlGF. Interestingly, the PAPP-A2/PlGF ratio alone showed remarkable value to predict pregnancy complications, being superior to sFlt-1/PlGF ratio in the case of maternal complications. CONCLUSIONS: Inhibin A and PAPP-A2 show significant potential to predict preeclampsia-related pregnancy complications and might prove beneficial on top of the angiogenic markers.

inhibin A ■ sFlt-1 ■ PlGF ■ preeclampsia ■ PAPP-A2,
Department of General Practice

Neuman, R.I., van Meer, M.M.P., Nieboer, D, Saleh, L, Verdonk, K, Kalra, B, … Danser, A.H.J. (2020). PAPP-A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia. Stroke, 9(19). doi:10.1161/jaha.120.018219