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.     

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.     

Trends in overweight among US adults from 1987 to 1993: a multistate telephone survey.

OBJECTIVES: Using data from the Behavioral Risk Factor Surveillance System, this study describes trends in the prevalence of overweight between 1987 and 1993. METHODS: Data were examined from 33 states participating in an ongoing telephone survey of health behaviors of adults (n = 387,704). Self-reported weights and heights were used to calculate sex-specific prevalence estimates of overweight for each year from 1987 to 1993. Time trends were evaluated with the use of linear regression. RESULTS: Between 1987 and 1993, the age-adjusted prevalence of overweight increased by 0.9% per year for both sexes (from 21.9% to 26.7% among men and from 20.6% to 25.4% among women). The increasing linear trend was observed in all subgroups of the population but was most notable for Black men (1.5% per year) and men living in the Northeast (1.4% per year). Secular changes in smoking and leisure-time physical activity did not entirely account for the increase in overweight. CONCLUSIONS: The prevalence of overweight among American adults increased by 5% between 1987 and 1993. Efforts are needed to explore the causes of this adverse trend and to find effective strategies to prevent obesity.     

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.     

Trends in neural tube defects in Western Australia in Indigenous and non-Indigenous populations

Neural tube defects (NTD) were 43% more common in Indigenous than in non-Indigenous infants in Western Australia in the 1980s, and there has been a fall in NTD overall in Western Australia since promotion of folate and voluntary fortification of food has occurred. In order to investigate whether the fall had occurred in both indigenous and non-Indigenous infants, data on NTD (births and terminations) were obtained from the WA Birth Defects Registry, and on all births from the Maternal and Child Health Research Data Base. Knowledge of folate was asked in a survey of indigenous women interviewed postpartum. Before the promotion of folate (1980-92), there has been a 42% increase in NTD in Indigenous compared with non-Indigenous infants (prevalence ratio (PR)=1.42 [95% confidence interval (CI) 1.04, 1.94]); while in the most recent period (1996-2000), the prevalence in Indigenous infants was almost twice that of non-Indigenous infants (PR 1.98 [CI 1.25, 3.15]). Fifty-five per cent of Indigenous women knew about folate in pregnancy. Similar to sudden infant death syndrome, this study has highlighted health promotion that has been successful in reducing the risk of a childhood condition overall, but has failed to be effective for Indigenous children.     

Cobalamin, folic acid, and homocysteine

Cobalamin deficiency can lead to several adverse health consequences: folate trapping in the methylation cycle and subsequent impaired DNA biosynthesis; pernicious anemia hematologically, similar to that caused by folate deficiency; elevated blood homocysteine (tHcy) (risk factor for cardiovascular disease and adverse pregnancy outcomes); and neural tube defects (NTDs). Population-wide folate status is expected to improve where folic acid fortification policies for reducing NTD occurrence are established. However, there is concern that cobalamin deficiency and its characteristic neuropathy could be masked when hematological abnormalities in risk groups such as the elderly and vegetarians are reversed through folic acid supplementation. Folate-cobalamin interactions and their impact on health are reviewed here.     

Dietary and blood folate status of Malaysian women of childbearing age

The protective role of folic acid taken during the periconceptual period in reducing the occurrence of neural tube defects (NTD) has been well documented by epidemiological evidence, randomized controlled trials and intervention studies. Much of the evidence is derived from western populations while similar data on Asian subjects is relatively nascent. Baseline data on folate status of Malaysian women is lacking, while NTD prevalence is estimated as 10 per 10,000 births. This study was conducted with the objective of determining the dietary and blood folate status of Malaysian women of childbearing age. A total of 399 women comprising 140 Malay, 131 Chinese and 128 Indian subjects were recruited from universities and worksites in the suburbs of Kuala Lumpur. Inclusion criteria were that the subjects were not pregnant or breastfeeding, not taking folic acid supplements, not habitual drinkers or smokers. Based on a 24-hour recall, the median intake level for folate was 66 microg (15.7-207.8 microg), which amounts to 16.5% of the Malaysian Recommended Nutrient Intakes level. The median (5-95th percentiles) values for plasma and red cell folate (RBC) concentrations were 11 (4-33) nmol/L and 633 (303-1209) nmol/L respectively. Overall, nearly 15.1% showed plasma folate deficiency (< 6.8 nmol/L), with Indian subjects having the highest prevalence (21.5%). Overall prevalence of RBC folate deficiency (<363 nmol/L) was 9.3%, and an almost similar level prevailed for each ethnic group. Only 15.2% had RBC concentration exceeding 906 nmol/L, which is associated with a very low risk of NTD. The result of this study point to the need for intervention strategies to improve the blood folate status of women of childbearing age, so that they have adequate protection against the occurrence of NTD at birth.     

Genetic variation in genes of folate metabolism and neural-tube defect risk

Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50-70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C677T single-nucleotide polymorphism (SNP) in the methylenetetrahydrofolate reductase (MTHFR) gene, and the observation that elevated plasma homocysteine levels are associated with NTD, research has focused on genetic variation in genes encoding for enzymes of folate metabolism and the closely-related homocysteine metabolism. In the present review relevant SNP in genes that code for enzymes involved in folate transport and uptake, the folate cycles and homocysteine metabolism are summarised and the importance of these SNP discussed in relation to NTD risk.     

Session 1: Public health nutrition. Folic acid food fortification: the Irish experience

Adequate intake of folic acid by women during very early pregnancy can markedly reduce risk of the development of neural-tube defects (NTD). The effectiveness of advice to women to take folic acid supplements is limited, mainly because 50% of pregnancies are unplanned. However, mandatory folic acid food fortification programmes in North America have been very successful in reducing NTD rates. In Ireland higher rates of pregnancies are affected by NTD and the option of termination is illegal. Consequently, the much higher burden of disease makes primary prevention of NTD an important public health issue in Ireland. During 2006 a decision was taken in Ireland to initiate mandatory folic acid fortification of most bread to prevent NTD. Priority work was immediately undertaken to establish reliable and comprehensive baseline information on factors that will be affected by fortification. This information included data on: the national prevalence of pregnancies affected by NTD; the current extent of voluntary folic acid fortification of food on the Irish market and how it affects folic acid intakes; blood folate status indicators assessed for various subgroups of the Irish population. In addition, scientific developments that have arisen since 2006 relating to the risks and benefits of folic acid intake are under ongoing review. The present paper summarises the rationale for mandatory folic acid food fortification in Ireland and recent scientific developments relating to risks and benefits of folic acid intake. In this context, preliminary findings of baseline monitoring investigations in Ireland are considered.     

Five decades of trends in anemia in Israeli infants: implications for food fortification policy

OBJECTIVE: To describe the secular trends in the prevalence rates of iron-deficiency anemia (IDA) in infants in Israel, identify population group differences and assess the effectiveness of the 1985 Public Health directives on iron supplementation and avoidance of cow's milk in the first year of life. DESIGN: A systematic analysis of published and unpublished cross-sectional studies. METHODS: IDA rates in 1-y-old infants between 1946 and 1997 were assessed from published papers and reports. Rates for Arab infants were available from 1984. Data on routine hemoglobin tests on 1-y-old infants for Arabs and Jews separately were obtained from four health districts for the period 1987 to 1997. Analyses were done for the periods prior to and following the Public Health directives. RESULTS: The prevalence of IDA in Jewish infants declined from 68% in 1946 to 50% in 1985 at an average annual rate of -1.43%. Following the iron supplementation directives, the average annual rate of decline increased to -4.0% and reached a prevalence of about 11% in 1996. IDA rates in Arab infants declined by an annual average of -3.7%, and were consistently almost twice as high as for Jewish infants. CONCLUSIONS: Despite the contribution of the iron supplementation program to the reduction in TDA, the persistently high rates indicate inadequate iron content in the diet. This emphasizes the important role of a national food fortification program, using staple foods commonly consumed.     

Periconceptional multivitamin folic acid use,dietary folate,total folate and risk of neural tube defects in South Carolina

PURPOSE: To investigate whether dietary folate or multivitamin folic acid taken 3 months before conception and during the first 3 months of pregnancy reduces the risk of isolated occurrent neural tube defect (NTD)-affected pregnancies. METHODS: This population-based case control study conducted between 1992 and 1997 included 179 women with NTD-affected pregnancies and 288 randomly selected controls. Women completed a food frequency questionnaire and were interviewed about lifestyle behaviors, pregnancy histories and use of multivitamins. RESULTS: Use of 0.4 mg or more of multivitamin folic acid at least 3 times per week during the periconceptional period showed no statistically significant reduction in NTD risk [adjusted odds ratio (AOR) = 0.55, 95% confidence interval (CI) = 025, 1.22]. After adjusting for covariates, protective effects for NTDs were observed at the highest quartiles of dietary folate and total folate (daily dietary folate plus daily multivitamin folic acid); the respective odds ratios were 0.40 (95% CI = 0.19, 0.84) and 0.35 (95% CI = 0.17, 0.72). CONCLUSIONS: This study illustrates some of the difficulties in determining effects of folic acid and dietary folate in a population where the consumption of foods rich in folate and the use of multivitamins are increasing and the rate of NTDs is declining. Studies are needed to monitor future changes in folate levels and their effect on health.     

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.     

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.     

East Ireland 1980-1994: epidemiology of neural tube defects

STUDY OBJECTIVE: The objective of the study was to describe the epidemiology of neural tube defects (NTD) in the eastern region of Ireland using the EUROCAT register of congenital malformations. DESIGN, SETTING AND PATIENTS: EUROCAT registries monitor the prevalence of congenital anomalies in defined populations using multiple sources for case ascertainment. All cases of NTD on the Dublin EUROCAT register born between 1980 and 1994 were extracted and analysed. The crude birth prevalence rate for all NTD, spina bifida, anencephaly and encephalocoele were calculated for each year. Parameters measured were: sex ratio, stillbirth rate, proportion of low birth-weight babies (< 2500 g) and the proportion who were premature (< 37 weeks gestation). MAIN RESULTS: Of 821 NTD cases, 419 (51.0%) had spina bifida, 322 (39.2%) had anencephaly, 69 (8.4%) had encephalocoele and 11 (1.3%) were iniencephalic. The crude birth prevalence of NTD decreased fourfold from 46.9/10,000 births in 1980 to 11.6/10,000 in 1994. The downward trend ceased during the early 1990's. Younger mothers had significantly higher rates of NTD affected births. Twenty two per cent of NTD cases had additional non-central nervous system anomalies. In 40 cases, there was a previous family history of NTD in siblings. Seasonal effects in birth prevalence were observed. Birth notification was the most frequent mechanism of ascertainment. CONCLUSION: There was a marked fall in the birth prevalence of NTD during the 15 year period. This change was real and not accounted for by pre-natal screening and diagnostic practises with termination of pregnancy, which is not legally permissible in Ireland. Dietary factors may have had an influence. Rates of NTD in this region are still higher than many other parts of Europe. Primary prevention strategies through increased folic acid intake are necessary to further reduce NTD affected births.     

Reassessing folic acid consumption patterns in the United States (1999 2004): potential effect on neural tube defects and overexposure to folate

BACKGROUND: In the United States, folic acid fortification of cereal- grain foods has significantly increased folate status. However, blood folate concentrations have decreased from their postfortification high as a result, in part, of decreasing food fortification concentrations and the popularity of low-carbohydrate weight-loss diets. OBJECTIVES: The objectives of the study were to quantify changes in folate intake after folic acid fortification and to estimate the effect on neural tube defect (NTD) occurrence. DESIGN: Expanding on an earlier model, we used data from 11 intervention studies to determine the relation between chronic folate intervention and changes in steady state serum folate concentrations. With serum folate data from the National Health and Nutrition Examination Survey (NHANES), we used reverse prediction to calculate postfortification changes in daily folate equivalents (DFEs). With the use of NHANES red blood cell folate data and a published equation that related NTD risk to maternal red cell folate concentrations, we calculated NTD risk. RESULTS: Folate intake decreased by approximately 130 microg DFE/d from its postfortification high, primarily as a result of changes seen in women with the highest folate status. This decrease in folate intake was predicted to increase the incidence of NTD by 4-7%, relative to a predicted 43% postfortification decrease. In addition, the number of women consuming >1 mg bioavailable folate/d decreased. CONCLUSIONS: Folate consumption by women of childbearing age in the United States has decreased. However, the decrease in those women with the lowest folate status was disproportionately small. Consequently, the effect on NTD risk should be less than would be seen if a uniform decrease in folate concentrations had occurred. These results reinforce the need to maintain monitoring of the way fortification is implemented.     

Folate supplementation after heart transplantation: effects on homocysteine plasma levels and allograft vascular disease

BACKGROUND AND AIMS: After heart transplantation, the effects of folate supplementation on total homocysteine plasma levels (THcy) and heart allograft vascular disease (AVD) remain unclear. METHODS: Accordingly, we prospectively analyzed 48 heart transplant receipients referred for routine follow-up from July to September 1998 (age 54+/-11 years, 75% male, 35+/-27 months from transplant). Among these patients, 17 were treated with folate supplementation for 12 months (Group F), while 31 cross-matched for age, gender, serum creatinine and time from transplant (P>0.3 vs Group F for all) did not assume folate supplementation (Group NF). Routine coronary angiography for AVD detection was routinely obtained in every patient. RESULTS: THcy overall increased during the study period (from 16.6+/-6.5 to 19.4+/-7.6 micromol/l, P<0.001), and a strong trend toward higher THcy was observed in patients presenting AVD (22.4+/-8.7 vs 17.6+/-6.8 micromol/l, P=0.051). After 12 months THcy was lower in Group F as compared to Group NF (16.2+/-5.6 vs 21.1+/-8.1 micromol/l, respectively, P=0.033). CONCLUSIONS: Our results demonstrate that THcy increases over time in heart transplant recipients, and a strong trend toward higher THcy is observed in the presence of AVD. Since folate supplementation appears to positively influence THcy, a favorable effect of folate on AVD can be hypothesized.     

Differences in folic-acid policy and the prevalence of neural-tube defects in Europe; recommendations for food fortification in a EUROCAT report

The European Registration Of Congenital Anomalies and Twins (EUROCAT), a network of 40 European registries of congenital anomalies, has published a special report on the prevention of neural-tube defects by, periconceptional folic-acid supplementation in Europe. This report reviews the progress made in 17 European countries since i99I in terms of developing and implementing public health policies to raise periconceptional folate status. Data on the prevalence of neural-tube defects in 1980-2000 were also analysed. - At the beginning of 2002, 10 of the 17 countries had an official government recommendation that women planning a pregnancy should take folic-acid supplementation daily. Only 7 countries implemented official health-education initiatives. - Despite the various measures taken to date, the majority of women in all countries surveyed are not taking periconceptional folic-acid supplements. Even in the Netherlands, where the percentage of planned pregnancies is estimated at 85%, only 36% of women take folic-acid supplements during the advised period. - Overall, the number of neural-tube defects has not decreased in Europe. A slight decrease was seen in those countries with an official policy regarding periconceptional folic-acid supplementation. - It is clear from the report that more effective prevention of neuraltube defects could be achieved with folic-acid fortification of staple foods; this approach has led to a reduction in the prevalence of neuraltube defects in the US and Canada. This approach can also prevent the majority of neural-tube defects in unplanned pregnancies and reduce the socioeconomic differences in prevalence.     

Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions

BACKGROUND: Folate metabolism pathway genes have been examined for association with neural tube defects (NTDs) because folic acid supplementation reduces the risk of this debilitating birth defect. Most studies addressed these genes individually, often with different populations providing conflicting results. OBJECTIVES: Our study evaluates several folate pathway genes for association with human NTDs, incorporating an environmental cofactor: maternal folate supplementation. METHODS: In 304 Caucasian American NTD families with myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase 1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and cystathionine-beta-synthase. RESULTS: Only single nucleotide polymorphisms (SNPs) in BHMT were significantly associated in the overall data set; this significance was strongest when mothers took folate-containing nutritional supplements before conception. The BHMT SNP rs3733890 was more significant when the data were stratified by preferential transmission of the MTHFR rs1801133 thermolabile T allele from parent to offspring. Other SNPs in folate pathway genes were marginally significant in some analyses when stratified by maternal supplementation, MTHFR, or BHMT allele transmission. CONCLUSIONS: BHMT rs3733890 is significantly associated in our data set, whereas MTHFR rs1801133 is not a major risk factor. Further investigation of folate and methionine cycle genes will require extensive SNP genotyping and/or resequencing to identify novel variants, inclusion of environmental factors, and investigation of gene-gene interactions in large data sets.     

Dietary methionine is involved in the etiology of neural tube defect-affected pregnancies in humans

Research has provided evidence of the role of multivitamin supplementation in the prevention of neural tube defects (NTD). Failure of the neural tube to close is one of the most frequent and severe human developmental defects. The etiology of NTD is complex, encompassing genetic, dietary and environmental factors. 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. We hypothesized that women with high maternal dietary methionine intake were at a decreased risk for a NTD. Combinations of methionine, folate and vitamin B-12 intakes and NTD risk were also examined. Data from a 5-y, population-based, case-control study of 170 NTD-affected pregnancies and 269 controls were provided by the South Carolina NTD Surveillance, Prevention, and Research Project. There was a 30-55% lower NTD risk among women whose average daily dietary intake of methionine was greater than the lowest quartile of intake (>1580 mg/d). The odds ratios associated with the three quartiles of methionine intake > 1580 mg/d after adjusting for energy, race and body mass index were 0.72 (P < 0.07), 0.68 (P < 0.07) and 0.45 (P < 0.06), respectively. These findings indicate that a reduction in the risk of having a NTD-affected pregnancy is associated with maternal dietary intake of methionine (3 mo pre- to 3 mo postconception). This finding is consistent with the hypothesis that methionine plays a role in the etiology of NTD and suggests the need for further research in the area of maternal diet and pregnancy.     

Prevalence of neural tube defects in Australia prior to mandatory fortification of bread‐making flour with folic acid

Objective: To establish baseline prevalence of neural tube defects (NTDs) prior to mandatory folic acid fortification in Australia. Method: Retrospective population based study. Data from the Australian Congenital Anomalies Monitoring System, for 1998–2005 were used to calculate birth prevalence including live/stillbirths of at least 20 weeks gestation or 400 g birthweight. Total prevalence and trends of NTD including terminations of pregnancy (TOPs) before 20 weeks were established using data from South Australia, Victoria and Western Australia because of the incomplete ascertainment in other states. Results: The birth prevalence of NTDs from 1998–2005, was 5/10,000 births. The total prevalence including TOPs was 13/10,000 births. A 26% declining trend in total prevalence was seen from 1992–2005, but the main decline occurred prior to 1998. Women who were Indigenous, socially disadvantaged, young, living in remote areas and had multiple gestations were more likely to give birth to babies with NTDs. Conclusion: The prevalence of NTD has been stable since 1998. Reporting of the birth prevalence alone underestimates the actual prevalence of NTD. Implications: From a public health perspective, future monitoring of NTD following implementation of fortification of bread‐making flour with folic acid should include a mixed methods approach; reporting birth prevalence on national data and total prevalence on tri‐state data.