Protocol for the trial to establish a causal linkage between mycotoxin exposure and child stunting: a cluster randomized trial

Abstract

Background: The number of stunted children has fallen globally but continues to increase in Africa. Stunting is estimated to contribute to 14-17% of child deaths under 5 years of age and is a risk factor for poor cognitive and motor development and educational outcomes. Inadequate dietary intake and disease are thought to be the immediate causes of undernutrition and stunting. However, improving infant diets through complementary feeding interventions has been shown to only modestly reduce stunting. Multiple observational studies demonstrate a dose response relationship between fetal and post-natal aflatoxin exposure and reduced linear growth. Methods: This community-based cluster randomized trial will measure the effect of a reduced aflatoxin diet on length-forage Z scores at 18 months in central Tanzania. All 52 health facilities in the Kongwa District of Dodoma Region were randomized into two groups. Starting at 6 months of age, participants in the intervention group receive a low-aflatoxin pre-blended porridge flour containing maize and groundnut (ratio 4:1 respectively) and lowaflatoxin groundnut flour, whereas in the control group the same porridge mix and groundnut flour are promoted through education but acquired by the household. Both groups will receive the same infant and young child feeding education and a thermos flask. A total of 3120 infants between 6 weeks and 3 months of age will be recruited into the study over 1 year. Data will be collected four timesat recruitment and when the infants are 6, 12 and 18 months of age. In a cohort of 600 infants, additional data will be collected at 9 and 15 months of age. The primary outcome is length-forage at 18 months. Secondary outcomes include the Z scores for weight-forage , middle upper arm circumference and head circumference, and the blood biomarker aflatoxin-albumin in the full sample, with the urine biomarker aflatoxin M1 analyzed in the cohort only. Discussion: Better understanding the etiology of childhood stunting can lead to more appropriate interventions and policies to further reduce linear growth faltering and meet the Sustainable Development Goals. Trial registration: NCT03940547, (April 24, 2019).

Early life exposure to dietary aflatoxins, health impact and control perspectives: A review

“…Diversified complementary foods formulated through nutritious recipes resulted in higher reduction in urinary AFM1 (64% as compared to 11% in control) and increased Z-score for stunting, underweight, and wasting by 0.459, 0.493 and 0.252, respectively (Anitha et al, 2020). Similarly, the consumption of low-aflatoxin pre-blended mix (prepared by combination of maize and groundnuts) in the ongoing intervention study by Phillips et al (2020) reduced the prevalence of urinary AFM1 (by 81%) in infants.…”

“…Education for agricultural interventions was mostly provided by agricultural extension services accompanied by provision of technological and food-replacement access to the intervention groups. The nutritional interventions to reduce aflatoxin exposure were usually aimed at educating mothers/caregivers of infants about increasing diversified foods in the diet, adopting optimal food preparation methods (Anitha et al, 2020) and choosing foods at low risk of aflatoxin contamination for complementary food preparations (Phillips et al, 2020).…”

Human Breast Milk Contamination with Aflatoxins, Impact on Children’s Health, and Possible Control Means: A Review

“…Additionally, the contribution of AFB1 carry-over to the extent of breast milk contamination with AFM1 is dependent on the carry-over rate (COR), i.e., the proportion of AFB1 converted into AFM1 in the liver and possibly in the mammary glands. While the carry-over rate has been extensively studied in lactating domestic animals exposed to different amounts of aflatoxins [ 22 , 38 , 39 , 40 , 41 ], such studies are lacking in lactating mothers due the ethical considerations severely restricting the use of human subjects in experiments where they can be intentionally given aflatoxin-contaminated foods [ 42 , 43 , 44 ]. Nevertheless, the correlation between AFB1 dietary intake and human milk contamination with AFM1 is well established [ 32 , 45 , 46 , 47 ].…”

An overview of mycotoxin biomarker application in exposome-health studies

“…Child growth may be impaired by AF or FBs, as revealed by observational studies that applied established biomarkers (AF-albumin and AFB-lys in blood or urinary FB) conducted in sub-Saharan African countries such as Tanzania, Benin, Togo or Gambia. On this basis, a novel study design based on a community-based cluster randomized trial has been recently proposed to assess the causal associations between AF and growth of infants from central Tanzania [16].…”