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Grant Abstract: Stress-Lead Interactions and Child Development

Grant Number: 5R01ES013744-09
PI Name: Wright
Project Title: Stress-Lead Interactions and Child Development

Abstract: Inadequate folate intake during pregnancy and early childhood impairs normal neurodevelopment. Exposure to lead (Pb) during these critical time points similarly impairs neurodevelopment. To date, few studies have investigated the neurodevelopmental impact of co-exposure to inadequate folate (either below the Estimated Average Requirement [EAR] or above the tolerable Upper Limit [UL]) and Pb during pregnancy and early childhood. Rodent studies suggest that Pb and inadequate folate each impair hippocampal function and memory processes. Accounting for the combined effect of both exposures during neural development may be mechanistically informative and may yield actionable recommendations for risk adjusted folic acid intake.
In this supplement we aim to leverage the expansive PROGRESS data to examine the associations between prenatal and early childhood folate/ folic acid intake, Pb exposure and neurodevelopment at age 4. PROGRESS is a Mexico City based longitudinal birth cohort study designed to document the effects of prenatal and early childhood environmental exposures on behavior and cognition among children. Preliminary data from PROGRESS suggests that maternal prenatal lead levels (2nd trimester) are associated with significantly decreased performance on a child’s neurocognitive testing (McCarthy) at age 4. Inadequate folate intake is prevalent as 22% (2nd trimester) and 33% (3rd trimester) of mothers in pregnancy and 43% of children at age 4 appear to have inadequate intake. We hypothesize that inadequate folate intake, prenatally or during early childhood, exacerbates the adverse effects that early life exposure to Pb has on neurodevelopment.
PROGRESS’ dataset includes longitudinal data on dietary and supplement intake, Pb exposure and neurodevelopment. However nutrient content tables used to calculate nutrient intake in PROGRESS do not reflect the synthetic folic acid content of non-industrialized foods containing fortified wheat and corn flour (fortified at high level in Mexico) although these are highly consumed by the PROGRESS cohort and by Mexicans in general. We propose to update the PROGRESS nutrient content tables using direct measures of folate and folic acid concentrations from non-industrialized staple foods regularly consumed by PROGRESS participants. We will re-calculate prenatal and 4 year intake accounting more fully for dietary folate and folic acid, determining inadequacy (EAR or UL) in order to examine the effect of inadequate folate intake on lead associated neurotoxicity. We will conduct stratified analyses to determine the time-varying association between pre and post-natal Pb levels and neurotoxicity at age 4 years, comparing children with adequate and inadequate folate/folic acid intake, accounting for both prenatal and concurrent intake. Assessing the effects of inadequate folate intake on neurodevelopment, in the setting of Pb exposure, may inform policy on folic acid intake and is timely as the National Toxicology Program Expert Panel on High Folic Acid intake meets 2015.

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