The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: a cross-sectional study in a high burden setting of southern Mozambique
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Barcelona Institute for Global Health, Barcelona, Spain
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Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
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Department of Pathology, Hospital Clinic de Barcelona, Barcelona, Spain
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Department of Pathology, Maputo Central Hospital, Maputo, Mozambique
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Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique
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Manhiça Health Research Center, Manhiça, Mozambique
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National Institution of Health, Ministry of Health, Maputo, Mozambique
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Obstetrics and Gynecology Department, Maputo Central Hospital, Maputo, Mozambique
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Department of Microbiology, Hospital Clinic de Barcelona, Barcelona, Spain
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Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain
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Department of Biochemistry and Molecular Genetics-CDB, Hospital Clinic de Barcelona, Barcelona, Spain
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IDIBAPS, Biomedicine Department-University of Barcelona, Consorcio de Investigación Biomédica en Red de Enfermedad Hepática y Digestiva, Barcelona, Spain
Popul. Med. 2026;8(Supplement Supplement 1):A2343
ABSTRACT
BACKGROUND:
Estimating the contribution of preeclampsia(PE) to perinatal mortality in low resource settings remains difficult due to limited diagnostic capacity and lack of specific histopathological changes, which often hamper cause of death assignment1-3. While PE angiogenic biomarkers (sFlt-1, PlGF) predict adverse pregnancy outcomes, their post-mortem diagnostic utility is unclear4-6. We evaluated the potential role of these biomarkers in identifying PE-related perinatal deaths.
METHODS:
This cross-sectional study was carried out in pregnant women delivering a stillborn or had an early neonatal death at the Maputo Central Hospital, 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 enrolled 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%), with significantly reduced PlGF levels in PE associated deaths. sFlt-1/PlGF cutoffs of ≥85 and ≥110 in maternal and placental blood were reliable cutoffs 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 high burden settings7-10. Study findings highlight the potential value of biomarker measurement for both risk stratification and mortality surveillance.