Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania
Miles A. Kirby,
Jacqueline M. Lauer,
Alfa Muhihi,
Nzovu Ulenga,
Said Aboud,
Enju Liu,
Robert K.M. Choy,
Michael B. Arndt,
Jianqun Kou,
Andrew Gewirtz,
Wafaie W. Fawzi,
Christopher P. Duggan,
Karim P. Manji,
Christopher R. Sudfeld
Affiliations
Miles A. Kirby
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States
Jacqueline M. Lauer
Department of Health Sciences, Sargent College, Boston University, Boston, MA, United States
Alfa Muhihi
Management and Development for Health, Dar es Salaam, Tanzania
Nzovu Ulenga
Management and Development for Health, Dar es Salaam, Tanzania
Said Aboud
Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
Enju Liu
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, United States
Robert K.M. Choy
PATH, Center for Vaccine Innovation and Access, Seattle, WA, United States
Michael B. Arndt
Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, United States
Jianqun Kou
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States
Andrew Gewirtz
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States
Wafaie W. Fawzi
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
Christopher P. Duggan
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Corresponding author.
Karim P. Manji
Department of Pediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
Christopher R. Sudfeld
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
Summary: Background: Environmental enteric dysfunction (EED) may contribute to adverse birth outcomes in low-resource settings. We examined the associations of EED biomarkers with birth outcomes in pregnant women living with human immunodeficiency virus in Dar es Salaam, Tanzania. Methods: We performed a cohort study of 706 HIV-infected pregnant women. Maternal serum samples collected at 32 weeks gestation were analyzed for markers of EED (anti-flagellin and anti-LPS immunoglobulins, intestinal fatty acid-binding protein [I-FABP] and soluble CD14), systemic inflammation (C-reactive protein and α1-acid glycoprotein [AGP]), and growth hormone resistance (insulin-like growth factor 1 [IGF-1] and fibroblast growth factor 21 [FGF21]. Associations of biomarkers categorized into quartiles with birth outcomes (birthweight, gestational duration, birthweight-for-gestational age, and stillbirth) were assessed using linear and log-binomial regression models adjusted for multiple sociodemographic and clinical variables. Findings: Maternal EED biomarkers were not significantly associated with birthweight, gestation duration, or birthweight-for-gestational age. However, higher quintiles of I-FABP concentrations were associated with greater risk of stillbirth (ptrend=0·02). Higher AGP was associated with lower birthweight and was associated with increased risk of small-for-gestational age births. Higher IGF-1 was associated with higher birthweight and birthweight-for-gestational age while higher FGF21 was associated with shorter gestation and higher risk of preterm birth. Interpretation: Maternal biomarkers of EED, systemic inflammation, and growth hormones were differentially associated with birth outcomes. Biomarkers of EED may be useful to identify pregnant women at risk of adverse birth outcomes, but further research is needed to confirm these findings and elucidate biological mechanisms. Funding: National Institutes of Health.
