Abstract
BackgroundEnvironmental enteric dysfunction (EED) may be an important modifiable cause of child stunting. We described the evolution of EED biomarkers from birth to 18 months in rural Zimbabwe and tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF), on EED.Methodology and findingsThe Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial was a 2x2 factorial cluster-randomised trial of improved IYCF and improved WASH on child stunting and anaemia at 18 months of age. 1169 infants born to HIV-negative mothers provided plasma and faecal specimens at 1, 3, 6, 12, and 18 months of age. We measured EED biomarkers that reflect all domains of the hypothesized pathological pathway. Markers of intestinal permeability and intestinal inflammation declined over time, while markers of microbial translocation and systemic inflammation increased between 1–18 months. Markers of intestinal damage (I-FABP) and repair (REG-1β) mirrored each other, and citrulline (a marker of intestinal epithelial mass) increased from 6 months of age, suggesting dynamic epithelial turnover and regeneration in response to enteric insults. We observed few effects of IYCF and WASH on EED after adjustment for multiple comparisons. The WASH intervention decreased plasma IGF-1 at 3 months (β:0.89, 95%CI:0.81,0.98) and plasma kynurenine at 12 months (β: 0.92, 95%CI:0.87,0.97), and increased plasma IGF-1 at 18 months (β:1.15, 95%CI:1.05,1.25), but these small WASH effects did not translate into improved growth.ConclusionsOverall, we observed dynamic trends in EED but few effects of IYCF or WASH on biomarkers during the first 18 months after birth, suggesting that these interventions did not impact EED. Transformative WASH interventions are required to prevent or ameliorate EED in low-income settings.
Highlights
Child stunting, defined as an attained length or height >2 standard deviations below the ageand sex-matched standard population median [1], is a persistent global health challenge
We described the evolution of enteric dysfunction (EED) biomarkers from birth to 18 months in rural Zimbabwe and tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF), on EED
We have previously reported the trial primary outcomes: the IYCF intervention modestly increased length-for-age Z-score (LAZ) by 0.16 and reduced stunting by 20% at 18 months, but the WASH intervention had no impact on linear growth or diarrhoea [46]
Summary
Child stunting, defined as an attained length or height >2 standard deviations below the ageand sex-matched standard population median [1], is a persistent global health challenge. Stunting is associated with reductions in child survival, early childhood development, educational attainment and adult economic productivity [2,3,4]. Interventions to reduce stunting have largely focused on improved complementary feeding and prevention of diarrhoea. Evidence to support other nutrition-sensitive interventions, which address the underlying determinants of stunting during the first 1000 days of life, is currently limited [9]. The need to identify modifiable causal mechanisms underlying stunting is a paramount global health need. Environmental enteric dysfunction (EED) may be an important modifiable cause of child stunting. We described the evolution of EED biomarkers from birth to 18 months in rural Zimbabwe and tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF), on EED
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