Do folic acid supplements reduce facial clefts?

Abstract

Design: This was a national population-based case-control study in Norway. CASE AND CONTROL SELECTION: Cases consisted of all newborn infants born from 1996-2001 who had been referred for surgical treatment of a cleft [either cleft lip with or without cleft palate (377 children) or cleft palate only (196 children)]. Controls (763) were a randomly selected at an average of four per 1000 live births (identified through the medical birth registry of Norway).

Data analysis: Data were collected using questionnaires. Crude odds ratios (OR) were calculated and adjustments for potential confounders (diet and multivitamins, mother's education, mother's employment during early pregnancy, smoking, alcohol consumption, and year of baby's birth) were made.

Results: Folic acid supplementation during early pregnancy (400 microg/day) was associated with a reduced risk of isolated cleft lip with or without cleft palate after adjustment for multivitamins, smoking, and other potential confounding factors [adjusted OR, 0.61; 95% confidence interval (CI), 0.39-0.96]. Independent of supplements, diets rich in fruits, vegetables and other high-folate-containing foods reduced the risk somewhat (adjusted OR, 0.75; 95% CI, 0.50-1.11). The lowest risk of cleft lip was among women who ate folate-rich diets who also took folic acid supplements and multivitamins (adjusted OR, 0.36; 95% CI, 0.17-0.77). Folic acid provided no protection against cleft palate alone (adjusted OR, 1.07; 95% CI, 0.56-2.03).

Conclusions: Folic acid supplements during early pregnancy seem to reduce the risk of isolated cleft lip (with or without cleft palate) by about a third. Other vitamins and dietary factors may provide additional benefit.