A major new study of Vitamin A has found that doses only slightly above the maximum recommended levels during the early stages of pregnancy significantly increase the risk of birth defects. The results prompted researchers to recommend that women of childbearing age consume Vitamin A primarily from their diet, along with modest levels in multivitamin supplements.
Researchers had already known that moderately high intake of Vitamin A, on the order of 25,000 International Units per day or more, causes severe birth defects. But the new results from the Boston University School of Medicine, based on a study of more than 22,000 pregnant women, indicate that any dose above 10,000 IU per day can carry some risk.
The danger increases steadily with intake, and women consuming 20,000 IU per day were about four times as likely to have a child with a birth defect as those consuming less than 10,000 IU, according to the study, which is scheduled to be published in the New England Journal of Medicine in November.
The journal eased its normally stringent rules on pre-publication release of results to allow the study to be publicized "because of the potential public health importance of the findings," said its editor, Dr. Jerome P. Kassirer.
The study's chief investigator, epidemiologist Kenneth J. Rothman, cautioned that many commercial multivitamins contain 10,000 IU of Vitamin A, enough to push women into the dangerous range, and that some contain as much as 25,000 IU.
He emphasized, however, that there are no known adverse effects of Vitamin A at the maximum recommended levels--about 8,000 IU per day for pregnant women--and that moderate amounts of the vitamin are crucial for normal development of the fetus.
But among the children of women who took more than 10,000 IU per day, he said, one in every 57 suffered defects ranging from cleft lips and palates to severe heart defects, about twice the rate among mothers who consumed less than 10,000 IU.
Echoing Kassirer, the Food and Drug Administration noted that the study "raises serious public health concerns." According to Dr. Elizabeth Yetley of the FDA's Office of Special Nutritionals, "We've known for a long time that Vitamin A is associated with these types of birth defects, but had always thought it had occurred at much higher levels."
The FDA may eventually take action based on the study, she noted, "but we need time to look at the article, talk to experts and so on."
The findings "don't really surprise me at all," said John Hathcock of the Council for Responsible Nutrition, which represents vitamin manufacturers. The council, he noted, has recommended since 1987 that pregnant women consume no more than 8,000 IU per day.
But biochemist James A. Olson of Iowa State University warned that publicity about the study may do more harm than good if women reduce their Vitamin A intake too much. He noted recent research showing that 30% of pregnant women in lower socioeconomic groups are already getting less than the minimum recommended daily dose of Vitamin A of 2,700 IU, and that the risk of birth defects from taking too little may be greater than the risk from taking too much.
And Michelle Kling, a spokeswoman for the March of Dimes Birth Defects Foundation, noted that "Multivitamins are very important for pregnant women. They make up for [essential nutrients] that are not gotten from the diet." The March of Dimes recommends taking multivitamins that contain no more than 5,000 IU of Vitamin A and against taking supplements containing only Vitamin A.
But virtually everyone agreed that there may be an easy way out of the dilemma: switching from supplements containing Vitamin A to those containing beta carotene, an antioxidant vitamin that is beneficial to the heart and that is converted to Vitamin A in the body. It is also present in a variety of vegetables.
Beta carotene has not been shown to have any adverse effects in either adults or fetuses, and the body only converts as much of it to Vitamin A as it actually needs. "Supplements that contain high levels of beta carotene should not pose a problem with respect to birth defects, nor should high levels of beta carotene in the diet," Rothman said.
Switching from Vitamin A to beta carotene "is the easiest thing to do," Yetley said. Hathcock noted that many multivitamin manufacturers have already begun to replace Vitamin A with beta carotene in their formulations.
Rothman and his colleagues studied 22,748 pregnant women between October, 1984, and June, 1987, as part of a study of neural tube defects. Only recently did they examine the data from the survey pertaining to Vitamin A.
While the women were pregnant, they were interviewed about many aspects of their diet, including multivitamin consumption and Vitamin A supplements. Only 1.4% of the women averaged more than 10,000 IU per day from supplements.
The researchers found that the increased occurrence of defects was concentrated among babies born to women who consumed high levels of Vitamin A before the seventh week of pregnancy.
Because the potential damage from Vitamin A may occur before a woman realizes she is pregnant, Rothman said, "Any woman who may become pregnant should be aware of the potential risks of excess Vitamin A intake."
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Vitamin A and Pregnancy
The best advice for pregnant women and those who might become pregnant, according to the experts:
* Take a multivitamin every day, but only one, and make sure that it contains no more than 5,000 IU of Vitamin A.
* Don't take Vitamin A supplements.
* Eat lots of tomatoes, carrots and yellow vegetables, all of which are high in beta carotene.
* Don't combine multivitamin supplements with large servings of liver, which is high in Vitamin A, or fortified cereals, many of which contain 5,000 IU of Vitamin A per bowl.