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Markers of Environmental Enteric Dysfunction Are Associated With Neurodevelopmental Outcomes in Tanzanian Children.

ABSTRACT: BACKGROUND:Chronic exposure to enteropathogens may result in environmental enteric dysfunction (EED), a subclinical condition associated with poor child growth. Growth faltering is strongly associated with poor neurodevelopment, and occurs during sensitive periods of postnatal brain development. We investigated the role of novel EED biomarkers, systemic inflammation, and micronutrient status on neurodevelopment in Tanzanian children. METHODS:Non-stunted subjects with 6-week and 6-month blood samples and neurodevelopmental measures (n?=?107) were included in this study. Samples were tested for biomarkers of gastrointestinal function (citrulline, antibodies to lipopolysaccharide, and flagellin), micronutrient status (iron, retinol binding protein [RBP], and vitamin D), systemic inflammation (C-reactive protein [CRP] and alpha-1-acid glycoprotein), and growth (insulin-like growth factor and insulin-like growth factor binding protein 3). RESULTS:Cognitive scores at 15 months were associated with higher concentrations of 6-month anti-lipopolysaccharide IgG (??=?1.95, P?=?0.02), anti-flagellin IgA (??=?2.41, P?=?0.04), and IgG (??=?2.99, P?=?0.009). Higher receptive language scores were positively associated with anti-flagellin IgG (??=?0.95, P?=?0.05), and receptive language and gross motor scores were positively associated with citrulline at 6 months (??=?0.09, P?=?0.02; ??=?0.10, P?=?0.03, respectively). Gross motor scores were positively associated with RBP at 6 months (??=?1.70, P?=?0.03). Markers of systemic inflammation were not significantly associated with neurodevelopment. CONCLUSIONS:Plasma citrulline, a marker of gastrointestinal mucosal surface area, and vitamin A status were associated with higher gross motor development scores. Novel markers for EED, but not inflammation, were positively associated with cognitive scores, suggesting a possible mechanistic pathway involving immune response and neuroprotection.

SUBMITTER: Etheredge AJ

PROVIDER: S-EPMC5964017 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Markers of Environmental Enteric Dysfunction Are Associated With Neurodevelopmental Outcomes in Tanzanian Children.

Etheredge Analee J AJ Manji Karim K Kellogg Mark M Tran Hao H Liu Enju E McDonald Christine M CM Kisenge Rodrick R Aboud Said S Fawzi Wafaie W Bellinger David D Gewirtz Andrew T AT Duggan Christopher P CP

Journal of pediatric gastroenterology and nutrition 20180601 6

<h4>Background</h4>Chronic exposure to enteropathogens may result in environmental enteric dysfunction (EED), a subclinical condition associated with poor child growth. Growth faltering is strongly associated with poor neurodevelopment, and occurs during sensitive periods of postnatal brain development. We investigated the role of novel EED biomarkers, systemic inflammation, and micronutrient status on neurodevelopment in Tanzanian children.<h4>Methods</h4>Non-stunted subjects with 6-week and 6- ...[more]

PMID: 29613921

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Project description:OBJECTIVES:Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. METHODS:In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. RESULTS:EED prevalence (L:M?>?0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or ?-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and ?-1 antitrypsin (r?=?0.33, P?<?0.01), and biomarker values did not differ by supplementation history. A 1-factor partial least squares model with L:M as the dependent variable explained only 8.6% of L:M variability. In adjusted models, L:M was associated with child sex and socioeconomic status index, whereas systemic inflammation was predicted mainly by recent illness, not EED. CONCLUSIONS:Impaired intestinal health is widespread in this setting of prevalent stunting, but a panel of serum and stool biomarkers demonstrated poor agreement with L:M. Etiologies of intestinal and systemic inflammation are likely numerous and complex in resource-poor settings, underscoring the need for a better case definition with corresponding diagnostic methods to further the study of EED.

Project description:OBJECTIVE:To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania. STUDY DESIGN:Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood. RESULTS:One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood. CONCLUSIONS:Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric dysfunction. TRIAL REGISTRATION:ClinicalTrials.gov: NCT00197730 and NCT00421668.

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Markers of Environmental Enteric Dysfunction Are Associated With Neurodevelopmental Outcomes in Tanzanian Children.

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Markers of Environmental Enteric Dysfunction Are Associated With Neurodevelopmental Outcomes in Tanzanian Children.

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