Maternal Periconceptional Folic Acid Supplementation and the Risk of Non-Syndromic Oral Clefts in Offspring: A Population-Based Case-Control Study in Chengdu, China

Maternal periconceptional folic acid supplementation (FAS) has been documented to be associated with decreased risk of nonsyndromic oral clefts (NsOC). However, the results remain inconclusive. In this population-based case-control study of 807 singletons affected by NsOC and 8070 healthy neonates who were born between October 2010 and September 2015 in Chengdu, China, we examined the association of maternal FAS with the risk of nonsyndromic cleft lip with or without cleft palate (NsCL/P), and cleft palate (NsCP). Unconditional logistic regression analysis was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidential intervals (CI). Significant associations were found between maternal periconceptional FAS and decreased risk of NsCL/P (aOR = 0.41, 95% CI: 0.33–0.51). This protective effect was also detected for NsCL (aOR = 0.42, 95% CI: 0.30–0.58) and NsCLP (aOR = 0.41, 95% CI: 0.31–0.54). Both maternal FAS started before and after the last menstrual period (LMP) were negatively associated with NsCL/P (before LMP, aOR = 0.43, 95% CI: 0.33–0.56; after LMP, aOR = 0.41, 95% CI: 0.33–0.51). The association between NsCP and maternal FAS initiating before LMP was significant (aOR = 0.52, 95% CI: 0.30–0.90), but the statistical power seemed weak due to limited number of NsCP cases. The findings suggest that maternal periconceptional FAS can reduce the risk of each subtype of NsCL/P in offspring, while the potential effect on NsCP needs further investigations.