Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled-analysis

BACKGROUND This study examines gene–environment interaction between the MTHFR C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled‐analytical approach on four studies that used similar methods. METHODS We used logistic regression to analyze the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal MTHFR C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non‐syndromic clefts lip or without cleft palate (CL(P)) and non‐syndromic cleft palate (CP)] and control groups. RESULTS There was a reduced risk of CL(P) with maternal folic acid use (p = 0.008; OR = 0.70, 95% CI: 0.65–0.94) and with supplements containing folic acid (p = 0.028, OR = 0.80, 95% CI: 0.65–0.94). Maternal smoking increased the risk of both CL(P) (p