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Folic Acid in Pregnancy

By Reed Mangels, PhD, RD

I’ve recently gotten some questions about the use of folic acid supplements prior to and during pregnancy. Folic acid is one form of folate, an essential vitamin. Folic acid is the form of folate that is used in supplements and fortified foods because it is the form that is most stable. It is added to enriched grain products including breads, pasta, and breakfast cereals. There are several forms of folate that are found naturally in foods; these are called “food folates.” Foods that are naturally high in folate include green leafy vegetables, dried beans, and oranges.

The Centers for Disease Control (CDC) urges women to take 400 micrograms of folic acid every day, starting at least one month before getting pregnant and continuing during pregnancy, to help prevent major birth defects of the baby’s brain and spine (1). They specifically call for use of folic acid from fortified foods and/or supplements, in addition to getting folate from foods.

The first few weeks of pregnancy are important times for the development of the fetus’ brain and spinal cord. Taking folic acid in the period from about 1 month before to 6 weeks after conception is associated with reduced risk of having a baby with a neural tube defect. Neural tube defects include spina bifida, anencephaly, and other serious birth defects. Folic acid is also associated with reduced risk of cleft lip/palate (2).

You may be wondering if you can just get the folate you need for pregnancy from foods. Somewhat surprisingly, no studies have been published that look at food folate and the prevention of neural tube defects. All of the studies that have been done looking at neural tube defects have compared women who used folic acid supplements or foods fortified with folic acid to women who did not use these products. In these studies, women who used folic acid had a 35% to over 70% lower risk of having a baby with a neural tube defect.

It’s unfortunate that food folate studies have not been done but, at this point, there may be ethical questions about doing such studies since folic acid has shown such impressive effects in terms of risk reduction.

Numerous factors affect how well humans absorb food folate. These include genetics and race/ethnicity (3). Folic acid is not affected as much by these variations in absorption. This may be another reason why folic acid supplements are recommended before and during pregnancy in addition to getting folate from foods.

Because of the significant impact of folic acid, specifically on the reduction of the risk of having a child with a serious birth defect, and the lack of evidence for similar benefits of food folate, I would not personally be comfortable with telling someone contemplating pregnancy to avoid folic acid supplements or fortified foods at the recommended levels. That said, food sources of folate also contain many other important nutrients. These foods including dried beans and green leafy vegetables should be a part of everyone’s diet.

Some websites raise concern about health risks of using folic acid. Many of these concerns do not apply for the short-term used of folic acid just before and during pregnancy. For example, one study is pointed to as suggesting a higher risk of breast cancer with use of folic acid (4). This study was conducted in postmenopausal women, not in women who took folic acid only around the time of pregnancy, so is not really relevant to this discussion.

Similarly, a report of higher risk of colon cancer (5) found no increased risk in those taking supplements for up to 3 years.

One study which found a correlation between use of folic acid in pregnancy and breast cancer (6) had some subjects taking more than 10 times as much folic acid as is recommended. The number of subjects in this study was small and the researchers themselves comment that their results could be due simply to chance. No other study has replicated the findings of this study.

Some websites raise the issue of whether or not children whose mothers take folic acid in pregnancy have a higher risk of asthma. There have been 4 studies of the relation between supplemental folic acid in pregnancy and childhood asthma. Two found statistically significant associations between childhood asthma and late (but not early) pregnancy maternal folic acid exposure. Another found a statistically significant association between childhood wheeze and early (but not late) pregnancy maternal folic acid exposure. A fourth study found little association between maternal dietary folate in pregnancy and infantile wheeze. (7) One group of researchers commented, “We would remind women that respiratory risks from late pregnancy folic acid are unproven, but that even if they are real, the absolute increase in risk to an individual child would be fairly small. Hypothetically, if the relative risk increase of asthma from standard dose late pregnancy folic acid was 10–20% (consistent with the Australian and English studies), and assuming an Australian childhood asthma prevalence of 20%, a pregnant woman taking folic acid in late pregnancy would increase her child’s risk of asthma by 2–4%. Couching the statistics in these terms may help patients make an informed decision (7).”

Bottom line (my opinion): We don’t have enough information to recommend food folate in place of folic acid to reduce risk of neural tube defects. Based on what we know now, the benefits of folic acid supplements prior to conception and during pregnancy outweigh the risks.

References
1. Centers for Disease Control. Facts About Folic Acid. http://www.cdc.gov/ncbddd/folicacid/about.html
2. Wilcox AJ, Lie RT, Solvoll K, et al. Folic acid supplements and the risk of facial clefts: A national population-based control study BMJ, 2007 Mar 3;334(7591):464.
3. Caudill MA. Folate bioavailability: implications for establishing dietary recommendations and optimizing status. Am J Clin Nutr. 2010 May;91(5):1455S-1460S.
4. Stolzenberg-Solomon RZ et al. Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr. 2006 Apr;83(4):895-904.
5. Fife J et al. Folic acid supplementation and colorectal cancer risk; a meta-analysis. Colorectal Dis. 2011 Feb;13(2):132-7.
6. Charles D et al. Taking folate in pregnancy and risk of maternal breast cancer. BMJ 2004;329:1375;6.
7. Sharland E, Montgomery B, Granell R. Folic acid in pregnancy – is there a link with childhood asthma or wheeze? Aust Fam Physician. 2011 Jun;40(6):421-4.