Vitamin A and Pregnancy

Women who take large doses of vitamin A around the time of conception or early in their pregnancy run a higher than average risk of delivering infants with birth defects.

That's the finding of a study that flashed across hundreds of newspaper headlines in October 1995. The New England Journal of Medicine released the findings more than a month ahead of the study's scheduled Nov. 23, 1995, publication date.

The epidemiological study, which analyzed the dietary and vitamin supplement habits of 22,748 pregnant women, was conducted by Kenneth J. Rothman, DrPH, of the Boston University School of Medicine. Rothman found that women taking more than 10,000 IU of vitamin A daily, either in food or supplements, were three times more likely to deliver infants with deformities of the head, heart, and brain.

Such amounts of vitamin A are found in some multivitamin formulas. Over the past few years, however, many vitamin companies have switched from vitamin A to beta-carotene, which is safe and does not cause birth defects. A 3-ounce serving of liver provides about 30,000 IU of vitamin A.

In Rothman's retrospective study, women were queried about their eating and vitamin supplement habits before becoming pregnant and during the first three months of pregnancy. After delivery, either the women or their physicians completed a questionnaire about the health of the baby.

The researchers found that 121 cases of "cranial neural crest" deformities occurred. These deformities included cleft lip, cleft palate, water on the brain, and heart defects.

Women taking more than 10,000 IU of vitamin A during the first three months of pregnancy were 2.4 times more likely to deliver children with the birth defects. Women taking 20,000 IU were four times more likely to deliver children with birth defects.

While the risk of birth defects increased with high vitamin A, only 1 baby in 57 actually developed defects because of its mother's use of the vitamin. Conversely, 56 of 57 infants born to mothers consuming large doses of vitamin A had no birth defects.

Vitamin A is essential for normal cellular differentiation and in regulating organ development in the fetus. The researchers recommended that pregnant women either limit their vitamin A consumption to 4,000 to 8,000 IU daily or, alternatively, take beta-carotene.

Researchers responded to the study with a number of criticisms. Pre-publication release of research is discouraged in the scientific community and, in this case, many detailed criticisms of the vitamin A study will not be possible until it's actually published.

Richard Miller, PhD, director of the Prenatal Environmental and Drug Exposure Consultation Service at the University of Rochester, felt the study would discourage pregnant women from taking vitamin supplements in general. This, he told The Nutrition Reporter™, was particularly disturbing because he and other researchers have been trying to get women to increase their consumption of vitamins, particularly folic acid.

At a press conference, Rothman emphasized the safety of beta-carotene. "Beta-carotene, a constituent of many fruits and vegetables, can also be converted to vitamin A in the body," he explained. "Other studies show, however, that high beta-carotene intake does not elevate vitamin A levels in the body enough to surpass the threshold for teratogenic effects [birth defects]. 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. We know of no reason for anyone to avoid eating carrots, tomatoes, or other carotene-containing foods, and we know of no adverse effect associated with beta-carotene dietary supplements."

"We stress that there is no indication of any adverse effect of vitamin A at recommended levels, nor do our findings relate to any other vitamin," Rothman added. "Vitamin supplements in general are important dietary adjuncts for those whose diet is deficient in vitamins. We hope that our findings will enable women to maintain levels of intake that are neither too high nor too low."

Commentary...
Vitamin A and Pregnancy:
How Many People Will The Panic Injure?

Recent newspaper headlines on the dangers of vitamin A broke the custom of not disclosing data before its publication in a scientific journal. Some researchers complained because they would not be able to read details of the study for several weeks.

Lead investigator Kenneth J. Rothman, DrPH, of the Boston University School of Medicine, and the New England Journal of Medicine (which planned to publish the study Nov. 23, 1995) contended that they released the findings early because it was a matter of urgent public health.

It seemed more like an excuse for grandstanding and headline grabbing. The NEJM has not seen similar public health value in pre-releasing studies showing that folic acid and vitamin E reduce the risk of coronary heart disease, or that calcium supplements prevent osteoporosis. Such acts would help far more people than excess vitamin A would hurt.

Still, Rothman's findings are important. He reported that women consuming large amounts of vitamin A, either from food or supplements, had about a two- to four-time greater risk of delivering children with craniofacial defects than did women with lower vitamin A intake. The study was based on women's recollections of what they ate and the vitamins they took.

The period of greatest risk was around the time of conception or during the first several months of pregnancy. Taking vitamin A at these times did not mean that a baby would definitely suffer defects-only that there was a higher risk of defects.

According to Rothman, 1 in 57 babies born to women taking high-dose vitamin A had birth defects. Another way to look at this is to say that 56 of the 57 infants born to the high vitamin A group were normal.

Often overlooked in the vitamin A headlines and stories were a number of other important issues.

First, vitamin A is essential for normal cell differentiation, and there is evidence that vitamin A deficiency also leads to birth defects. (Bendich A and Langseth L, "Safety of vitamin A," American Journal of Clinical Nutrition, February 1989;49:358-71) Yet Rothman concentrated on vitamin A excesses, not deficiencies. In his paper, he stated that 98.6 percent of the women consumed "safe" levels of vitamin A, but these were approximately RDA levels or below. When queried, Rothman said he did not analyze data as to how many women actually consumed less than the RDA for vitamin A. (E-mail communication, October 12, 1995) If he had, he might have better demonstrated the effects of low vitamin A, as well as an optimal dose for pregnant women.

Second, the risk of vitamin A in pregnancy does not apply to beta-carotene, which is completely safe. The body converts beta-carotene to vitamin A only as needed. Even Rothman pointed this out in his paper and at his press conference.

Third, Rothman's study was based on women questioned from 1984 to 1987. Since that time, a large number of vitamin companies selling multiple vitamins have replaced vitamin A with beta-carotene. That means women today are now less likely to encounter high doses of vitamin A-and therefore the practical risk of vitamin A overdose is less than it was.

Fourth, vitamin A is one of the most potent and worthwhile immune stimulants and is especially protective against respiratory infections. (Neuzil KM, et al., Journal of Pediatrics, March 1994;124:433-6) It is essential for the formation of epithelial cells, which function as a physical barrier against infections, and it also stimulates the production of T cells, and antibody-producing B cells. (Dennert G, in: Sporn MB, Roberts AB, and Goodman DS, eds. The Retinoids. Orlando: Academic Press, 1984,2:373-390.) One recent study reported that occasional high doses of vitamin A improved the well being of infants with HIV infections. (Coutsoudis' A, et al, American Journal of Public Health, Aug. 1995;85:1076-1081)

Fifth, the bigger problem (from a public health standpoint) is not a small number of cases of vitamin A overdose, but widespread vitamin A deficiency. In the 1980s, Alfred Sommer, MD, of Johns Hopkins University documented that one or two very high doses of vitamin A (more than 100,000 IU) could prevent one-third of childhood deaths from measles in developing nations. (Sommer A, Journal of Infectious Diseases, May 1993;167:1003-7) The World Health Organization (WHO) and UNICEF now routinely recommend occasional vitamin A supplements for children at risk of dying from measles, and the American Academy of Pediatrics has issued similar recommendations. (Committee on infectious diseases, American Academy of Pediatrics, Pediatrics, May 1993, 91;1014-1015)

Although the latest edition of the Recommended Dietary Allowances, published by the National Academy of Sciences, describes vitamin A deficiency as "rare" in the United States, (Recommended Dietary Allowances, National Academy Press, 1989) evidence suggests that the opposite is really true. According to one major survey, one-half of Americans consume 19 percent or less of the RDA for vitamin A, and one-fourth of the population consumes no more than 11 percent of the RDA. (Block G, Nutrition Reviews, June 1992;50:207-213)

So, what conclusions should you draw from the vitamin A and pregnancy study?
There is a risk of vitamin A overdose, but the risk is generally overstated. Women likely to become pregnant should exercise caution taking high doses of vitamin A or eating liver (a 3-ounce serving provides 30,000 IU), but there is no need for worry with beta-carotene. If you're not likely to become pregnant-and this includes the male half of the population and older women-vitamin A toxicity is less of an issue.

It is also worthwhile being watchful of symptoms of vitamin A overdose, including chronic headache, vomiting, loss of hair, dryness of the mucous membranes, and liver damage. But according to the American Academy of Pediatrics, vitamin A toxicity generally doesn't occur unless someone consumes more than 1,000,000 IU in a two- to three-week period. (Committee on infectious diseases, American Academy of Pediatrics, Pediatrics, May 1993, 91;1014-1015)

Let's be sensible and remember that most vitamin problems are related to deficiencies, not overdoses.