Browsing by Author "Smith, Laura"

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The effect of an intervention to reduce aflatoxin consumption from 6 to 18 mo of age on length-for-age z-scores in rural Tanzania: a cluster-randomized trial
(Elsevier, 2025-02-01) Phillips, Erica; Ngure, Francis; Kassim, Neema; Turner, Paul; Makule, Edna; Smith, Laura; Makori, Nyabasi; Cramer, Benedikt; Humpf, Hans-Ulrich; Nelson, Rebecca; Stoltzfus, Rebecca
Background Linear growth faltering continues to negatively affect children in low- and middle-income countries and is associated with poor cognitive, developmental, and educational outcomes. Laboratory and observational data suggest that aflatoxin (AF) is a contributor to stunting. Objective The Mycotoxin Mitigation Trial was a cluster-randomized, community-based 2-group trial conducted in Kongwa District, Tanzania, between 2018 and 2020. The trial assessed whether a 12-mo intervention to reduce AF consumption increased length-for-age z-scores (LAZ) at 18 mo. Methods Low-AF maize and groundnut flours were provided to the intervention group each month; skin lotion was distributed to the control group monthly. Infant and young child feeding education was delivered equally in 52 health facilities (clusters). Anthropometry and the AF blood biomarker serum AF-albumin (AF-alb) were assessed at 6, 12, and 18 mo of age. Outcomes were analyzed as intention-to-treat and per-protocol using linear mixed-effects models. Results Two thousand eight hundred forty-two maternal–infant dyads were recruited into the study. The intervention did not create a contrast in AF-alb. At 18 mo, 36% (n = 186/520) of infants had detectable levels of AF-alb compared with 54% (n = 195/364) at baseline, with no difference between groups. Mean LAZ in the intervention group at 18 mo was −1.83 (n = 1231, 95% CI: −1.93, −1.73) compared to −1.90 (n = 1287, 95% CI: −1.99, −1.82) in the control group (P = 0.28). Conclusions An intervention to reduce AF exposure did not alter AF-alb nor anthropometric measures between treatment groups. Drought and agricultural data indicated less favorable conditions for toxin production, resulting in low levels of exposure in both trial arms. Annual, seasonal, and geographic heterogeneity of AF contamination make it difficult to study in an ethically designed trial. Our formative research and early trial data indicate that stunting and intermittent AF exposure continue to be a problem in this region. However, the low-AF exposure levels during the trial led to inconclusive results.
Ethical considerations in the design and conduct of a cluster-randomised mycotoxin mitigation trial in Tanzania
(Wageningen Academic Publishers, 2022-01-24) Phillips, Erica; Turner, Paul; Ngure, Francis; Kassim, Neema; Makule, Edna; Smith, Laura; Nelson, Rebecca; Stoltzfus, Rebecca
Aflatoxins are fungal metabolites that commonly contaminate staple food crops in tropical regions. Acute aflatoxin consumption in very high concentration causes aflatoxicosis and acute liver failure, while chronic, moderate levels of intake cause hepatocellular carcinoma. The effects of frequent moderate- to high-level exposure during infancy, however, is less clearly understood. Half a billion people in low- and middle-income countries continue to be exposed to aflatoxins through dietary consumption, in part because of lack of enforcement of regulatory limits and few feasible long-term mitigation options in these settings. Several epidemiologic studies have shown an association between aflatoxin exposure in infants and young children and growth failure, but strong experimental evidence is lacking. The Mycotoxin Mitigation Trial conducted in Tanzania was a cluster-randomised trial to assess the effect of a reduced aflatoxin diet on linear growth. Prior to the design and implementation of this trial, a group of multi-disciplinary and multi-national scientists reviewed literature in biomedical, public health, environmental health ethics. In this paper we outline the most salient ethical questions and dilemmas in the potential conduct of such a study and describe the ethical precedents and principles that informed our decision-making processes and ultimate study protocol.
Ethical Considerations of the Trial to Establish a Causal Linkage Between Mycotoxin Exposure and Child Stunting
(Elsevier, 2021-06-21) Phillips, Erica; Turner, Paul; Kassim, Neema; Makule, Edna; Nelson, Rebecca; Ngure, Francis; Smith, Laura; Stoltzfus, Rebecca
Objectives Aflatoxins are fungal metabolites that commonly contaminate staple crops in tropical regions. Aflatoxin is a carcinogen and consumption at high-levels can lead to acute liver failure and aflatoxicosis. Multiple epidemiologic studies have shown an association between aflatoxin exposure in infants and young children and growth failure, but strong experimental evidence is lacking. The Trial to Establish a Causal Linkage Between Mycotoxin Exposure and Child Stunting being conducted in Tanzania is a cluster-randomized trial to assess the effect of reduced aflatoxin exposure on linear growth. Methods Prior to its design and launch, the multi-disciplinary research team conducted a critical review to determine the most salient ethical questions and dilemmas in the potential conduct of such a study and debated if and how this study could be designed to meet human subject ethical criteria. This critical review included trial protocols, methodologies and historical controversies in the areas of bio-medical, public health and environmental health research. Results This critical review identified three major questions: 1) Given what is already known about aflatoxin, should a question about the effect of this toxin on child growth be studied further in human subjects? 2) If the relationship between aflatoxin and stunting can be studied in humans, what is the most ethical study design to employ? 3)What is the most ethical intervention to randomly allocate? Conclusions Based on the critical review and in alignment with human subject principles and guidelines, we concluded that it was possible to conduct such a study. The trial and intervention were designed to advance scientific knowledge, maintain a favorable risk/benefit ratio, and respect participants, among other ethical principles.
Protocol for the trial to establish a causal linkage between mycotoxin exposure and child stunting: a cluster randomized trial.
(BMC Public Health, 2020-05-01) Phillips, Erica; Ngure, Francis; Smith, Laura; Makule, Edna; Turner, Paul; Nelson, Rebeca; Kimanya, Martin; Stoltzfus, Rebecca; Kassim, Neema
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-for-age 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 times – at 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-for-age at 18 months. Secondary outcomes include the Z scores for weight-for-age, 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
Provision of low‐aflatoxin local complementary porridgeflour reduced urinary aflatoxin biomarker in childrenaged 6–18 months in rural Tanzania
(Wiley Online Library, 2023-03-09) Kassim, Neema; Ngure, Francis; Smith, Laura; Turner, Paul; Stoltzfus, Rebecca; Makule, Edna; Makori, Nyabasi; Phillips, Erica
Aflatoxins are toxic secondary metabolites of fungi that colonize staple food crops, such as maize and groundnut, frequently used in complementary feeding. In preparation for a large trial, this pilot study examined if provision of a low‐aflatoxin infant porridge flour made from local maize and groundnuts reduced the prevalence of a urinary aflatoxin biomarker in infants. Thirty‐six infants aged 6–18 months were included from four villages in Kongwa District, Tanzania. The study was conducted over 12 days with a three‐day baseline period and a 10 days where low‐AF porridge flour was provided. Porridge intake of infants was assessed using quantitative 24‐h recalls by mothers. Household food ingredients used in infant porridge preparation and urine samples were collected on Days 1–3 (baseline) and 10–12 (follow‐up). Aflatoxins were measured in household foods, and AFM1 was measured in urine. At baseline and follow‐up, 78% and 97%, respectively, of the infants consumed porridge in the previous 24 h, with a median volume of 220 mL (interquartile range [IQR]: 201, 318) and 460 mL (IQR: 430, 563), respectively (p < 0.001). All 47 samples of homemade flour/ingredients were contaminated with AFs (0.3–723 ng/g). The overall prevalence of individuals with detectable urinary AFM1 was reduced by 81%, from 15/36 (42%) at baseline to 3/36 (8%) at follow‐ up (p = 0.003). Provision of low‐aflatoxin porridge flour was acceptable to caregivers and their infants and successfully reduced the prevalence of detectable urinary AFM1 in infants, thus, confirming its potential to be tested in future large‐scale health outcomes trial.