Folic acid and oral contraceptives: Will women see a combined product?

Concept: One pill to prevent unintended pregnancy, birth defects

The next patient in your office is a nervous 23-year-old newlywed. While she was given a prescription for oral contraceptives (OCs) at her last visit, she admits she has not been diligent in taking them. A lab test confirms she is two months into her pregnancy.

More than 10 million U.S. women rely on OCs as their preferred form of contraception; the Pill is second only to female sterilization as the most widely-used method.1 However, as family planning providers know, the efficacy of the Pill depends on its consistent use. According to A Pocket Guide to Managing Contraception, of every 1,000 women who take pills consistently and correctly for one year, just one will become pregnant in the first year. However, with typical use, the Pill’s failure rate rises to 8%.2

Women at risk of unintended pregnancy also may be at risk of inadequate intake of folic acid, a necessary vitamin for proper cell growth and development of the embryo. When taken one month before conception and throughout the first trimester, folic acid in a 400-mcg vitamin supplement has been proven to reduce the risk of two major neural tube defects, spina bifida and anencephaly, by 50%-70%.3 The average additional lifetime cost to society for each infant born with spina bifida is approximately $532,000 per child; for many children, the total cost may exceed an additional $1,000,000.4

What if there was a combined oral contraceptive/folic acid product designed to prevent pregnancy and raise serum folate levels? What would be the potential advantages and disadvantages of such a product?

One oral contraceptive manufacturer, Ortho-McNeil Pharmaceutical Inc. of Raritan, NJ, is exploring the concept of such a combination pill. The company is scheduled to have a preliminary discussion of the concept of a combination oral contraceptive/folic acid pill with the FDA’s Reproductive Health Advisory Committee later this year, confirms Andrew Friedman, MD, the company’s director of women’s health research.

Why supplementation?

The Washington, DC-based Institute of Medicine and U.S. Public Health Service now recommends that every woman capable of becoming pregnant consume 400 mcg of synthetic folic acid daily in addition to a diet rich in natural folates.5 To aid in this goal, the Food and Drug Administration (FDA) in 1998 mandated grain fortification in bleached wheat flour. Despite the grain fortification program, as well as a public awareness campaign on vitamin supplementation, just 20% of women participating in a 2002 March of Dimes survey knew that folic acid could prevent certain birth defects. The proportion who stated that they took a vitamin supplement containing folic acid daily increased from 25% in 1995 to only 31% in 2002.6

"I like to make an immunization analogy that this is as serious as polio, and it is as if we had the polio vaccine, and we have only given it to one out of five people," states Godfrey Oakley, MD, MSPM, visiting professor of epidemiology at the Rollins School of Public Health, Emory University in Atlanta, and former director of the Center for Disease Control and Prevention’s (CDC’s) Division of Birth Defects and Developmental Disabilities. "There isn’t a state in the country that would sit still for two cases of polio a year, and we have in Georgia alone, 100 cases of spina bifida and anencephaly that can be prevented [annually] with more folic acid."

What if there was a combined oral contraceptive/folic acid product designed to prevent pregnancy and raise serum folate levels? What would be the potential advantages and disadvantages of such a product?

One oral contraceptive manufacturer, Ortho-McNeil Pharmaceutical Inc. of Raritan, NJ, is exploring the concept of such a combination pill. The company is scheduled to discuss the concept of a combination oral contraceptive/folic acid pill with the FDA’s Reproductive Health Advisory Committee later this year, confirms Andrew Friedman, MD, the company’s director of women’s health research.

Most providers know that up to 70% of neural tube defects may be prevented by folic acid supplementation; what many of them don’t realize is that the neural tube closes around the 28th day after conception, before most women know that they are pregnant.7

For supplementation to work, women must start taking folic acid prior to conception and continue through the first three months of pregnancy; most women don’t learn they are pregnant until the sixth or eighth week.7 According to the Atlanta-based CDC, only 13% of women know that folic acid can prevent neural tube defects, and just 7% know that folic acid must be taken before pregnancy.8 (See handout, "What is Folic Acid, and Where Can I Get It?".)

While about three-quarters of providers report discussing folic acid use with their pregnant patients, just 26% bring the subject up with their nonpregnant patients.7 Talking about folic acid with "pregnancy noncontemplators" (a term coined by the CDC’s National Center on Birth Defects and Developmental Disabilities) is key, say public health officials. These women, ages 18-24, are not planning to become pregnant immediately and are more resistant than contemplators to behaviors that improve pregnancy outcomes.9 These women need to hear that "your body is ready for pregnancy even if you’re not planning a pregnancy now."9

Protection in the Pill?

What if women could get their daily dose of folic acid in their oral contraceptive? Oakley points to a study of Georgia family planning clinics to make his point: While 42% of women in the clinics used oral contraceptives, just 17% were taking a multivitamin fortified with folic acid.10

"If there were folic acid in those oral contraceptive pills, and that was the standard in that clinic, with no behavior change, you would have 42% of women in that age group who don’t think they’re going to get pregnant, but if they do they would be protected [against neural tube defects]," says Oakley.

But if such a combined pill were to become available, how would clinicians provide counseling on a pill that would provide pregnancy protection, yet also afford the folic acid levels needed to prevent neural tube defects?

"I think the challenge to clinicians, should they be able to prescribe folic acid-fortified pills, would be, on the one hand, to reassure patients that when taken effectively, today’s birth control pills are highly effective, but on the other hand, a number of women do get pregnant on the Pill because they don’t take it properly, and should such a pregnancy occur, since there is folic acid in the pill, the risk of a neural tube defect would be reduced," says Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville. "I think our challenge would be to keep both of those messages clear, so they do not conflict or contradict one another."

Allan Rosenfield, MD, dean of the Mailman School of Public Health and DeLamar Professor of Public Health and obstetrics/gynecology at Columbia University in New York City, sees the potential use of such pills as a plus for those women using OCs for spacing purposes and for those who have a contraceptive failure. It would be important for clinicians to instruct women to continue folic acid supplementation after discontinuation of the pill, he comments.

Begin the Dialogue

If folic acid was added to an oral contraceptive, it would add a point of entry for clinicians to discuss the importance of folic acid supplementation during the contraceptive counseling session, says Oakley. Even if a woman were to choose another form of contraception, she would be made aware of the importance of folic acid, he notes.

Would the concept of a vitamin-supplemented birth control pill be accepted? "Whether we are talking about acne, menstrual cramps, or perimenopausal symptoms, U.S. clinicians and their patients have gotten quite comfortable treating the Pill as both a contraceptive or sometimes for mixed use, or increasingly, just for noncontraceptive use," states Kaunitz. "The idea of some nutritional benefit that could help prevent birth defects, I don’t think that would be hard for clinicians or women to comprehend."

References

1. Piccinino LJ, Mosher WD. Trends in contraceptive use in the United States: 1982-1995. Fam Plann Perspect 1998; 30:4-10, 46.

2. Hatcher RA, Nelson AL, Zieman M, et al. A Pocket Guide to Managing Contraception. Tiger, GA: Bridging the Gap Foundation; 2002.

3. Johnston RB Jr. Folic acid: New dimensions of an old friendship. Adv Pediatr 1997; 44:231-261.

4. National Center for Birth Defects and Developmental Disabilities. What are neural tube defects (NTDs)? Accessed at: www.cdc.gov/ncbddd/fact/folicfaqs.htm.

5. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC; 2000.

6. March of Dimes Birth Defects Foundation. Folic acid and the prevention of birth defects: A national survey of pre-pregnancy awareness and behavior among women of childbearing age, 1995-2002. Conducted by the Gallup Organization. White Plains, NY: March of Dimes Foundation; May 2002. Publication no. 31-1677-02.

7. Pregnancy Foresight Project. Inadequate Pre-Pregnancy Education — A Continuing and Serious Problem. Accessed at: www.swedishmedical.org/PregnancyForesight/Home.html.

8. CDC. Knowledge and use of folic acid by women of childbearing age — United States, 1995 and 1998. MMWR 1999; 48:325-327.

9. National Center on Birth Defects and Developmental Disabilities, Folic Acid Now Campaign. Overview. Accessed at: www.cdc.gov/ncbddd/folicacid/folcamp.htm.

10. Than LC, Watkins M, Daniel KL. Serum folate levels among women attending family planning clinics — Georgia, 2000. MMWR Recomm Rep 2002; 51(RR-13):4-8.

Resources

For resources on folic acid, consider the following:

National Center on Birth Defects and Develop-mental Disabilities, Folic Acid Now Campaign. Web: www.cdc.gov/ncbddd/folicacid/.

The Folic Acid Now web site is operated by the center, an agency of the Atlanta-based Centers for Disease Control and Prevention (CDC). It offers several publications for purchase, as well as free downloading in Adobe Acrobat Portable Document Format (PDF). Click on "Resources" to review available options. The "Ready, Not" series of brochures, posters, print ads, and public service announcements are intended for women who are not considering pregnancy now or in the near future. A portion of the web site also is presented in Spanish.

National Folic Acid Campaign. Web: www.folicacidinfo.org.

The CDC, the March of Dimes, and the National Council on Folic Acid have organized the National Folic Acid Campaign to promote the use of folic acid to prevent the neural tube defects spina bifida and anencephaly. The goal of the campaign is to educate all women who could possibly become pregnant to consume 400 mcg of synthetic folic acid daily from vitamin supplements and/or fortified foods in addition to eating food folate in a healthful diet. The Alexandria, VA-based National Healthy Mothers, Healthy Babies Coalition assumed leadership of the National Council on Folic Acid in 2002. The site carries a calendar of events and links to other resources. A portion of the web site also is presented in Spanish.

Pregnancy Foresight Project. Web: www.swedishmedical.org/PregnancyForesight/home.html.

This site is funded by the March of Dimes as part of the Pregnancy Foresight Project and maintained by Swedish Medical Center in Seattle. It provides information about preconceptional and prenatal health, patient education materials in multiple languages, and links to other helpful information. Its goals are to improve preconception and prenatal patient education, increase the use and awareness of preconception folic acid supplementation, and facilitate patient education through the development of multilingual patient brochures covering the topics of preconception/prenatal folic acid use, smoking and alcohol use, and genetic screening. Providers can download a patient brochure in PDF format, "Before You Get Pregnant . . . Planning Is the Key." The brochure addresses timing of pregnancy, good and bad habits, and important issues to discuss with health care providers when considering pregnancy. It is available in eight languages: English, Spanish, Ukrainian, Somali, Russian, Korean, traditional Chinese, and Vietnamese.

March of Dimes. Web: www.marchofdimes.com

Click on "Professionals and Researchers" to visit the organization’s clinician site. It offers continuing education information, fact sheets, and lists of available materials for educational use. A fact sheet, "Folic Acid," is available in a printable format for patient use; click on "March of Dimes Fact Sheets," then "Folic Acid."