ArticlePloS one2026
The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: A cross-sectional study in a high burden setting of southern Mozambique.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Estimating the contribution of preeclampsia (PE) to perinatal mortality in low-resource settings remains difficult due to limited diagnostic capacity. Lack of specific histopathologic changes in stillbirth, foetuses and/or placenta often hampers assignment of PE as cause of death. While PE angiogenic biomarkers (sFlt-1, PlGF) predict adverse pregnancy outcomes, their post-mortem diagnostic utility is unclear. We evaluated the potential role of these biomarkers in identifying PE-related perinatal deaths. This cross-sectional study was conducted among pregnant women who delivered a stillborn infant or experienced an early neonatal death at Maputo Central Hospital in Mozambique. Concentrations of sFlt-1, PlGF and their ratio (sFlt-1/PlGF) were assessed in maternal blood and post-mortem foetal/neonatal and placental blood. Causes of death were determined via minimally invasive tissue sampling (MITS) and diagnostic accuracy was assessed using ROC curves for standardized and optimal biomarker cut-offs. A total of 100 women with perinatal deaths (98 stillbirths and 2 early neonatal deaths) were included in the study between March 2021 and April 2022. Maternal sFlt-1/PlGF ratios showed the highest diagnostic accuracy for PE-related deaths (area under curve [AUC]=82%), followed by placental (AUC = 75%) and foetal blood (AUC = 61%). PlGF levels were significantly reduced in PE-associated deaths. sFlt-1/PlGF cutoffs of ≥85 and ≥110 in maternal and placental blood were reliable cut-offs for identifying PE-related foetal/neonatal deaths. Optimal ratio cut-offs were ≥50 (maternal blood), ≥ 230 (placental blood), and ≥140 (foetal blood), with maternal and placental sFlt-1/PlGF ratios showing significant associations with PE-related death (OR=10.58 and 5.98 respectively). Sensitivity and specificity in maternal and placental blood were 84% and 73%, and 67% and 78%, respectively, with a positive predictive value (PPV) of 84% in both. In conclusion, maternal and placental angiogenic biomarkers enable reliable identification of preeclampsia-related perinatal deaths and could significantly enhance cause-of-death determination in low-resource, high-burden settings. These findings underscore the potential value of biomarker measurement for both risk stratification and mortality surveillance.
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