Periconceptional folate intake by supplement and food reduces the risk of nonsyndromic cleft lip with or without cleft palate

Abstract

Background. Inadequate maternal vitamin intake during pregnancy has been suggested as a risk factor for cleft lip with or without cleft palate (CLP). The independent role of folate has not been clarified. Methods. To investigate the association between maternal folate intake by supplement and food and the risk of CLP offspring, a case-control study was conducted in the Netherlands (1998–2000) among 174 mothers of a child with nonsyndromic CLP and 203 mothers of a child without congenital malformations. Results. Daily use of a folic acid supplement by mothers starting from 4 weeks before until 8 weeks after conception gave a 47% CLP risk reduction compared to mothers who did not use these supplements [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33, 0.85]. Ninety-three percent of the users took a supplement containing folic acid only. Dietary folate intake reduced CLP risk independently in a dose–response manner. The largest risk reductions were found on those mothers who had a diet of more than 200 μg folate per day in combination with a folic acid supplement (OR: 0.26, 95% CI: 0.09, 0.72). Conclusions. We demonstrated that periconceptional maternal folic acid supplement use was beneficial to reduce the risk for CLP. An additional effect of food folate was shown.