Utility of Placental Growth Factor (PlGF) for preeclampsia prediction in pregnancies complicated by Sickle Cell Disease Open Access

• Low PlGF in non-SCD pregnancies can predict preeclampsia. Upregulation of PlGF in SCD, rendered its role in preeclampsia prediction unclear

• PlGF <100 pg/mL at 20-24 weeks' gestation has 100% sensitivity and specificity for prediction of early-onset preeclampsia in context of SCD

Outside of pregnancy, Placental Growth Factor (PlGF), is produced by erythroid cells in typically undetectable levels. In pregnancy, PlGF is strongly expressed by the trophoblast layer covering the placental villi. PlGF levels rise progressively due to placental growth, peak at 28-30 weeks' gestation, then slowly decline towards term. Low PlGF has emerged as a powerful diagnostic test for preterm preeclampsia. However its interpretation in context of sickle cell disease (SCD) is potentially confounded by: upregulation of cellular PlGF expression in non-pregnant SCD individuals, and higher 3rdtrimester circulating PlGF levels documented in healthy Black compared with Caucasian individuals. Primary objectives were to determine the distribution of PlGF at mid-trimester in pregnant individuals with SCD compared to unaffected Black controls and to explore the diagnostic accuracy of PlGF in the context of suspected preeclampsia in SCD pregnancies. Secondary objective was to examine the relationship between low PlGF and placental disease in SCD pregnancies. Pregnant individuals with SCD at Mount Sinai Hospital in Canada (Jan. 2017-Sept. 2021) with at least one PlGF measurement 20+0 - 35+6 weeks' gestation and pregnant Black controls without SCD, with suspected preeclampsia or growth restriction, were included in this retrospective study. Maternal and neonatal outcomes were extracted from medical records. For early-onset, but not late-onset, preeclampsia, a PlGF cut-off <100 pg/mL demonstrated 100% sensitivity and specificity at 20-24 weeks' gestation. This study is the first to demonstrate the utility of PlGF in predicting early-onset preeclampsia in SCD pregnancies, allowing clinicians to anticipate and mitigate adverse pregnancy outcomes.