ItemArticle

Maternal circulating sFlt-1/placental growth factor is a biomarker of fetal death associated with placental lesions of maternal vascular malperfusion

Title
Maternal circulating sFlt-1/placental growth factor is a biomarker of fetal death associated with placental lesions of maternal vascular malperfusion
Creator
Chaiworapongsa, Tinnakorn; Romero, Roberto; Mcclure, Elizabeth M.; Goudar, Shivaprasad; Somannavar, Manjunath; Tikmani, Shiyam Sunder; Saleem, Sarah; Ghanchi, Najia; Ahmed, Imran; Zafar, Afia; Patil, Sanyukta; Sunilkumar, B.K.; Yogeshkumar, S.; Kim, Jean; Moore, Janet; Meyyazhagan, Arun; Awonuga, Awoniyi; Gudicha, Dereje; Tarca, Adi L.; Goldenberg, Robert L.
Description
Objectives: Fetal death is a major pregnancy complication, with rates of 5.5 per 1,000 births in the United States and substantially higher in India (24.7/1,000) and Pakistan (44.5/1,000). Maternal vascular malperfusion (MVM) is the most frequent placental lesion associated with fetal death, occurring in 58 % of fetal deaths and 31 % of preterm neonatal deaths in South Asia. Angiogenic imbalance, characterized by a low placental growth factor (PlGF) to soluble fms-like tyrosine kinase-1 (sFlt-1) ratio, has been associated with MVM and fetal death in high-income countries. We examined whether maternal serum concentrations of PlGF, sFlt-1, and their ratio differ between mothers with and without MVM among stillbirths and preterm neonatal deaths in India and Pakistan. Methods: This retrospective cohort analysis used data from the PURPOSe study (Project to Understand and Research Preterm Pregnancy Outcomes and Stillbirths in South Asia). Maternal blood was collected at delivery, and placental histopathology was classified according to the Amsterdam criteria. Serum PlGF and sFlt-1 were measured using Elecsys immunoassays, with analyses stratified by gestational age. Results: Placental MVM was present in 44-57 % of stillbirths and 31-38 % of preterm neonatal deaths. Between 28 and 36 weeks, women with MVM had significantly lower PlGF and higher sFlt-1 and sFlt-1/PlGF ratios (p<0.001). A tenfold decrease in PlGF or increase in the ratio was associated with MVM (OR 0.5 and 1.7, respectively). Conclusions: The maternal sFlt-1/PlGF ratio identifies pregnancies with fetal or neonatal death associated with placental MVM, particularly between 28 and 36 weeks' gestation. 2025 the author(s)
Source
Journal of Perinatal Medicine;Volume;54;Issue;3;pp.550-565
Date
01-01-2026
Publisher
Walter de Gruyter GmbH
Subject
great obstetrical syndromes; perinatal death; placenta histology; PlGF; sFlt-1; South Asia
Coverage
Chaiworapongsa T., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States; Romero R., Division of Intramural Research, Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, United States, Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, United States; Mcclure E.M., Social, Statistical and Environmental Health Sciences, RTI International, Durham, NC, United States; Goudar S., Women's and Children's Health Research Unit, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, India; Somannavar M., Women's and Children's Health Research Unit, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, India; Tikmani S.S., Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan; Saleem S., Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan; Ghanchi N., Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan; Ahmed I., Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan; Zafar A., Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan; Patil S., Women's and Children's Health Research Unit, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, India; Sunilkumar B.K., Jagadguru Jayadeva Murugarajendra Medical College, Davangere, India; Yogeshkumar S., Women's and Children's Health Research Unit, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, India; Kim J., Social, Statistical and Environmental Health Sciences, RTI International, Durham, NC, United States; Moore J., Social, Statistical and Environmental Health Sciences, RTI International, Durham, NC, United States; Meyyazhagan A., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States, Division of Intramural Research, Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States, Department of Life Sciences, Christ University, Bengaluru, India; Awonuga A., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States; Gudicha D., Division of Intramural Research, Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States; Tarca A.L., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States, Department of Computer Science, Wayne State University College of Engineering, Detroit, MI, United States; Goldenberg R.L., Columbia University, New York, NY, United States
Rights
All Open Access; Gold Open Access; Green Open Access
Relation
ISSN: 3005577; CODEN: JPEMA
Format
online
Language
English
Type
Article

Citation

Chaiworapongsa, Tinnakorn; Romero, Roberto; Mcclure, Elizabeth M.; Goudar, Shivaprasad; Somannavar, Manjunath; Tikmani, Shiyam Sunder; Saleem, Sarah; Ghanchi, Najia; Ahmed, Imran; Zafar, Afia; Patil, Sanyukta; Sunilkumar, B.K.; Yogeshkumar, S.; Kim, Jean; Moore, Janet; Meyyazhagan, Arun; Awonuga, Awoniyi; Gudicha, Dereje; Tarca, Adi L.; Goldenberg, Robert L., “Maternal circulating sFlt-1/placental growth factor is a biomarker of fetal death associated with placental lesions of maternal vascular malperfusion,” CHRIST (Deemed To Be University) Institutional Repository, accessed June 18, 2026, https://archives.christuniversity.in/items/show/23325.

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