July 22, 1997
NIH - Moderate Doses of Vitamin A Do Not Pose Risk of Birth Defects
Contrary to what many researchers had feared, doses of vitamin A commonly taken during pregnancy do not increase the chances that a woman will have a child with a birth defect, according to a study conducted by the National Institute of Child Health and Human Development (NICHD).
Specifically, the study found that taking daily doses of between 8,000 and 10,000 International Units (I.U.) of vitamin A during pregnancy does not appear to cause birth defects. The study also showed that it is very rare for women to take more than 10,000 I.U. of the vitamin each day. Although this finding indicates that few women are taking doses that potentially could increase the risk of birth defects, the small number of women in this group limited the study's ability to determine if such high doses do indeed cause birth defects.
The study appears in the July issue of the American Journal of Obstetrics and Gynecology.
"There is no reason for women to take more than the Recommended Daily Allowance of vitamin A," said the study's principal investigator, James Mills, Chief of NICHD's Pediatric Epidemiology Section. "But this study suggests that the larger doses that some women take during pregnancy is not likely to cause any problems."
The Recommended Daily Allowance (RDA) for vitamin A is 2,670 International Units. Dr. Mills explained that some women may consume between 8,000 and 10,000 IU of vitamin A (roughly triple the RDA), by taking vitamin pills and perhaps eating vitamin A fortified cereal as well.
Isotretinoin (13-cis-retinoic acid), a drug used to treat acne, chemically is very similar to vitamin A and small quantities of this compound are produced by the body after consumption of vitamin A. Because Isotretinoin has been found to cause birth defects, many researchers feared that vitamin A might also cause birth defects.
In their study, Dr. Mills and his coworkers compared women pregnant with a child having a birth defect to women pregnant with infants who did not have a birth defect. The researchers enrolled 548 women whose pregnancies produced offspring with either a neural tube defect (a class of birth defects affecting the brain and spinal cord) and 387 women whose pregnancies produced a major birth defect other than neural tube defects. This group of women included women pregnant with a child having a cranial neural crest defect. Cranial neural crest defects are a major class of birth defects resulting in cleft palate, facial abnormalities, and abnormalities of the heart valves and have been shown to occur in children whose mothers took Isotretinoin shortly before, and just after, conception.
The women in both of these groups were then compared to 573 women having normal pregnancies.
The women were interviewed by telephone, between 1 month and 5 months after the birth defect was detected--either as a result of amniocentesis or ultrasound testing, or after birth. The women were asked about how much vitamin A they consumed, either from food of vitamin tablets, from about 30 days before their last menstrual period to about 45 days after.
When compared to women in the control group, neither the women in the neural tube defect group nor those in the group pregnant with children having other major malformations were found to have been more likely to have consumed between 8,000 and 10,000 IU of vitamin A.
Dr. Mills noted that some of the previous studies had found an association between birth defects and vitamin A, and some had not. He added that the NICHD study had strengths that these earlier studies lacked. For the most part, the NICHD study obtained more detailed information on the types and doses of Vitamin A the women took. It also questioned the women shortly after the time of diagnosis. This helped to ensure that the women were more accurately able to recall how much vitamin A they had consumed. By comparison, many of the earlier studies did not question participants about vitamin A consumption until a few years after the diagnosis of a birth defect.
Dr. Mills added, that, because few of the women in the study took large doses of vitamin A (more than 25,000 I.U.) it was not possible to ascertain whether large doses of the vitamin could cause birth defects.
"Because at least one vitamin A metabolite, 13-cis-retinoic acid or its metabolites, is teratogenic at high concentrations (those present during therapy with Isotretinoin), there is good reason to be concerned that very large doses of vitamin A cause birth defects," the authors wrote. "Thus, women should be advised not to consume high levels of vitamin A."
The study was conducted at Northwestern University in Chicago, Illinois, and at the California Public Health Foundation in Berkeley, under NICHD sponsorship.
Other authors of the paper were:
Joe Leigh Simpson, MD,
Baylor College of Medicine;
George C. Cunningham, MD, MPH,
California Department of Health Services;
Mary R. Conley, MA,
also of NICHD; and
George G. Rhoads, MD, MPH,
The University of Medicine and Dentistry of New Jersey.
