Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring

Low maternal socioeconomic status (SES) is considered as a risk factor of congenital heart diseases (CHDs) in offspring. However, the pathways underpinning the SES-CHDs associations are unclear. We assessed if first trimester maternal folic acid supplementation (FAS) is a mediator of the SES-CHDs associations. This case-control study included 8379 CHD cases and 6918 CHD-free controls from 40 participating centers in Guangdong, Southern China, 2004-2016. All fetuses were screened for CHDs using ultrasound and cases were confirmed by echocardiogram. We collected SES and FAS information during face-to-face interview by obstetricians using a structured questionnaire. Low SES was defined as education attainment12 years, household individual income3000 Chinese Yuan/person/month or unemployment. FAS referred to at least 0.4 mg of daily folic acid intake over 5 days/week continuously. We used causal mediation analysis to estimate the direct, indirect and proportion mediated by FAS on the SES-CHDs associations adjusted for confounders. Both low maternal income and education were significantly associated with increased risks of CHDs and lower prevalence of FAS. Low maternal FAS prevalence mediated 10% [95%CI:5%,13%] and 3% [95%CI:1%,5%] of the maternal low income-CHDs and the maternal low education-CHDs associations, respectively. In addition, FAS mediated the highest proportion of the associations between income and multiple critical CHDs [46.9%, 95%CI:24.7%,77%] and conotruncal defects [31.5%, 95%CI:17.1%,52.0%], respectively. Maternal FAS partially mediated the SES-CHDs associations, especially among the most critical and common CHDs. Promoting FAS in low SES women of childbearing age may be a feasible intervention to help prevent CHDs.