The Study Of Inhibin A, Activin A, Placental Growth Factor And Uterine Artery Doppler Pulsatility Index As Markers Of Pre-eclampsia

Objective Pre-eclampsia is a pregnancy-specific disorder.It contributes substantially to perinatal morbidity and mortality of both mother and newborn.A number of biochemical agents were evaluated as markers for predicting pre-eclampsia.But none of them has been proved to be of clinical value yet.Much effort has been put into assessing novel potential markers and their combination with other screening methods such as Doppler sonography.The purpose of this study is to evaluate whether measurement of maternal serum inhibin A,activin A and placental growth factor(PLGF) at 12+0 to 16+0 weeks of gestation alone or in combination with second-trimester uterine artery pulsitility measured by Doppler velocimetry is useful in predicting those women who will develop pre-eclampsia.Methods This was a nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage time for the maternal serum.Samples were collected as those pregnant women at 12-16weeks' gestation came to Shanghai First Maternity and Infant Health Hospital for their first routine examination.The samples were then stored at -70℃.Samples from women developing pre-eclampsia were retrieved from frozen storage,and samples from unaffected pregnancies,covering the same gestational age and storage period,were used as controls,inhibin A,activin A and placental growth factor (PLGF) were tested using an enzyme linked immunosorbent assay(ELISA) by an examiner who was blinded to pregnancy outcome.All patients underwent uterine artery Doppler flow velocimetry to measure the mean pulsatility index(PI) at 22-24 weeks' gestation.Results There were 30 cases with preeclampsia and 93 controls.Mean MoMs of mean PI were 1.02±0.25 and 1.45±0.31(P＜0.001) for controls and cases,respective ly.Mean MoMs of inhibin A were 1.08±0.43 and 1.57±0.34(P＜0.001).Mean Mo Ms of activin A were 1.06±0.42 and 1.68±0.38(P＜0.001).Mean MoMs of PLGF were 1.00±0.26 and 0.69±0.23(P＜0.001).Receiver-operating characteristics curve(R OC) was analysis for cases and controls yielded areas under the curve for inhibin A,activin A,PLGF and PI respectively of 0.796(95%CI,0.712～0.880;P＜0.01),0.8 23(95%CI,0.746～0.899;P＜0.01),0.831(95%CI,0.752～0.910;P＜0.01) and 0.851(9 5%CI,0.783～0.920;P＜0.01).Combing activin A,inhibin A and PI using logistic regr ession analysis yielded an area under the curve of 0.907(95%CI,0.830～0.938;P＜0. 01) and a sensitivity of 82%at a specificity of 80%.Activin A,PLGF with PI gav e an area under the curve of 0.925(95%CI,0.852～0.978;P＜0.01) and a sensitivity of 90%at a specificity of 80%.Combing the four markers gave an area under the curve of 0.941(95%CI,0.891～0.990;P＜0.01) and a sensitivity of 93%at a specifi city of 80%.Conclusion Early second-trimester serum activin A,PLGF and uterine artery Doppler PI provide some prediction for pre-eclampsia.But their sensitivity and specificity limit their alone use in a clinical context.Inhibin A has low sensitivity and specificity as alone markers,but it added sensitivity when combining other markers.The combination of activin A,inhibin A and PI and activin A,PLGF and PI may be useful in predicting pre-eclampsia.Combination of the three serum markers and uterine artery Doppler PI has a high value of the prediction of prediction.