Association between maternal folic acid and/or multivitamin supplementation time and fetal congenital heart disease: based on the China birth cohort study

<b>Background:</b> A multitude of studies have presented inconsistent outcomes regarding the association between maternal folic acid (FA) and/or multivitamin (MV) supplementation and congenital heart disease (CHD) in offspring. This study aimed to estimate supplementation time and CHD based on a prospective China birth cohort study (CBCS). <b>Methods:</b> In the CBCS, 114,670 singleton pregnant women who had pregnancy outcomes until August 2021 and responded to the early pregnancy questionnaire were recruited. The participants were divided into three groups: no FA or MV supplementation, supplementation commencing before pregnancy, and supplementation commencing from early pregnancy. Unadjusted and adjusted logistic regression analyses were employed to calculate the odds ratio (OR) to estimate the relative risk (RR) value of CHD exposure to FA and/or MV. Additionally, the results of this study were combined with previous studies to calculate the pooled RR. Finally, stratification and sensitivity analyses, including the propensity score matching method, were conducted to identify the robustness of the association. <b>Results:</b> Compared with the non-supplemented group, the RRs of CHD in groups with FA and/or MV supplementation, with supplementation before pregnancy, and with supplementation from early pregnancy were 1.23 (95% confidence interval [CI]: 0.76-2.00), 1.30 (95% CI: 0.80-2.13) and 1.19 (95% CI: 0.73-1.93), all demonstrating no statistically significant difference. The pooled RR from the forest plot was 0.98 (95% CI: 0.95-1.01), which is consistent with the findings of this study. Furthermore, the results remained approximately the same in the stratification or sensitivity analyses in different datasets, including performing 1:1 or 1:2 propensity score matching. <b>Conclusions:</b> The present study suggests that FA or MV supplementation before or during early pregnancy may not influence the risk of offspring developing CHD.