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First-Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case-Control Study.

ABSTRACT: Background Maternal folic acid supplementation (FAS) reduces the risk of neural tube defects in offspring. However, its effect on congenital heart disease (CHDs), especially on the severe ones remains uncertain. This study aimed to assess the individual and joint effect of first-trimester maternal FAS and multivitamin use on CHDs in offspring. Methods and Results This is a case-control study including 8379 confirmed CHD cases and 6918 controls from 40 healthcare centers of 21 cities in Guangdong Province, China. Adjusted odds ratios (aORs) of FAS and multivitamin use between CHD cases (overall and specific CHD phenotypes) and controls were calculated by controlling for parental confounders. The multiplicative interaction effect of FAS and multivitamin use on CHDs was estimated. A significantly protective association was detected between first-trimester maternal FAS and CHDs among offspring (aOR, 0.69; 95% CI, 0.62-0.76), but not for multivitamin use alone (aOR, 1.42; 95% CI, 0.73-2.78). There was no interaction between FAS and multivitamin use on CHDs (P=0.292). Most CHD phenotypes benefited from FAS (aORs ranged from 0.03-0.85), especially the most severe categories (ie, multiple critical CHDs [aOR, 0.16; 95% CI, 0.12-0.22]) and phenotypes (ie, single ventricle [aOR, 0.03; 95% CI, 0.004-0.21]). Conclusions First-trimester maternal FAS, but not multivitamin use, was substantially associated with lower risk of CHDs, and the association was strongest for the most severe CHD phenotypes. We recommend that women of childbearing age should supplement with folic acid as early as possible, ensuring coverage of the critical window for fetal heart development to prevent CHDs.

SUBMITTER: Qu Y

PROVIDER: S-EPMC7670504 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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First-Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case-Control Study.

Qu Yanji Y Lin Shao S Zhuang Jian J Bloom Michael S MS Smith Maggie M Nie Zhiqiang Z Mai Jinzhuang J Ou Yanqiu Y Wu Yong Y Gao Xiangmin X Tan Hongzhuan H Liu Xiaoqing X

Journal of the American Heart Association 20200702 13

Background Maternal folic acid supplementation (FAS) reduces the risk of neural tube defects in offspring. However, its effect on congenital heart disease (CHDs), especially on the severe ones remains uncertain. This study aimed to assess the individual and joint effect of first-trimester maternal FAS and multivitamin use on CHDs in offspring. Methods and Results This is a case-control study including 8379 confirmed CHD cases and 6918 controls from 40 healthcare centers of 21 cities in Guangdong ...[more]

PMID: 32613868

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Project description:IntroductionTaking folic acid containing supplements prior to and during early pregnancy reduces the risk of neural tube defects. Neural tube defects occur prior to 28 days postconception, after which, there is no proven benefit of continuing to take folic acid. However, many women continue to take folic acid containing supplements throughout the pregnancy. At higher intakes, folic acid is not converted to its active form and accumulates in circulation as unmetabolised folic acid (UMFA). Recently, concerns have been raised about possible links between late gestation folic acid supplementation and childhood allergy, metabolic disease and autism spectrum disorders. We aim to determine if removing folic acid from prenatal micronutrient supplements after 12 weeks gestation reduces circulating levels of maternal UMFA at 36 weeks gestation.Methods and analysisThis is a parallel-design, double-blinded randomised controlled trial. Women ≥12 and <16 weeks' gestation with a singleton pregnancy and able to give informed consent are eligible to participate. Women (n=100; 50 per group) will be randomised to receive either a micronutrient supplement containing 0.8 mg of folic acid or a micronutrient supplement without folic acid daily from enrolment until delivery. The primary outcome is plasma UMFA concentration at 36 weeks gestation. Secondary outcomes include red blood cell folate and total plasma folate concentration. We will assess whether there is a difference in mean UMFA levels at 36 weeks gestation between groups using linear regression with adjustment for baseline UMFA levels and gestational age at trial entry. The treatment effect will be described as a mean difference with 95% CI.Ethics and disseminationEthical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/19/WCHN/018). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numberACTRN12619001511123.

Dataset Information

First-Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case-Control Study.

Publications

First-Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case-Control Study.

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