CDC Grand Rounds: Additional Opportunities to Prevent Neural Tube Defects with Folic Acid Fortification

CDC Grand Rounds: Additional Opportunities to Prevent Neural Tube Defects with Folic Acid Fortification
Weekly
August 13, 2010 / 59(31);980-984


This is another in a series of occasional CDC Grand Rounds reports. These reports are based on grand rounds presentations at CDC on high-profile issues in public health science, practice, and policy. Information regarding CDC Grand Rounds is available at http://www.cdc.gov/about/grand-rounds.

Neural tube defects (NTDs) are serious birth defects that result from the failure of the neural tube to close in the cranial region (anencephaly) or more caudally along the spine (spina bifida) by the 28th day of gestation. Infants born with anencephaly usually die within a few days of birth, and those with spina bifida have life-long disabilities with varying degrees of paralysis. Currently, identified risk factors for NTDs include a mother who previously had an NTD-affected pregnancy, maternal diabetes, obesity, hyperthermia, certain antiseizure medications, genetic variants, race/ethnicity, and nutrition (particularly folic acid insufficiency). In the United States, during 1995--1996, approximately 4,000 pregnancies were affected by an NTD. This number declined to 3,000 pregnancies in 1999--2000 after fortification of enriched cereal grain products with folic acid was mandated (1). Worldwide, in 1998, approximately 300,000 births were affected by an NTD (Figure 1).

Both observational and intervention studies, including randomized, controlled trials, have demonstrated that adequate consumption of folic acid periconceptionally can prevent 50%---70% of NTDs (2). Three approaches can increase intake of folate/folic acid*: dietary improvement, supplementation, and food fortification. Efforts to improve women's dietary habits so that they consume more foods rich in folate or daily vitamin supplements have had little success because they require behavior change, improved accessibility, affordability, or sustainability (3). Supplementation alone also has not been an effective approach because approximately 50% of pregnancies are unplanned. Fortifying foods with folic acid has been a highly effective and more uniform intervention, because fortification makes folic acid accessible to all women of childbearing age without requiring behavior change.

In 1992, the U.S. Public Health Service (USPHS) recommended that all women of childbearing age capable of becoming pregnant consume 400 µg of folic acid daily for prevention of NTDs. In 1996, the Food and Drug Administration (FDA) established regulations that required that by 1998 all standardized enriched cereal grain products sold in the United States include 140 µg folic acid/100 g and provided for the addition of folic acid to breakfast cereals, corn grits, infant formulas, medical foods, and foods for special dietary use. Also in 1998, the Institute of Medicine (IOM) conducted an independent review, with conclusions supporting the USPHS recommendations for folic acid consumption; in 2009, the U.S. Preventive Services Task Force published updated guidelines reinforcing these recommendations (4).

Impact of Fortification with Folic Acid

U.S. NTD and blood folate trends. The mandatory fortification of standardized enriched cereal grain products in the United States resulted in a substantial increase in blood folate concentrations and a concomitant decrease in NTD prevalence. The percentage of the population with low serum folate (<3 ng/mL) declined from 21% in the period before fortification (1988--1994) to <1% of the total population in the period immediately following fortification (1999--2000) (5). NTD prevalence decreased by 36% after fortification, from 10.8 per 10,000 population during 1995--1996 to 6.9 at the end of 2006 (6).

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CDC Grand Rounds: Additional Opportunities to Prevent Neural Tube Defects with Folic Acid Fortification