Low placental growth factor (PlGF) levels during pregnancy, long established as a marker for pre-eclampsia risk in the general population, can accurately predict early-onset pre-eclampsia in individuals with sickle cell disease (SCD), according to new research from Mount Sinai Hospital, Canada, and collaborators.
PlGF and Pregnancy Complications
While PlGF is nearly undetectable outside of pregnancy, its levels rise as the placenta grows, peaking before term. Low PlGF in non-SCD pregnancies is a powerful diagnostic marker for preterm pre-eclampsia, but its interpretation in SCD has been contentious because SCD patients express higher PlGF at baseline, even outside pregnancy. Researchers set out to clarify PlGF’s diagnostic value for predicting pre-eclampsia in SCD pregnancies, an urgent need, as these patients face a doubled risk for placental complications and pre-eclampsia compared to unaffected individuals.
New Study and Key Findings
In a retrospective study from 2017-2021, researchers collected mid-trimester PlGF levels from pregnant SCD patients and Black controls, cross-referencing these with pregnancy outcomes. Among SCD pregnancies, a PlGF cut-off below 100 picograms per millilitre at 20–24 weeks’ gestation demonstrated an unprecedented 100% sensitivity and specificity for predicting early-onset pre-eclampsia, outperforming established thresholds used for non-SCD pregnancies. For late-onset pre-eclampsia, however, this threshold lost accuracy, and much higher cut-offs were required, indicating different pathophysiological mechanisms.
Implications for Maternal Care
These findings establish low PlGF as a highly reliable early warning tool for pre-eclampsia in SCD pregnancies, allowing clinicians to anticipate complications and improve outcomes for mothers and babies. Researchers also demonstrated a link between low PlGF and placental vascular disease in SCD, further supporting its value as a marker of placental health.
Next Steps
Experts urge validation in larger, multicentre trials, and suggest integrating PlGF with other biomarkers to optimise pre-eclampsia prediction for vulnerable pregnancies. This breakthrough could transform pregnancy monitoring in individuals with SCD
Reference
Vlachodimitropoulou E et al. Utility of placental growth factor (plgf) for preeclampsia prediction in pregnancies complicated by sickle cell disease. Blood Adv. 2025:bloodadvances.2025016821.
