Fecal Markers of Environmental Enteropathy and Subsequent Growth in Bangladeshi Children

Michael B. Arndt Department of Epidemiology, University of Washington, Seattle, Washington.

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Barbra A. Richardson Department of Biostatistics, University of Washington, Seattle, Washington.
Department of Global Health, University of Washington, Seattle, Washington.

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Tahmeed Ahmed Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

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Mustafa Mahfuz Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

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Rashidul Haque Parasitology Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

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Grace C. John-Stewart Department of Epidemiology, University of Washington, Seattle, Washington.
Department of Global Health, University of Washington, Seattle, Washington.
Department of Medicine, University of Washington, Seattle, Washington.
Department of Pediatrics, University of Washington, Seattle, Washington.

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Donna M. Denno Department of Global Health, University of Washington, Seattle, Washington.
Department of Pediatrics, University of Washington, Seattle, Washington.
Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

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William A. Petri Jr. Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia.

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Margaret Kosek Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Asociación Benéfica Proyectos de Informática, Salud, Medicina, y Agricultura (PRISMA), Lima, Peru.

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Judd L. Walson Department of Epidemiology, University of Washington, Seattle, Washington.
Department of Global Health, University of Washington, Seattle, Washington.
Department of Medicine, University of Washington, Seattle, Washington.
Department of Pediatrics, University of Washington, Seattle, Washington.
Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
The Childhood Acute Illness and Nutrition Network (CHAIN), Nairobi, Kenya.

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Environmental enteropathy (EE), a subclinical intestinal disorder characterized by mucosal inflammation, reduced barrier integrity, and malabsorption, appears to be associated with increased risk of stunting in children in low- and middle-income countries. Fecal biomarkers indicative of EE (neopterin [NEO], myeloperoxidase [MPO], and alpha-1-antitrypsin [AAT]) have been negatively associated with 6-month linear growth. Associations between fecal markers (NEO, MPO, and AAT) and short-term linear growth were examined in a birth cohort of 246 children in Bangladesh. Marker concentrations were categorized in stool samples based on their distribution (< first quartile, interquartile range, > third quartile), and a 10-point composite EE score was calculated. Piecewise linear mixed-effects models were used to examine the association between markers measured quarterly (in months 3–21, 3–9, and 12–21) and 3-month change in length-for-age z-score (ΔLAZ). Children with high MPO levels at quarterly time points lost significantly more LAZ per 3-month period during the second year of life than those with low MPO (ΔLAZ = −0.100; 95% confidence interval = −0.167 to −0.032). AAT and NEO were not associated with growth; however, composite EE score was negatively associated with subsequent 3-month growth. In this cohort of children from an urban setting in Bangladesh, elevated MPO levels, but not NEO or AAT levels, were associated with decreases in short-term linear growth during the second year of life, supporting previous data suggesting the relevance of MPO as a marker of EE.

Author Notes

* Address correspondence to Michael B. Arndt, Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195. E-mail: marndt@uw.edu

Financial support: This research and publication were made possible with support from the Bill & Melinda Gates Foundation EED Planning Grant.

Authors' addresses: Michael B. Arndt, Department of Epidemiology, University of Washington, Seattle, WA, E-mail: marndt@uw.edu. Barbra A. Richardson, Department of Biostatistics, University of Washington, Seattle, WA, and Department of Global Health, University of Washington, Seattle, WA, E-mail: barbrar@uw.edu. Tahmeed Ahmed and Mustafa Mahfuz, Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh, E-mails: tahmeed@icddrb.org and mustafa@icddrb.org. Rashidul Haque, Parasitology Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh, E-mail: rhaque@icddrb.org. Grace C. John-Stewart and Judd L. Walson, Department of Epidemiology, University of Washington, Seattle, WA, Department of Global Health, University of Washington, Seattle, WA, Department of Medicine, University of Washington, Seattle, WA, and Department of Pediatrics, University of Washington, Seattle, WA, E-mails: gjohn@uw.edu and walson@uw.edu. Donna M. Denno, Department of Global Health, University of Washington, Seattle, WA, and Department of Pediatrics, University of Washington, Seattle, WA, E-mail: ddenno@uw.edu. William A. Petri Jr., Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, E-mail: wap3g@virginia.edu. Margaret Kosek, Division of Global Disease Epidemiology and Control, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: mkosek@jhu.edu.

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