PlGF (Placental Growth Factor) testing in clinical practice – identifying the optimal threshold

Abstract

Accurate diagnosis of preterm preeclampsia (PE) may improve the management of affected pregnancies. Previous studies have demonstrated that reduced levels of Placental growth factor (PlGF) levels (< 100 pg/mL) provide superior diagnostic performance to evaluate pregnant individuals with suspected hypertension. A single cut-off may not provide optimal test interpretation, since PlGF levels vary considerably across gestational age (GA) range. Our group recently generated centile curves for PlGF levels by combining data from Toronto and Cambridge, UK. We compared the diagnostic accuracy of GA-specific percentile values of PlGF, vs. a single cutoff of 100 pg/mL, in the setting of diagnostic testing for suspected preeclampsia in a single high-risk pregnancy center. Secondary analysis of published data in 979 high-risk pregnant women with singleton pregnancies evaluated between 2017-2019 at Mount Sinai Hospital, Toronto, Canada. PlGF testing was performed between 20+0 and 35+6 weeks of gestation. We compared the diagnostic accuracy of PlGF< 100 pg\mL vs. PlGF< 2.5% for GA. Primary outcomes were prediction of early-onset PE and preterm birth (PTB)< 32 weeks’ gestation. Overall, 374 (38.2%) had a normotensive pregnancy, 244 (24.9%) developed gestational hypertension19.3%, 189 () developed late-onset PE, and 172 (17.6%) developed early-onset PE. PlGF< 2.5% for GA provided better sensitivity with comparable specificity for diagnosis of early-onset PE and PTB< 32 weeks, when compared to a single threshold of 100 pg\mL, thereby improving the area under the ROC curve (Figure 1). Table 1 compares adjusted odds ratios (aOR) for maternal and fetal outcomes, between PlGF interpretation methods. Compared to PlGF< 100 pg\mL., PlGF < 2.5% for GA increased aOR for early-onset PE and PTB< 32 weeks (58.2 vs to 95.1 and 15.7 vs. 20.6 respectively). Low PlGF levels in high-risk pregnant women are strongly associated with adverse pregnancy outcomes. Adopting a PlGF < 2.5% for GA interpretation approach provides better diagnostic accuracy for the diagnosis of early-onset PE and PTB< 32 weeks.View Large Image Figure ViewerDownload Hi-res image Download (PPT)