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Wilcox AJ, Lie RT et al. BMJ 2007; 334: 464–467

In early pregnancy, folic acid reduces the risk of neural tube defects, but there is conflicting evidence on facial clefts. In Norway, which has a high rate of clefts, families who had infants born over a 5 year period and referred for cleft surgery (n = 652) were asked to participate, and 573 did so. Of a random sample of 1006 controls, 763 took part.

After assessing folic acid intake from diet, FAS and multivitamin supplements, no association was found between low dose folate (<400 μg/day) and cleft palate. The groups at lowest risk for cleft lip were those who took 400+ μg/day of folic acid in combination with either multivitamins or good diet. Relative risk for women who took all three was 0.36 (95% CI: 0.17-0.77). The authors estimate that if all pregnant women in Norway took 400+ μg/day of folic acid, 22% of cleft lip cases could be averted.