Dataset Information

Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania.

ABSTRACT:

Background

Environmental enteric dysfunction (EED) may contribute to adverse birth outcomes in low-resource settings. We examined the associations of EED biomarkers with birth outcomes in pregnant women living with human immunodeficiency virus in Dar es Salaam, Tanzania.

Methods

We performed a cohort study of 706 HIV-infected pregnant women. Maternal serum samples collected at 32 weeks gestation were analyzed for markers of EED (anti-flagellin and anti-LPS immunoglobulins, intestinal fatty acid-binding protein [I-FABP] and soluble CD14), systemic inflammation (C-reactive protein and α1-acid glycoprotein [AGP]), and growth hormone resistance (insulin-like growth factor 1 [IGF-1] and fibroblast growth factor 21 [FGF21]. Associations of biomarkers categorized into quartiles with birth outcomes (birthweight, gestational duration, birthweight-for-gestational age, and stillbirth) were assessed using linear and log-binomial regression models adjusted for multiple sociodemographic and clinical variables.

Findings

Maternal EED biomarkers were not significantly associated with birthweight, gestation duration, or birthweight-for-gestational age. However, higher quintiles of I-FABP concentrations were associated with greater risk of stillbirth (p_trend=0·02). Higher AGP was associated with lower birthweight and was associated with increased risk of small-for-gestational age births. Higher IGF-1 was associated with higher birthweight and birthweight-for-gestational age while higher FGF21 was associated with shorter gestation and higher risk of preterm birth.

Interpretation

Maternal biomarkers of EED, systemic inflammation, and growth hormones were differentially associated with birth outcomes. Biomarkers of EED may be useful to identify pregnant women at risk of adverse birth outcomes, but further research is needed to confirm these findings and elucidate biological mechanisms.

Funding

National Institutes of Health.

SUBMITTER: Kirby MA

PROVIDER: S-EPMC9486615 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania.

Kirby Miles A MA Lauer Jacqueline M JM Muhihi Alfa A Ulenga Nzovu N Aboud Said S Liu Enju E Choy Robert K M RKM Arndt Michael B MB Kou Jianqun J Gewirtz Andrew A Fawzi Wafaie W WW Duggan Christopher P CP Manji Karim P KP Sudfeld Christopher R CR

EBioMedicine 20220918

<h4>Background</h4>Environmental enteric dysfunction (EED) may contribute to adverse birth outcomes in low-resource settings. We examined the associations of EED biomarkers with birth outcomes in pregnant women living with human immunodeficiency virus in Dar es Salaam, Tanzania.<h4>Methods</h4>We performed a cohort study of 706 HIV-infected pregnant women. Maternal serum samples collected at 32 weeks gestation were analyzed for markers of EED (anti-flagellin and anti-LPS immunoglobulins, intesti ...[more]

PMID: 36130475

Similar Datasets

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:Background: Environmental enteric dysfunction (EED) is a major impediment to the Sustainable Development Goals of improved childhood survival and healthy growth worldwide. Few studies have longitudinally and endoscopically examined EED in children, limiting the development of effective interventions. Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM, Pakistan) followed 416 at-risk children prospectively from birth to 24 months of age in a rural district of Pakistan with a high prevalence of undernutrition. The duodenal genome-wide methylome and transcriptome was determined in 52 undernourished SEEM participants refractory to nutritional interventions and 42 North American pediatric controls and coeliac disease patients. Biomarkers were measured at 9 months and tested for association with growth at 24 months. Findings: The EED core transcriptome exhibited suppression of genes regulating antioxidant and detoxification functions and lipid metabolism, and induction of genes encoding anti-microbial responses, interferon signaling, and lymphocyte activation. Relative to coeliac disease, suppression of genes encoding antioxidant and detoxification functions and induction of anti-microbial responses were EED-specific. At the epigenetic level, EED was notable for hyper-methylation of genes involved in epithelial metabolism and barrier function, and hypo-methylation of genes involved in immune responses and cell proliferation. Duodenal co-expression modules revealed associations between genes regulating lymphocyte proliferation and epithelial metabolism with histologic severity, faecal energy loss, and wasting (weight-for-height Z<-2.0), with data supporting epigenetic regulation. Immune response genes were attenuated by Giardia colonization. After accounting for growth at study entry, IGF-1 and ferritin predicted linear growth, whereas leptin correlated with expression of epithelial carbohydrate metabolism and stem cell renewal genes, and weight gain. Interpretation: Data suggest immune and metabolic pathways which may inform more effective interventions to improve outcomes in EED. A validated model may be used to identify infants at greatest risk for future poor growth.

Project description:BACKGROUND:Because Helicobacter pylori (H. pylori) infection and Environmental Enteric Dysfunction (EED) follow a similar mode of transmission, there can be a complex interplay between H. pylori infection and EED, both of which can influence childhood growth. We sought to investigate the factors associated with H. pylori infection and identify its relationship with the fecal biomarkers of EED including Myeloperoxidase (MPO), Neopterin (NEO), Calprotectin, Reg1B and Alpha-1 antitrypsin (AAT), and nutritional status of the children. METHODOLOGY:Data from an on-going community-based nutrition intervention study was used for this analysis. Total 319 children aged between 12-18 months were evaluated at enrolment and at the end of a 90-day nutrition intervention. Multivariable linear regression with generalized estimating equations was done to examine the association of H. pylori infection with stool biomarker of EED and nutritional status of the children. PRINCIPAL FINDINGS:One-fifth of the participants had H. pylori infection at both the time points, with 13.8% overall persistence. Children living in crowded households had higher odds of being infected by H. pylori (AOR = 2.02; 95% CI = 1.02, 4.10; p-value = 0.045). At enrolment, 60%, 99%, 69% and 85% of the stool samples were elevated compared to the reference values set for MPO, NEO, AAT and Calprotectin in the non-tropical western countries. The proportions reduced to 52%, 99%, 67%, and 77% for the same biomarkers after the nutrition intervention. Infection with H. pylori had significant positive association with fecal AAT concentrations (Coefficient = 0.26; 95% CI = 0.02, 0.49; p-value = 0.03) and inverse relationship with Reg1B concentrations measured in the stool samples (Coefficient = -0.32; 95% CI = -0.59, -0.05; p-value = 0.02). However, H. pylori infection was not associated with the indicators of childhood growth. CONCLUSIONS:The study findings affirmed that the acquisition and persistence of H. pylori infection in the early years of life may exert an adverse impact on intestinal health, induce gut inflammation and result in increased intestinal permeability.

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.

Dataset Information

Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania.

Background

Methods

Findings

Interpretation

Funding

Publications

Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania.

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