Folic Acid Supplements May Help Prevent Cleft Lip Birth Defect
Abstracted by Marcia J. Egles, MD, February 6, 2007, from Folic acid supplements and risk of facial clefts: national population based case-control study by Allen J. Wilcox et al in British Medical Journal, Online First, doi:10.1136/bmj.39079.618287.OB
A new study from Norway has found that women who take folic acid supplements early in pregnancy may reduce by a third the risk of having a baby born with a cleft lip. Facial clefts, which include cleft lips and cleft palates, are birth defects in which the tissues of the lip or mouth do not properly form. A cleft lip appears as a gap in the upper lip. The tissues of the upper lip normally fuse together during the 5th and 6th weeks after conception. A cleft palate is a split in the roof of the mouth. The palate normally forms during the 10th to 13th weeks of development. A cleft lip and palate can occur together, or either deformity can occur by itself. Facial clefts are one of the most common serious birth defects, affecting one in 700 to 1000 babies born in the United States each year. Prior studies done in rodents have shown that folate deficiencies produce facial clefts,1 but studies done in humans have been less consistent.(2,3)
The Norway study looked at the role of folic acid supplements and dietary folate in the prevention of facial clefts in Norway in infants born from1996-2001. The participants included the mothers of 377 infants with cleft lip with or without cleft palate, the mothers of 196 infants with cleft palate alone, and 763 controls.
The studys data was collected in two mailed questionnaires. The main questionnaire included demographic characteristics, smoking, alcohol use, drugs and other exposures. Most mothers in the study completed the questionnaire 13-17 weeks after giving birth. After returning the main questionnaire, mothers were sent a second questionnaire on nutrition which included a food frequency questionnaire and questions on folic acid supplements taken prior to and for the first three months of pregnancy. Those who reported supplement use were interviewed by phone concerning dosage. The study reported a high participation rate of 88% for those mothers with babies having facial clefts and a rate of 76% for the controls.
The study found that 400 micrograms per day of folic acid supplementation during early pregnancy was associated with a one third reduction in the risk of cleft lip, and cleft lip with cleft palate, when compared to controls. No reduction in risk was found for cleft palate that occurred without cleft lip. The mothers who consumed folate-rich diets, but no supplements, reduced the risk of cleft lip by about 25%. A 40% risk reduction in cleft lip was found in mothers who ate folate-rich diets, and took folic acid and multi-vitamin supplements.
The benefit of folic acid supplementation in the prevention of neural tube defects such as spina bifida has been proven in clinical trials.4 This study adds even more importance to the role of folate in healthy pregnancies.
1 Munger RG. Maternal nutrition and oral clefts. In:Wyszynski DF, ed. Cleft lip and palate: from origin to treatment. Oxford:Oxford University Press, 2002:170-92
2 Shaw et al. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 1995:346:393-6
3 Shaw GM et al. Maternal nutrient intakes and the risk of human orofacial clefts. Epidemiology 2006: 17: 285-91
4 Botto LD,Moore CA, KhouryMJ, Erickson JD.Medical progress: neural tube defects. N Engl J Med 1999;341:1509-19
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