Predictive values of multiple serum biomarkers in women with suspected preeclampsia: a prospective study

Abstract

Background: Preeclampsia is a common obstetric multisystem disorder causing maternal and fetal morbidity and mortality; it’s been shown that the prediction improves preeclampsia outcomes in pregnancy. However, the current serum biomarkers had low clinical application values and still lack validation studies. Here we aimed to evaluate the preeclampsia prediction values of a series of serum biomarkers in Chinese pregnant women of > 20 weeks of gestation. Methods: Singleton pregnant women with preeclampsia-related clinical and/or laboratory presentations were recruited and had blood drawn at their first visits. The prospective cohort was further divided into preeclampsia-positive and preeclampsia-negative groups based on the follow-up results. The following markers were tested using the collected serum samples: soluble fms-like tyrosine kinase-1 (sFlt-1); placental growth factor (PlGF); thrombomodulin (TM); tissue plasminogen activator inhibitor complex (tPAI-C); compliment factors C1q, B, and H; glycosylated fibronectin (GlyFn); pregnancy-associated plasma protein-A2 (PAPP-A2); blood urea nitrogen (BUN); creatinine (Cre); uric acid (UA); and cystatin C (Cysc). Results: A total of 196 women with suspected preeclampsia were recruited with follow-up medical records. Twenty-five percent (n=49) of the recruited subjects developed preeclampsia before delivery, and 75% remained preeclampsia-negative (n=147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). With the cut-off values obtained from the ROC analyses, the positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. Conclusions: Although several serum markers were found to be significantly changed with current prospective cohort, their limited predictive values in preeclampsia development posed potential barrier in clinical implementation. Further studies with larger cohort are warranted to further reveal the clinical utilities of the serum markers in preeclampsia prediction.