Soluble Fms-like tyrosine kinase-1 to placental growth factor ratio in mid-pregnancy as a predictor of preterm preeclampsia in asymptomatic pregnant women

Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict early-onset, preterm and severe preeclampsia at mid-pregnancy in asymptomatic women. Methods: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 111 women who developed preeclampsia and 69 women with gestational hypertension matched with 338 normotensive women. Serum sFlt-1 and PlGF were measured between 20 and 32 weeks of gestation. The performance of the sFlt-1/PlGF ratio, expressed as raw values and multiples of the median (MoM) for the prediction of early-onset, preterm and severe preeclampsia was evaluated. Results: Women who developed preeclampsia had significantly higher MoM sFlt-1/PlGF ratio (p<0.001). In the early-onset preeclampsia group, the median of the MoM distribution was 24.0 and the area under the receiver operating characteristic curve (AUC) was 0.977, giving sensitivities of 77.8% and 88.9% at false-positive rates of 5% and 10%. Positive predictive values (PPV) were 2.5% and 1.5%, respectively. In a subset between 26 and 32 weeks of gestation, at a threshold of 30, the sFlt-1/PlGF ratio yielded 100% specificity and identified, respectively, 85.7% and 65.2% of women who developed early-onset and preterm preeclampsia. Conclusions: The sFlt-1/PlGF ratio has the potential to predict early-onset and preterm preeclampsia at mid-pregnancy in asymptomatic women. However, care must be paid to the prevalence of early-onset preeclampsia in the population since low prevalence reduces PPV and may hamper clinical utility.