Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood.

Stunting is common in young children in developing countries, and is associated with increased morbidity, developmental delays, and mortality. Its complex pathogenesis likely involves poor intrauterine and postnatal nutrition, exposure to microbes, and the metabolic consequences of repeated infections. Acquired enteropathy affecting both gut structure and function likely plays a significant role in this outcome, especially in the first few months of life, and serve as a precursor to later interactions of infection and malnutrition. However, the lack of validated clinical diagnostic criteria has limited the ability to study its role, identify causative factors, and determine cost-effective interventions. This review addresses these issues through a historical approach, and provides recommendations to define and validate a working clinical diagnosis and to guide critical research in this area to effectively proceed. Prevention of early gut functional changes and inflammation may preclude or mitigate the later adverse vicious cycle of malnutrition and infection.

HighlightsChildren living in these settings had a high prevalence of enteropathogens, high levels of intestinal inflammation, abnormal intestinal permeability, high markers of systemic inflammation, and postnatal acquired linear growth deficits when compared to children living in the US or EuropeThis study contributes empiric evidence to demonstrate that enteric infection alters both fecal markers of inflammation and permeabilityCurrent markers of enteropathy fail to account for a large portion of the observed shortfalls in linear growth in these populations, and markers of systemic inflammation appear as the most promising predictive biomarkers for identifying linear growth failure in childrenEnvironmental enteropathy (EE) is hypothesized as a mediator of growth faltering, but few prospective studies have evaluated pathways linking enteropathogen exposure, intestinal inflammation and permeability, and growth. The MAL-ED study represents a novel analytical framework and explicitly evaluates multiple putative EE pathways in combination and using an unprecedented quantity of data. Despite evidence that gut inflammation and altered gut permeability are frequently present and that associations between enteropathogen exposure and gut dysfunction exist, the observed attributable effects of EE on growth faltering in young children were small.

Changes in small bowel function early in infancy in developing countries are increasingly being demonstrated, probably accompanied by altered mucosal architecture in most individuals, including reduced enterocyte mass and evidence of immune activation and inflammation in the mucosa. These alterations appear to be the result of factors of uncertain nature in the environment, and may be a cause of growth faltering and stunting in young children. For these reasons, this constellation of findings is being referred to as environmental enteropathy, or as we propose herein, environmental enteric dysfunction. If the causes were known and effective interventions were available, strategies and policies to intervene at—or possibly before—birth could be developed and promoted in order to prevent subsequent malnutrition and recurrent infection, which are known to interact in a cyclical and synergistic manner in a downward clinical course often ending in death. Resources would be mobilized and applied differently, and the emphasis would change from treatment to prevention. In order to move in this highly desired direction, investments in research will be required to establish the criteria to assess environmental enteric dysfunction, determine its predictive value for growth faltering and stunting, identify the causes, and propose and test potential interventions. The concepts and tools are available. What is required is the decision to move forward along this pathway to better health for infants and children in low-income countries.

Background:Childhood obesity is an emerging global public health challenge. Evidence for the transition in nutrition in Indo-Asian developing countries is lacking. We conducted these analyses to determine the trends in nutritional status of school-aged children in urban Pakistan.Methods:Data on the nutritional status of children aged 5 to 14 years from two independent population-based representative surveys, the urban component of the National Health Survey of Pakistan (NHSP; 1990–1994) and the Karachi survey (2004–2005), were analysed. Using normative data from children in the United States as the reference, trends for age- and gender-standardised prevalence (95% CI) of underweight (more than 2 SD below the weight-for-age reference), stunted (more than 2 SD below the height-for-age reference) and overweight and obese (body mass index (BMI) 85th percentile or greater) children were compared for the two surveys. The association between physical activity and being overweight or obese was analysed in the Karachi survey using logistical regression analysis.Results:2074 children were included in the urban NHSP and 1675 in the Karachi survey. The prevalence of underweight children was 29.7% versus 27.3% (p = 0.12), stunting was 16.7% versus 14.3% (p = 0.05), and prevalence of overweight and obese children was 3.0 versus 5.7 (p<0.001) in the NHSP and Karachi surveys, respectively. Physical activity was inversely correlated with being overweight or obese (odds ratio, 95% CI, 0.51, 0.32–0.80 for those who engaged in more than 30 minutes of physical activity versus those engaged in less than 30 minutes’ activity).Conclusions:Our study highlights the challenge faced by Pakistani school-aged children. There has been a rapid rise in the number of overweight and obsese children despite a persistently high burden of undernutrition. Focus on prevention of obesity in children must include strategies for promoting physical activity.