Present status of sFLT1 and PlGF as diagnostic and therapeutic targets for preeclampsia.

OBJECTIVE

To review the current role of soluble fms-like tyrosine kinase-1 (sFLT1) and placental growth factor (PlGF) in the pathophysiology, diagnosis, prediction, and treatment of preeclampsia.

BACKGROUND

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide and has increased in prevalence in the United States. It is characterized by new-onset hypertension, proteinuria, and/or end-organ dysfunction, with early-onset disease often associated with placental ischemia, placental insufficiency, and fetal growth restriction. A central mechanism in preeclampsia is angiogenic imbalance, characterized by increased antiangiogenic factors, particularly sFLT1, and reduced proangiogenic signaling mediated by VEGF and PlGF.

METHODS

This review summarizes current evidence regarding sFLT1 biology, the clinical utility of the sFLT1/PlGF ratio, and emerging therapeutic strategies targeting sFLT1 in preeclampsia.

RESULTS

sFLT1 is a soluble splice variant of VEGF receptor-1 that binds circulating VEGF and PlGF, thereby promoting endothelial dysfunction, vasoconstriction, and systemic manifestations of preeclampsia. The sFLT1/PlGF ratio has emerged as a clinically useful biomarker, particularly for short-term risk stratification in women with suspected preeclampsia, with strong negative predictive value for ruling out progression to severe disease within 1 to 2 weeks in appropriately selected patients. The ratio has been incorporated into clinical practice in multiple countries and was approved by the US Food and Drug Administration in 2023 for inpatient risk assessment in singleton pregnancies between 23 and 34 weeks and 6 days of gestation with hypertensive disorders of pregnancy. In parallel, therapeutic approaches targeting sFLT1, including small interfering RNA, antibodies, VEGF or PlGF-based molecular strategies, and apheresis, have shown promise in preclinical and early translational studies.

CONCLUSION

sFLT1 is central to the pathophysiology of preeclampsia and has substantial clinical relevance as both a biomarker and a potential therapeutic target. The sFLT1/PlGF ratio is reshaping risk assessment and management of preeclampsia, while sFLT1-directed therapies may offer future disease-modifying treatment options. Further refinement of biomarker-guided use and therapeutic development is needed before broader implementation.