Periconceptional vitamin use, dietary folate and occurrent neural tube defected pregnancies in a high risk population

PURPOSE: This 5 year (1992-1997) population-based case control study was conducted to determine if supplemental or dietary folate taken during the periconceptional period reduces the risk of occurrent neural tube defect (NTD) affected pregnancies in a high risk population.METHODS: Cases were all NTD pregnancies including elective terminations, fetal deaths and live births in South Carolina. Only isolated, occurrent NTD affected pregnancies were included (N = 179). Controls (N = 288) were randomly selected from each hospital in proportion to the hospital's contribution to the total live births in the state for the previous year. All mothers were interviewed in person using a modified Centers for Disease Control and Prevention Birth Defect Risk Factor Surveillance Mother's Questionnaire and the Harvard Food Frequency Questionnaire.RESULTS: Women who used a vitamin with 0.4 mg or more of folate at least 3 times per week during the 3 months before and 3 months after conception had a lower risk of having an NTD affected pregnancy than women who took no folate supplementation at any time during pregnancy [adjusted odds ratio (AOR) = 0.42; 95% confidence interval (CI) = 0.19-0.94]; women who used a vitamin with 0.4 mg or more of folic acid for less than 3 times per week or in partial months during the 6 month periconceptional period also had a slightly lower risk of having an NTD affected pregnancy relative to women who used no folate supplementation at any time during pregnancy [AOR =.72; 95% CI = 0.41-1.30]. The risk of NTD affected pregnancy was also lower for women who daily consumed foods containing higher levels of folate: AORs were 0.36 (95% CI = 0.18-0.73), 0.72 (95% CI = 0.42-1.22), and 0.61 (95% CI 0.36-1.04) from the highest to lowest quartile of dietary folate which were 0.457-3.12 mg, 0.322-0.457 mg, and 0.236-0.322 mg respectively.CONCLUSIONS: A reduction in occurrent NTD risk associated with folate supplementation and dietary intake was observed.     

Neural tube defects among Mexican Americans living on the US-Mexico border: effects of folic acid and dietary folate

Populations of Mexican descent have high occurrences of neural tube defects (NTDs). A recent study suggested that folic acid supplements may not protect these populations from NTDs. In a case-control study, the authors investigated the role of folic acid and dietary folate intake in NTD risk among Mexican Americans living along the Texas-Mexico border. From January 1995 to February 1999, 148 Mexican-American women with NTD-affected pregnancies and 158 women with normal live births were interviewed in person about use of vitamin supplements and dietary intakes during a 6-month periconceptional period (from 3 months before conception to 3 months after conception). Daily preconceptional consumption of vitamin supplements containing folic acid was 2.5% in control women and 2.0% in case women (odds ratio = 0.77; 95% confidence interval (CI): 0.19, 3.22). With adjustment for maternal age, education, obesity, and previous stillbirth or miscarriage, the risk estimate was essentially null (odds ratio = 1.12; 95% CI: 0.22, 5.78). Combined folic acid intake from diet and supplements showed only a modest risk reduction for intakes of > or = 1.0 mg per day (adjusted odds ratio = 0.73; 95% CI: 0.31, 1.72). The fact that the primary folic acid exposure was in the form of dietary polyglutamates rather than the more easily absorbed supplemental monoglutamates may explain an apparent decreased effect in this population.     

Folate intake and the risk of neural tube defects: an estimation of dose-response

BACKGROUND: Studies have shown that folic acid supplementation in early pregnancy markedly reduces the risk of neural tube defects (NTDs). Investigation of the relation between relative dose of supplemental folic acid or total folate intake and NTD risk is limited. METHODS: We used data from 23,228 women, predominantly from the northeastern United States, enrolled between October 1984 and June 1987 in a prospective study of early prenatal exposures and pregnancy outcomes. Diet and vitamin intake data were gathered in the early second trimester. NTDs were ascertained through prenatal testing and by report of the delivering physician. Data analyses included multiple logistic regression and restricted spline regression modeling. RESULTS: For each additional 500 dietary folate equivalents consumed per day, the prevalence of NTDs decreased by 0.78 cases (95% confidence interval [CI] = 0.47-1.09) per 1,000 pregnancies. Compared with women having the lowest total folate intakes (0-149 folate equivalents per day), the prevalence of NTDs declined by 34%, 30%, 56% and 77% among the offspring of those women consuming 150-399, 400-799, 800-1199 and > or = 1200 folate equivalents per day, respectively (P-value for linear trend = 0.016). CONCLUSIONS: Our results suggest that NTD risk declines markedly with modest increases of total folate in early pregnancy. Total folate dose, rather than supplemental folate alone, should be considered in formulating public health guidelines for NTD prevention.     

Methionine in the multifactorial etiology of neural tube defect affected pregnancies

PURPOSE: Research in the last 40 years has provided evidence of the role of dietary nutrients in the development of NTDs. Failure of the neural tube to close is one of the most frequent and severe fetal developmental defects. The etiology of NTDs is complex encompassing genetic, dietary, and environmental factors. With regard to diet, it appears that in humans, a combination of low levels of methionine, folate, and Vitamin B(12) may lead to the occurrence of NTDs. The purpose of this study was to explore the relationship between maternal dietary intake of methionine and the risk of having a NTD affected pregnancy.METHODS: It was hypothesized that women with high maternal dietary methionine intake were at a decreased risk for NTDs. Combinations of methionine and folate without supplements, methionine and folate with supplements, and methionine and Vitamin B(12) and NTD risk were also examined. Data from a case-control study of 170 NTD-affected pregnancies and 269 controls were provided by a CDC sponsored NTD Surveillance, Prevention, and Research Project.RESULTS: There was an approximately 30-55% reduction in NTD risk among women whose average daily dietary intake of methionine was greater than the lowest quartile of intake (>1580 mg/day). The odds ratios (95% CI) associated with the 3 quartiles of methionine intake greater than 1580 mg/day after adjusting for Kcal, race, and BMI were 0.72 (0.4030-1.288), 0.68 (0.3390-1.347), and 0.45 (0.1830-1.088).CONCLUSIONS: These findings indicate a reduction in the risk of having a NTD affected pregnancy is associated with maternal periconceptional dietary intake of methionine.     

A multivitamin supplementation and education intervention as an effective means of increasing multivitamin use among postpartum women of Mexican origin

Postpartum Hispanic women in the USA are at elevated risk for neural tube defects in subsequent pregnancies from the combined effects of ethnicity, folate depletion from the prior pregnancy and lactation, and high parity rates with short inter-birth intervals. This study evaluated an education programme and distribution of a 3-month starter package of multivitamins among Hispanic women attending nutrition clinics for low-income women in El Paso, Texas. At 1-6 weeks postpartum, 329 subjects were selected to receive education only, multivitamins only, education and multivitamins, or no intervention. Multivariable regression obtained odds ratios (OR) and 95% confidence intervals [CI] to measure the association between intervention status and self-reported multivitamin use at least four times per week at 6 and 12 months postpartum, while controlling for potential confounding variables. Multivitamin distribution was related to consumption at both 6 months (OR = 3.5 [95% CI 1.1, 11.2]) and 12 months (OR = 6.5 [95% CI 1.5, 28.3]). Multivitamins plus education was most effective in increasing multivitamin use at both periods: 6 months (OR = 4.0 [95% CI 1.53, 11.7]) and 12 months (OR = 6.4 [95% CI 1.7, 24.2]). At enrolment, 66% of women regularly took vitamins, and approximately 35% took them at both 6 and 12 months postpartum. The education intervention alone was not associated with multivitamin use at either 6 months (OR = 0.79 [95% CI 0.3, 2.4]) or 12 months (OR = 3.1 [95% CI 0.8, 12.1]). Multivitamin use declines precipitously during postpartum at the time Hispanic women may be susceptible to a subsequent pregnancy. This study provides evidence that multivitamin starter packs sustain multivitamin usage up to 1 year postpartum for a specific high-risk group, but the effect of educational intervention alone should be further studied.     

Adequacy of prenatal care as a major determinant of folic acid, iron, and vitamin intake during pregnancy

This study aimed to quantify the association between adequacy of prenatal care and prevalence of folic acid, iron, and multivitamin intake during pregnancy. Data were obtained on socio-demographics, prenatal care, pregnancy complications, and use of vitamin/mineral supplements for 836 women, using a postpartum interview. Associations with the use of vitamin/mineral supplements were quantified with risk ratios (RR), computed by generalized binomial regression. A high proportion of women reported the use of folic acid (81.9%), iron (55.4%), and multivitamins (76.2%) as supplements during pregnancy. Use of supplements was independently associated with adequacy of prenatal care (adequate vs. inadequate: folic acid, RR = 2.28; 95%CI: 1.58-3.29; iron, RR = 1.99; 95%CI: 1.57-2.52, multivitamins, RR = 1.97; 95%CI: 1.54-2.51). Higher schooling was also associated with increased use of folic acid (RR = 1.42; 95%CI: 1.18-1.70), but not multivitamins (RR = 0.87; 95%CI: 0.77-0.98). Use of folic acid was less prevalent in single women (RR = 0.67; 95%CI: 0.48-0.95) and during unplanned pregnancies (RR = 0.81; 95%CI: 0.71-0.92). Adequacy of prenatal care is a major determinant of vitamin/mineral intake during pregnancy.     

Understanding optimal nutrition among women of childbearing age in the United States and Puerto Rico: employing formative research to lay the foundation for national birth defects prevention campaigns

Neural tube defects (NTDs) are serious birth defects of the brain and spine that affect approximately 3,000 pregnancies in the United States each year and affected 404 pregnancies in Puerto Rico from 1996 to 2002. Consuming the B vitamin folic acid can reduce the incidence of NTDs 50%-70%, and recent efforts to reduce NTD rates have focused on increasing the number of childbearing-aged women who take a vitamin containing folic acid every day. As the first stage of formative research in campaign planning, two exploratory, qualitative studies were conducted in order to (a) understand the complexity of vitamin use among women in the United States and Puerto Rico and (b) serve as a foundation on which to develop national communication and education interventions. Also, this information shed light on theories that might be used to guide campaign development. Results indicated that campaign messages designed to increase folic acid use through multivitamin supplementation in the United States must address women's barriers to vitamin use (e.g., cost, time), increase women's perceived need for multivitamins (e.g., identify immediate, tangible results from taking a daily multivitamin), and address the relationship between daily food choices and the need for supplementation. Future campaign messages in Puerto Rico must focus on many of these same issues, in addition to increasing women's knowledge about when folic acid should be taken in relation to pregnancy and addressing women's perceptions that vitamins cause weight gain (an undesirable outcome for most participants). The practical and theoretical implications of these results are discussed in terms of their contribution to the development of a creative new approach to increase multivitamin consumption among women of childbearing age in the United States and Puerto Rico.     

Periconceptional dietary intake of choline and betaine and neural tube defects in offspring

Periconceptional intake of folic acid prevents some neural tube defects (NTDs). Other nutrients may also contribute to NTD etiologies; a likely candidate is choline. Similar to folic acid, choline is involved in one-carbon metabolism for methylation of homocysteine to methionine. The authors investigated whether maternal periconceptional dietary intakes of choline and its metabolite betaine influence NTD risk. Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 424 NTD cases and with mothers of 440 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake. Dietary intakes of choline were associated with reduced NTD risks. Controlling for intake of supplemental folic acid, dietary folate, dietary methionine, and other covariates did not substantially influence risk estimates for choline. NTD risk estimates were lowest for women whose diets were rich in choline, betaine, and methionine. That is, for women whose intake was above the 75th percentile compared with below the 25th percentile for all three nutrients, the odds ratio was 0.17 (95% confidence interval: 0.04, 0.76). Study findings for dietary components other than folic acid offer additional clues about the complex etiologies of NTDs.     

The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States

OBJECTIVE: Since January 1998, the Federal Drug Administration has required folic acid fortification of all enriched cereal-grain products in the U.S. This program intended to increase folic acid intake among women of childbearing age in order to decrease their risk of pregnancies affected by neural tube defects. The aim of this study was to explore the changes in serum and erythrocyte folate status of the adult U.S. population following folic acid fortification of enriched cereal-grain products and to explore accompanying changes in food sources and dietary total folate intake. METHODS: We compared data from two National Health and Nutrition Examination Surveys (NHANES): NHANES III, conducted during 1988 to 1994, reflecting the time prior to folate fortification, and NHANES 1999-2000, reflecting the time period after fortification. RESULTS: Mandatory folic acid fortification led to significant increases in both serum and erythrocyte folate concentrations in all sex and age groups. In the overall study population the mean serum folate concentration increased more than two-fold (136%), from 11.4 nmol/L to 26.9 nmol/L, and the mean erythrocyte folate concentration increased by 57 percent, from 375 nmol/L to 590 nmol/L. Less than 10% of women of childbearing age reached the recommended erythrocyte folate concentration of greater than 906 nmol/L that has been shown to be associated with a significant reduction in neural tube defect (NTD) risk. After fortification, the category "bread, rolls, and crackers" became the single largest contributor of total folate to the American diet, contributing 15.6% of total intake, surpassing vegetables, which were the number one folate food source prior to fortification. Dietary intake of total folate increased significantly in almost all sex and age groups, except in females over 60 years of age. The mean dietary total folate intake of the study population increased by 76 microg/d (28%), from 275 microg/d to 351 microg/d. CONCLUSIONS: The fortification of enriched cereal-grain products with folic acid led to a significant improvement of blood folate status of the overall adult, non-supplement using, US population. However, women of childbearing age may take folic acid supplements to reach erythrocyte folate levels that have been associated with decreased risk of NTDs.     

Red cell folate and predicted neural tube defect rate in three Asian cities

BACKGROUND: Periconceptional folic acid reduces neural tube defect (NTD) risk. Red blood cell folate concentration is inversely associated with NTD risk. In many countries there is a lack of information on NTD rates. Red cell folate status in women of childbearing age may be a surrogate for NTD rates and may be helpful in identifying countries or regions most likely to benefit from improved folate status. OBJECTIVE: To predict NTD rates using red cell folate concentrations in women of childbearing age living in three Asian cities Design: Cross-sectional convenience samples of non-pregnant women living in Beijing (n=220), Kuala Lumpur (n=389), and Jakarta (n=129). RESULTS: Red cell folate concentrations were highest (p<0.001) in women from Jakarta at 872 nmol/L (95% CI; 833, 910) followed by Kuala Lumpur at 674 nmol/L (95% CI: 644, 704) and lowest in Beijing at 563 nmol/L (95% CI: 524, 601). Accordingly, predicted NTD rates were highest in Beijing at 30/10000 (95% CI: 27, 33), followed by Kuala Lumpur at 24/10000 (95% CI: 22, 25), and lowest in Jakarta at 15/10000 (95% CI: 14,15). CONCLUSION: Our red blood cell folate data suggests that of the three cities improving the folate status of women in Beijing would have the greatest impact on NTD rates.     

Lowered weight gain during pregnancy and risk of neural tube defects among offspring

BACKGROUND: Maternal nutritional factors have been implicated in the complex aetiology of neural tube defects (NTD). We investigated whether the amount of weight a woman gained during pregnancy was associated with her risk of delivering an infant with an NTD. METHODS: We conducted a population-based case-control study within the cohort of 708 129 live births and fetal deaths occurring in selected California counties in 1989-1991. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) NTD cases (including those electively terminated, stillborn, or liveborn) and with mothers of 539 (88%) non-malformed liveborn controls within an average of 5 months from the term delivery date. Respondent-reported weight gain during pregnancy (kg) was analysed. Risks of infants having NTD were estimated among women who gained <10 kg compared to those who gained > or =10 kg during > or =38 week gestations. RESULTS: Compared to women who gained > or =10 kg, an increased risk for NTD offspring was observed among women who gained <10 kg (odds ratio [OR] = 3.2, 95% CI : 2.3-4.6). The OR was 5.0 (95% CI : 2.6-9.7) among those women who gained <5 kg during pregnancy. The increased risk was not attributable to maternal non-use of a multivitamin containing folic acid, diabetes, NTD-pregnancy history, age, race/ethnicity, education, gravidity, alcohol use, cigarette use, prepregnant obesity, low socioeconomic status, dieting, nausea, nor to lower dietary intakes of folate, zinc, energy, protein, fat, carbohydrates, and methionine. An increased risk was observed even after simultaneous adjustment for most of these factors (OR = 2.2, 95% CI : 1.2-3.8). The risk associated with gaining <10 kg was greater for anencephaly, but still elevated for spina bifida. CONCLUSIONS: We did not have information on weight gain during early pregnancy. Because weight gain during the relevant embryological period for NTD (first month post-conception) is relatively small and often variable, it seems less likely that elevated NTD risks indicate a causal association between lowered weight gain throughout pregnancy and abnormal development of the neural tube. It seems more likely that lowered weight gain is a consequence of carrying an NTD-affected fetus. However, what this consequence is and why risk was substantially larger for anencephaly is unknown.     

Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age

Daily consumption of 400 microg folic acid prior to conception and during early pregnancy is recommended for the prevention of neural tube defects (NTD). Strategies to increase folic acid consumption include supplements and fortified foods. Milk is consumed by women and can be fortified with folic acid but little is known about the effect of fortified milk on blood folate concentration in women of childbearing age. The objective of this study was to determine whether daily consumption of milk fortified with 375 microg folic acid increases blood folate and lowers homocysteine concentrations in women of childbearing age. Seventy-three non-pregnant women (aged 18-47 y) were randomized to receive either 75 g/d of a fortified or unfortified (control) milk powder for 12 weeks. Women who consumed the folic acid fortified milk had mean (95% CI) red blood cell and plasma folate concentrations that were 539 nmol/L (436, 641) and 35 nmol/L (30, 41) higher, respectively, than in the control group. Women drinking fortified milk had a 14% lower mean plasma homocysteine concentration at week 12 than women consuming the control milk. Daily consumption of fortified milk powder providing 375 microg folic acid increases blood folate and lowers homocysteine concentrations over 12 weeks in women of childbearing age. Daily consumption of fortified milk would be expected to reduce NTD risk.     

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.     

Changes in knowledge and attitudes of folate, and use of dietary supplements among women of reproductive age in Norway 1998-2000

AIMS: From March 1998, Norwegian nutrition authorities have recommended that women consume a folic acid supplement before and early in pregnancy to prevent neural tube defects. The authors wished to establish Norwegian data on knowledge of, use of, and attitudes to folic acid supplement and dietary supplements before and after implementing national information campaigns on folate and pregnancy. METHODS: Telephone surveys were carried out in late 1998 and in late 2000 among, respectively, 1,146 and 1,218 Norwegian women of reproductive age. RESULTS: Overall, 50% of the women in 1998 and 60% of the women in 2000 had heard about folate, 33% and 46% knew about its role in pregnancy, and 9.5% and 21% knew that it may prevent a congenital malformation. Only 4.0% and 8.5% of the women, respectively, knew that the critical period for folic acid supplement to reduce the risk of neural tube defect is before and early in pregnancy. Knowledge and increase in knowledge between the two surveys were highest among women close to pregnancy (woman planning pregnancy, pregnant women, or women who had given birth within the last 12 months), and among women with high education. Among the 54 women in 1998 and the 55 women in 2000 whose last birth was within the previous year, use of a folic acid supplement before or early in the last pregnancy was reported by 10% (95% confidence interval (CI) 5-21%) and by 47% (95% CI 35-60%), respectively. Among women close to pregnancy, 76% in 1998 and 87% in 2000 stated that they would use a folic acid supplement in a future pregnancy. CONCLUSIONS: Knowledge and use of folate among Norwegian women increased from 1998 to 2000. Future information strategies on folate and pregnancy should in particular aim at increasing women's knowledge on the critical period for folic acid supplementation, as well as reducing socio-demographic differences in use and knowledge of folate.     

Folate status of reproductive age women and neural tube defect risk: the effect of long-term folic acid supplementation at doses of 140 µg and 400 µg per day

Primary prevention of most folate-responsive neural tube defects (NTDs) may not require 400 μg folic acid/day but may be achieved by attaining a high maternal folate status. Using RBC folate ≥906 nmol/L as a marker for NTD risk reduction, the study aimed to determine the change in blood folate concentrations in reproductive age women in response to long-term folic acid supplementation at 400 μg/day and 140 μg/day (dose designed to mimic the average daily folic acid intake received from New Zealand's proposed mandatory bread fortification program). Participants were randomly assigned to a daily folic acid supplement of 140 μg (n = 49), 400 μg (n = 48) or placebo (n = 47) for 40 weeks. RBC folate concentrations were measured at baseline, and after 6, 12, 29 and 40 weeks. At 40 weeks, the overall prevalence of having a RBC folate <906 nmol/L decreased to 18% and 35% in the 400 μg and 140 μg groups, respectively, while remaining relatively unchanged at 58% in the placebo group. After 40 weeks, there was no evidence of a difference in RBC folate between the two treatment groups (P = 0.340), nor was there evidence of a difference in the odds of a RBC folate <906 nmol/L (P = 0.078). In conclusion, the average daily intake of folic acid received from the proposed fortification program would increase RBC folate concentrations in reproductive age women to levels associated with a low risk of NTDs.     

Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid

The natural diastereoisomer [6S]-5-methyltetrahydrofolate ([6S]-5-MTHF) may be a safer fortificant than folic acid for neural tube defect (NTD) prevention because it is unlikely to mask vitamin B-12 deficiency. An inverse relationship between NTD risk and blood folate concentrations has been reported. In this randomized, placebo-controlled, double-blind trial, we compared the effects of [6S]-5-MTHF and folic acid supplementation for 24 wk on plasma folate and red cell folate (RCF) in women of childbearing age (18-49 y). Women (n = 104) were randomly assigned to receive a supplement containing [6S]-5-MTHF (113 micro g/d), folic acid (100 micro g/d) or placebo. The mean estimated linear increase in plasma folate concentration was 0.3 [95% confidence interval (CI): 0.1, 0.5], and 0.4 (0.2, 0.6) nmol/(L. wk) in the [6S]-5-MTHF and folic acid groups, respectively. The mean estimated linear increase in RCF was 7.4 (95% CI: 4.5, 10.3), and 8.3 (4.4, 12.3) nmol/(L. wk) in the [6S]-5-MTHF and folic acid groups, respectively. There were no differences in the slopes between the [6S]-5-MTHF group and the folic acid group in either plasma folate (P = 0.48) or RCF (P = 0.70). At 24 wk, estimated mean increases in plasma folate concentrations were 6.9 (95% CI: 1.7, 12.2) and 9.2 (3.3, 15.1) nmol/L, and in RCF, 251 (143, 360) and 275 (148, 402) nmol/L, in the [6S]-5-MTHF and folic acid groups, respectively, relative to the placebo group. These data suggest that low dose [6S]-5-MTHF and folic acid supplementation increase blood folate indices to a similar extent. A steady state in the blood indices had not been reached by 24 wk.     

Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial.

Elevated total plasma homocysteine (tHcy) concentrations are considered a risk factor for neural tube defects (NTD) and cardiovascular disease. Supplementation with folic acid decreases the risk of women having children with NTD. In both sexes, it decreases tHcy levels. We investigated the efficacy of natural dietary folate in improving folate and homocysteine status. We performed a 4-wk dietary controlled, parallel design intervention trial with 66 healthy subjects (18-45 y) divided into 3 treatment groups: the dietary folate group, the folic acid group and the placebo group. Each day each group was fed a different diet. The dietary folate group received a diet high in vegetables and citrus fruit (total folate content approximately 560 microgram) plus a placebo tablet. The folic acid group received a diet naturally low in folate (approximately 210 microgram) plus 500 microgram folic acid and placebo tablet on alternate days, i.e., 250 microgram folic acid/d. And the placebo group received the same low-folate diet as the folic acid group plus a placebo tablet. After 4 wk of intervention, folate status improved, and tHcy concentrations decreased in both the dietary folate and the folic acid groups. From the amount of additional folate (350 microgram/d) and folic acid (250 microgram/d) consumed, the relative bioavailability of dietary folate compared to folic acid was calculated to be 60-98%, depending on the endpoint used. In conclusion, increasing the consumption of vegetables and citrus fruit, both good sources of folate, will improve folate status and decrease tHcy concentrations. This may contribute to the prevention of cardiovascular disease and NTD in the general population     

Implementation and outcomes of recommended folic acid supplementation in Mexican-American women with prior neural tube defect-affected pregnancies

BACKGROUND: Upon discovering an NTD incidence rate of 27/10,000 in a Texas border county, the Texas Department of Health initiated folic acid intervention for prevention of recurrent NTDs in this predominantly Mexican-American population. This paper describes compliance of this population with USPHS folic acid recommendations and the impact of supplementation on pregnancy outcomes. METHODS: Based upon information from active surveillance, field teams personally contacted women having NTD-affected pregnancies to enroll them in FA intervention. Enrollees were provided FA at home visits at 3-month intervals throughout the project. RESULTS: Of 405 women identified with NTD-affected pregnancies, 299 (73.8%) enrolled in the intervention. One hundred ninety-three pregnancies occurred among 138 women. FA supplementation of 0.4 mg/day or more occurred during the last month preconception in 161 (83.4%) of the 193 pregnancies. No NTDs were detected in the 130 livebirths to women who received supplementation nor were NTDs detected in the 23 supplemented women who experienced pregnancy loss. CONCLUSIONS: Supplementation was successful in preventing recurrent NTDs in Mexican-American women.     

Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region

Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China.     

Serum folate levels among women attending family planning clinics--Georgia, 2000.

Since 1998, serum folate levels have increased nationally after mandatory fortification of cereal grain products with folic acid. Whether serum folate levels have increased among all women has not been well-studied. Identifying characteristics of women with lower serum folate levels would also be helpful in designing educational campaigns. Data for this report were collected during January 2000-January 2001. During 2000, blood samples were collected from 1,059 women aged 18-45 years who attended six family planning clinics in Georgia and analyzed for serum folate levels. This sample included women aged 18-25 years (60%), black women (41%), and women who had a high school education or less (49%). The median serum folate level (8.9 ng/mL) among this population was lower than the median of women of childbearing age (13.0 ng/mL) who participated in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). In logistic regression analysis, women who were black (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.48, 3.96), who smoked (OR = 2.1; 95% CI = 1.26, 3.43), or who used Depo-Provera contraceptive injection (manufactured by Pharmacia Corporation, Peapack, New Jersey) (OR = 2.3; 95% CI = 1.15, 4.62) were more likely to be ranked in the lowest quartile (< or = 62 ng/mL) of serum folate concentrations when compared with the highest quartile (> 12.4 ng/mL). Women who consumed cereal regularly (OR = 0.4; 95% CI = 0.26, 0.62) or folic acid supplements (OR = 0.2; 95% CI = 0.09, 0.30) were the least likely to be in the lowest serum folate quartile. This study indicates that certain women are at greater risk for having lower serum folate levels, including women who are black, smokers, Depo-Provera users, and those less likely to eat cereal regularly or to take folic acid supplements. In Georgia, these data are useful in defining target populations (e.g., black women and smokers) for folic acid education campaigns because public health officials can develop contextually appropriate messages and outreach approaches for targeting women for folic acid interventions. Ongoing surveillance of serum folate status among women can guide future intervention efforts.