Folic acid and prevention of spina bifida and anencephaly. 10 years after the U.S. Public Health Service recommendation.

In September 1992, the U.S. Public Health Service (USPHS) recommended that all women capable of becoming pregnant should consume 400 microg of folic acid/day on an ongoing basis to reduce their risk for having a pregnancy affected by spina bifida and anencephaly (i.e., neural tube defects [NTDs]). The recommendation was preceded a year earlier by a CDC recommendation for women at high risk (i.e., those women who have had an earlier pregnancy affected by an NTD). The 1991 CDC recommendation stated that women at high risk should plan subsequent pregnancies and consume 4,000 microg/day of folic acid from the time they begin trying to become pregnant through the first trimester of pregnancy to reduce their risk. The 1992 USPHS recommendation specified that women at high risk should follow the general population recommendation for consumption of 400 microg/day when not trying to become pregnant.     

Folate status in women of childbearing age,by race/ethnicity--United States, 1999-2000

In September 1992, the U.S. Public Health Service (PHS) recommended that women of childbearing age (i.e., aged 15-44 years) who are capable of becoming pregnant should consume 400 microg of the B-vitamin folic acid to reduce the number of cases of spina bifida and anencephaly (neural tube defects [NTDs]). Since then, an ongoing national effort has encouraged women to consume dietary supplements containing folic acid. In 1998, the Food and Drug Administration (FDA) required the fortification of enriched cereal grain products with folic acid, and manufacturers have voluntarily added more folic acid to many ready-to-eat breakfast cereals (CDC, unpublished data, 2002). To assess temporal changes in serum and red blood cell (RBC) folate concentrations among childbearing-aged women, CDC compared folate concentrations for childbearing-aged women who participated during 1988-1994 and 1999-2000 in the National Health and Nutrition Examination Survey (NHANES). This report outlines the results of this comparison and describes serum and RBC folate levels by race/ethnicity. The results indicate that over the period studied, the median serum folate concentration for women aged 15-44 years increased approximately threefold, and the median RBC folate concentration increased approximately twofold. These findings indicate that the national health objective for 2010 to increase the median RBC folate level among women of childbearing age to 220 ng/mL RBC (objective 16.16b) has been met for Mexican-American and non-Hispanic white women but not for non-Hispanic black women. To reduce the number of pregnancies affected by NTDs further, all women of childbearing age capable of becoming pregnant should consume the PHS-recommended level of folic acid daily.     

Spina bifida and anencephaly prevalence--United States, 1991-2001.

Spina bifida and anencephaly are serious birth defects. To reduce the occurrence of these birth defects, the Food and Drug Administration authorized the fortification of all enriched cereal grain products with folic acid in March 1996, with compliance mandatory by January 1998. This report reviews data reported to CDC's National Center for Health Statistics (NCHS) regarding spina bifida and anencephaly prevalence for live births in the United States during 1991-2001. Since 1989, NCHS has compiled birth defect data from checkboxes that appear on birth certificates. For consistency in trends, this report uses data for 1991-2001 from all U.S. reporting areas except Maryland, New Mexico, and New York. Data for 2001 are preliminary. During 1996-2001, a 23% decline occurred in neural tube defects (spina bifida and anencephaly combined). Spina bifida declined 24% during this period, and anencephaly declined 21%. The United States has experienced declines in spina bifida and anencephaly cases since folic acid fortification of all enriched cereal grain products. The observed declines have translated into approximately 920 infants being born without these serious defects each year. Continued monitoring of the occurrence of spina bifida and anencephaly will be necessary to evaluate the effectiveness of folic acid fortification.     

Knowledge and use of folic acid among women of reproductive age--Michigan, 1998

Neural tube defects (NTDs), which include spina bifida and anencephaly, are serious malformations that occur in the developing fetus during the first 17-30 days after conception. Consumption of supplements containing folic acid can reduce NTDs 50%-70%. In the United States, approximately 4000 pregnancies are affected by NTDs each year, including approximately 140 infants in Michigan. In 1992, the U.S. Public Health Service recommended that all women of childbearing age consume at least 400 microg of folic acid daily. In 1998, the Institute of Medicine reaffirmed that recommendation and added that women capable of becoming pregnant take 400 microg of synthetic folic acid daily from fortified foods and/or supplements and consume a balanced, healthy diet of folate-rich foods. This report summarizes findings from the 1998 Behavioral Risk Factor Surveillance System (BRFSS) about multivitamin use and folic acid knowledge among women of reproductive age in Michigan. The findings suggest that public health campaigns that promote the consumption of folic acid should target women who are young, unmarried, obese, smoke, eat few fruits and vegetables, and have a low level of education.     

Use of supplements containing folic acid among women of childbearing age--United States, 2007

Neural tube defects (NTDs) are serious birth defects of the brain (anencephaly) and spine (spina bifida) that affect approximately 3,000 pregnancies each year in the United States. In 1992, the U.S. Public Health Service recommended that all women of childbearing age in the United States capable of becoming pregnant consume 400 microg of folic acid daily to reduce their risk for having a pregnancy affected by NTDs. To assess awareness, knowledge, and behavior related to folic acid among women of childbearing age (aged 18-45 years), CDC analyzed the results of a national survey conducted annually by the Gallup Organization during the period 2003-2007. This report summarizes the results of that analysis, which indicated that, among all women of childbearing age, those aged 18-24 years had the least awareness regarding folic acid consumption (61%), the least knowledge regarding when folic acid should be taken (6%), and the lowest reported daily use of supplements containing folic acid (30%). Because women in this age group account for nearly one third of all births in the United States, promotion of folic acid consumption should be targeted to this population.     

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. 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 microg of folic acid daily to reduce the occurrence of NTD-affected pregnancies.     

Use of vitamins containing folic acid among women of childbearing age--United States, 2004

Neural tube defects (NTDs) are serious birth defects of the spine (spina bifida) and brain (anencephaly), affecting approximately 3,000 pregnancies each year in the United States. Periconceptional consumption of the B vitamin folic acid reduces the occurrence of NTDs by 50%-70%. To prevent these defects, the U.S. Public Health Service (1992) and Institute of Medicine (1998) issued separate recommendations that all women capable of becoming pregnant consume 400 micro g of folic acid daily, and the Food and Drug Administration mandated fortification of cereal grain products with folic acid to increase women's daily intake. Fortification of the U.S. food supply with folic acid has resulted in a 26% reduction in NTDs. However, even with fortification, not all women receive adequate levels of folic acid from their diets. Therefore, increasing the use of vitamins containing folic acid remains an important component of NTD prevention. To monitor the use of vitamins containing folic acid among women of childbearing age, the Gallup Organization has conducted a series of surveys for the March of Dimes Birth Defects Foundation since 1995. This report presents results from the 2004 survey, which indicated that although no substantial increase in the proportion of women who use vitamins containing folic acid daily occurred during 1995-2003, a substantial increase was observed in 2004, with 40% of women aged 18-45 years reporting daily consumption of a vitamin containing folic acid. This report also presents information about women's dieting behaviors. Regardless of dieting status, public health programs should stress the importance of women in their childbearing years consuming 400 micro g of folic acid daily through supplements, fortified foods, and a diet containing folate-rich foods.     

Folic acid campaign and evaluation--southwestern Virginia, 1997-1999

A needs assessment conducted in rural southwestern Virginia in 1996 indicated higher rates of birth defects in that region than in the entire state. In response to these findings, in January 1997 the regional perinatal council conducted a community folic acid information campaign designed to raise awareness about the 1992 Public Health Service recommendation that all women who are capable of becoming pregnant consume 400 microg (0.4 mg) of the B vitamin folic acid every day to decrease their risk for having a pregnancy affected with spina bifida or other neural tube defects (NTDs). This report describes the information campaign and the findings from precampaign and postcampaign surveys, which showed a significant increase in reported awareness and knowledge of the benefits of folic acid and reported knowledge about the sources of folic acid.     

Use of dietary supplements containing folic acid among women of childbearing age--United States, 2005

Neural tube defects (NTDs) are serious birth defects of the spine (spina bifida) and brain (anencephaly), affecting approximately 3,000 pregnancies each year in the United States. Daily periconceptional consumption of 400 mug of folic acid, as recommended by the Public Health Service (PHS) since 1992, reduces the occurrence of NTDs by 50%-70%. The Food and Drug Administration ordered mandatory fortification with folic acid of U.S. cereal grain products, beginning in 1998. However, despite a 26% reduction in NTDs, not all women of childbearing age receive adequate levels of folic acid from their diets. Therefore, increasing the number of women who take dietary supplements containing 400 mug of folic acid daily remains an important component of NTD prevention. This report summarizes results from the 2005 March of Dimes Gallup survey, which determined a decrease in the proportion of childbearing-aged women who reported taking folic acid in dietary supplements daily, from 40% in 2004 to 33% in 2005, returning to a level consistent with that reported during 1995-2003. These results emphasize the need for innovative programs to increase folic acid consumption to further reduce NTDs.     

The changing prevalence of neural tube defects: a population-based study in the north of England, 1984-96. Northern Congenital Abnormality Survey Steering Group

Using data from the Northern Congenital Abnormality Survey, we describe trends in the prevalence of neural tube defects (NTDs), maternal age-specific prevalence, outcome of pregnancy and the sensitivity of antenatal diagnosis of NTD-affected pregnancies in the Northern Region during 1984-96. This population-based sample consisted of 934 NTDs: there were 403 (43.1%) with anencephaly, 472 (50.5%) with spina bifida and 59 (6.3%) with encephalocele. The total prevalence at birth was 17.9 per 10,000 births and terminations (95% confidence interval [CI] = 16.7, 19.0) with a significant reduction over time (chi(2) for trend = 7.2; P = 0.007). The overall birth prevalence was 5.6 per 10,000 births [95% CI = 5.0, 6.3]; there was also a significant reduction in birth prevalence with time (chi(2) for trend = 68.3; P < 0.0001). Maternal age-specific prevalence rates decreased with increasing age. The proportion of NTD pregnancies terminated increased from 60.3% (325 cases) during 1984-90 to 78.6% (293 cases) during 1991-96, whereas the proportion of livebirths declined from 31.7% (171 cases) to 15.0% (56 cases) (P < 0.001). The sensitivity of antenatal diagnosis was consistently high for anencephaly (98%) and increased significantly for spina bifida from 60% during 1984-90 to 85% during 1991-96 (P < 0.05). Ascertainment of all cases of NTD in the Northern Region revealed a twofold reduction in birth prevalence between 1984-90 and 1991-96. This has resulted from improvements in the accuracy of antenatal detection of NTD-affected pregnancies with an increase in terminations of pregnancy.     

Cost-effectiveness of a folic acid fortification program in Chile

ObjectivePericonceptional intake of folic acid reduces the risk of neural tube defects (NTDs), a frequent birth defect that can cause significant infant mortality and disability. In Chile, fortification of wheat flour with folic acid has resulted in significant reduction in the risk of anencephaly and spina bifida. We investigated the cost-effectiveness implications of this policy.MethodsWe conducted an ex-post economic analysis of this intervention. Estimates of the effect of fortification in decreasing NTDs and deaths were derived from a prospective evaluation. The costs of fortification and provision of medical care to children with spina bifida in Chile were based on primary data collection.FindingsThe intervention costs per NTD case and infant death averted were I$ 1200 and 11,000, respectively. The cost per DALY averted was I$ 89, 0.8% of Chile's GDP per capita. Taking into account averted costs of care, fortification resulted in net cost savings of I$ 2.3 million.ConclusionFortification of wheat flour with folic acid is a cost-effective intervention in Chile, a middle income country in the post-epidemiological transition. This result supports the continuation of the Chile fortification program and constitutes valuable information for policy makers in other countries to consider.     

Folic Acid Fortification of Wheat Flour: Chile

Neural tube defects (open spina bifida, anencephaly, and encephalocele) represent the first congenital malformations to be preventable through public health measures such as supplementation and/or food fortification with folic acid. In Chile, starting in January 2000, the Chilean Ministry of Health legislated to add folic acid to wheat flour (2.2 mg/kg) to reduce the risk of NTDs. This policy resulted in an estimated mean additional supply of 427 μg/d in significant increases in serum folate and red cell folate of 3.8 and 2.4-fold, respectively, in women of fertile age, one year after fortification. The impact on the rate of NTDs is presently being studied in all births, both live births and still births, with birth weight >500 g in the city of Santiago. Preliminary results show a reduction of 40% in the rates on NTDs from the pre-fortification period (1999–2000) to post-fortification period (2001-June 2002). Fortification of wheat flour with folic acid in Chile is effective in preventing NTDs in Chile.     

Effect of folic acid fortification on the incidence of neural tube defects

Amarin ZO, Obeidat AZ. Effect of folic acid fortification on the incidence of neural tube defects. Paediatric and Perinatal Epidemiology 2010. In a few countries enriched cereal grains have been fortified with folic acid to reduce the incidence of neural tube defects. The objective of this study was to analyse the effect of folic acid fortified foods on the incidence of neural tube defects in live newborns at Princess Badea Teaching Hospital, in the north of Jordan, before and after the national food fortification with folic acid was implemented. For the 7‐year period from 1 January 2000 to 31 December 2006, we retrospectively extracted the total number of births at Princess Badea Hospital, as well as the number of pregnancies affected by spina bifida and anencephaly, per 1000 births during the periods before (2000–01), during (2002–04) and after (2005–06) folic acid fortification of grain products, was implemented. Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD‐10): anencephaly, encephalocele and spina bifida. A total of 78 subjects with neural tube defects were recorded among 61 447 births during the study period. The incidence of neural tube defects decreased from 1.85 per 1000 births before fortification [95% confidence interval (CI) 1.2, 2.4] to 1.07 per 1000 births during the fortification period [95% CI 0.7, 1.5], and 0.95 after full fortification [95% CI 0.5, 1.5], a 49% reduction. The difference between incidence of neural tube defects in the periods before and after food fortification with folic acid was statistically significant. We conclude that food fortification with folic acid was associated with a significant reduction in the rate of neural tube defects in north Jordan.     

Prevalence of neural tube defects and folic acid knowledge and consumption--Puerto Rico, 1996-2006

Birth defects are one of the leading causes of infant mortality in both the mainland United States and Puerto Rico. Neural tube defects (NTDs) are serious birth defects of the spine and brain; two of the most common NTDs are spina bifida and anencephaly. In the United States, NTD prevalence is higher among Hispanic women than among non-Hispanic white or non-Hispanic black women. In Puerto Rico, where most residents are Hispanic, the prevalence of NTDs (8.68 per 10,000 live births) is higher than in the mainland United States (5.59). Consumption of folic acid before and during early pregnancy can prevent NTDs. To assess trends in NTD prevalence and prevalence of knowledge and consumption of folic acid supplements in Puerto Rico, data were analyzed from the Birth Defects Surveillance System (BDSS) for 1996-2005 and the Behavioral Risk Factor Surveillance System (BRFSS) for 1997-2006. This report describes the results of those analyses, which indicated that prevalence of folic acid knowledge and consumption among women of childbearing age increased from 1997 to 2003 but decreased from 2003 to 2006. During similar periods, NTD prevalence declined from 1996 to 2003 but did not change significantly from 2003 to 2005. To resume the decline in prevalence of NTDs, additional measures might be needed to increase folic acid supplement use among Puerto Rican women of childbearing age.     

Neural tube defect surveillance and folic acid intervention--Texas-Mexico border, 1993-1998

Neural tube defects (NTDs) are common and serious malformations that originate early in pregnancy. In the United States, approximately 4000 pregnancies each year are affected by the two most common NTDs (spina bifida and anencephaly). In 1992, the Texas Department of Health (TDH), with support from a CDC cooperative agreement, implemented the Texas Neural Tube Defect Project (TNTDP), a program of NTD surveillance and risk-reduction activities in the 14 counties that border Mexico. The project was initiated in response to an anencephaly cluster identified during 1990-1991 in Brownsville (Cameron County), Texas (1). Whether the high anencephaly rate (19.7 per 10,000 live births) was unique to Cameron County or was characteristic of the entire border was unknown. This report summarizes NTD surveillance rates for the 14 Texas-Mexico border counties for 1993-1998 and presents preliminary results of TNTDP efforts to prevent the recurrence of NTDs by providing folic acid to high-risk women. Findings indicate that the baseline rate along the border is high (13.4 per 10,000 live births) and largely reflects the rate among Hispanics (13.8). Although a longer period is needed to obtain definitive results, folic acid appears to be effective for reducing the risk for NTD recurrence in Hispanics.     

Sociodemographic patterns in spina bifida birth prevalence trends--North Carolina, 1995-1999.

Previous studies have documented a decline in neural tube defects (NTDs) in the United States after the addition of folic acid to enriched grain products and other folic acid initiatives. The decrease generally has been greater for spina bifida than for other NTDs. However, the extent to which the decline varies by maternal sociodemographic characteristics has not been examined. In this study data from the North Carolina Birth Defects Monitoring Program, a statewide, population-based birth defect surveillance program, were used to assess the impact that folic acid public health initiatives have had on spina bifida rates among various sociodemographic subpopulations in North Carolina. This report covers data from 1995 through 1999. The overall prevalence of spina bifida decreased by 27.2% during 1995-1996 and 1998-1999 (p = 0.014). The magnitude of the decline varied considerably by sociodemographic characteristics of the mother. The decline was greatest among mothers who were aged > or = 30 years (prevalence ratio [PR] = 0.53), who had more than a high school education (PR = 0.57), whose prenatal care was not paid by Medicaid (PR = 0.67), and who were non-Hispanic white (PR = 0.72). Geographically the decrease in the western and Piedmont regions of the state was almost threefold that occurring in the eastern region. The decline in spina bifida after fortification varied considerably by sociodemographic subpopulations. More effort is needed to target folic acid education programs at disadvantaged populations.     

Urban–rural residence and the occurrence of neural tube defects in Texas, 1999–2003

Neural tube birth defects (NTDs) affect more than 4000 pregnancies in the US annually. The etiology of NTDs is believed to be multifactorial, but much remains unknown. We examined the pattern and magnitude of urban–rural variation in anencephaly, spina bifida without anencephaly, and encephalocele in Texas in relation with urban–rural residence for the period 1999–2003. There was no evidence that urban–rural residence was associated with changes in the rate of anencephaly or spina bifida without anencephaly in unadjusted or adjusted analyses. In contrast, rates of encephalocele were statistically significantly higher in areas classified as suburban or more rural compared to urban areas using four different urban–rural residence indicators.     

Folate and neural tube defects

A protective effect of folate against the development of neural tube defects (NTDs), specifically, anencephaly and spina bifida, is now well recognized, having been established by a chain of clinical research studies over the past half century. This article summarizes the more important of these studies, which have led to the current situation in which all women capable of becoming pregnant are urged to ingest folic acid regularly. The recommended intakes are 4 mg/d for those at high risk (by virtue of a previous NTD pregnancy outcome) and 0.4 mg/d for all others. However, a reduction in NTD births did not follow promulgation of these recommendations, and so folic acid fortification was mandated in the United States and some other countries. Although some controversy remains about the adequacy of fortification levels, the process was followed by significant improvement in folate indexes and a reduction of 25-30% in NTD frequency (about one-half of the proportion of cases assumed to be responsive to folate). The folate-NTD relation represents the only instance in which a congenital malformation can be prevented simply and consistently. Nevertheless, several research gaps remain: identification of the mechanism by which the defect occurs and how folate ameliorates it; characterization of the relative efficacy of food folate, folic acid added to foods, and folic acid by itself; delineation of the dose-response relations of folate and NTD prevention; and more precise quantification of the dose needed to prevent recurrences.     

Neural tube defects and maternal folate intake among pregnancies conceived after folic acid fortification in the United States

Rates of neural tube defects have decreased since folic acid fortification of the food supply in the United States. The authors' objective was to evaluate the associations between neural tube defects and maternal folic acid intake among pregnancies conceived after fortification. This is a multicenter, case-control study that uses data from the National Birth Defects Prevention Study, 1998-2003. Logistic regression was used to compute crude and adjusted odds ratios between cases and controls assessing maternal periconceptional use of folic acid and intake of dietary folic acid. Among 180 anencephalic cases, 385 spina bifida cases, and 3, 963 controls, 21.1%, 25.2%, and 26.1%, respectively, reported periconceptional use of folic acid supplements. Periconceptional supplement use did not reduce the risk of having a pregnancy affected by a neural tube defect. Maternal intake of dietary folate was not significantly associated with neural tube defects. In this study conducted among pregnancies conceived after mandatory folic acid fortification, the authors found little evidence of an association between neural tube defects and maternal folic acid intake. A possible explanation is that folic acid fortification reduced the occurrence of folic acid-sensitive neural tube defects. Further investigation is warranted to possibly identify women who remain at increased risk of preventable neural tube defects.     

When will we eliminate folic acid-preventable spina bifida?

Mandatory vitamin B12 fortification of enriched grain products is long overdue in the United States and Canada. Fortification would help provide the 2.4 mug of synthetic vitamin B12 that the US Institute of Medicine recommends for all persons 50 years and older. The findings of Ray and colleagues in this issue suggest that B12 may also help to prevent neural tube defects. If recommendations for B12 fortification were followed, it is possible that cases of spina bifida and anencephaly would be prevented. Two hundred twenty thousand children each year acquire folic acid-preventable spina bifida because many governments, including all in Europe, have yet to implement mandatory folic acid fortification. Fortification with folic acid and vitamin B12 is safe and should be implemented in all countries.