Angiogenic factors combined with clinical risk factors to predict preterm pre‐eclampsia in nulliparous women: a predictive test accuracy study

Objectives To assess the performance of clinical risk factors, uterine artery D oppler and angiogenic markers to predict preterm pre‐eclampsia in nulliparous women. Design Predictive test accuracy study. Setting Prospective multicentre cohort study S creening for P regnancy E ndpoints ( SCOPE ). Methods Low‐risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor ( P l GF ), soluble endoglin and soluble fms‐like tyrosine kinase‐1 (s F lt‐1) were measured at 14–16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Main outcome measure Preterm pre‐eclampsia (delivered before 37 +0  weeks of gestation). Results Of the 3529 women recruited, 187 (5.3%) developed pre‐eclampsia of whom 47 (1.3%) delivered preterm. Controls ( n  = 188) were randomly selected from women without preterm pre‐eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve ( AUC ) of 0.76 (95% CI 0.67–0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of P l GF measured at 14–16 weeks (0.84; 95% CI 0.77–0.91), but no further improvement was observed with the addition of uterine artery D oppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31–0.59) (5% false‐positive rate) and post‐test probability of 11% (95% CI 9–13) were observed using clinical risk variables and P l GF measurement. Conclusions Addition of plasma P l GF at 14–16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre‐eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility.