In this issue:
• The Importance of Periconceptual Folate Counseling

The Importance of Periconceptual Folate Counseling
Neil S. Silverman, MD

Diet is one of the major, and most controllable, environmental influences on the development of the embryo and fetus. It has been over 40 years since folic acid was recognized, among dietary influences on pregnancy, as one that was critical for the normal development of the neural tube, among other major organ systems.

Neural tube defects (NTDs) occur in 1-2/1000 pregnancies, with 95% of affected fetuses being the first diagnosed in a family, limiting the ability to predict occurrence, especially with first pregnancies.^1,2 Proven preventive measures against NTDs, such as folic acid supplementation, are important not just for all pregnancies, therefore, but for all women of reproductive age, since up to 50% of pregnancies in the U.S.³ are unplanned. In these cases, the neural tube has usually closed by the time the pregnancy is confirmed, and the window for preventive folate supplementation has passed.

The Institute of Medicine, the March of Dimes, and the American College of Obstetricians and Gynecologists all support education and counseling of all women of reproductive age to inform them of the need for periconceptional folic acid supplementation in the event they become pregnant. Current recommendations entail at least 400 mcg of folic acid per day for non-pregnant adults, increasing to at least 600 mcg per day once pregnancy is confirmed.  With such appropriate periconceptional use of folic acid, the risk of NTDs has clearly been shown to be lowered in a number of well-conducted peer-reviewed studies, and the risk of other birth defects, such as congenital heart disease and orofacial clefts, may also be decreased.^1,4,5

Folate, a water-soluble B vitamin, is readily available in a diet that includes green leafy vegetables, legumes, and other folate-rich foods. However, Western diets have been shown to be increasingly suboptimal for these foods, and, as a result, cereal grains in the U.S. have been fortified with folic acid since 1998, with a diet containing cereal or enriched bread adding 200 mcg/day of folic acid, on average. Still, diet alone cannot be relied upon to ensure adequate folate intake; as a result, folate supplementation in the form of tablets is also recommended for reproductive-age women, at a minimum dose of 400mcg/day. Obese women may need higher doses for comparable preventive effects against NTDs; these dosing modifications are currently being studied. However, an excess dose of folate on a daily basis does not appear to be of concern in an otherwise healthy population since it is readily excreted by the kidneys. In fact, women who have had a prior pregnancy affected by an NTD are at increased risk of recurrence (3-5%), and it is recommended that they take 4 mg/day of folic acid supplementation pre- and periconceptionally.^1,2

Women in study cohorts have responded favorably to physician-guided counseling regarding the need for folic acid supplementation in the context of their routine gynecologic “well-woman” healthcare visits. It is critical that healthcare providers address this issue with all women who could be pregnant in the future and reinforce the wealth of potential benefits of prepregnancy folate supplementation against the essential negative risks for side effects or other adverse outcomes. Adolescents and minority populations are less aware of the role of folate in pregnancy;^6-9 it is particularly important to develop educational programs that reach all populations of women, with specific focus on these higher-risk, frequently underserved women. That folic acid supplementation works to prevent adverse pregnancy outcomes is not in question; what remains is to develop the best way to reach out to and educate all reproductive-age women effectively.

1. ACOG. Neural tube defects. Practice Bulletin # 44. Washington, DC; July 2003.
2. Shaer CM, Chescheir N, Schulkin J. Myelomeningocele: a review of the epidemiology, genetics, risk factors for conception, prenatal diagnosis, and prognosis for affected individuals. Obstet Gynecol Surv 2007; 62: 471-9.
3. Henshaw SK. Unintended pregnancy in the United States. Fam Plann Perspect 1998; 3: 24-9.
4. Cetin I, Berti C, Calabrese S. Role of micronutrients in the periconceptional period. Human Repro Update 2010; 16: 80-95.
5. Johnston RB Jr. Will increasing folic acid in fortified grain products further reduce neural tube defects without causing harm? Consideration of the evidence.  Pediatr Res 2008; 63: 2-8.
6. CDC. Use of supplements containing folic acid among women of childbearing age – United States, 2007. MMWR 2008; 57: 5-8.
7. Cleves MA, Hobbs CA, Collins HB, et al. Folic acid use by women receiving routine gynecologic care. Obstet Gynecol 2004; 103: 746-53.
8. Hammer HC, Mulinare J, Cogswell ME, et al. predicted contribution of folic acid fortification of corn masa flour to the usual folic acid intake for the US population: National Health and Nutrition Examination Survey 2001-2004. Am J Clin Nutr 2009; 89¨305-15.
9. Robbins JM, Cleves MA, Collins HB, et al. Randomized trial of a physician-based intervention to increase the use of folic acid supplements among women. Am J Obstet Gynecol 2005; 192: 1126-32.

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