Placental Growth Factor Predicts Early-Onset Pre-Eclampsia in Pregnant Patients with Sickle Cell Disease
In a recent retrospective observational study presented at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, CA, researchers, for the first time, assessed the utility of placental growth factor (PlGF) predicting early-onset pre-eclampsia in pregnant individuals with sickle cell disease (SCD).
PlGF, a pro-angiogenic factor, stimulates angiogenesis and promotes vascular remodeling. While its levels are typically low in healthy non-pregnant individuals, they rise in those with SCD, reflecting disease severity and hemolysis. Pregnancies in individuals with SCD are characterized by heightened risks of complications, including pre-eclampsia. In non-SCD pregnancies, low PlGF levels (<100 pg/mL) during the second trimester have been validated as a strong predictor of pre-eclampsia, particularly early-onset forms. However, this threshold's applicability to pregnancies complicated by SCD has not been previously studied.
In this retrospective study, researchers reviewed data from 83 pregnancies in individuals with SCD at Mount Sinai Hospital in Toronto, Canada, between 2017 and 2021. PlGF measurements taken between 20 and 35 weeks of gestation were analyzed alongside maternal and neonatal outcomes. Receiver operating characteristic (ROC) curves were used to determine the optimal PlGF thresholds for predicting early- and late-onset pre-eclampsia, balancing sensitivity and specificity.
Researchers identified pre-eclampsia in 13% of pregnancies, with early-onset pre-eclampsia accounting for 36% of cases. A PlGF threshold of less than 100 pg/mL at 20-24 weeks’ gestation was found to have good discriminatory ability for predicting early-onset pre-eclampsia, achieving 100% sensitivity and specificity (ROC AUC = 1.000). This threshold offered a positive predictive value (PPV) and negative predictive value (NPV) of 100%, making it a reliable biomarker for this subset of hypertensive complications.
However, the same threshold poorly predicted late-onset pre-eclampsia, demonstrating a sensitivity of only 20%. Accurate prediction of late-onset pre-eclampsia required a much higher PlGF threshold of 832 pg/mL at 20-24 weeks, achieving 100% sensitivity but at the cost of a specificity of 7% and a false positive rate of 93%.
“Our findings corroborate current understanding derived from non-SCD pregnancies that differing mechanisms are likely involved in the pathogenesis of early and late-onset pre-eclampsia necessitating distinct predictive strategies and underscore the importance of tailoring PlGF thresholds to specific gestational ages and types of hypertensive disorders to achieve optimal predictive performance,” the researchers concluded.
Reference
Vlachodimitropoulou E, Balasubramanian T, Shehata N, et al. The utility of maternal placental growth factor (PlGF) for prediction of pre-eclampsia in pregnancies complicated by sickle cell disease. Paper presented at: 66th ASH Annual Meeting & Exposition. San Diego, CA. December 7, 2024. https://ash.confex.com/ash/2024/webprogram/Paper206330.html.