Study protocol to assess aflatoxin M1 health risks versus benefits of dairy consumption in Ethiopian children: an epidemiological trial and risk-benefit analysis.

INTRODUCTION: In Sidama, Ethiopia, animal-source foods can be difficult to access. Milk has important nutrients for child growth, but carries the risk of aflatoxin M1 (AFM1) contamination. AFM1 is a metabolite of the mycotoxin aflatoxin B1 (AFB1) in dairy feed; cows secrete AFM1 in milk when their feed contains AFB1 produced by Aspergillus fungi in maize, nuts and oilseeds. It is unknown whether AFM1 compromises child growth and health. METHODS AND ANALYSIS: This protocol paper describes our study in Sidama to determine the impact of milk consumption and AFM1 on child growth in the first 18 months of life. We will collect baseline and end-line data on dairy production, socioeconomic and nutritional factors of 1000 dairy-owning households with children ages 6-18 months at baseline; and gather samples of milk and dairy feed and child anthropometrics. We will conduct phone interviews every 6 months to ascertain changes in practices or child health. Dairy feed will be tested for AFB1; milk for AFM1, pathogens and nutrients. Controlling for herd size, socioeconomic, nutritional and behavioural factors, we will determine the association between child anthropometrics and milk consumption, as well as AFM1 exposure. We will examine whether AFM1 exposure affects child growth in the first 18 months of life, and weigh the benefits and risks of milk consumption. ETHICS AND DISSEMINATION: The protocol is approved by the Institutional Review Boards of the Ethiopian Public Health Institute (EPHI-IRB-481-2022), Michigan State University (STUDY00007996) and International Food Policy Research Institute (DSGD-23-0102). Written informed consent will be obtained from all participants, who may withdraw from the study at any time. Confidentiality of collected data will be given high priority during each stage of data handling. The study's findings will be disseminated through stakeholder workshops, local and international conferences, journal articles and technical reports.

Health burden associated with tillage-related PM2.5 pollution in the United States, and mitigation strategies.

Exposure to airborne particulate matter of diameter less than 2.5 µm (PM2.5) is associated with cardiovascular diseases (CVD) and chronic obstructive pulmonary disease (COPD). In agriculture, the practice of tilling generates PM2.5 emissions that can jeopardize human health. This paper estimates the annual deaths and disability-adjusted life years (DALYs) from CVD and COPD attributable to PM2.5 emissions from corn, soybean, cotton, and wheat tillage in the contiguous United States. Primary PM2.5 from crop-tillage combination was calculated using values obtained from the Environmental Protection Agency's National Emissions Inventory, 2017, while deaths and DALYs estimates were calculated using data from the Institute of Health Metrics and Evaluation's global burden of risk factors study, the US decennial census, and the US Centers for Disease Control. We also propose and implement a conceptual framework for identifying the optimal subsidy upon accounting for health benefits arising from reducing conventional tillage, and we discuss strategies to achieve conservation tillage. Annual PM2.5 emissions from crop tillage is about 0.25 million tons. We estimate that approximately 1000 annual deaths and 22,000 DALYs from CVD, as well as 300 annual deaths and 7400 DALYs from COPD, were attributable to tillage-related PM2.5 emissions. Tillage related primary PM2.5 emissions contribute about 0.002 % of total CVD and COPD deaths in the United States, and its related health economic value loss is about 12.9 billion USD annually. About 350 annual deaths may be averted upon a shift from conventional to conservation tillage. Conservation tillage is generally adopted when the pecuniary and soil health benefits exceed those from adopting intensive tillage. Agricultural policies and on-farm measures that may help reduce intensive tillage, and the related PM2.5 emissions, include subsidies for adopting conservation tillage and carbon capture credits, use of herbicides and herbicide-tolerant crops, protecting herbicide-tolerance traits, planting cover crops, and use of windbreaks.

Dietary exposure to cadmium from six common foods in the United States.

Recently, the United States (US) Food and Drug Administration (FDA) launched a Closer to Zero Action Plan to assess the risks of and develop action levels for certain heavy metals in food including cadmium (Cd). The problem of foodborne metal contamination has taken on new urgency, thanks in part to a 2021 US Congressional Report detailing high levels of metals found in infant food. Our risk assessment aids this FDA Action Plan by estimating the American population's Cd exposures in food, by age group and consumption patterns of certain high-risk foods; and by determining circumstances in which exposures exceed tolerable daily intakes developed by policymaking groups in the US and worldwide. We found that the age groups 6-24 months and 24-60 month old are the most highly exposed to Cd in common foodstuffs. American infants and young children of these age groups who regularly consumed rice, spinach, oats, barley, potatoes, and wheat had mean Cd exposures exceeding maximum tolerable intake level was set by the Agency for Toxic Substances and Disease Registry (ATSDR). We have identified age groups at highest potential risk, and therefore of interest for developing food safety policies to improve safety of commercial food for children.

Relationship between Animal Sourced Food Consumption and Early Childhood Development Outcomes.

Early-childhood development (ECD) is an important determinant of a child's cognitive ability, learning, productivity, and lifetime earnings. Animal-sourced food (ASF), which is a rich source of high-quality protein and micronutrients, has been linked with ECD outcomes. This study investigates the relationship between the number, frequency, and cumulative consumption of ASF at 6, 9, 12, and 18 months of age and ECD outcomes at 24 months of age, controlling for physical growth. The study uses data collected from 701 mother−child pairs from an observational birth cohort study carried out in Banke, Nepal. ECD outcomes were assessed through a standardized ages and stages questionnaire (ASQ-3) tool. Separate multivariable ordinary least squares regression models were used to test for associations. Significant positive association was seen between total ASQ-3 score at 24 months of age and any ASF consumption at 18 months (ß = 8.98, p-value < 0.01), controlling for growth outcomes. The study findings highlight the positive contribution and the accumulating benefit of consistent ASF consumption on ECD outcomes. This study recommends support and promotion of ASF intake among young children in Nepal through policy and programming actions relevant to female education; nutrition knowledge; quality ASF production; improved market access; cold storage; and poverty reduction.

Dietary determinants of aflatoxin B1-lysine adduct among infants in Nepal.

BACKGROUND: Aflatoxins are mycotoxins produced by naturally occurring fungi on food, and aflatoxin B1 (AFB1) is carcinogenic, immunotoxic and hepatotoxic. This study assesses the relationship between AFB1 in Nepali infants at 12 months of age and their diet at 9 and 12 months of age. METHODS: The study used data collected from 1329 infants enrolled in the AflaCohort Study. Aflatoxin exposure was assessed at 12 months using serum AFB1-lysine pg/mg albumin biomarker measured using high performance liquid chromatography-fluorescent detection. Dietary data were collected using food frequency questionnaire. We conducted ordinary least squares and quantile regression analyses with backward elimination to assess lagged (9-month diet and 12-month AFB1) and contemporaneous (12-month diet and 12-month AFB1) associations. RESULTS: Eighty-one percent of children at 12 months had detectable levels of serum AFB1-lysine (geometric mean: 0.79 pg/mg albumin, 95% CI: 0.74-0.83). The levels ranged from 0.4 to 85 pg/mg albumin. Dietary diversity at 9 and 12 months were not associated with serum AFB1-lysine levels. Consumption of fish and groundnuts at both 9 and 12 months and infant formula and cauliflower at 9 months were associated with higher serum AFB1-lysine while consumption of bananas and mangoes at 12 months were negatively associated with serum AFB1-lysine (p < 0.05). CONCLUSIONS: High prevalence of detectable AFB1-lysine among infants, and possible links to their dietary patterns argues for more urgent research into which foods in children's diets are most contaminated, and into optimal entry points in the food chain that would allow for effective actions to minimize exposure.

Exposure to multiple mycotoxins, environmental enteric dysfunction and child growth: Results from the AflaCohort Study in Banke, Nepal.

Evidence of the impact of exposure to multiple mycotoxins and environment enteric dysfunction (EED) on child growth is limited. Using data from a birth cohort study, the objectives of this study were to (a) quantify exposure to multiple mycotoxins (serum aflatoxin [AFB1 ] and ochratoxin A [OTA], urinary fumonisin [UFB1 ] and deoxynivalenol [DON]), as well EED (lactulose:mannitol [L:M] ratio); (b) examine the potential combined effects of multiple mycotoxin exposure and EED on growth. Multivariate regressions were used to identify associations between growth measurements (length, weight, anthropometric z-scores, stunting and underweight) at 24-26 months of age and exposure to mycotoxins and EED at 18-22 months (n = 699). Prevalence of AFB1 , DON, OTA and UFB1 exposure ranged from 85% to 100%; average L:M ratio was 0.29 ± 0.53. In individual mycotoxin models, AFB1 exposure was negatively associated with weight, WAZ, increased odds of stunting (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.08, 1.52; p = 0.004) and underweight (OR: 1.18, 95% CI: 1.00, 1.38; p = 0.046). Irrespective of other mycotoxin exposure and presence of EED, AFB1 was negatively associated with length, weight, head circumference, LAZ and WAZ, and with increased odds of stunting and underweight, UFB1 was associated with increased odds of underweight, and DON was negatively associated with head circumference. EED was associated with the impaired length and weight. These findings suggest that certain mycotoxins and EED may have independent impacts on different facets of growth and that aflatoxin dominates such impacts. Thus, programs reducing exposure to mycotoxin and EED through multi-sectoral nutrition-sensitive interventions have the potential to improve child growth.

Aflatoxin exposure and child nutrition: measuring anthropometric and long-bone growth over time in Nepal.

BACKGROUND: Naturally occurring aflatoxins may contribute to poor growth and nutritional statuses in children. OBJECTIVES: We analyzed the relationship between contemporary and lagged aflatoxin exposure and 1) length-for-age z-score (LAZ); and 2) length, knee-heel length, stunting, weight-for-age z-score (WAZ), and weight-for-length z-score (WLZ). METHODS: We conducted a longitudinal birth cohort study involving 1675 mother-infant dyads in rural Nepal. Participants were repeatedly visited from pregnancy to 2 years of age (2015-2019). One blood sample was collected during pregnancy and 4 samples were collected from the children at 3, 6, 12, and 18-22 months of age to measure concentrations of aflatoxin B1 (AFB1)-lysine adduct. Multivariate linear fixed-effects and logistic models with generalized estimating equations were used to identify associations between child growth and aflatoxin exposure. RESULTS: AFB1-lysine adducts were detected in the majority of children (at 3 months, 80.5%; at 6 months, 75.3%; at 12 months, 81.1%; and at 18-22 months, 85.1%) and in 94.3% of pregnant women. Changes in contemporary ln child AFB1-lysine adduct concentrations were significantly associated with changes in LAZ (ß, -0.05; 95% CI, -0.09 to -0.02; P = 0.003), length (ß, -0.19; 95% CI, -0.29 to -0.10; P < 0.001), knee-heel length (ß, -0.09; 95% CI, -0.13 to -0.05; P < 0.001), and WAZ (ß, -0.04; 95% CI, -0.07 to -0.005; P = 0.022). Serum aflatoxin concentrations were associated with stunting (OR, 1.18; 95% CI, 1.05-1.32; P = 0.005). Similar results were found in the models using changes in contemporary ln AFB1 adjusted for changes in child weight, with significant associations with changes in WLZ (ß, -0.07; 95% CI, -0.10 to -0.03; P < 0.001). Changes in time-lagged ln AFB1 (unadjusted and adjusted for changes in child weight) were associated with changes in length and knee-heel length. CONCLUSIONS: Our results add to the growing body of evidence confirming chronic aflatoxin exposure and suggest that exposure is significantly correlated with various negative growth outcomes, which may vary by child weight status. This trial was registered at clinicaltrials.gov as NCT03312049.

Dietary determinants of aflatoxin B1-lysine adduct in pregnant women consuming a rice-dominated diet in Nepal.

BACKGROUND: Aflatoxins are found in diverse foods widely consumed worldwide. This study investigated the association between aflatoxin exposure and (a) consumption of specific foods, (b) dietary diversity (DD), and (c) seasonality. METHODS: Women enrolled in the AflaCohort Study in Banke, Nepal (n = 1648) were asked how often they ate certain food items in the past 7 days and 24 h. Serum aflatoxin B1-lysine (AFB1-lys) adduct levels, measured during pregnancy, were determined using high-performance liquid chromatography. Multivariable ordinary least squares and quantile regression models were used to examine incremental increases in AFB1-lys adduct levels per frequency of food consumption and the relationship between DD, seasonality, and increases in AFB1-lys adduct. RESULTS: Roughly 94% of women were exposed to aflatoxin (geometric mean 1.37 pg/mg). Women in the 30th, 50th, and 70th quantiles of aflatoxin exposure who reported one more occasion of maize consumption in the past week showed increases in AFB1-lys adduct levels: 0.094, 0.112, and 0.109 pg/mg (p < 0.05, all). Women in the 30th, 50th, 70th, and 90th quantiles of exposure who reported one more occasion of groundnut consumption in the past week also showed increases in AFB1-lys adduct levels: 0.058 (p < 0.001), 0.085 (p < 0.01), 0.133 (p < 0.001), and 0.133 (p < 0.001) pg/mg. Winter month recruitment was positively associated with AFB1-lys adduct levels at all quantiles of aflatoxin exposure (range: 0.313-1.101 pg/mg, p < 0.001). DD was not predictive of aflatoxin exposure. CONCLUSIONS: Our findings justify integrated approaches to aflatoxin reduction, including regulatory, agricultural, and food safety interventions across the value chain and at the household level.

Relatively Low Maternal Aflatoxin Exposure Is Associated with Small-for-Gestational-Age but Not with Other Birth Outcomes in a Prospective Birth Cohort Study of Nepalese Infants.

BACKGROUND: Exposure to aflatoxin has garnered increased attention as a possible contributor to adverse birth outcomes. OBJECTIVE: The objective of this study was to investigate the relation of maternal aflatoxin exposure with adverse birth outcomes such as birth weight, birth length, anthropometric z scores, low birth weight (LBW), small-for-gestational-age (SGA), stunting, and preterm birth (PTB). METHODS: This study used maternal and newborn data from the AflaCohort Study, an ongoing birth cohort study in Banke, Nepal (n = 1621). Data on aflatoxin B1 (AFB1)-lysine adducts in maternal serum were collected once during pregnancy (at mean ± SD: 136 ± 43 d of gestation). Maternal serum AFB1-lysine adduct concentration was measured via HPLC. Linear and logistic regression analyses were used to determine if maternal aflatoxin exposure was associated with 1) birth weight and length (primary outcomes) and 2) anthropometric z scores, LBW (weight <2.5 kg), SGA (weight <10th percentile for gestational age and sex), stunting at birth (length-for-age z score less than -2), or PTB (born <37 weeks of gestation) (secondary outcomes). RESULTS: The geometric mean of maternal serum AFB1-lysine adduct concentration was 1.37 pg/mg albumin (95% CI: 1.30, 1.44 pg/mg albumin). Twenty percent of infants were of LBW and 32% were SGA. Sixteen percent of infants were stunted at birth. In addition, 13% of infants were born preterm. In logistic multivariate regression models, mean maternal serum AFB1-lysine adduct concentrations were significantly associated with SGA (OR: 1.13; 95% CI: 1.00, 1.27; P < 0.05). CONCLUSIONS: Findings from this study suggest a small but significant association between serum AFB1-lysine adduct concentrations in pregnant women and SGA. Maternal aflatoxin exposure was not associated with other birth outcomes. These results highlight the need for future research on a threshold level of aflatoxin exposure needed to produce detectable adverse birth outcomes. This trial was registered at clinicaltrials.gov as NCT03312049.

Nutrition-specific and nutrition-sensitive factors associated with mid-upper arm circumference as a measure of nutritional status in pregnant Ethiopian women: Implications for programming in the first 1000 days.

Poor nutritional status in pregnancy expressed as low mid-upper arm circumference (MUAC) is associated with low birth weight. The study aims were to assess the nutritional status of pregnant Ethiopian women using MUAC and examine association with nutrition-specific and nutrition-sensitive factors, using baseline data of a prospective longitudinal observational birth cohort study conducted in three rural districts in the Oromia region of Ethiopia. Recruitment into the cohort was rolling over a period of nine months, and the data used for this analysis were collected while the women were between 12-32 weeks of gestation. Detailed household socio-demographics, agricultural production, women's health, morbidity and diets, with weights, heights and MUAC, and anemia prevalence (HemoCue) were collected. The prevalence of low MUAC (< 23 cm) was 41%. Controlling for location and clustering, wealth quintile (OR = 0.88, CI = 0.82 to 0.96, p<0.01) was associated with decreased risk of low MUAC, while trimester (OR = 1.31, CI = 1.16 to 1.48, p<0.001) was associated with increased risk of low MUAC. The only significant factor amenable to nutrition-specific interventions was altitude-adjusted anemia, which was associated with increased risk of low MUAC (OR = 1.28, CI = 1.09 to 1.49, p<0.01). Significant factors amenable to nutrition-sensitive factors and associated with higher odds of low MUAC were household food insecurity (OR = 1.04, CI = 1.02 to 1.06, p<0.001), distance to the clinic in minutes (OR = 1.01, CI = 1.0 to 1.01, p<0.0001) and season of recruitment (lean versus non lean) (OR = 1.30, CI = 1.10 to 1.54, p<0.01). Literacy (OR = 0.85, CI = 0.74 to 0.98, p<0.05) and numeracy (OR = 0.75, CI = 0.62 to 0.91, p<0.01) were also significantly associated with lower odds of low MUAC. Poor nutritional status in pregnancy expressed as percent with low MUAC was high in Ethiopian women. It was associated with several nutrition-specific and -sensitive factors indicating the importance of multisectoral actions in improving outcomes within the first 1000 days.

Predictors of anemia in pregnant women residing in rural areas of the Oromiya region of Ethiopia.

BACKGROUND: Anemia in pregnancy is associated with higher risk of low birth weight and both maternal and perinatal mortality. While previous studies in Ethiopia have examined factors associated with anemia, which factors are the most important determinants of anemia in this population remain unclear. The objective of this study was to examine the association between anemia status in pregnant women with different health, behavioral, and socioeconomic factors in Oromiya province of Ethiopia. METHODS: This study used pregnancy enrollment data from a longitudinal birth cohort study conducted in Ethiopia. Survey data on maternal and household characteristics were collected at enrollment and maternal hemoglobin levels were measured. The analysis includes 4600 pregnant women. Logistic regression models were used to identify factors associated with maternal anemia in pregnancy. RESULTS: Controlling for geographic location and religion, low maternal MUAC and previous pregnancies were associated with increased odds of anemia, with odds ratios of 1.30 (p < 0.001, CI 1.12-1.51), and 1.50 (p = 0.002, CI 1.16-1.95), respectively. For each additional point on the handwashing score scale, the odds of being anemic were reduced by 12% (p < 0.001, CI 0.82-0.94). Numerate women compared to non-numerate women had 30% lower odds (p < 0.001, CI 0.57-0.85). CONCLUSION: Controlling for woreda and religion, low maternal MUAC, and previous pregnancy increased odds of anemia while numeracy and better handwashing practices significantly reduced the odds of anemia in pregnancy. Further investigation is needed to determine the cause of anemia in pregnant women in Oromiya and to determine the effects of maternal anemia on birth outcomes.