Environmental Enteric Dysfunction, Aflatoxin Exposure, and Poor Growth Outcomes During the First 1,000 Days in Uganda
Lauer, Jacqueline.
2018
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Abstract: Background: Stunting remains a pervasive form of undernutrition globally, affecting ~155 million children < 5 years of age. Growth failure frequently begins in utero and continues until at least 24 months of life (called the "first 1,000 days"), after which time its effects are largely irreversible. While inadequate diets and diarrheal disease are commonly cited as immediate determina... read morents, they fail to explain much of the burden. Meanwhile, less is known about the role of chronic, asymptomatic gastrointestinal inflammation (environmental enteric dysfunction, or EED) and/or aflatoxin (AF) exposure during the first 1,000 days and their implications for poor child growth. Objectives: The goal of this PhD thesis was to examine the associations among EED, AF exposure, and poor growth outcomes during the first 1,000 days in Uganda. Specifically, the objective of aim #1 was to examine the associations among poor household drinking water quality, EED, and poor growth outcomes in children 12-16 months of age living in rural southwestern Uganda. The objective of aims #2 and #3 were to examine the association between EED biomarkers (aim #2) and AF exposure (aim #3) in pregnant women aged 18-45 and subsequent adverse birth outcomes in Mukono District, Uganda. Methods: For aim #1, we conducted a cross-sectional, observational study within a longitudinal birth cohort study. A lactulose: mannitol (L:M) test was performed on 385 children ages 12-16 months living in 7 sub-counties of southwestern Uganda. Water quality data were obtained using a compartment bag test, and safe water was defined as water lacking E. coli contamination. Data on child anthropometry and covariates were extracted from an existing birth cohort study. For aims #2 and #3, we conducted a prospective cohort study in Mukono, Uganda with a sample of 258 pregnant women who were enrolled at their first prenatal visit. We measured maternal EED biomarkers, namely L:M ratios and serum anti-flagellin and anti-lipopolysaccharide (LPS) antibodies, as well as maternal aflatoxin B1 (AFB1) concentrations. Data on maternal anthropometry and covariates were obtained at enrollment and 3 weeks prior to participants' estimated date of delivery. For all aims, statistical analyses were conducted using STATA 15 software and results were obtained from multivariate linear regression models. Results: Aim #1: Children from households with safe drinking water had significantly lower mean ln L:M ratios (0.23-point difference, 95% CI: 0.09, 0.38) and significantly higher length-for-age (LAZ) (β: 0.34, 95% CI: 0.07, 0.61) and weight-for-age (WAZ) (β: 0.24, 95% CI: 0.10, 0.38) Z-scores at 12-16 months of age. Additionally, children with higher LAZ at 6 and 9 months had significantly lower ln L:M ratios at 12-16 months of age (β: -0.06, 95% CI: -0.13, 0.00 and β: -0.05, 95% CI: -0.10, -0.001, respectively). Aim #2 and #3: Higher concentrations of maternal anti-flagellin IgG and anti-LPS IgG were significantly associated with shorter length of gestation [(β: -1.35, 95% CI: -2.64, -0.07) and (β: -0.89 [95% CI: -1.52, -0.25)] and with lower length at birth [(β: -0.97, 95% CI: -1.79, -0.14) and (β: -0.45, 95% CI: -0.87, -0.02)] and lower LAZ at in infants at birth [(β -0.52, 95% CI: -0.95, -0.08) and (β: -0.25, 95% CI: -0.48, -0.03)]. Furthermore, elevations in maternal ln AFB1 levels were associated with lower weight (β: -0.07; 95% CI: -0.13, -0.002), lower WAZ (β: -0.16; 95% CI: -0.30, -0.03), smaller head circumference (β: -0.27; 95% CI: -0.51, -0.03), and lower head circumference-for-age Z-score (HCZ) (β: -0.23; 95% CI: -0.41, -0.04) in infants at birth. Conclusions: Maternal and child EED and AF exposure were associated with significant decreases in growth at birth, infancy, and early childhood. Efforts to improve nutrition and reduce stunting may be enhanced by simultaneously addressing EED and AF exposure.
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Food Policy & Applied Nutrition.
Advisor: Shibani Ghosh.
Committee: Lynne Ausman, Christopher Duggan, Jeffrey Griffiths, and Patrick Webb.
Keywords: Nutrition, and Public health.read less - ID:
- k643bc587
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