This month, the Society of Obstetricians and Gynecologists of Canada is releasing new guidelines on folic acid supplementation in pregnant women, recommending prenatal vitamins that include 5 mg of folate in certain patients. Unless providers can ensure excellent daily compliance with the typical prenatal vitamin containing 0.8–1.1 mg of folate, the society is recommending this higher folate dose during pregnancy.
The basis of the new recommendation is evidence indicating that compliance with prenatal vitamins is not ideal, and as a result, prevention of neural tube defects with folate supplementation is suboptimal, as shown by several studies.
The current recommendation in the United States and Canada is that women of reproductive age consume at least 400 mcg of folic acid/day through a prenatal multivitamin, foods fortified with folic acid, or both to reduce their risk of having a baby with a neural tube defect (NTD) such as spina bifida, anencephaly, and other malformations. The amount of folic acid currently recommended for women who have already had a child with an NTD is 4 mg/day.
The recommendation for folic acid supplementation prenatally and during pregnancy was formed in the early 1990s. Subsequent fortification of enriched cereal grain products in 1998 in North America has had a marked impact on the rate of babies born with NTDs over the last decade.
Over the last several years, however, there have been questions raised about whether the folic acid dose included in prenatal vitamins is adequate to prevent NTDs.
For example, in a report published in 2001, using data from studies correlating the folic acid supplementation and the associated serum folate concentrations, and a large cohort study of the NTD risk based on serum folate, the authors determined that 5 mg of folic acid per day would prevent almost 90% of women from having a baby with an NTD. Nicholas Wald and his colleagues concluded that the currently recommended dose would protect only part of the population from NTDs, and recommended that women planning to become pregnant should take a 5-mg dose of folic acid per day (Lancet 2001;358:2069–73).
Corroborating this calculation were findings from a study of a large group of reproductive-aged Ontario women aged 15–45 years in 2005 and 2006, whose folic acid intake was unknown. We measured erythrocyte folate levels and determined that 40% of these women did not achieve the 900-nmol level needed to protect against NTDs, despite the fortification of flour and the recommendation that all women of reproductive age consume 400 mcg of folic acid daily. These findings, published in an abstract last year, strengthened our belief that the 5-mg recommendation is probably correct.
One of the two main arguments against an increase in folic acid is that an excess of folic acid in the diet can mask pernicious anemia, caused by vitamin B12 deficiency in older people. However, since flour was fortified, there has been no evidence of an increasing problem with pernicious anemia.
The second major concern is the potential effect of folate in increasing the risk of some cancers, which includes evidence that folic acid supplementation may increase the growth or number of colorectal polyps. However, the bulk of currently available data indicate that an adequate folic acid level decreases the risk of about 10 cancers, including colon cancer. Clearly, if a risk of cancer exists, it would be associated with long-term exposure to folic acid and would be a potential concern for people who consume a large amount of folic acid in flour-based products, not pregnant women who take an increased amount for a limited period of time.
In a recently completed clinical study of pregnant women at the Motherisk Program, we found that despite the women being under supervision, the compliance rate with prenatal multivitamins was surprisingly low—an average of 53%–58%, ranging from 0% to 100%. The likelihood that a substantial proportion of women prescribed a prenatal vitamin containing 1 mg of folic acid per tablet will miss a few days every week strengthens the recommendation that the inclusion of a higher dose of folic acid in prenatal vitamins would be beneficial for women who may not be entirely compliant with their daily vitamin intake, and that many more women, with less than ideal compliance, would have protective folate levels if the supplement contained 5 mg/day.
In October, the Centers for Disease Control and Prevention reported on a California Department of Public Health survey of women in the state who were aged 18–44 years, which found that the overall prevalence of women taking folic acid-containing supplements was stable from 2002 (40%) to 2006 (41%). But the rate decreased among Hispanic women, who are at a greater risk of having a baby with an NTD, from about 33% in 2002 to about 30% in 2006, a significant difference (MMWR 2007; 56:1106–9).