First-Trimester Maternal Folic Acid Supplementation Modifies the Effects of Risk Factors Exposures on Congenital Heart Disease in Offspring
Yanji Qu,
Shao Lin,
Michael S. Bloom,
Ximeng Wang,
Zhiqiang Nie,
Yanqiu Ou,
Jinzhuang Mai,
Xiangmin Gao,
Yong Wu,
Jimei Chen,
John Justino,
Hongzhuan Tan,
Jian Zhuang,
Xiaoqing Liu
Affiliations
Yanji Qu
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Shao Lin
Department of Environmental Health Sciences, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA
Michael S. Bloom
Department of Global and Community Health, George Mason University, Fairfax, VA 22030, USA
Ximeng Wang
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Zhiqiang Nie
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Yanqiu Ou
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Jinzhuang Mai
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Xiangmin Gao
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Yong Wu
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Jimei Chen
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
John Justino
Department of Health Policy, Management and Behavior, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA
Hongzhuan Tan
Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China
Jian Zhuang
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Xiaoqing Liu
Guangdong Cardiovascular Institute, WHO Collaborating Center for Research and Training in Cardiovascular Diseases, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004–2016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.
