VITAMIN A AND BIRTH DEFECTS

The claim that intakes of vitamin A over 10,000 IU per day can increase the risk of birth defects can be traced back to a 1995 paper published by a group of researchers led by Dr. Kenneth Rothman of Boston University.²¹ The researchers followed almost 23,000 women over the course of their pregnancies and found that women who consumed more than 10,000 IU of vitamin A during the first trimester gave birth to offspring with a 2.4-fold greater risk of total birth defects and a 4.8-fold greater risk of cranial-neural-crest defects (a rather broad group of defects whose classification is controversial). Among the 188 women who consumed this amount of vitamin A from “food” alone, there was an 80 percent increase in the risk of total birth defects and two times the risk of cranial-neural-crest defects. Because there were so few women consuming vitamin A from “food” alone, however, the researchers could not conclusively distinguish the association from the effect of chance.

This study has a number of important flaws. Most of the vitamin A came from multivitamins. The authors did not distinguish between various food sources—and most “food” vitamin A comes from fortified breakfast cereals. Three groups of experts wrote to the journal questioning the authors’ classification of cranial-neural-crest defects.22,23,24 Perhaps most important, the authors may have underestimated the rate of certain types of birth defects. The rate of total birth defects among the 20,000 women consuming less than 10,000 IU was only 1.5 percent; by contrast, the generally accepted background rate is 3-4 percent. The rate of defects among the 3,000 women consuming more than 10,000 IU of vitamin A was 3 percent—on the lower end of normal.²⁴

The most important objection to this study is the fact that it conflicts with all the other evidence:

• An earlier 1990 study conducted in Spain found that among 25,000 births, doses of vitamin A over 40,000 IU per day carried a 2.7-fold higher risk of birth defects, but doses of vitamin A up to 20,000 IU or between 20,000 and 40,000 IU both carried a 50 percent lower risk of birth defects compared to no supplementation.²⁵
• A 1996 study of 522,601 births found that the children of women supplementing with at least 10,000 IU of vitamin A in addition to a multivitamin had a lower risk of birth defects than those of women who did not supplement, although the association could not be distinguished from the effect of chance.²⁶
• A 1997 study of 1,508 births found no relationship between birth defects and use of vitamin A supplements, fortified breakfast cereals, organ meats or liver.²⁷
• A 1999 prospective study of 311 mothers who consumed between 10,000 and 300,000 IU of vitamin A in the first trimester and a similarly sized group that did not supplement with vitamin A found no evidence of an increased risk of major malformations with increasing dose. The median dose was 50,000 IU. The group as a whole had a 50 percent lower risk of major malformations than those who did not supplement, and there were no major malformations in offspring born to mothers consuming more than 50,000 IU.

The preponderance of the evidence clearly favors the view that 20,000-25,000 IU of vitamin A during pregnancy is safe and may even reduce the risk of birth defects.⁶³