Folate Status in Women of Childbearing Age, by Race/Ethnicity --- United States, 1999--2000, 2001--2002, and 2003--2004

Fortification of enriched cereal-grain products with folic acid to help prevent pregnancies affected by a neural tube defect (NTD) (e.g., spina bifida or anencephaly) became mandatory in the United States in January 1998. Data from the 1999--2000 National Health and Nutrition Examination Survey (NHANES) indicated that median serum folate* concentrations in nonpregnant women of childbearing age had increased substantially, compared with concentrations during a period (1988--1994) before fortification was mandated ( 1). This report uses NHANES data to update those findings and assess trends in serum folate and red blood cell (RBC) folate levels^† by race/ethnicity from the 1999--2000 survey through the 2003--2004 survey. The results of these comparisons indicated that median serum folate concentrations among nonpregnant women of childbearing age decreased 16% from 1999--2000 through 2003--2004, and RBC folate concentrations decreased 8%. All women of childbearing age who are capable of becoming pregnant should consume 400 µg of folic acid daily to reduce the occurrence of NTD-affected pregnancies ( 2).

In 1992, the Public Health Service recommended that all women of childbearing age who are capable of becoming pregnant consume 400 µg of folic acid daily to reduce the number of cases of NTDs ( 2). In 1996, a final rule published by the Food and Drug Administration (FDA) required the addition of folic acid to a range of enriched cereal-grain products (e.g., bread, rolls, macaroni products, rice, corn meal, corn grits, and farina); the manufacturers' full-compliance date was January 1998 ( 3). In addition to improved dietary habits and folic acid fortification, the Public Health Service also recommended the use of dietary supplements containing folic acid ( 2); however, survey data have not indicated a substantial change in supplement use since the fortification mandate ( 4).

NHANES 1999--2000, 2001--2002, and 2003--2004 are annual surveys of persons of all ages selected through a stratified, multistage probability sampling of the civilian, noninstitutionalized U.S. population. A household interview and physical examination are conducted for each survey participant; blood samples are collected by venipuncture during the physical examination. For all study years, serum folate and RBC folate concentrations were measured by CDC ( 1). Long-term quality-control data for these assays indicated no analytic drift; external proficiency testing challenges also indicated stable performance. Serum folate and RBC folate concentrations for nonpregnant women aged 15--44 years were distributed by percentile, and medians were calculated. Because no satisfactory nonparametric approach exists for statistical analysis of survey data that compares medians, geometric mean serum folate and RBC folate concentrations were calculated; trends in geometric means from 1999--2000 through 2003--2004 were evaluated using a t test calculated from a linear regression model. The values derived for the medians and geometric means were consistent.

During 2001--2002 and 2003--2004, median (50th percentile) serum folate concentrations among women aged 15--44 years were 11.4 ng/mL and 10.6 ng/mL, respectively. Thus, a statistically significant 16% decline was observed from 1999--2000 (12.6 ng/mL) through 2003--2004 based on comparison of geometric means (p<0.001) (Table 1). Similarly, RBC folate concentrations decreased 8%, from 255 ng/mL during 1999--2000 to 235 ng/mL during 2003--2004 (p=0.028).

When analyzed by race/ethnicity, median serum folate concentrations declined significantly from 1999--2000 through 2003--2004 among all three populations considered (non-Hispanic whites [p=0.008], non-Hispanic blacks [p=0.023], and Mexican Americans [p<0.001]). The largest decrease (16%) was noted among non-Hispanic whites (Table 2). However, the median serum folate concentration was lowest among non-Hispanic blacks during all three survey periods.

Although non-Hispanic white and Mexican-American women exceeded the 2010 national health objective (objective 16-16b) for median RBC folate concentration (220 ng/mL) during all three survey periods, non-Hispanic black women had not met this objective. Trend differences from 1999--2000 through 2003--2004 in RBC folate concentrations were not statistically significant among each of the three racial/ethnic populations (non-Hispanic whites [p=0.106], non-Hispanic blacks [p=0.076], and Mexican Americans [p=0.064]).

Reported by: SL Boulet, DrPH, Q Yang, PhD, C Mai, MPH, J Mulinare, MD, National Center on Birth Defects and Developmental Disabilities; CM Pfeiffer, PhD, National Center on Environmental Health, CDC.

Editorial Note:

Previous data for all (pregnant and nonpregnant) women aged 15--44 years indicated that median serum folate levels increased from 4.8 ng/mL during 1988--1994 (NHANES III) to 13.0 ng/mL during NHANES 1999--2000; similar increases were noted in RBC folate concentrations ( 1). However, the findings in this report suggest that folate concentrations among nonpregnant U.S. women of childbearing age declined from 1999--2000 through 2003--2004. These findings extend results from a recent study using NHANES data that observed a decrease in the mean serum folate concentration among women of all ages from 1999--2000 to 2001--2002 ( 5). Another recent study reported decreases in the prevalence of spina bifida and anencephaly among infants born to non-Hispanic white and Hispanic women when comparing data from 1995--1996 and 1997--1998 with data from 1998--2002 (the most recent available); these data suggest an association between NTD decreases and folic acid fortification ( 6). During 1995--2002, no significant change in the prevalence of NTDs was observed among infants born to non-Hispanic black women ( 6).

Changes in laboratory techniques or sampling biases between survey periods are unlikely to account for the declines in folate levels described in this report. More likely explanations include 1) changes over time in the proportion of women taking supplements containing folic acid, 2) decreased consumption of foods rich in natural folates or foods fortified with folic acid (i.e., enriched cereal-grain products), 3) variations in the amounts of folic acid added to enriched grain products since fortification was mandated, and 4) increases in risk factors associated with lower folate concentrations such as obesity. However, evidence to support these explanations is mixed. With the exception of an increase in 2004, no substantial change was observed during 1995--2005 in the proportion of women of childbearing age who reported using a dietary supplement containing folic acid ( 4). Slight and conflicting changes in U.S. food consumption patterns have been noted; these include lower fruit and vegetable intake during 1999--2000 than during 1994--1996 but increased consumption of whole grains since 1970 ( 7). In a 2005 survey, approximately 26% of women aged 18--45 years reported dieting during the preceding 6 months, and approximately 27% of dieters reported following low-carbohydrate diets; such diets might result in reductions in the amounts of fortified foods consumed ( 4). Another analysis also suggests that the mean folate content of certain enriched breads might have been reduced during 2000--2003; other enriched cereal-grain products were not tested in this analysis ( 8). Finally, the prevalence of obesity among women aged 17--49 years increased from 21.8% during 1988--1994 to 32.3% during 1999--2000 ( 9).

Disparities in serum folate and RBC folate concentrations among racial/ethnic groups have been reported previously ( 1,5); these might be attributable to differences in awareness of folic acid and use of dietary supplements containing folic acid ( 4). In this report, non-Hispanic white women, a population with historically higher levels of folate intake, had the largest decreases in both median serum folate and median RBC folate and accounted for most of the decreases in the overall study population. Although non-Hispanic whites and Mexican Americans have met the Healthy People 2010 objective for median RBC folate concentration since 1999--2000, if folate intake continues to decrease overall, median concentrations might decrease to <220 ng/mL.

The findings in this report are subject to at least one limitation. No data from the National Birth Defects Prevention Network (NBDPN)^§ were available regarding the prevalence of NTDs during 2003--2004. This prevents comparison of NTD trends for 1999--2004 with trends in serum folate and RBC folate levels in women of childbearing age during the same period. Consequently, evaluating the effect of recent declines in folate levels on NTD prevalence will require additional data.

In 1993, FDA's Folic Acid Subcommittee recommended a fortification strategy that would enable 90% of women of childbearing age to receive at least 400 µg of folic acid per day from all sources ( 10). However, fortification alone, at the levels used, was not expected to provide 400 µg of folic acid daily. To reduce the number of cases of NTDs, U.S. women of childbearing age who are capable of becoming pregnant should consume at least 400 µg of folic acid daily through dietary supplements and fortified foods, in addition to a diet containing folate-rich foods. Continued monitoring of serum folate and RBC folate concentrations in U.S. women of childbearing age can help public health agencies modify existing policies and programs or implement new ones aimed at reducing the number of cases of NTDs.

Acknowledgments

The findings in this report are based, in part, on contributions by RS Kirby, PhD, Univ of Alabama at Birmingham, Alabama. JS Collins, PhD, Greenwood Genetic Center, Greenwood, South Carolina. JM Robbins, PhD, Univ of Arkansas for Medical Sciences, Little Rock, Arkansas. R Meyer, PhD, North Carolina State Center for Health Statistics, Raleigh, North Carolina. MA Canfield, PhD, Texas Dept of State Health Svcs. TJ Flood, MD, Arizona Dept of Health Svcs.

References

1. CDC. Folate status in women of childbearing age, by race/ethnicity---United States, 1999--2000. MMWR 2002;51:808--10.
2. CDC. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR 1992;41(No. RR-14).
3. Food and Drug Administration. Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Federal Register 1996;61:8781--97.
4. CDC. Use of dietary supplements containing folic acid among women of childbearing age---United States, 2005. MMWR 2005;54:955--8.
5. Ganji V, Kafai MR. Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: analysis of data from National Health and Nutrition Examination Surveys, 1988--1994, 1999--2000, and 2001--2002. J Nutr 2006;136:153--8.
6. Williams LJ, Rasmussen SA, Flores A, Kirby RS, Edmonds LD. Decline in the prevalence of spina bifida and anencephaly by race/ethnicity: 1995--2002. Pediatrics 2005;116:580--6.
7. Briefel RR, Johnson CL. Secular trends in dietary intake in the United States. Annu Rev Nutr 2004;24:401--31.
8. Johnston KE, Tamura T. Folate content in commercial white and whole wheat sandwich breads. J Agric Food Chem 2004;52:6338--40.
9. Mojtabai R. Body mass index and serum folate in childbearing age women. Eur J Epidemiol 2004;19:1029--36.
10. Food and Drug Administration. Food labeling: health claims and label statements; folate and neural tube defects. Federal Register 1993;58: 53254--95.

* Folate is the form of the B vitamin that occurs naturally in foods. Folic acid is the synthetic form of folate used in vitamin supplements and to fortify foods.

^† The two measurements conventionally used to assess the amount of folate in the body. Serum folate fluctuates with daily intake; RBC folate integrates folate intake over a period of several months.

^§ NBDPN data are used by Healthy People 2010 to track NTD prevalence.

Table 1 Serum folate and red blood folate concentration among nonpregnant women aged 15-44 years

Table 2 Median serum folate and red blood cell folate concentrations among nonpregnant women aged 15 - 44 years.

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Date last reviewed: 1/4/2007