The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: A cross-sectional study in a high burden setting of southern Mozambique
13 affiliations
- 1ISGlobal, Barcelona, Spain
- 2Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
- 3Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain
- 4Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique
- 5Department of Pathology, Maputo Central Hospital, Maputo, Mozambique
- 6National Institution of Health, Ministry of Health, Maputo, Mozambique
- 7Manhiça Health Research Center, Manhiça, Mozambique
- 8Obstetrics and Gynecology Department, Maputo Central Hospital, Maputo, Mozambique
- 9Department of Microbiology, Hospital Clínic of Barcelona, Barcelona, Spain
- 10Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain
- 11Department of Biochemistry and Molecular Genetics-CDB, Hospital Clínic of Barcelona, Barcelona, Spain
- 12IDIBAPS, Biomedicine Department-University of Barcelona, Barcelona, Spain
- 13Consorcio de Investigación Biomédica en Red de Enfermedad Hepática y Digestiva, Madrid, Spain
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.
Related
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BibTeX
@article{chileshe2026value,
title = {{The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: A cross-sectional study in a high burden setting of southern Mozambique}},
author = {Maureen N. Chileshe and Natalia Rakislova and Carla Carrilho and Fabiola Fernandes and Tacilta Nhampossa and Alba Morató and Lorena Marimon and Núria Peñuelas and Anete Mendes and Elvira Luis and Jahit Sacarlal and Isaac Casas and Jessica Navero-Castillejos and Antía Figueroa-Romero and Manuel Morales-Ruiz and Juan Carlos Hurtado and Miguel J. Martinez and Jaume Ordi and Clara Menendez and Raquel González},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0339830},
url = {https://doi.org/10.1371/journal.pone.0339830},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: A cross-sectional study in a high burden setting of southern Mozambique
AU - Maureen N. Chileshe
AU - Natalia Rakislova
AU - Carla Carrilho
AU - Fabiola Fernandes
AU - Tacilta Nhampossa
AU - Alba Morató
AU - Lorena Marimon
AU - Núria Peñuelas
AU - Anete Mendes
AU - Elvira Luis
AU - Jahit Sacarlal
AU - Isaac Casas
AU - Jessica Navero-Castillejos
AU - Antía Figueroa-Romero
AU - Manuel Morales-Ruiz
AU - Juan Carlos Hurtado
AU - Miguel J. Martinez
AU - Jaume Ordi
AU - Clara Menendez
AU - Raquel González
PY - 2026
DA - 2026/10/15
JO - PLOS One
DO - 10.1371/journal.pone.0339830
UR - https://doi.org/10.1371/journal.pone.0339830
AB - 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.
SN - 1932-6203
ER -