Mycotoxin Exposure, Child Stunting and Birth Outcomes: Future Directions for the SHINE Trial

Clockwise from left: Loveness Nyanga (Faculty University of Zimbabwe), Nabila Ismail (UB PharmD Student), Charles Maponga (UB Faculty), Nadia Koyratty (UB EEH PhD Student), Laura Smith (UB faculty).

Clockwise from left: Loveness Nyanga (Faculty University of Zimbabwe), Nabila Ismail (UB PharmD Student), Charles Maponga (UB Faculty), Nadia Koyratty (UB EEH PhD Student), Laura Smith (UB faculty)

Low height-for-age, or stunting, is a major contributor to childhood mortality globally and is often used as a marker of malnutrition in children. Stunting is most likely to occur in the first 24 months of life, and is characterized by a child having a length-for-age z-score (LAZ), or height-for-age z-score (HAZ), below two standard deviations. Stunted children are more likely to have cognitive delays, face higher rates of mortality, and can have decreased economic productivity in adulthood. Compounding on this, children are at increased risk of stunting if their parents were stunted as children themselves, establishing an intergenerational cycle of decreased economic productivity and increased mortality. Rural regions in Sub-Saharan Africa and South Asia especially suffer from a high prevalence of stunting in children under the age of 5. 

SHINE Trial

To examine the effects of malnutrition and poor water, sanitation, and hygiene (WASH), thought to be two of the largest contributors to child stunting, on child stunting in the rural districts of Chirumanzu and Shurugwi in Zimbabwe, the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial was conducted from November, 2012 until August, 2017. SHINE was a cluster-randomized, community-based, 2x2 factorial trial of pregnant mothers permanently living in one of the clustered catchment areas, covered by between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Clusters were randomized (1:1:1:1) into one of four experimental groups; standard of care (control), an improved infant and young child feeding (IYCF) intervention, an improved WASH intervention, and a combined improved IYCF and WASH intervention. Participating mothers and children were then followed up through birth and the 18 months following birth. A variety of outcomes were measured throughout the study; however, the primary outcomes were child stunting and anemia, in children born to HIV-negative mothers, at the age of 18 months.

Preliminary results for the SHINE trial were published in January, 2019 in the Lancet. Briefly, researchers found a 0.16 (95% CI 0.08–0.23) greater mean LAZ and 2.03 g/L (1.28–2.79) greater mean hemoglobin concentration in IYCF intervention groups when compared to groups who did not receive the IYCF intervention. Comparatively, these effects reduced the number of stunted children from 620 (35%) in the non-IYCF groups to 514 (27%) in the IYCF groups, and the number of children with anemia from 245 (13.9%) in the non-IYCF groups to 193 (10.5%) in the IYCF groups. There was no effect on either anemia or stunting from the WASH intervention, and researchers concluded that combination WASH/IYCF interventions were unlikely reduce stunting and anemia in children more than IYCF interventions alone. Dr. Laura Smith is a co-investigator on this trial. Funding was provided by the Bill & Melinda Gates Foundation, the UK Department for International Development, the Wellcome Trust, the Swiss Development Cooperation, UNICEF, and the US National Institutes of Health.

Mycotoxin Exposure in Pregnancy and Birth Outcomes

In addition to the primary outcomes and exposures, the SHINE trial measured a large variety of complementary covariates and outcomes. This includes mycotoxin exposure and the birth outcomes of the children involved. Mycotoxins are toxic secondary metabolites of molds which contaminate staple foods of the region, including maize and groundnuts. Communities are often dependent on staple foods for a large portion of their diet, yet little research has been done into chronic mycotoxin exposure in humans, especially during pregnancy.

The objective of our project is to characterize pregnancy exposure to multiple mycotoxins and their relation to birth outcomes in the SHINE trial. We hypothesize exposure to the mycotoxins aflatoxin, fumonisin, and deoxynivalenol, are important contributing components to adverse birth outcomes globally. Dr. Laura Smith is a co-investigator on this trial. Funding is provided by National Institutes of Health (1R21 ES023980-01A1).

Establishing the Link between Mycotoxin Exposure, Gut Dysfunction and Stunting in Zimbabwean Infants

Environmental enteropathy (EED), or enteropathy caused by environmental exposures, is thought to be associated with stunting and be on the causal pathway for the interventions addressed in SHINE trial. A variety of environmental factors may influence EED in children, including mycotoxins. The objective of this project will be to characterize the potential association between mycotoxin exposure, gut dysfunction and stunting in participating children from the SHINE trial. Dr. Laura Smith is a co-investigator on this trial. Funding is provided by the Bill and Melinda Gates Foundation (OPP1066254).

Long term, we hope to understand the effect of mycotoxin exposure on maternal and child health in Zimbabwe, and help to inform and develop more effective child health interventions and food safety policy globally.

Latest News

Publications and Presentations

Humphrey JH, Mbuya MN, Ntozini R, Moulton LH, Stoltzfus RJ, Tavengwa NV, Mutasa K, Majo F, Mutasa B, Mangwadu G, Chasokela CM Chigumira A, Chasekwa B, Smith LE, Tielsch JM, Jones AJ, Manges AR, Maluccio JA, and Prendergast AJ. Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial. The Lancet Global Health. 2019;7(1):e132-47.

Prendergast AJ, Chasekwa B, Evans C, Mutasa K, Mbuya MN, Stoltzfus RJ, Smith LE, Majo FD, Tavengwa NV, Mutasa B, Mangwadu GT, Chasokela CM, Chigumira A, Moulton LH, Ntozini R, and Humphrey JH. Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on stunting and anaemia among HIV-exposed children in rural Zimbabwe: a cluster-randomised controlled trial. The Lancet Child & Adolescent Health. 2018 Dec 18.

Chasekwa B, Maluccio JA, Ntozini R, Moulton LH, Wu F, Smith LE, Matare CR, Stoltzfus RJ, Mbuya MMN, Tielsch JM, Martin SL, Jones A, Humphrey JH, and Fielding K. Measuring wealth in rural communities: Lessons from the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) Trial. Under Review. PLoS one.2018; 13(6): e0199393

Smith LE, Mbuya MN, Prendergast AJ, Turner PC, Rukobo, S, Humphrey JH, Nelson, RJ, Chigumira A, Kembo G and Stoltzfus RJ. Determinants of Recent Aflatoxin Exposure among Pregnant Women in Rural Zimbabwe. Molecular Nutrition and Food Research. 2017; 61(9): 1601049. doi: 10.1002/mnfr.201601049.

Smith LE, Prendergast AJ, Turner, PC, Humphrey, JH, and Stoltzfus RJ.  Aflatoxin exposure during pregnancy, maternal anemia and adverse birth outcomes: a review. American Journal of Tropical Medicine and Hygiene. 2017; 96(4): 770-776.​

Smith LE, Prendergast AJ, Turner P, Mbuya MN, Mutasa K, Kembo G, Stoltzfus RJ and the SHINE Trial Group. The potential role of mycotoxins as a contributor to stunting in the SHINE Trial. Clinical and Infectious Diseases 2015. 71 Suppl 7: S733-7.

Desai A, Smith LE, Mbuya M, Chigumira A, Fundira D, Tavengwa NV, Malaba TR, Majo F, Humphrey JH, Stoltzfus RJ and the SHINE Trial Group. The SHINE Trial infant feeding intervention:  Pilot study of effects on maternal learning and infant diet quality in rural Zimbabwe. Clinical and Infectious Diseases 2015. 71 Suppl 7: S710-715.

Smith, LE, Stoltzfus, RJ, and A Prendergast. Food chain mycotoxin exposure, gut health and impaired growth: A conceptual framework. Advances in Nutrition. 2012; 3: 526-531.

Our Team

Laura Smith

Co-Lead Early Life Exposome Team; Assistant Professor

Epidemiology and Environmental Health and Community for Global Health Equity

Jean H. Humphrey, ScD - Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe

Mduduzi N. N. Mbuya, PhD - Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA; Global Alliance for Improved Nutrition, Washington, DC, USA

Robert Ntozini - Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe

Lawrence H. Moulton, PhD - Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA

Rebecca J. Stoltzfus, PhD - Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA

Naume V. Tavengwa, MSW - Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe

Kuda Mutasa, MPH - Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe

Florence Majo, RN - Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe

Batsirai Mutasa, MPH - Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe

Goldberg Mangwadu, MSc – Ministry of Health and Child Care, Harare, Zimbabwe

Cynthia M. Chasokela, PhD – Ministry of Health and Child Care, Harare, Zimbabwe

Ancikaria Chigumira, MSc – Ministry of Health and Child Care, Harare, Zimbabwe

Bernard Chasekwa, MSc - Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe

James M. Tielsch, PhD - Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, USA

Andrew D. Jones, PhD - Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA

Amee R. Manges, PhD - University of British Columbia, Vancouver, BC, Canada

John A. Maluccio, PhD - Middlebury College, Middlebury, VT, USA

Andrew J. Prendergast, DPhil - Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Blizard Institute, Queen Mary University of London, London, UK

Paul Turner, PhD - Maryland Institute for Applied Environmental Health, School of Public Health, University of Maryland, College Park, Maryland.

George Kembo – Food and Nutrition Council, Zimbabwe

The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team (https://doi.org/10.1093/cid/civ844)