Dataset Information

Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study.

ABSTRACT:

Background

Stunting is the most prevalent manifestation of childhood malnutrition. To characterize factors that contribute to stunting in resource-poor settings, we studied a priori selected biological and social factors collected longitudinally in a cohort of newborns.

Methods and findings

We enrolled 1,868 children across 7 resource-poor settings in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania shortly after birth and followed them for 24 months between 2 November 2009 and 28 February 2014. We collected longitudinal anthropometry, sociodemographic factors, maternal-reported illnesses, and antibiotic use; child feeding practices; dietary intake starting at 9 months; and longitudinal blood, urine, and stool samples to investigate non-diarrheal enteropathogens, micronutrients, gut inflammation and permeability, and systemic inflammation. We categorized length-for-age Z-scores into 3 groups (not stunted, ?-1; at risk, <-1 to -2; and stunted, <-2), and used multivariable ordinal logistic regression to model the cumulative odds of being in a lower length-for-age category (at risk or stunted). A total of 1,197 children with complete longitudinal data were available for analysis. The prevalence of having a length-for-age Z-score below -1 increased from 43% (range 37%-47% across sites) shortly after birth (mean 7.7 days post-delivery, range 0 to 17 days) to 74% (16%-96%) at 24 months. The prevalence of stunting increased 3-fold during this same time period. Factors that contributed to the odds of being in a lower length-for-age category at 24 months were lower enrollment weight-for-age (interquartile cumulative odds ratio = 1.82, 95% CI 1.49-2.23), shorter maternal height (2.38, 1.89-3.01), higher number of enteropathogens in non-diarrheal stools (1.36, 1.07-1.73), lower socioeconomic status (1.75, 1.20-2.55), and lower percent of energy from protein (1.39, 1.13-1.72). Site-specific analyses suggest that reported associations were similar across settings. While loss to follow-up and missing data are inevitable, some study sites had greater loss to follow-up and more missing data than others, which may limit the generalizability of the findings.

Conclusions

Neonatal and maternal factors were early determinants of lower length-for-age, and their contribution remained important throughout the first 24 months of life, whereas the average number of enteropathogens in non-diarrheal stools, socioeconomic status, and dietary intake became increasingly important contributors by 24 months relative to neonatal and maternal factors.

SUBMITTER: MAL-ED Network Investigators

PROVIDER: S-EPMC5656304 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study.

PLoS medicine 20171025 10

<h4>Background</h4>Stunting is the most prevalent manifestation of childhood malnutrition. To characterize factors that contribute to stunting in resource-poor settings, we studied a priori selected biological and social factors collected longitudinally in a cohort of newborns.<h4>Methods and findings</h4>We enrolled 1,868 children across 7 resource-poor settings in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania shortly after birth and followed them for 24 months between 2 No ...[more]

PMID: 29069076

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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:ImportanceAlthough there has been a reduction in stunting (low-height-for-age and low-length-for-age), a proxy of malnutrition, the prevalence of malnutrition in Ethiopia is still high. Child growth patterns and estimates of stunting are needed to increase awareness and resources to improve the potential for recovery.ObjectiveTo estimate the prevalence, incidence, and reversal of stunting among children aged 0 to 24 months.Design, setting, and participantsThis population-based cohort study of the Birhan Maternal and Child Health cohort in North Shewa Zone, Amhara, Ethiopia, was conducted between December 2018 and November 2020. Eligible participants included children aged 0 to 24 months who were enrolled during the study period and had their length measured at least once. Data analysis occurred from Month Year to Month Year.Main outcomes and measuresThe primary outcome of this study was stunting, defined as length-for-age z score (LAZ) at least 2 SDs below the mean. Z scores were also used to determine the prevalence, incidence, and reversal of stunting at each key time point. Growth velocity was determined in centimeters per month between key time points and compared with global World Health Organization (WHO) standards for the same time periods. Heterogeneity was addressed by excluding outliers in sensitivity analyses using modeled growth trajectories for each child.ResultsA total of 4354 children were enrolled, out of which 3674 (84.4%; 1786 [48.7%] female) had their length measured at least once and were included in this study. The median population-level length was consistently below WHO growth standards from birth to 2 years of age. The observed prevalence of stunting was highest by 2 years of age at 57.4% (95% CI, 54.8%-9 60.0%). Incidence of stunting increased over time and reached 51.0% (95% CI, 45.3%-56.6%) between ages 12 and 24 months. Reversal was 63.5% (95% CI, 54.8%-71.4%) by age 6 months and 45.2% (95% CI, 36.0%-54.8%) by age 2 years. Growth velocity point estimate differences were slowest compared with WHO standards during the neonatal period (-1.4 cm/month for girls and -1.6 cm/month for boys). There was substantial heterogeneity in anthropometric measurements.Conclusions and relevanceThe evidence from this cohort study highlights a chronically malnourished population with much of the burden associated with growth faltering during the neonatal periods as well as after 6 months of age. To end all forms of malnutrition, growth faltering in populations such as that in young children in Amhara, Ethiopia, needs to be addressed.

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: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.

Dataset Information

Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study.

Background

Methods and findings

Conclusions

Publications

Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study.

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