Prenatal screening for pre-eclampsia using PlGF and SFlt-1 in the early second trimester

To assess the performance of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (SFlt-1), and SFlt-1/PlGF ratio for pre-eclampsia (PE) prediction in early second trimester. This is a retrospective case-control study using frozen residual blood samples from women who had a multiple marker screening for fetal aneuploidy and delivered at a tertiary center in Toronto, Ontario, Canada between January 1, 2014 and November 30, 2017. The blood samples were taken between 15+0 and 19+6 weeks of gestation. Pregnancy outcomes were obtained from the Maternal & Newborn Program database. The case group included all pregnancies with gestational hypertension or pre-eclampsia (PE). PE cases was further classified as preterm PE (women with PE who gave birth < 37 weeks of gestation) and early-onset PE (women with PE who gave birth < 34 weeks of gestation). Each case was matched with three controls by sample date, gestational age, maternal age and ethnicity. The concentrations of PlGF and sFlt were expressed as multiple of the medians (MoM) of normal pregnancies at the same gestational age. Mann-Whitney U tests were used to assess the associations between the MoM values of PlGF, SFlt-1 and SFlt/PlGF ratio and risk of PE. Logistic regressions were used to assess if the risk of PE can be predicated using a combination of serum markers and maternal characteristics. In total, 346 cases and 1047 controls were identified from 15,640 singleton pregnancies. Second trimester PlGF was lower and SFlt-1/PlGF ratio was higher in the PE sub-groups compared to the control group. The Lowest PlGF (0.39 MoM) and highest SFlt-1/PlGF (31.1) were seen in the early-onset PE group. At 5% and 10% false positive rates (FPR), 67% and 80% of the early-onset PE was predicted using maternal characteristics and PlGF, respectively. At 5% and 10% FPR, the detection rate for the early-onset PE using characteristics and SFlt-1/PlGF was unchanged at 53 %. Our results showed that, in the early second trimester, PlGF alone provided better prediction for PE compared to the SFlt-1/PlGF ratio.