How sFlt-1/PlGF ratio predicts preeclampsia risk

How sFlt-1/PlGF ratio predicts preeclampsia risk | Image Credit: © vchalup - © vchalup - stock.adobe.com.

Introduction

The odds of progression to preeclampsia (PE) may be assessed by the utilization of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio within clinical practice, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Approximately 5% to 8% of pregnancies are impacted by preeclampsia, making it a leading cause of maternal and neonatal morbidity and mortality worldwide.² Delivery is the only intervention that has been indicated as effective for treatment, which may lead to short- and long-term complications.¹

Challenges in PE diagnosis

“Unnecessary prolonged hospitalizations and serial laboratory testing may not only lead to increased health care costs but also cause significant undue stress to pregnant patients,” wrote investigators. “Furthermore, traditional diagnostic clinical criteria for PE, such as elevated blood pressure, proteinuria, and headaches, have a poor predictive value.”

A PE risk model utilizing proangiogenic and antiangiogenic factor imbalance in maternal circulation has been developed, allowing prediction based on sFlt-1 and PlGF concentrations.To determine the benefits and risks of this testing method, investigators conducted a prospective cohort study.

Study design and methodology

Data was obtained from electronic medical records following implementation of the sFlt-1/PlGF test. Individuals with a singleton pregnancy at 23- to 34-weeks’ gestation and a hypertensive disorder of pregnancy (HDP) were included in the analysis. Exclusion criteria included hemolysis symptoms, elevated liver enzymes, low platelet syndrome, and eclampsia.

Feedback from maternal-fetal medicine providers was referenced to develop a management algorithm for sFlt-1/PlGF biomarker testing indications, management recommendations, patient counseling, and documentation protocols. Education was provided at department-wide presentations prior to rollout.

Increased surveillance was recommended in patients with higher risk based on biomarker tests, while expectant management was recommended in those with low risk. Guidance for patient counseling was also given, but decisions were made by treating physicians. Management decisions were recommended to be based on standard clinical practice guidelines.

Primary outcomes included delivery as clinically indicated, progression to PE with severe features, latency between biomarker measurement data and delivery, and adverse maternal or perinatal outcomes. Serum samples were obtained through venipuncture after delivery.

Patient characteristics and findings

There were 65 encounters across 58 patients included in the final analysis. The median body mass index at admission among these patients was 35.4, and 66.2% self-reported their race as Black.

Prior PE was reported in 32.3% of encounters and preexisting chronic hypertension in 44.6%. A higher average age and BMI were reported in patients with an sFlt-1/PlGF under 40 vs 40 or higher.

The low ratio and high ratio groups had median sFlt-1/PlGF ratios of 4 and 176, respectively, at enrollment. Median systolic blood pressures (SBPs) were 128 and 143, respectively, and median diastolic blood pressures (DBPs) were 76 and 89, respectively.

Blood pressure and treatment outcomes

At 2 weeks, median SBPs were 134 and 161, respectively, and median DBPs were 82 and 94, respectively. Severe hypertension rates were 16.7% vs 55.2%, respectively, highlighting a reduction in the low ratio group. Additionally, low ratio patients were significantly less likely to be using an antihypertensive within 2 weeks of enrollment, with rates of 36.1% and 79.3%, respectively.

Median gestational ages at delivery were 37.1 weeks and 32.6 weeks, respectively, while median periods between the first biomarker draw and delivery were 33 vs 7 days, respectively. Corticosteroid administration was reported in 22.9% and 82.8%, respectively, within 2 weeks of enrollment.

When evaluating adverse perinatal outcomes, investigators noted significantly reduced odds of indications related to HDPs among low ratio patients vs high ratio patients, with rates of 5.6% and 72.4%, respectively. Low ratio patients also had a longer time to indicated delivery.

Conclusion

These results indicated reliability from sFlt1-1/PlGF biomarker testing toward assessing risk in patients with HDP. This was especially the case for patients with clinical uncertainty.

“Additional studies with larger sample sizes are needed to evaluate whether biomarker-based risk assessment may lower hospitalization days for mother and baby and associated costs,” wrote investigators.

References

1. Burns LP, Potchileev S, Mueller A, et al. Real-world evidence for the utility of serum soluble fms-like tyrosine kinase 1/placental growth factor test for routine clinical evaluation of hospitalized women with hypertensive disorders of pregnancy. Am J Obstet Gynecol. 2025;232:385.e1-21. doi:10.1016/j.ajog.2024.07.015
2. Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):1-7. doi:10.1016/j.ejogrb.2013.05.005