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Folate-Rich Diet May Cut Cleft Palate Risk
By Merritt McKinney Apr 05, 2003

NEW YORK (Reuters Health) - Women who have certain variations in a folate-processing gene are at greater risk of having a child with a cleft lip or palate, but the risk is increased only if women do not consume enough folic acid in pregnancy, according to a new study.

Getting enough folate in the diet and taking a folic acid supplement may "significantly reduce the risk" that women will give birth to a child with a cleft lip or palate, study author Dr. Regine P. M. Steegers-Theunissen told Reuters Health.

"The effect of the use of a folic acid supplement is most pronounced," said Steegers-Theunissen, who is at University Medical Center Nijmegen in the Netherlands.

Cleft lip and cleft palate, which can occur alone but more often arise together, are two of the most common major birth defects in infants. Cleft lip appears as a split in the upper lip, and cleft palate is marked by a hole in the roof of the mouth.

Since the late 1990s, the U.S. has required that certain grain foods, including bread, cereals, flour and pasta be fortified with folic acid. A major reason that the U.S. took this step was to prevent neural tube defects, such as spina bifida. These birth defects have been linked to inadequate folate consumption.

There is some evidence that consuming too little folate increases a woman's chances of having a child with cleft lip or palate. Cleft palate and lip often occur as a part of a larger syndrome of birth defects, but they can also occur in children who are otherwise completely healthy.

One possible influence on the risk of cleft lip and palate is the gene for an enzyme called MTHFR, which is involved in processing folate. Certain variations of the MTHFR gene result in an enzyme that makes the breakdown of folate less efficient. These variations have been suspected of increasing the risk of cleft lip and palate, although research on the topic is inconclusive.

Now, Steegers-Theunissen and her colleagues have found that certain MTHFR variations do seem to increase the risk of these birth defects but only in women who do not consume enough folate from food, or in the supplement form, folic acid.

The researchers compared 179 families with a child with cleft palate, lip or both with 204 families whose children did not have the birth defect.

In the study, women who had a certain MTHFR variation that affected folate metabolism had about a six-fold increased risk of having a child with cleft palate, lip or both if they did not take folic acid supplements around the time of conception. About 25% of mothers of children with oral cleft had this gene variation compared with 16% of the mothers of healthy children.

The risk was about three times higher than normal in women with this particular variation if they did not get enough folate in the diet and about 10 times higher than normal if they neither took supplements nor consumed enough dietary folate.

The risk was about seven times higher than normal in women with another MTHFR variation who did not take supplements or consume enough folate in their diet.

The findings are reported in the American Journal of Epidemiology.

How a decrease in folate might increase the risk of cleft lip or palate is uncertain, but the results of the study suggest, according to the authors, that consuming more folate -- either in supplements, in food or both -- could counteract any increased risk caused by gene variations that impair folate metabolism.

Foods rich in folates include green, leafy vegetables, citrus fruits and juices, whole wheat bread and dried beans. U.S. guidelines recommend that women of child-bearing age consume 400 micrograms of folic acid per day. Pregnant women are advised to take a supplement that contains the recommended dose of folic acid.

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