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

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 F...

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Main Authors: Yanji Qu, Shao Lin, Jian Zhuang, Michael S. Bloom, Maggie Smith, Zhiqiang Nie, Jinzhuang Mai, Yanqiu Ou, Yong Wu, Xiangmin Gao, Hongzhuan Tan, Xiaoqing Liu
Format: Article
Language:English
Published: Wiley 2020-07-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.119.015652
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author Yanji Qu
Shao Lin
Jian Zhuang
Michael S. Bloom
Maggie Smith
Zhiqiang Nie
Jinzhuang Mai
Yanqiu Ou
Yong Wu
Xiangmin Gao
Hongzhuan Tan
Xiaoqing Liu
author_facet Yanji Qu
Shao Lin
Jian Zhuang
Michael S. Bloom
Maggie Smith
Zhiqiang Nie
Jinzhuang Mai
Yanqiu Ou
Yong Wu
Xiangmin Gao
Hongzhuan Tan
Xiaoqing Liu
author_sort Yanji Qu
collection DOAJ
description 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.
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spelling doaj.art-4b8028718171445182ee0e8f0c1544962022-12-22T02:38:38ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802020-07-0191310.1161/JAHA.119.015652First‐Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case‐Control StudyYanji Qu0Shao Lin1Jian Zhuang2Michael S. Bloom3Maggie Smith4Zhiqiang Nie5Jinzhuang Mai6Yanqiu Ou7Yong Wu8Xiangmin Gao9Hongzhuan Tan10Xiaoqing Liu11Department of Epidemiology and Health Statistics Xiangya School of Public Health Central South University Changsha Hunan ChinaDepartment of Environmental Health SciencesUniversity at AlbanyState University of New York Rensselaer NYGuangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong ChinaDepartment of Environmental Health SciencesUniversity at AlbanyState University of New York Rensselaer NYDepartment of Environmental Health SciencesUniversity at AlbanyState University of New York Rensselaer NYGuangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong ChinaGuangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong ChinaGuangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong ChinaGuangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong ChinaGuangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong ChinaDepartment of Epidemiology and Health Statistics Xiangya School of Public Health Central South University Changsha Hunan ChinaGuangdong Cardiovascular Institute WHO Collaborating Center for Research and Training in Cardiovascular Diseases Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong ChinaBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.119.015652congenital heart diseasefolatemultivitaminpregnancyprevention
spellingShingle Yanji Qu
Shao Lin
Jian Zhuang
Michael S. Bloom
Maggie Smith
Zhiqiang Nie
Jinzhuang Mai
Yanqiu Ou
Yong Wu
Xiangmin Gao
Hongzhuan Tan
Xiaoqing Liu
First‐Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case‐Control Study
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
congenital heart disease
folate
multivitamin
pregnancy
prevention
title First‐Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case‐Control Study
title_full First‐Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case‐Control Study
title_fullStr First‐Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case‐Control Study
title_full_unstemmed First‐Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case‐Control Study
title_short First‐Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case‐Control Study
title_sort first trimester maternal folic acid supplementation reduced risks of severe and most congenital heart diseases in offspring a large case control study
topic congenital heart disease
folate
multivitamin
pregnancy
prevention
url https://www.ahajournals.org/doi/10.1161/JAHA.119.015652
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