sFLT1/PLGF ratio may improve risk stratification for birth outcomes

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Introduction

Risk stratification for clinical deterioration, intrapartum fetal distress, and mode of birth may be improved from the soluble fms-like tyrosine kinase 1 (sFLT1) to placental growth factor (PLGF) ratio among patients with suspected preeclampsia, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

The sFLT1 to PLGF ratio is traditionally used as a clinical biomarker for adverse pregnancy outcomes, including preeclampsia and preterm birth.² This method has a high negative predictive value, highlighting its diagnostic strength.¹ Additionally, increased sFLT1 to PLGF levels have been linked to increased preeclampsia odds.

“Since an increased sFLT1/PLGF ratio is correlated with placentatal dysfunction, it has been postulated that it could also have important implications for risk stratification around birth,” wrote investigators.

Study design and methodology

To evaluate the link between the sFLT1 to PLGF ratio and the odds of operative delivery and emergency cesarean section, investigators conducted a secondary analysis. The initial trial included women with preeclampsia symptoms, randomized to a reveal arm and nonreveal arm.

In the reveal arm, clinicians were told the results of the ratio to consider during clinical management, while the results remained hidden in the nonreveal arm. Data about the sFLT1 to PLGF ratio and delivery outcomes was obtained for the current analysis, with patient groups included sFLT1/PLGF up to 38, over 38 and under 85, and 85 or higher.

These groups were reported as category 1, 2, and 3, respectively. The time from the blood test to delivery was reported as the primary outcome, while mode of delivery, cesarean section classification, birthweight, birthweight z score, fetal distress, induction of labor (IOL), and small for gestational age (SGA) were reported as secondary outcomes.

Key findings

There were 370 women included in the final analysis. Those with category 2 ratios reported a higher gestational age at recruitment, while those with categories 1 and 3 ratios had a similar gestational age. Increased median systolic and diastolic blood pressures were noted in patients with higher ratios.

Median times to delivery of 37 days, 13 days, and 10 days were reported for categories 1, 2, and 3, respectively. This indicated a significantly increased risk of earlier birth from higher ratio categories, with a hazard ratio of 1.99 for category 2 and 5.64 for category 3.

The ratio had an area under the curve (AUC) of 0.819 for predicting any delivery within 2 weeks, highlighting its efficacy. Predictive ability was superior for sFLT1 alone vs PLGF alone, with AUCs of 0.846 vs 0.754, respectively. Similar results were reported for preeclampsia-indicated deliveries.

Secondary outcomes

Category 3 patients had the lowest spontaneous vaginal delivery (SVD) rate of 32.1%, followed by categories 2 and 1 with rates of 43.3% and 47.9%, respectively. In the logistic regression analysis, the odds ratio (OR) for SVD was 0.47 among category 3 patients. Operative vaginal delivery rates did not differ between groups.

A decrease in the odds of planned cesarean section was reported in category 3 patients, with an OR of 0.08. However, these patients reported increased odds of emergency cesarean section, with a rate of 49% vs 31.7% for category 2 and 15.2% for category 1.

Fetal distress rates were 25.5%, 16.7%, and 11.76%, respectively, while IOL rates were 62.3%, 55%, and 45.1%, respectively. Higher ratios were also associated with reduced neonatal birthweights.

Conclusion

These results indicated a shorter latency to delivery among suspected preeclampsia patients with a higher sFLT1 to PLGF ratio. These patients were also more susceptible to fetal distress, emergency cesarean section, and IOL.

“These data suggest that sFLT1/PLGF ratio is related to placentally mediated birth outcomes beyond preeclampsia, and could provide useful patient counseling as well as guidance for planning and monitoring of labor and delivery in these patients,” concluded investigators.

References

1. Palma Dos Reis CR, O'Sullivan J, Ohuma EO, et al. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor predicts time to delivery and mode of birth in patients with suspected preeclampsia: a secondary analysis of the INSPIRE trial. Am J Obstet Gynecol. 2025;232:317.e1-17. doi:10.1016/j.ajog.2024.06.010
2. Ukah UV, Mbofana F, Rocha BM. Diagnostic performance of placental growth factor in women with suspected preeclampsia attending antenatal facilities in Maputo, Mozambique. Hypertension. 2017;69(3):469-474. doi:10.1161/HYPERTENSIONAHA.116.08547