Cleves, Mario A. PhD; Hobbs, Charlotte A. MD, PhD; Collins, H Breck MD; Andrews, Nancy MD; Smith, Laura N.; Robbins, James M. PhD
Daily folic acid supplementation of 0.4 mg/d, beginning at least 3 months before conception, has been shown to reduce the risk of neural tube defects (NTDs) by as much as 70%.1,2 The United States Public Health Service, Centers for Disease Control and Prevention, March of Dimes, Institute of Medicine, and The American College of Obstetricians and Gynecologists (ACOG) recommend that all women who are able to become pregnant consume at least 0.4 mg of folic acid daily.3,4 This dosage is found in most over-the-counter multivitamins and is easily accessible.
Despite strong publicized support for folic acid supplementation, there remains a great discrepancy between awareness of the benefits of folic acid and daily intake by reproductive-aged women. In a 2002 March of Dimes survey of women aged 18–40 years, 80% of women reported that they had heard of folic acid, and 20% knew of the link between folic acid and birth defects, but only 31% took a daily multivitamin containing folic acid.5
According to the March of Dimes survey, folic acid recommendations are not being followed partly because many health care providers have not incorporated the folic acid message into their routine counseling sessions. In the March of Dimes survey, 82% of women report that they would take folic acid if advised to do so by a health care provider, although only 35% state that their provider had recommended folic acid supplementation.6 In a recent survey of 488 ACOG fellows, only 54% reported that they routinely screen nonpregnant patients for folic acid intake.7
To date, studies have estimated the level of folic acid knowledge and intake among several groups: women seeking preconceptional counseling,8–10 women attending an initial prenatal visit,8,11–17 women who have had NTD-affected pregnancies,18 and women seeking care for infertility.10,19 Because these women should be highly motivated to take folic acid, they do not represent the majority of women who may not be planning a pregnancy and for whom advice to take folic acid from the obstetrician–gynecologist may have a significant effect. This study determines the level of folic acid supplement use among nonpregnant women receiving routine gynecologic care who may be at risk of an unintended or unplanned pregnancy. This study also examines demographics, health beliefs, and health behavior characteristics of women that could potentially affect their acceptance of physician advice about folic acid and their regular intake of folic acid.
MATERIALS AND METHODS
Following approval by the Institutional Review Board of the University of Arkansas for Medical Sciences, 322 women aged 18–45 years were recruited during a visit to 1 of 4 participating clinics in Little Rock for a routine gynecologic visit between August 2001 and September 2002. Participants completed a questionnaire on folic acid knowledge and use as well as items addressing other preventive health behaviors and attitudes toward doctors. Women were excluded if they were currently pregnant, had a prior NTD-affected pregnancy, were seeking preconception care, were seeking nonroutine care, had a hysterectomy or tubal ligation or were infertile for other documented reasons, or were unable to speak English or Spanish.
Women were enrolled from a university-based women's health clinic staffed primarily by resident physicians serving patients from a range of socioeconomic classes, ages, and ethnicity (clinic 1); a women's clinic staffed by university-based gynecologists serving primarily privately insured women (clinic 2); and offices of 2 private practice obstetrician–gynecologists (private practices 1 and 2). Clinics were selected to represent the range of socioeconomic and racial characteristics of the population of women receiving gynecologic care in Little Rock.
During enrollment periods, each clinic was staffed with a registered nurse from the Arkansas Center for Birth Defects Research and Prevention. An attempt was made to enroll 100% of all eligible women visiting these clinics during the enrollment periods. Nurses were instructed how to administer the study interview. All procedures in this study were conducted in compliance with ethical standards for research involving human subjects. All subjects provided informed consent before completing the interview. Interviews were administered exclusively by the project's registered nurses in the examination room before the patients were seen by the physician.
The primary study outcome, daily folic acid supplementation, was assessed by self-reported use of folic acid pills or multivitamins containing folic acid. Secondary outcomes included intake of folic acid at least weekly, knowledge about the association between folic acid and birth defects, and intention to begin taking folic acid in the future. Supplementation was determined by 2 questions: “In the past month, how often, if at all, have you taken multivitamins or prenatal vitamins?” and “In the past month, how often, if at all, have you taken folic acid pills?” A response to either question of “every day” was used to define daily folic acid intake. Other potential responses included “5 or 6 days a week,” “3 or 4 days a week,” “1 or 2 days a week,” “less often than once per week,” and “not at all.” Women who reported taking a supplement at least 1–2 days a week were considered to be taking folic acid at least weekly.
Accurate knowledge of the benefits of folic acid was determined by a question worded: “Some experts recommend that women take 400 micrograms of the B vitamin folic acid for which of the following reasons?” Women were given 5 possible responses: “to make strong bones,” “to prevent birth defects,” “to prevent high blood pressure,” “some other reason,” and “don't know.” Women who responded “to prevent birth defects” were considered to have accurate knowledge of the preconceptional and pregnancy-related benefits of folic acid.
Intention to take folic acid in the future was measured by a question derived from the “stages of change” model20: “How long, if at all, have you taken folic acid supplements, multivitamins containing folic acid, or prenatal vitamins containing folic acid on a daily basis?” Women who responded either “I haven't been using folic acid, but I intend to in the next 30 days,” or “I haven't been using folic acid, but I intend to in the next 6 months” were defined as contemplators, or those who intend to begin taking folic acid.
Folic acid use has been shown to increase with a woman's educational level, income, and age.21 Also, more married women take folic acid than single or divorced women, and use among Caucasian women is higher than that among women of other races.21 Additional factors may be involved in a woman's decision to take folic acid. These include experiences with taking medicine in pill form, perceived susceptibility to a pregnancy affected by a birth defect, perceived benefits of actions to prevent birth defects,13,22,23 trust in advice offered by a physician, other preventive health habits,24 and pregnancy intentions.21,25 Questions to measure each of these factors were developed for this study or adapted from prior studies. Questions addressing pill-taking experience included extent of unpleasantness associated with taking pills (responses ranging from “no difficulty” to “extremely unpleasant”), and willingness to take pills when experiencing a serious headache (“rarely” to “always”).
Perceived susceptibility to a birth defect was measured by questions about whether the woman has had a previous pregnancy affected by a birth defect and whether friends or family have had a pregnancy affected by a birth defect.
Trust in physician advice was measured by 2 questions: whether the woman follows doctors’ advice (responses ranged from “never” to “always”), and whether the woman is confident that advice from the doctor is useful (“not at all confident” to “very confident”). Three questions were designed to assess the women's usual preventive health behaviors: whether she uses sunscreen (“never” to “always”), whether she does monthly breast self-exams (“never” to “every month”), and whether she uses a seatbelt (“never” to “always”).
Pregnancy intention was measured by asking participants: “Which of the following best describes your pregnancy plans?” Possible responses included 1) “I am planning to become pregnant within the next year,” 2) “I am planning to become pregnant, but not within the next year,” 3) “I wish to become pregnant at some point, but time is completely unplanned,” and 4) “I do not intend ever to become pregnant.”
Project nurses examined all data forms for completion, missing information, and discrepancies before data entry. Data were entered within 72 hours of collection into a Microsoft Access (Redmond, WA) database through tailored data-entry screens designed for this study. Initial data entry errors were curtailed by online edits with pop-up menus for selection, range, and consistency checks and by within-form consistency and logic checks during data entry. Subsequent data entry or data recording collection errors were examined during exploratory data analysis of outliers, missing data, and data inconsistencies between fields. All questionable data items identified were referred back to project nurses for correction or clarification.
Statistical analysis included the computation of proportions and corresponding exact binomial confidence intervals (CIs)26 as well as crude odds ratios (ORs) of the effect of subject characteristics on knowledge and folic acid supplementation.27 Unconditional logistic regression was used to compute adjusted ORs for predictors of knowledge and intake of folic acid controlling for the enrollment clinic and the demographics characteristics listed in Table 1.28 All statistical analyses were performed with the STATA statistical package (Stata Corporation, College Station, TX).
Demographic characteristics of women are presented in Table 1. Three hundred twenty-two women participated in the study. Virtually all eligible women who were asked to participate in the study did participate. Only 5 women who were approached over the 12-month study accrual period declined to enroll. The sample consisted primarily of African-American (51%) and Caucasian (44%) women. Less than one third of the women were younger than 25 years of age. The majority was single (47%), had completed some education after high school (65%), and had annual household income under $30,000 (60%).
Of the 322 women asked to state why experts recommend that women take folic acid, 199 (61.8%) responded “to prevent birth defects,” 113 (35.1%) responded that they did not know or were not sure, and 10 (3.1%) gave other reasons.
Education and income levels were significantly associated with knowledge about folic acid. Women with education beyond high school were approximately 3 times more likely to know of the relationship between folic acid and birth defects (P < .001) than women with high school education or less. Those with annual household incomes over $30,000 were more than 3 times more likely to know of the relationship (P < .001) than women in households with incomes of less than $30,000. Age, race, and marital status were not found to be associated with knowledge of the benefits of folic acid in preventing birth defects.
Although 61.8% of women reported to be aware of the protective effect of folic acid in preventing birth defects, only 27.1% (95% CI 21.1%, 33.9%) of these women and 22.7% (95% CI 18.2%, 27.6%) of all women reported taking folic acid or multivitamins daily (Table 1).
Daily folic acid supplementation was particularly unlikely among African-American women (17.1%, 95% CI 11.7%, 23.7%) compared with Caucasian women (28.9%, 95% CI 21.6%, 37.1%). This gap was most pronounced among 18- to 24-year-old subjects (not shown), of which only 4 of 52 (7.7%) of African Americans reported taking folic acid supplements daily compared with 12 of 45 (26.7%) of Caucasian women (P = .012). Married women were almost twice as likely to take daily folic acid supplements than single or divorced women (OR 1.89; 95% CI 1.08, 3.32) and women with household incomes greater than or equal to $30,000 were more than twice as likely to take folic acid supplements daily than women with household incomes below $30,000 (OR 2.19; 95% CI 1.25, 3.85).
Of the 322 women, 128 or 39.8% (95% CI 34.4%, 45.3%) reported taking folic acid pills or multivitamins at least 1 day per week (Table 1). Similar to results for daily folic acid supplementation, weekly supplementation was also particularly deficient among African-American women compared with Caucasian women (P = .001). Compared with younger women, those aged 25 years and older were 2 times more likely to report some level of weekly folic acid supplementation (P = .004), with those aged more than 35 most likely to use supplements weekly. Married women, women with graduate education, and women with household incomes of $30,000 and above were also more likely to be taking folic acid at least weekly.
ORs for predictors of knowledge and intake of folic acid, adjusted for demographic covariates and the enrollment clinic, are presented in Table 2. Pill-taking experience, perceived susceptibility to birth defects, and attitudes toward physician advice were not related to correct knowledge about folic acid. Women who regularly engaged in other preventive health behaviors, including sunscreen use and breast self-examination, were more likely to know about the benefits of folic acid than those who practiced preventive health less regularly.
Pill-taking experience and salience of birth defects were not related to daily use of folic acid. Daily use was highly associated with following doctors’ advice and pregnancy intent. Only 6.8% of women who rarely or never follow doctors’ advice took folic acid on a daily basis. Of the 39 women contemplating pregnancy within the next year, 38.5% were on daily supplements compared with only 17.8% of those not wanting ever to get pregnant (OR 2.89; 95% CI 1.29, 6.51). The odds of taking a daily folic acid supplement increased with the proximity of the pregnancy intent. Daily supplementation among women wanting to get pregnant in the future but with no specific plan was approximately equal to that of women never wanting to get pregnant (OR 1.19; 95% CI 0.58, 2.43).
Knowledge of the relationship between birth defects and folic acid was also significantly associated with daily folic acid supplementation. Women aware of this relationship were twice as likely to report being on daily folic acid supplementation than women who did not know or were not sure of the association. Daily supplementation was also significantly more likely among women who regularly practiced breast self-examination and used seat belts. Each of these significant relationships remained significant when controlling for demographic characteristics and enrollment clinic (Table 2).
Weekly folic acid use was more likely among women who were aware of the benefits of folic acid in preventing birth defects and women intending to become pregnant. The odds of weekly supplementation for women contemplating pregnancy within the next year were 3 times that of women with no pregnancy intent. Preventive health behaviors were also consistently associated with weekly folic acid use. Women who used seat belts and conducted regular breast self-examination were significantly more likely to take folic acid weekly.
Of the 194 women who reported not taking folic acid pills or multivitamins in the past month, 149 (76.8%; 95% CI 70.2%, 82.5%) reported no intention of beginning to take folic acid in the next 6 months. Approximately half of the remaining women (11.3%; 95% CI 7.2%, 16.7%) reported that they intended to begin supplementation within 30 days and the other half (11.9%; 95% CI 7.7%, 17.3%) within the next 6 months. Thus, the vast majority of women not currently taking folic acid or multivitamins replied that they have no intention of beginning supplementation within the next 6 months. No demographic characteristic or other predictor was significantly associated with intention to begin supplementation among those not currently taking folic acid.
African-American women were less likely than Caucasian women to engage in preventive health behaviors and to take folic acid. As shown in Table 3, stratified by preventive health behavior, only 16% of African-American women who never do breast self-exams take folic acid weekly compared with almost 54% of Caucasian women who regularly do breast self-exams. Similarly, less than a quarter of African-American women who do not always use seat belts take folic acid weekly compared with 54% of Caucasian women who always wear seat belts. These differences were significant even after controlling for demographic characteristics and enrollment clinic (OR 4.86; 95% CI 1.44, 46.39 and OR 4.51; 95% CI 1.55, 13.12, respectively).
Our results support earlier analyses on diverse samples by documenting a large gap between women's knowledge of folic acid and intake of folic acid. In this study of women receiving routine gynecologic care, 62% knew of the benefits of folic acid whereas only 23% were taking a supplement containing folic acid daily. Consistent with other reports, women were more likely to be taking folic acid if they were older,24,29,30 more highly educated,15,16,24,30 had greater income,12,14,21 and were anticipating becoming pregnant sometime in the future.11,12,21–25,30 Similarly, Caucasian women and women who regularly engage in preventive health behaviors were also more likely to be taking folic acid. In contrast, younger women, African-American women, and women not in the habit of preventive health behaviors were least likely to take folic acid.
ACOG has joined the March of Dimes, Centers for Disease Control and Prevention, and Institute of Medicine in recommending that women take 400 μg of folic acid daily. The ACOG primary care committee suggests that women be advised to take folic acid beginning with their visit at age 13. Women aged 15–44 make an average of 2.8 visits to their physician and 0.48 visits to their obstetrician/gynecologist each year.31 The routine gynecologic checkup is therefore an ideal opportunity to deliver the folic acid message. Although this message must be incorporated into a full preventive health agenda, it can have substantial impact on many patients10,30 and can be delivered simply within the time constraints of a health maintenance visit.
Our study has shown that certain groups of women are less likely to incorporate folic acid into their daily routine. These women may require greater convincing by the physician. For example, older Caucasian women who anticipate becoming pregnant and who regularly engage in preventive health activities may require less convincing than younger, African-American women who are not in the habit of reducing their health risk by specific preventive behaviors. The latter group of women is at increased risk of a folate-deficient pregnancy and thus may require a more intensive and targeted folic acid message.
This study is limited by self-reported use of folic acid and by a geographically and ethnically narrow sample of women. Folic acid use was determined by a standard question used in multiple surveys. Neither red blood cell nor serum folate levels were determined. There is substantial evidence that self-report of intake of folic acid supplements is strongly related to red blood cell10,32–34 and serum folate levels.34–36 Nevertheless, some women may have incorrectly estimated their use of folic acid.
Although less than a quarter of women receiving routine gynecologic care were taking folic acid daily, we should be encouraged that a much greater proportion (40%) were taking folic acid at least weekly. Of those who take a supplement at least weekly, 57% take folic acid daily, 17% take folic acid 5 to 6 days per week, 16% take folic acid 3 to 4 days per week, and 10% take folic acid 1 to 2 days per week. Intake of 400 μg of folic acid an average of 3.5 days a week translates into an average daily consumption of approximately 200 μg. With a half life of 100 days,32 the bioavailability of folic acid is only minimally affected by intermittent intake throughout the week. Based on estimates by Daly et al,37 200 μg of folic acid per day should result in a 41% reduction in risk of NTDs.
Although our message should remain that daily intake of 400 μg of folic acid is the goal of all women capable of becoming pregnant, practitioners should be encouraged that some movement toward the goal of daily intake will likely have a beneficial effect by reducing the risk of NTDs. Consideration should also be given to fortification of grains with an increased amount of folic acid. Despite substantial national efforts to educate women about the benefits of folic acid, the rate of daily folic acid intake has remained relatively constant at about 30% over the past 7 years.5,6
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