ENVIRONMENTAL ENTERIC DYSFUNCTION IN EARLY CHILDHOOD: BRIDGING THE GAP BETWEEN DIET AND STUNTING IN A RANDOMIZED TRIAL OF COMPLEMENTARY FOOD SUPPLEMENTATION IN RURAL BANGLADESH

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Date
2016-03-30
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Johns Hopkins University
Abstract
Background: Stunting continues to burden low- and middle-income countries, with lifelong and intergenerational consequences for health and human capital. Environmental enteric dysfunction (EED), a subclinical abnormality of the intestinal wall, may explain the intractability of stunting and provide avenues for more effective intervention. Objective: This PhD thesis aims to evaluate novel biomarkers of EED and to characterize its epidemiology and the pathways linking it to diet and to stunting. Methods: In a substudy nested within a cluster-randomized controlled trial of complementary food supplements (CFSs) in Bangladesh, 539 18-month-old children were enrolled after completing one year of trial interventions. EED was assessed using lactulose:mannitol (L:M) in urine and a panel of intestinal and systemic health biomarkers in stool (myeloperoxidase, neopterin, α-1 antitrypsin) and serum (endotoxin core antibody IgG, glucagon-like peptide-2, C-reactive protein, α-1 acid glycoprotein). EED scores were developed from principal component analysis (PCA) factor loadings. Associations between EED scores and L:M ratio and between EED supplementary feeding, dietary intakes and anthropometric indicators were assessed with regression models. Results: L:M ratio was elevated (>0.07) in 39.0% of children. PCA-generated inflammation (IS) and permeability (PS) scores together explained only 2.3% of L:M ratio variability. Mean L:M ratio, IS and PS did not differ by CFS group. Dairy consumption was associated with 41% reduction in odds of elevated L:M ratio (p=0.02); no other food group – EED marker associations were observed. Energy and zinc intakes from complementary foods and CFSs were inversely associated with L:M ratio (p≤0.01), while higher iron intake was associated with higher L:M ratio (p=0.04). Prevalence of stunting and wasting was 45% and 15%, respectively, at 18 months and 41% and 21% at 24 months. L:M ratio was not associated with any anthropometric indicators at 18 or 24 months. Greater PS values, indicative of worse intestinal health, were associated with lower LAZ and WAZ at 18 months (p-values<0.01), while IS was not associated with concurrent anthropometry. Higher IS values, also indicative of worse intestinal health, were associated with smaller gains in WAZ and WLZ from 18 to 24 months (p<0.03), while PS was not associated with prospective weight gain, and no EED marker was associated with prospective linear growth. Conclusions: Elevated L:M ratio was common in this population and associated with weight gain, though not with linear growth, and was not impacted by CFSs. Divergence between L:M ratio and biomarker scores and in their associations with diet and anthropometry highlights the urgent need for an improved gold standard diagnostic test. Dietary micronutrient links suggest an avenue for future interventions but require further study.
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Keywords
Environmental enteric dysfunction, stunting, undernutrition, Bangladesh
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