Maternal serum soluble fms-like tyrosine kinase-1 at 22 and 32 weeks in the prediction of pre-eclampsia

Abstract

Objective To investigate the potential value of repeat measurements of maternal serum concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) at 22 and 32 weeks' gestation in the prediction of pre-eclampsia (PE) in women delivering after 32 weeks. Methods The data were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 19-24 and/or 30-34 weeks' gestation in one of two maternity hospitals in England. Serum sFlt-1 was measured in 7565 and 8264 singleton pregnancies at 19-24 and 30-34 weeks, respectively. Bayes' theorem was used to combine the a-priori risk from maternal factors with sFlt-1 multiples of the median (MoM) values. The performance of screening for PE developing after the 30-34-week visit by sFlt-1, measured at 19-24, 30-34 and at both 19-24 and 30-34 weeks was examined. Results In pregnancies with PE, sFlt-1 in both the second and third trimesters was increased and the deviation from normal was inversely related to the gestational age at which delivery became necessary for maternal or fetal indications. Serum sFlt-1 at 19-24 weeks was not useful in predicting PE beyond the 30-34-week visit, but the addition of sFlt-1 at 19-24 weeks improved the prediction of PE provided by sFlt-1 at 30-34 weeks. Screening by maternal factors and sFlt-1 at 30-34 weeks predicted 94% of preterm PE and 54% of term PE, at a false-positive rate of 10%; this was improved to 99% and 64%, respectively, by the additional measurement of sFlt-1 at 19-24 weeks. Conclusions Measurement of sFlt-1 in the second trimester improves the prediction of PE provided by screening in the early third-trimester.