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The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: a cross-sectional study in a high burden setting of southern Mozambique

Article scientifique 2025 Autre

Résumé

ABSTRACT Background 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. Methods 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. Results 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. Conclusions 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. Research in context What is already known on this topic sFlt-1, PlGF, and their ratio, are well-established in predicting and diagnosing preeclampsia during pregnancy. However, their utility in identifying preeclampsia-related perinatal deaths particularly in postmortem investigations such as minimally invasive tissue sampling (MITS) samples, is underexplored. What this study adds This study is the first to evaluate diagnostic accuracy of these biomarkers using postmortem placental and foetal/neonatal blood samples from MITS to identify preeclampsia-related perinatal deaths. We show that maternal and placental sFlt-1/PlGF ratios can reliably identify preeclampsia-related perinatal deaths at standardized ratio cutoffs of ≥85 and ≥110 respectively. Whilst significantly reduced PlGF concentrations, lower placental and perinatal anthropometric measurements were hallmark features of PE-related deaths. The study suggests optimal sFlt-1/PlGF ratio cut-offs for maternal (≥50) and placental (≥230) blood, providing robust diagnostic thresholds for use in perinatal mortality surveillance and antenatal risk stratification in high-burden settings. How this study might affect research, practice or policy The use of preeclampsia biomarker analysis in determining causes of perinatal death offers a feasible, scalable, and objective method that may help overcome challenges in accurate cause of death attribution in LMICs. This has important implications for mortality surveillance system monitoring and pregnancy risk assessments, where autopsy is rare and clinical records are often incomplete. Incorporating biomarker-based diagnostics into existing perinatal death investigations could significantly improve mortality data and guide targeted health interventions.

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Chileshe, M., Rakislova, N., Carrilho, C., Fernandes, F., Nhampossa, T., Morató, A., Marimon, L., Peñuelas, N., Mendes, A., Luis, E., Sacarlal, J., Casas, I., Navero-Castillejos, J., Figueroa-Romero, A., Morales-Ruiz, M., Hurtado, J., Martinez, M., Ordi, J., Menendez, C., González, R. (2025). The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: a cross-sectional study in a high burden setting of southern Mozambique. https://doi.org/10.64898/2025.12.15.25342319

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Auteur(s)

Maureen N. Chileshe Natalia Rakislova Carla Carrilho Fabiola Fernandes Tacilta Nhampossa Alba Morató Lorena Marimon Núria Peñuelas Anete Mendes Elvira Luis Jahit Sacarlal Isaac Casas Jessica Navero-Castillejos Antía Figueroa-Romero Manuel Morales-Ruiz Juan Carlos Hurtado Miguel J. Martinez Jaume Ordi Clara Menendez Raquel González

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