PAPP‐A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia

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.