Maternal Serum Inhibin-A Augments the Value of Maternal Serum PlGF and of sFlt-1/PlGF Ratio in the Prediction of Preeclampsia and/or FGR Near Delivery—A Secondary Analysis

Adi Sharabi-Nov,Vesna Fabjan Vodušek,Tanja Premru Sršen,Kristina Kumer,Hamutal Meiri,Teja Fabjan,Joško Osredkar,Nataša Tul,Kypros H Nicolaides

doi:10.3390/reprodmed2010005

Abstract

Objective: We previously provided evidence to confirm that maternal serum levels of soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this secondary analysis, we further examine the potential additive value of maternal serum Inhibin-A, which is a hormone marker of the transforming growth factor family, to the accuracy provided by maternal serum PlGF and sFlt-1. Methods: We conducted a secondary analysis where we extracted the data of a cohort of 125 pregnant women enrolled near delivery at the clinics of the University Medical Center of Ljubljana, Slovenia. The dataset included 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 10 of PE, 12 of FGR, 28 of PE+FGR, and 6 of PTD. In addition to the recorded demographic characteristics and medical history and the maternal serum levels of PlGF and sFlt-1/PlGF ratio, which were previously published, we evaluated the added value of maternal serum Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations were estimated from areas under the curve (AUC) of receiver operating characteristics (ROC) curves, Box and Whisker plots, and by multiple regression. We estimated accuracy by the continuous marker model and a cutoff model. Results: In this study, we combined Inhibin-A with PlGF or with the sFlt-1/PlGF ratio and showed a 10–20% increase in AUCs and 15–45% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR and FGR in all cases but not for FGR in early cases delivered < 34 weeks. The use of a cutoff model was adequate, although a bit higher accuracy was obtained from the continuous model. The highest correlation was found for PlGF with all three complications. Conclusion: In this secondary analysis, we have found that maternal serum Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by maternal serum angiogenic markers alone, bringing the results to a diagnostic level; thus, it could be considered for directing clinical management. Inhibin-A had smaller or no added value for the accuracy of predicting FGR alone, mainly of early cases delivered <34 weeks.

Highlights

Preeclampsia (PE) is a major pregnancy disorder unique to pregnancy that is associated with new-onset hypertension, which occurs most often after 20 weeks of gestation and frequently near term
Objective: We previously provided evidence to confirm that maternal serum levels of soluble Fms-like tyrosine kinase-1, placental growth factor (PlGF), and their ratio are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery
We further examine the potential additive value of maternal serum Inhibin-A, which is a hormone marker of the transforming growth factor family, to the accuracy provided by maternal serum PlGF and soluble Fms-like tyrosine kinase-1 (sFlt-1)

Summary

Introduction

Preeclampsia (PE) is a major pregnancy disorder unique to pregnancy that is associated with new-onset hypertension, which occurs most often after 20 weeks of gestation and frequently near term. It develops when the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus, which is termed placental insufficiency, and/or as a result of individual’s genetic makeup, nutrient availability from the mother, and environmental factors, coupled with the capacity of the placenta to adequately transfer nutrients and oxygen to the fetus. Endocrine modulation of these interactions is the basic determinant of fetal growth [11,12,13]. Both PE and FGR can result in preterm delivery (PTD); there are many similarities between early onset PE and/or FGR and PTD itself, because all three often require emergency delivery by cesarean section, and they are associated with low birth weight and neonatal complications due to prematurity [14,15]

Results

Discussion

Conclusion