Q&A with Michael Gottlieb, Ph.D., FNIH Deputy Director of Science: The Significant Role of Malnutrition, Intestinal Infection and Disease on Child Development

October 11, 2017 — For almost a decade, the Foundation for the National Institutes of Health (FNIH), in collaboration with the National Institutes of Health’s Fogarty International Center (FIC), has managed the most comprehensive multicenter study to better understand the complicated relationships among intestinal infections, nutrition and other environmental exposures early in life on child development. “The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development” (MAL-ED) study, supported by a grant from the Bill & Melinda Gates Foundation, captured the significant burden that such exposures have on the health, physical growth and cognitive development of children from birth to early childhood at eight sites in Africa, Asia and South America.

In the following Q&A, Michael Gottlieb, Ph.D., FNIH Deputy Director of Science and lead Principal Investigator for the MAL-ED study, discusses the findings of the study obtained to date.

Watch a video about the study and learn more at https://fnih.org/MAL-ED.

1. Describe how and why MAL-ED was designed with research conducted on three continents.

Previous studies have shown that children living in developing countries with limited resources are more likely to suffer from growth and development shortfalls compared to those living in environments with better resources. The MAL-ED study closely followed approximately 200 children at each of the project’s eight sites from the first two weeks after birth until 24 months of age. Using a standardized protocol to reduce methodological differences among sites, the children were continuously and carefully monitored for illness, enteric (gut) infections, immune responses to childhood vaccines, breastfeeding and other nutrient intakes, and cognitive development. In addition, information regarding a number of socioeconomic factors (such as water quality, household income and maternal education) were collected in and around each child’s household to assess and compare overall living conditions. The children were subsequently visited periodically until they reached five years of age to assess cognitive development and psychosocial achievement.

The sites (located in Iquitos, Peru; Fortaleza, Brazil; Haydom, Tanzania; Limpopo, South Africa; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Vellore, India; Dhaka, Bangladesh) chosen for the study allowed for comparisons to be made among and between children living in geographically and culturally disperse urban and rural environments and in countries at different levels of economic development.

2. What were the key findings of MAL-ED? Were they what you expected after eight years of research?

The MAL-ED study provides some of the strongest evidence linking the burden of enteropathogens (gut bacteria, parasites and viruses), even in the absence of overt symptoms (especially diarrhea), to growth and developmental shortfalls in infancy and early childhood. Despite the differences in environmental conditions and the children’s experiences at the study sites, one significant factor stood out: the exposure to, and infection with, enteric pathogens in the environment was most strongly and consistently identified with physical growth and other developmental deficits. In particular, repeated exposure to enteropathogens leads to a less-than-optimal growth rate, with significantly lower weight and length at 24 months of age when compared to internationally-accepted norms for these measures. Suboptimal growth is compounded by reduced dietary intake of complementary foods with protein of poor quality.

Although diarrheal disease has been long associated with growth and development deficits, the MAL-ED study showed that the enteropathogen burden in the gut contributed more to these deficits than did diarrhea. While the project’s analysis of the various types of data collected revealed the complexity of interactions leading to growth and development shortfalls, the clear association of asymptomatic enteropathogen burden with each of the various outcome measures (physical growth and cognitive development) was somewhat unexpected.

In contrast to one-time, clinic-based studies of symptomatic disease (especially moderate to severe diarrhea), the longitudinal and community-based nature of the MAL-ED study revealed the effects of poor environmental conditions on an individual’s growth and development, even in the absence of symptomatic disease. These effects collectively have long-term consequences on a child’s development and performance, and have the potential to influence a society’s future economic productivity and social advancement.

3. What do the findings from MAL-ED tell us about the role of nutrition on the growth and development of children?

The MAL-ED study of nutrient intake by young children in developing countries is among the most robust of its type ever conducted. Appropriate nutrient intake is one important factor that contributes to optimal growth and development. The MAL-ED study revealed the differences in breastfeeding practices among the sites, as well as the amounts and types of food available to the children. Differences in breastfeeding practices were attributed to cultural differences and a mother’s education. Analyses indicated the benefit of a diverse diet and one containing a significant amount of protein on growth and development.

4. What was the FNIH’s role in the study?

FNIH personnel played a key role in overall scientific, administrative and budgetary management of the study. In collaboration with FIC and other MAL-ED investigators, the FNIH oversaw the development and implementation of the project’s standardized protocol, ensured that ethical approvals were up-to-date, and organized and convened meetings to review progress and undertake data analyses. The FNIH also supported training and related efforts to promote and obtain the highest quality of the collected data and biospecimens. Additionally, FNIH staff developed a Research Consortium Agreement that bound all collaborating investigators and their institutions to a core set of principles, policies and practices related to ownership, stewardship and sharing of the data, as well as publishing the results of data analyses.

5. How will the study results be helpful to other researchers and organizations who want to reduce childhood diseases in the developing world?

While research on improving the treatment and prevention of overt clinical disease (including diarrhea and respiratory infections) must continue, attention must be given to improving the environmental conditions and exposures resulting primarily from contaminated water, food and unsanitary living conditions causing infections that lead to the growth and developmental shortfalls, which are indicators of poorer future school performance and economic productivity. The MAL-ED study findings on the role of enteropathogens, taken together with the findings on nutrition, suggest that a combined intervention strategy that seeks to reduce pathogen exposure and to improve the quantity and protein quality of complementary food intake (i.e. besides breastmilk) in infants and young children has the best chance of reducing impaired growth and cognitive development.

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