Abstract
We assessed the association between the use of lower- and higher-than-recommended doses of folic acid supplements (FAs) during pregnancy and attentional function in boys and girls at age of 4–5. We analyzed data from 1329 mother-child pairs from the mother-child cohort INfancia y Medio Ambiente Project (INMA) study. Information on FAs use during pregnancy was collected in personal interviews at weeks 12 and 30, and categorized in <400, 400–999 (recommended dose), and ≥1000 μg/day. Child attentional function was assessed by Conners’ Kiddie Continuous Performance Test. Multivariable regression analyses were used to estimate incidence rate ratios (IRR) and beta coefficients with 95% confidence intervals (CI). Compared to recommended FAs doses, the periconceptional use of <400 and ≥1000 μg/day was associated with higher risk of omission errors—IRR = 1.14 (95% CI: 1.01; 1.29) and IRR = 1.16 (95% CI: 1.02; 1.33), respectively. The use of FAs < 400 μg/day and ≥1000 μg/day was significantly associated with deficits of attentional function only in boys. FAs use < 400 μg/day was associated with higher omission errors with IRR = 1.22 and increased hit reaction time (HRT) β = 34.36, and FAs use ≥ 1000 μg/day was associated with increased HRT β = 33.18 and HRT standard error β = 3.31. The periconceptional use of FAs below or above the recommended doses is associated with deficits of attentional function in children at age of 4–5, particularly in boys.
Highlights
An adequate dietary intake and periconceptional use of folic acid supplements during the embryonic period is crucial in several fetal physiological and cellular processes [1]that are essential for the optimal early and late development of the child’s brain and cognitive function [2,3]
The associations between folic acid supplements (FAs) use of
We found that, compared to the periconceptional use of the recommended FAs doses, the use of FAs doses
Summary
An adequate dietary intake and periconceptional use of folic acid supplements during the embryonic period is crucial in several fetal physiological and cellular processes [1]that are essential for the optimal early and late development of the child’s brain and cognitive function [2,3]. The folic acid (synthetic form of folate) is an essential micronutrient required for many metabolic processes such as the metabolism of carbon-1 and for Sadenosylmethionine (SAM) production [4], nucleotide synthesis, DNA repair, methylation reactions, myelination, and synthesis of neurotransmitters [5,6]. There is evidence from animal studies suggesting that the effect of folic acid supplements (FAs) modulating DNA methylation reactions and the brain development of the child, may be different according to sex [7]. Based on the initial results of the Medical Research Council (MRC) clinical trial and subsequent evidence, a daily dose of 400 μg/day from folic acid (FA) in the periconceptional period is recommended to reduce the risk of neural tube defects [8,9]. In Spain, there is no information on FA status at national level, in a population-based mother-child cohort study in Valencia, the periconceptional mean daily
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