Environmental 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. Non-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. Children 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. The 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. Bill & Melinda Gates Foundation.

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor–derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto- N -neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N -glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.

Background: Stunting results from decreased food intake, poor diet quality, and a high burden of early childhood infections, and contributes to significant morbidity and mortality worldwide. Although food insecurity is an important determinant of child nutrition, including stunting, development of universal measures has been challenging due to cumbersome nutritional questionnaires and concerns about lack of comparability across populations. We investigate the relationship between household food access, one component of food security, and indicators of nutritional status in early childhood across eight country sites. Methods: We administered a socioeconomic survey to 800 households in research sites in eight countries, including a recently validated nine-item food access insecurity questionnaire, and obtained anthropometric measurements from children aged 24 to 60 months. We used multivariable regression models to assess the relationship between household food access insecurity and anthropometry in children, and we assessed the invariance of that relationship across country sites. Results: Average age of study children was 41 months. Mean food access insecurity score (range: 0–27) was 5.8, and varied from 2.4 in Nepal to 8.3 in Pakistan. Across sites, the prevalence of stunting (42%) was much higher than the prevalence of wasting (6%). In pooled regression analyses, a 10-point increase in food access insecurity score was associated with a 0.20 SD decrease in height-for-age Z score (95% CI 0.05 to 0.34 SD; p = 0.008). A likelihood ratio test for heterogeneity revealed that this relationship was consistent across countries (p = 0.17). Conclusions: Our study provides evidence of the validity of using a simple household food access insecurity score to investigate the etiology of childhood growth faltering across diverse geographic settings. Such a measure could be used to direct interventions by identifying children at risk of illness and death related to malnutrition.

Information on the association between stunting and child development is limited from low‐income settings including Bangladesh where 36% of children under‐ 5 are stunted. This study aimed to explore differences in early childhood development (ECD) between stunted (length‐for‐age z‐score [LAZ] < −2) and nonstunted (LAZ ≥ −2) children in Bangladesh. Children (n = 265) aged 6–24 months who participated in the MAL‐ED birth cohort study were evaluated by trained psychologists at 6, 15, and 24 months of age using the Bayley Scales of Infant and Toddler Development‐III; child length and weight were measured using standard procedures. ECD scores (z‐scores derived from cognitive, motor, language and socio‐emotional skills) were compared between stunted, underweight (weight‐for‐age z‐score < −2), and wasted (weight‐for‐length z‐score < −2) children, controlling for child age and sex and maternal age, education, body mass index (BMI), and depressive symptoms. Stunted children had significantly lower ECD scores than their nonstunted peers on cognitive (P = .049), motor (P < .001), language (P < .001) and social–emotional (P = .038) scales where boys had significantly lower fine motor skills compared with girls (P = .027). Mother's schooling and BMI were significant predictors of ECD. Similar to stunting, underweight children had developmental deficits in all domains (cognitive: P = .001; fine motor: P = .039, and P < .001 for both gross motor and total motor; expressive communication: P = .032; total language: P = .013; social–emotional development: P = .017). Wasted children had poor motor skills (P = .006 for the fine motor; P < .001 for both gross motor and total motor development) compared with the nonwasted peers. Early childhood stunting and underweight were associated with poor developmental outcomes in Bangladesh.

Bangladesh is one of the 20 countries with highest burden of stunting globally. A large portion (around 2.2 million) of the population dwells in the slum areas under severe vulnerable conditions. Children residing in the slums are disproportionately affected with higher burden of undernutrition particularly stunting. In this paper, findings of a prospective cohort study which is part of a larger multi-country study are presented. Two hundred and sixty five children were enrolled and followed since their birth till 24 months of age. Anthropometric measurements, dietary intake and morbidity information were collected monthly. Data from 9 to 12, 15–18 and 21–24 months were collated to analyze and report findings for 12, 18 and 24 months of age. Generalized estimating equation models were constructed to determine risk factors of stunting between 12 and 24 months of age. Approximately, 18% of children were already stunted (LAZ < -2SD) at birth and the proportion increased to 48% at 24 months of age. Exclusive breastfeeding prevalence was only 9.4% following the WHO definition at 6 months. Dietary energy intake as well as intakes of carbohydrate, fat and protein were suboptimal for majority of the children. However, in regression analysis, LAZ at birth (AOR = 0.40, 95% CI: 0.26, 0.61), household with poor asset index (AOR = 2.81, 95% CI: 1.43, 5.52; ref.: average asset index), being male children (AOR = 1.75, 95% CI: 1.04, 2.95; ref.: female) and age (AOR = 2.34, 95% CI: 1.56, 3.52 at 24 months, AOR = 2.13, 95% CI: 1.55, 2.92 at 18 months; ref.: 12 months of age) were the significant predictors of stunting among this population. As the mechanism of stunting begins even before a child is born, strategies must be focused on life course approach and preventive measurement should be initiated during pregnancy. Alongside, government and policymakers have to develop sustainable strategies to improve various social and environmental factors those are closely interrelated with chronic undernutrition particularly concentrating on urban slum areas.

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved me