Anthropometry relationship with duodenal histologic features of children with environmental enteric dysfunction: a multicenter cross-sectional study

Zehra Jamil; Kelley VanBuskirk; Monica Mweetwa; Samer Mouksassi; Gerald Smith; Tahmeed Ahmed; Kanta Chandwe; Donna M Denno; S Mohammad Fahim; Paul Kelly; Mustafa Mahfuz; Indika Mallawaarachchi; Chelsea Marie; Sean R Moore; William A Petri Jr; S Asad Ali; EEDBI Consortium

doi:10.1016/j.ajcnut.2024.02.027

Anthropometry relationship with duodenal histologic features of children with environmental enteric dysfunction: a multicenter cross-sectional study

Am J Clin Nutr. 2024 Sep:120 Suppl 1:S65-S72. doi: 10.1016/j.ajcnut.2024.02.027.

Authors

Zehra Jamil¹, Kelley VanBuskirk², Monica Mweetwa³, Samer Mouksassi⁴, Gerald Smith⁵, Tahmeed Ahmed⁶, Kanta Chandwe³, Donna M Denno⁷, S Mohammad Fahim⁶, Paul Kelly⁸, Mustafa Mahfuz⁶, Indika Mallawaarachchi⁹, Chelsea Marie¹⁰, Sean R Moore¹¹, William A Petri Jr¹², S Asad Ali¹³; EEDBI Consortium

Collaborators

EEDBI Consortium:
Kumail Ahmed¹⁴, Sheraz Ahmed¹⁵, Md Ashraful Alam¹⁶, Beatrice Amadi¹⁷, Rosemary Banda¹⁸, Shareef Dars¹⁹, Subhasish Das²⁰, Lee A Denson²¹, Md Shabab Hossain²², Aneeta Hotwani²³, Junaid Iqbal²⁴, Najeeha Talat Iqbal²⁵, Sadaf Jakhro²⁶, Furqan Kabir²⁷, Lydia Kazhila²⁸, Ta-Chiang Liu²⁹, Barbara J Mann³⁰, Waheeda Memon³¹, Christopher A Moskaluk³², Abdul Khalique Qureshi³³, Shyam S Ragahavan³⁴, Masudur Rahman³⁵, Najeeb Rahman³⁶, Kamran Sadiq³⁷, Shafiqul Alam Sarker³⁸, Peter B Sullivan³⁹, Phillip I Tarr⁴⁰, Guillermo J Tearney⁴¹, Fayaz Umrani⁴², Omer H Yilmaz⁴³

Affiliations

¹ Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
² Department of Global Health, University of Washington School of Public Health, Seattle, WA, United States.
³ Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.
⁴ Certara, Princeton, NJ, United States.
⁵ Cytel, Vancouver, British Columbia, Canada.
⁶ Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
⁷ Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States.
⁸ Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom.
⁹ Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States.
¹⁰ Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
¹¹ Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, United States.
¹² Department University of Virginia, Charlottesville, VA, United States.
¹³ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
¹⁴ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
¹⁵ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
¹⁶ International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh. Electronic address: [email protected].
¹⁷ Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia. Electronic address: [email protected].
¹⁸ Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia. Electronic address: [email protected].
¹⁹ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
²⁰ International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh. Electronic address: [email protected].
²¹ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: [email protected].
²² International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh. Electronic address: [email protected].
²³ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
²⁴ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
²⁵ Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
²⁶ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
²⁷ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
²⁸ Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia. Electronic address: [email protected].
²⁹ Department of Pathology and Immunology, Washington University, St. Louis, MO, USA. Electronic address: [email protected].
³⁰ Department of Medicine, University of Virginia, Charlottesville, Virginia, USA. Electronic address: [email protected].
³¹ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
³² Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, USA. Electronic address: [email protected].
³³ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
³⁴ Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, USA. Electronic address: [email protected].
³⁵ Department of Gastroenterology, Sheikh Russel National Gastroliver Institute and Hospital, Dhaka, Bangladesh. Electronic address: [email protected].
³⁶ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
³⁷ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
³⁸ International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh. Electronic address: [email protected].
³⁹ Department of Paediatrics, Children's Hospital, University of Oxford, Oxford, UK. Electronic address: [email protected].
⁴⁰ Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: [email protected].
⁴¹ Department of Pathology, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
⁴² Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. Electronic address: [email protected].
⁴³ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: [email protected].

PMID: 39300664
DOI: 10.1016/j.ajcnut.2024.02.027

Abstract

Background: Environmental enteric dysfunction (EED) is a precursor of growth faltering in children living in impoverished conditions who are frequently exposed to environmental toxins and enteropathogens, leading to small bowel inflammatory, malabsorptive, and permeability derangements and low-grade chronic systemic inflammation.

Objectives: We explored the association between anthropometrics and duodenal histologic features of EED among children from 3 lower middle-income country centers.

Methods: In this cross-sectional study, Pakistani children (n = 63) with wasting, Bangladesh children (n = 116) with stunting or at risk for stunting (height-for-age Z score [HAZ] <-1 but ≥-2), and Zambian children (n = 108) with wasting or stunting received nutritional intervention. Children with anthropometric status refractory to intervention underwent endoscopy. Linear regression models included anthropometric around endoscopy, scores of histology parameters, and a global index score of EED-the total score percent-5 (TSP-5). Multivariable models were adjusted for center, age, sex, and histology slide quality.

Results: Intersite variation was observed while exploring the association between anthropometrics and the TSP-5; for example, Pakistani children had the worst HAZ, yet their median TSP-5 score was lower than that of the other 2 centers. Even within each site, no overall pattern of higher TSP-5 score was observed with worsening HAZ. During univariate analysis, TSP-5 (coefficient: 0.01; 95% confidence interval [CI]: 0, 0.02), goblet cell depletion (coefficient: 0.22; 95% CI: 0.06, 0.37), and Paneth cell depletion (coefficient: 0.14; 95% CI: 0.01, 0.27) were associated with HAZ scores; however, they lost statistical significance in the multivariable models, with study center most strongly confounding the relationships seen in univariate models between anthropometry and histology.

Conclusions: This study contributes a crucial negative finding that duodenal morphological features did not associate with anthropometric phenotypes; hence, anthropometric measurements may not be a suitable outcome measure for use in EED trials. Trial outcomes may need to be defined by combining the functional and structural elements of the gut to monitor EED.

Keywords: anthropometry; duodenal histology; environmental enteric dysfunction; stunting; wasting.

Publication types

Multicenter Study

MeSH terms

Anthropometry*
Bangladesh
Child
Child, Preschool
Cross-Sectional Studies
Duodenum* / pathology
Female
Growth Disorders / etiology
Humans
Infant
Male
Pakistan
Zambia