Prenatal sFlt-1/PlGF value for prediction of adverse neonatal outcome of isolated ultrasonic small-for-gestational-age fetus in normotensive pregnant women: A prospective cohort study

Abstract Background Not only preeclampsia but also small-for-gestational-age (SGA) neonates in the absence of preeclampsia are at increased risk of morbidity and mortality. Early recognition of fetuses at increased risk of being growth-restricted enables more appropriate surveillance and optimization of management for reduced risk of adverse neonatal outcomes. We investigated potential value of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio, estimated in late-second and early-third trimester respectively, for prediction of SGA neonates with poor neonatal outcome. Methods Included in this case control study were 530 singleton pregnant women who had attended the prenatal screening program at single institution between January 2011 and March 2012. The maternal serum levels of sFlt-1 and PlGF at 24 to 28+6weeks and 29 to 36+6weeks of gestation were measured for comparing control and SGA group. Results After excluding 22 preeclampsia cases, 47 SGA group and 461 control-group were included. Mean gestational age at delivery in SGA group was 37.76 ± 2.05weeks, which showed no significant difference comparing to control group (38.43 ± 2.1weeks, p=0.122). The sFlt-1/PlGF ratios at late-second trimester and early-third trimester were both higher in the SGA group than control group (7.62 vs 3.74, p=0.63; 28.62 vs 14.42, p=0.037) and especially sFlt-1/PlGF ratio at early-third trimester was significantly higher in the SGA group. Among SGA group, 17 neonates had adverse neonatal outcome (36.1%, 17/47). Both sFlt-1/PlGF ratios in each trimester were also higher in poor SGA group than control group (6.73 vs 3.77, p = 0.379; 109.12 vs 15.27, p=0.002). As gestational age advances, rapid increase in sflt-1/PlGF ratio detected in poor SGA group comparing to SGA group with no adverse outcome. A cutoff value of 28.15 for the sFlt-1/PlGF ratio at 29 to 36+6weeks significantly predicted SGA neonates who had adverse outcome, with sensitivity and specificity of 76.9% and 88%, respectively. Conclusion In this study, sFlt-1/PlGF ratio of SGA with adverse neonatal outcome group was significantly higher than control group. This study suggests the feasibility of the sFlt-1/PlGF ratio as helpful objective measurement for predicting the adverse SGA neonatal outcome by providing sFlt-1/PlGF cutoff value, besides ultrasound biometry measurement.