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

Abstract

Background: It is well known that low maternal socioeconomic status (SES) is associated with a significantly greater risk of congenital heart disease (CHD) in offspring than high maternal SES. However, the pathway underpinning this association is unclear. To help to fill this knowledge gap, we assessed first trimester maternal folic acid supplementation (FAS) as a mediator of the association between maternal SES and CHD in offspring. Methods: In this case-control study, we enrolled 8,379 CHD cases and 6,918 CHD-free controls from Guangdong province in southern China. All fetuses were screened for cardiac anomalies using basic ultrasound and CHD cases were confirmed using echocardiogram by two cardiologists in 40 participating centers. We adopted education, income and employment as indicators of SES, and defined education attainment <12 years, household individual income <3000 CNY/person/month and unemployment as low SES. We used causal mediation analysis to estimate the direct, indirect and mediated effects of FAS in the association between maternal SES and CHD, adjusted for maternal demographic characteristics, medication use, lifestyle and environmental factors, reproductive history and paternal exposures. Results: Low FAS prevalence mediated 10% (95%CI: 5%-13%) and 3% (95%CI: 1%-5%) of the CHD-maternal low income and the CHD-maternal low education associations, respectively. In addition, FAS mediation effects were strongest when using income as an SES indicator and for the most severe CHDs. Both low maternal income and education were associated with greater odds of CHD among offspring (OR=1.17, 95%CI: 1.09-1.25; OR=1.48, 95%CI: 1.29-1.70, respectively) and a lower prevalence of FAS (OR=0.31, 95%CI: 0.27-0.37; OR=0.44, 95%CI: 0.26-0.75, respectively). Conclusions: Maternal FAS partially mediated the association between maternal SES and CHD. Promoting FAS in low SES women of childbearing age may be a low cost and feasible intervention to help prevent CHDs under the conditions as in China.