Dataset Information

Enteric dysfunction and other factors associated with attained size at 5 years: MAL-ED birth cohort study findings.

ABSTRACT:

Background

Poor growth in early childhood has been associated with increased risk of mortality and morbidity, as well as long-term deficits in cognitive development and economic productivity.

Objectives

Data from the MAL-ED cohort study were used to identify factors in the first 2 y of life that are associated with height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, BMIZ) at 5 y of age.

Methods

A total of 1017 children were followed from near birth until 5 y of age at sites in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania. Data were collected on their growth, environmental enteric dysfunction (EED), micronutrient status, enteric pathogen burden, illness prevalence, dietary intake, and various other socio-economic and environmental factors.

Results

EED biomarkers were related to size at 5 y. Mean lactulose:mannitol z-scores during the first 2 y of life were negatively associated with all of the growth measures (HAZ: -0.11 [95% CI: -0.19, -0.03]; WAZ: -0.16 [95% CI: -0.26, -0.06]; BMIZ: -0.11 [95% CI: -0.23, 0.0]). Myeloperoxidase was negatively associated with weight (WAZ: -0.52 [95% CI: -0.78, -0.26] and BMIZ: -0.56 [95% CI: -0.86, -0.26]); whereas ?-1-antitrypsin had a negative association with HAZ (-0.28 [95% CI: -0.52, -0.04]). Transferrin receptor was positively related to HAZ (0.18 [95% CI: 0.06, 0.30]) and WAZ (0.21 [95% CI: 0.07, 0.35]). Hemoglobin was positively related to HAZ (0.06 [95% CI: 0.00, 0.12]), and ferritin was negatively related to HAZ (-0.08 [95% CI: -0.12, -0.04]). Bacterial density in stool was negatively associated with HAZ (-0.04 [95% CI: -0.08, 0.00]), but illness symptoms did not have any effect on size at 5 y.

Conclusions

EED markers, bacterial density, and iron markers are associated with growth at 5 y of age. Interventions to reduce bacterial burden and EED may improve long-term growth in low-income settings.

SUBMITTER: Richard SA

PROVIDER: S-EPMC6599740 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Enteric dysfunction and other factors associated with attained size at 5 years: MAL-ED birth cohort study findings.

Richard Stephanie A SA McCormick Benjamin J J BJJ Murray-Kolb Laura E LE Lee Gwyneth O GO Seidman Jessica C JC Mahfuz Mustafa M Ahmed Tahmeed T Guerrant Richard L RL Petri William A WA Rogawski Elizabeth T ET Houpt Eric E Kang Gagandeep G Mduma Estomih E Kosek Margaret N MN Lima Aldo A M AAM Shrestha Sanjaya K SK Chandyo Ram K RK Bhutta Zulfiqar Z Bessong Pascal P Caulfield Laura E LE

The American journal of clinical nutrition 20190701 1

<h4>Background</h4>Poor growth in early childhood has been associated with increased risk of mortality and morbidity, as well as long-term deficits in cognitive development and economic productivity.<h4>Objectives</h4>Data from the MAL-ED cohort study were used to identify factors in the first 2 y of life that are associated with height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, BMIZ) at 5 y of age.<h4>Methods</h4>A total of 1017 children were followed from near birth until ...[more]

PMID: 31127812

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Project description:BackgroundEnvironmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries.MethodsNon-diarrheal stool samples (N=22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N=6363) and plasma alpha-1-acid glycoprotein (AGP) (N=2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0-2years of age.FindingsChildren in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated.InterpretationThe large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation.FundingBill & Melinda Gates Foundation.

Project description:Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study.From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression.The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years.Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestinal permeability and stunted growth.

Project description:BackgroundBreastfeeding is known to reduce the risk of enteropathogen infections, but protection from specific enteropathogens is not well characterized.ObjectiveThe aim was to estimate the association between full breastfeeding (days fed breast milk exclusively or with nonnutritive liquids) and enteropathogen detection.MethodsA total of 2145 newborns were enrolled at 8 sites, of whom 1712 had breastfeeding and key enteropathogen data through 6 mo. We focused on 11 enteropathogens: adenovirus 40/41, norovirus, sapovirus, astrovirus, and rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter spp., and typical enteropathogenic E. coli as well as entero-aggregative E. coli, Shigella and Cryptosporidium. Logistic regression was used to estimate the risk of enteropathogen detection in stools and survival analysis was used to estimate the timing of first detection of an enteropathogen.ResultsInfants with 10% more days of full breastfeeding within the preceding 30 d of a stool sample were less likely to have the 3 E. coli and Campylobacter spp. detected in their stool (mean odds: 0.92-0.99) but equally likely (0.99-1.02) to have the viral pathogens detected in their stool. A 10% longer period of full breastfeeding from birth was associated with later first detection of the 3 E. coli, Campylobacter, adenovirus, astrovirus, and rotavirus (mean HRs of 0.52-0.75). The hazards declined and point estimates were not statistically significant at 3 mo.ConclusionsIn this large multicenter cohort study, full breastfeeding was associated with lower likelihood of detecting 4 important enteric pathogens in the first 6 mo of life. These results also show that full breastfeeding is related to delays in the first detection of some bacterial and viral pathogens in the stool. As several of these pathogens are risk factors for poor growth during childhood, this work underscores the importance of exclusive or full breastfeeding during the first 6 mo of life to optimize early health.

Project description:BackgroundImmunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.MethodsPolio neutralizing antibody assays were conducted at 7 and 15?months of age for serotypes 1 and 3. Analyses were conducted on children receiving ?3 OPV doses (n?=?1449). History of vaccination, feeding patterns, physical growth, home environment, diarrhea, enteropathogen detection, and gut inflammation were examined as risk factors for non-response [Log2(titer)?<?3] and Log2(titer) by serotype using multivariate regression.FindingsSerotype 1 seroconversion was significantly higher than serotype 3 (96.6% vs. 89.6%, 15?months). Model results indicate serotypes 1 and 3 failure was minimized following four and six OPV doses, respectively; however, enteropathogen detection and poor socioeconomic conditions attenuated response in both serotypes. At three months of age, bacterial detection in stool reduced serotype 1 and 3 Log2 titers by 0.34 (95% CI 0.14-0.54) and 0.53 (95% CI 0.29-0.77), respectively, and increased odds of serotype 3 failure by 3.0 (95% CI 1.6-5.8). Our socioeconomic index, consisting of Water, Assets, Maternal education, and Income (WAMI), was associated with a 0.79 (95% CI 0.15-1.43) and 1.23 (95% CI 0.34-2.12) higher serotype 1 and 3 Log2 titer, respectively, and a 0.04 (95% CI 0.002-0.40) lower odds of serotype 3 failure. Introduction of solids, transferrin receptor, and underweight were differentially associated with serotype response. Other factors, including diarrheal frequency and breastfeeding practices, were not associated with OPV response.InterpretationUnder real-world conditions, improved vaccination coverage and socio-environmental conditions, and reducing early life bacterial exposures are key to improving OPV response and should inform polio eradication strategies.

Project description:BackgroundMost studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.MethodsWe undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through twice-weekly home visits by fieldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1-12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specific burdens of diarrhoea.FindingsBetween November 26, 2009, and February 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0-24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5·2%, 95% CI 3·0-7·1), rotavirus (4·8%, 4·5-5·0), Campylobacter spp (3·5%, 0·4-6·3), astrovirus (2·7%, 2·2-3·1), and Cryptosporidium spp (2·0%, 1·3-2·6) exhibited the highest attributable burdens of diarrhoea in the first year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7·9%, 3·1-12·1), norovirus GII (5·4%, 2·1-7·8), rotavirus (4·9%, 4·4-5·2), astrovirus (4·2%, 3·5-4·7), and Shigella spp (4·0%, 3·6-4·3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fifth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII.InterpretationThere was substantial heterogeneity in pathogen-specific burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These findings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the effect of such interventions on total diarrhoeal incidence at the community level might be limited.

Dataset Information

Enteric dysfunction and other factors associated with attained size at 5 years: MAL-ED birth cohort study findings.

Background

Objectives

Methods

Results

Conclusions

Publications

Enteric dysfunction and other factors associated with attained size at 5 years: MAL-ED birth cohort study findings.

Similar Datasets

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