Assessing the Effects of Mycotoxin Exposure on the Maternal-Fetal Dyad

<p>NON-TECHNICAL SUMMARY:<br/> Aflatoxins pose a threat to the safety of the US and global food supply, and may adversely affect the health of mothers and the health and development of their children. The overall goal of the proposed research is to inform public health and food safety policy in the United States and internationally by describing the effect of aflatoxin exposure on the health and wellbeing of mothers and their infants. This pre-doctoral fellowship research proposal specifically addresses the AFRI Challenge Area Food Safety and the AFRI foundational program Food Safety, Nutrition and Health by focusing on satisfying human food needs while enhancing the quality of life for society as a whole. Understanding the effects of aflatoxin is important in mitigating risks to vulnerable populations as US and global agriculture strives to meet food and feed needs. We will
explore the relationship between maternal mycotoxin exposure, maternal anemia and birth outcomes by assessing aflatoxin exposure during pregnancy in 4800 rural Zimbabwean mothers. The proposed research will generate new knowledge of the biological effects of aflatoxin exposure during pregnancy to inform the development of domestic and international food safety policy, as well as interventions to improve maternal and child health. This research supports US priorities in agriculture, food safety, nutrition and health, and additionally supports the Feed the Future goal to sustainably reduce global poverty and hunger and the Centers for Disease Control, March of Dimes and National Institutes of Health focus on pre-term birth.
<p>APPROACH:<br/> I plan to explore the relationship between maternal mycotoxin exposure, maternal anemia and birth outcomes by assessing AF exposure at two timepoints during pregnancy in 4800 rural Zimbabwean mothers. The biomarker for aflatoxin exposure, the aflatoxin-albumin adduct represents a 2-3 month exposure window. The first timepoint (3 months) will capture exposure during the first trimester of pregnancy and the second timepoint (7 months) will capture exposure during the 2nd and 3rd trimesters of pregnancy, allowing investigation of the effect of the level of exposure as well as the effect of timing of exposure during gestation. This research will be nested within the SHINE trial which aims to determine the independent and combined impact of improved sanitation/hygiene (i.e., the WASH Intervention) and improved infant feeding (i.e., the nutrition intervention)
on linear growth and anemia in 4800 children from birth through 18 months in a cohort of mothers enrolled during early pregnancy. The project will be a community-based, cluster-randomized trial among all households in which a woman becomes pregnant during the recruitment period. The project will be conducted in two rural districts (Chirumanzu and Shurugwi) comprising a total population of ~180,000 where the primary livelihood is subsistence farming. Only 7% of Zimbabwean women are classified as underweight, yet stunting and micronutrient deficiencies are common in this population. AFB1-albumin ELISA assay will be validated and conducted on 4800 pregnant women at 10-12 weeks gestation and 7 months gestation at the Zvitambo laboratory in Harare, Zimbabwe. We will use the procedure previously described by Wild et al. In brief, we will extract albumin from 50 µL plasma and quantify
AFB1-albumin by competitive ELISA against an AFB1-albumin standard. A random sample of maternal samples at each timepoint (200 samples total) will be selected to conduct LC-MS validation at the AiBMST. LC-MS quantification of AFB1-albumin will follow the procedure described by Scholl et al. I propose to analyze potential determinants and outcomes of AF exposure at two timepoints during pregnancy representing exposure during all trimesters. Seasonality, harvest practices and geographical location will be assessed as potential determinants of AF exposure. Primary outcomes include maternal anemia (assessed by hemoglobin), miscarriage, chronic IUGR (short-for-gestational-age), acute IUGR (small-for-gestational-age), spontaneous pre-term birth (birth before 37 weeks) and stillbirth. Additionally I will describe the variation of exposure in this population (Aim1). Aims 2 and 3 will test for
associations between exposure and adverse outcomes. I will consider covariates (including dietary diversity, food security, socioeconomic status (SES) randomization group, HIV status, dietary diversity, iron status, malaria and other maternal infections) as potential confounders and/or effect modifiers. Aim 1: To describe the distribution of Aflatoxin in Pregnant Women in Rural Zimbabwe: My first step will be to describe patterns of exposure across seasons as well as potential patterns in gestation (10/12 weeks vs. 7 months) and geographical variation across the study districts. I will explore potential cross-sectional associations between AF exposure, mother's health status, post-harvest practices, socio-economic status, dietary diversity and food security utilizing the comprehensive baseline survey that will be conducted in all study participants.. Aim 2: Test of the hypothesis
that aflatoxin exposure is associated with maternal anemia: I will test this hypothesis using multivariate regression models, with hemoglobin/anemia as the outcome variable and mycotoxin exposure at baseline as the independent variable along with covariates. Maternal anemia will be defined as Hemoglobin < 120 g/L assessed using the Hemocue hemoglobinometer at baseline. Aim 3: Test of the hypothesis that aflatoxin is associated with IUGR and adverse birth outcomes: I further hypothesize that the association will depend on the timing of exposure. Aflatoxin exposure during the first trimester could lead to miscarriage as well as both short-for-gestational age and small-for-gestational age. Aflatoxin exposure during later pregnancy could cause acute IUGR (small-for-gestational age), spontaneous preterm birth and stillbirth. First, I will investigate whether there is an association between
AF exposure and birthweight treated as a continuous variable. Second, I will use multinomial logistic regression including outcomes of normal birth, short-for-gestational age, small-for-gestational age, miscarriage, stillbirth and pre-term birth modeled as dichotomous variables.