Food fortification with folic acid and rate of multiple births, 1994-2000

Since fortification of cereal grain products with synthetic folic acid (FA) became mandatory in January 1998, women in the United States who have become pregnant have been exposed to a higher level of FA than women who became pregnant previously. Some studies have suggested that increased FA consumption might increase the risk of multiple gestation pregnancies.

Women who had a live birth in Kaiser Foundation Health Plan hospitals from January 1, 1994 through December 31, 2000; all multiple births; and the use of ovulation-inducing drugs were ascertained from electronic databases. Medical records of a sample of women with multiple births who did not use ovulation-inducing drugs were reviewed to determine whether they used assisted reproductive technology. Exposure to FA-fortified foods was based on date of delivery.

The rate of multiple births increased from 13.6 to 14.8 per 1000 live births from 1994 through 2000. The percentage of women who had a multiple birth and who filled a prescription for an ovulation-inducing drug in the 12 months before delivery increased from a low of 6.6% in 1994 to a high of 14.9% in 2000. After excluding women using ovulation-inducing drugs, the increased rate of multiple births was no longer observed.

While the rates of multiple births have increased since FA fortification became mandatory, this increase can be explained by the increased use of ovulation-inducing drugs. Our findings show no relationship between food fortification with FA and the rates of multiple births in this large, managed health care population.