SFlt-1, PlGF are limited predictors for adverse maternal events in women with preeclampsia

A prospective observational cohort study published in Pregnancy, the official journal of the Society for Maternal and Fetal Medicine, found that angiogenic markers offer limited value in predicting a composite of adverse maternal events in women already diagnosed with preeclampsia. While markers like soluble fms-like tyrosine kinase (sFlt-1) are currently being investigated for predicting the onset of the disease, their ability to forecast specific complications in a high-income country setting remains modest.¹

Preeclampsia is a pregnancy-induced disorder that represents a leading cause of maternal morbidity and mortality.² Clinical prediction of the disease's progression and associated complications remains a significant challenge for obstetricians. Recent research has focused on the angiogenic markers sFlt-1 and placental growth factor (PlGF), as well as the sFlt-1/PlGF ratio, to determine their utility in predicting delivery timing and maternal risks.¹

The study was a prospective observational cohort conducted between May 2019 and May 2024. Researchers enrolled 307 pregnant women admitted to hospitals with a confirmed diagnosis of preeclampsia. Within this group, 36.5% of the participants gave birth preterm. The investigators used a core set of outcomes developed in 2020 to standardize preeclampsia research and facilitate comparison between studies.

The primary outcome was a composite of 14 adverse maternal events, including maternal mortality, eclampsia, stroke, pulmonary edema, acute kidney injury, and placental abruption. Secondary outcomes included individual components of this composite, such as postpartum hemorrhage and elevated liver enzymes. To evaluate the predictive performance of the markers, researchers calculated the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

Predictive performance of angiogenic markers

The results indicated that 129 women in the cohort developed a total of 166 adverse maternal events, with the most frequent complications observed being postpartum hemorrhage (26.7%), elevated liver enzymes (11.1%), acute kidney injury (7.8%), and low platelet count (5.9%).

When evaluating the markers, sFlt-1 demonstrated the highest predictive performance for the composite outcome, with an AUC of 0.59 (95% CI, 0.52–0.65). This corresponded to a sensitivity of 67% and a specificity of 50%. Notably, PlGF and the sFlt-1/PlGF ratio failed to predict the composite outcome entirely.

Individual outcome prediction and clinical implications

While the markers showed limited utility for the broad composite outcome, sFlt-1 demonstrated better performance when predicting specific individual complications. The study found that sFlt-1 had a modest predictive value for:

• Renal impairment: AUC of 0.72 (95% CI, 0.60–0.83)
• Elevated liver enzymes: AUC of 0.68 (95% CI, 0.59–0.78)
• Thrombocytopenia (low platelet count): AUC of 0.68 (95% CI, 0.56–0.81)

Subgroup analyses revealed that these results remained consistent regardless of whether the preeclampsia was early-onset or late-onset, or whether the delivery occurred at term or preterm.

References:

1. Carlberg N, Hesse C, Thörn S E, et al. Soluble fms-like tyrosine kinase-1 and placental growth factor as predictors of adverse maternal events in women with a confirmed diagnosis of preeclampsia. Pregnancy. doi:10.1002/pmf2.70293
2. Chappell L, Cluver C, Kingdom J et al. Pre-eclampsia. The Lancet. 2021; 398, 341-354