Prevention of neural tube defects with folic acid

Neural Tube Defects (NTD's) include a large number of congenital malformations produced when the open neural tube presents a very early stages in the development of the human embryo fails to close on or before the first month post conception. NTD's are considered to be one of the most common forms of malformations with varying degrees depending of genetic and environmental conditions. The studies prove that the additional taken of folic acid plays an important role against the NTD's. Numerous studies prove this "B" vitamin has an important protective effect not only for the recurrence of NTD's, but for new cases too. In light of these, in 1992 the US Public Health Services issued the recommendation that all women in child-bearing age should consume at least 0.4 mg (400 micrograms) of folic acid daily.     

Evidence for suboptimal use of periconceptional folic acid supplements globally

OBJECTIVE: To systematically summarise the available evidence concerning the rate of folic acid supplement use pre- and periconceptionally, to identify those characteristics associated with low rates of use and to assess whether folic acid public awareness campaigns are associated with higher folic acid use. DESIGN: Systematic overview. SETTING: Survey studies. POPULATION: Women of reproductive age, most of whom were currently or recently pregnant. METHODS: Two investigators searched MEDLINE, Embase and Nutriotiongate databases between 1990 and 2003. Bibliographies of retrieved references were scanned for other relevant publications, and authors were contacted if necessary. Studies were included that evaluated the rate of folic acid supplement use either before conception or in early pregnancy. MAIN OUTCOME MEASURES: Rate of preconceptional and/or periconceptional folic acid use, rate of planned pregnancy in each study, as well as significant characteristics differentiating non-users from users of folic acid, including the effect of folic acid awareness campaigns. RESULTS: A total of 52 studies were included. In 34 studies, reported preconceptional folic acid use varied from 0.9% to 50%. In 49 studies, the reported rate of periconceptional supplement use ranged from 0.5% to 52%. Significant predictors of reduced periconceptional folic acid use were a low level of formal education, immigrant status, young maternal age, lack of a partner and an unplanned pregnancy. Four studies examined the effect of mass media campaigns on periconceptional folic acid use; the reported rates increased significantly, by a factor of 1.7 to 7.2, but in no study was the post-campaign rate above 50%. CONCLUSIONS: In many countries, fewer than 50% of women take periconceptional folic acid supplements. Consideration should be given to the practical advantages of folic acid fortification of centrally processed foods, such as wheat, corn and rice flour, while further promoting vitamin tablet supplement use and planned pregnancy.     

Awareness of the benefits of folic acid and prevalence of the use of folic acid supplements to prevent neural tube defects among Thai women

Objective To determine the level of knowledge about the usefulness of periconceptional folic acid supplementation among pregnant women. Materials and methods An anonymous questionnaire was completed by selected subjects to assess folic acid awareness. The questionnaire was administered to pregnant women who were seeking antenatal care at King Chulalongkorn Memorial Hospital May to December 2005. The questions covered their knowledge and use of folic acid supplements, pregnancy intention, and demographic and socioeconomic characteristics. Results Out of 401 women surveyed, 76.1% of them reported that they had heard of folate. Of these, only 24.4% of the total subjects knew that folate was something important. Overall, 9.7% of the total women took folic acid during periconceptional period. The most common information sources on folate were the media. Logistic regression analysis showed that education of mother was the strongest predictor of having taken folic acid during the correct period. Conclusion Although some pregnant women are aware of the need to take folic acid, the actual impact of the present recommendations is almost negligible. Information to specifically inform patients about the need to take folic acid to prevent neural tube defects by medias and healthcare personnel seem to improve the final intake of folic acid during the protective period.     

Preventing neural tube defects with folic acid: nearly 20 years on, the majority of women remain unprotected

Many countries, including the USA and Canada, have implemented fortification of foods with folic acid, however the British Government only issues advice that supplements should be taken before and after conceiving. In this study, information was collected from women attending antenatal clinics to understand current levels of compliance with health advice and to investigate what is driving womens' behaviour. Eighty-nine percent of women consumed supplements but only 31% took folic acid prior to conceiving. Hence, the vast majority are starting too late to prevent neural tube defects (NTDs). Educational achievement, income and marital status emerged as the most significant factors influencing non-compliance. GPs and midwives were the main catalyst for women starting folic acid, however, 81% of these women started post-conception. When asked why they took folic acid, the majority of women did not mention the association with NTDs. Forty-one percent of women who did not take the supplements at all were unaware that it was recommended that they should. Fortification of UK food products offers a major public health opportunity. In the absence of fortification, gaps in the public health message need to be addressed. GPs and midwives cannot be relied upon alone to educate these women.     

Influence of folic acid in primary prevention of neural tube defects

OBJECTIVE: The aim of the study was to analyze the incidence of neural tube defects in Lublin Province between 1990 and 2000 after application of primary prevention with folic acid. MATERIAL AND METHODS: A total of 293,039 newborns were analyzed. RESULTS: Neural tube defects were diagnosed in 53 newborns. CONCLUSION: Reduction of frequency of meningocele was shown after application of primary prevention with folic acid in 1998. Meningoceles were most frequent in 1992 (1.32/1000) and in 1998 frequency of these defects was reduced and in 2000 was down to 0.62/1000 births.     

Primary prevention of neural tube defects with folic acid supplementation: Cuban experience

Folic acid (5 mg) was given daily, for not less than one menstrual period before conception and until the tenth week of pregnancy, to 81 women (FS) with a history of a previous neural tube defect (NTD) birth. There was no NTD recurrence among this group or among the offspring of a further 20 women (PS) whose folic acid supplementation fell short of the full regime. In another 114 women who became pregnant without folic acid supplementation (US), there were four NTD recurrences (3.5 per cent). Our results suggest that folic acid supplementation might be an effective method of primary prevention of neural tube defects.     

Periconceptional folic acid use and the prevalence of neural tube defects in The Netherlands

OBJECTIVE: To study the effect of increased folic acid intake on the prevalence of neural tube defects (NTD) in The Netherlands. STUDY DESIGN: Using the capture-recapture method, the prevalence of NTD was estimated on the basis of five different registries on births affected by NTD. RESULTS: Total prevalence over the 1988-1998 period varied between 1.43 and 1.96 per 1000 live and still births. No decrease in total prevalence was found to have taken place during that period. Scrutiny of the last 2 years, 1997 and 1998, in which increased folic acid intake might be expected to have had an effect, did not give any indication that the prevalence of NTD was falling. CONCLUSIONS: A decrease in the Dutch prevalence of NTD during the study period could not be demonstrated due to the relatively small number of women using folic acid periconceptionally. This does not mean automatically that periconceptional folic acid use is ineffective in reducing the Dutch prevalence of NTD. Further monitoring is needed.     

Periconceptional supplementation with folic acid. Does it prevent neural tube defects?

There has been considerable controversy in recent years concerning the benefit of periconceptional vitamin supplementation in the prevention of neural tube defects. Recent reports of a successful randomized clinical trial have prompted official recommendations for folic acid supplementation in women with a history of an affected pregnancy. Periconceptional supplementation of low-risk women remains controversial.     

The importance of folic acid

Folic acid is necessary for cell development; for the metabolism of specific biochemical reactions in the body, such as the conversion of homocysteine to methionine; and for the metabolism of specific anticonvulsant drugs. Folic acid has an interrelationship with vitamin B12. A deficiency of folate increases the risk of NTDs, as well as contributing to hyperhomocystinemia, a condition associated with increased cardiovascular disease and NTDs. For the prevention of NTDs, it is recommended that a woman of childbearing age consume a daily folate intake of 400 micrograms; however, the average dietary folate intake is half that amount, and the FDA folate fortification of cereal grains adds only 100 micrograms daily. The woman in her childbearing years does not meet the recommendation with dietary and food fortification. Periconceptional folic acid supplementation is essential, because the neural tube closes 23 to 27 days after conception. Therefore, a multiple vitamin containing folic acid is the practical solution at present if the food fortification is not increased. The bioavailability of folate in the vitamin preparation is approximately double that of dietary folate. Most preparations contain 400 micrograms of folic acid, and if the woman took a multiple vitamin (400 micrograms of folate) in addition to her diet (230 micrograms of folate), she would not exceed 1000 micrograms (1 mg) daily, which is considered the upper limit of daily folate ingestion by dietary fortification and supplementation before the masking of vitamin B12 becomes a concern. However, in this group of patients, pernicious anemia is rare. Regarding cardiovascular disease in men and women, there are no long-term studies showing the benefit of folic acid in reducing the homocysteine level. At present, there are only estimations. However, they should not be ignored. Although it is not the current standard of practice, adding a multiple vitamin containing folic acid to the regimen of men and women starting anticonvulsant medication should be considered in order to prevent the folate lowering observed with such commonly used drugs as PHT and carbamazepine. Women in childbearing years should be on a folic acid supplement when taking an anticonvulsant drug. In general, it appears that all men and women would benefit from increased folate intake. This can be accomplished through vitamin supplementation when there is compliance. However, if the food fortification for folate is increased in the future, then the issue of vitamin supplementation will have to be readdressed.     

Vitamins, folic acid and neural tube defects: comments on investigations in the United States.

No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy-makers face difficulties in applying results of recurrence or occurrence studies in high-risk areas to low-risk areas in the U.S.     

Maternal periconceptional alcohol consumption and the risk of neural tube defects in offspring: a meta-analysis

Objective: Several studies have been conducted to examine the association between alcohol consumption during pregnancy and risk of neural tube defects (NTDs), while the results are inconsistent. In the present study, we aimed to clarify the relationship between maternal periconceptional alcohol consumption and NTDs risk in offspring.

Methods: PubMed, Springer Link, and Elsevier databases were searched up to November, 2014. All case–control and cohort studies of maternal alcohol consumption during pregnancy with risk of NTDs were included. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) for highest versus lowest category of alcohol consumption were calculated using a fixed- or random-effects model.

Results: The pooled ORs of maternal periconceptional alcohol consumption were 1.01 (95% CI: 0.71–1.45) for total NTDs and 1.03 (95% CI: 0.65–1.64) for NTDs subtype of spina bifida. Specifically, the pooled ORs of maternal alcohol consumption in the first trimester and binge drinking were 1.01 (95% CI: 0.71–1.43), and 1.07 (95% CI: 0.81–1.41), respectively.

Conclusions: Our findings suggested no association between maternal periconceptional alcohol consumption and NTDs risk in offspring.     

Awareness of the use of folic acid to prevent neural tube defects in a Mediterranean area

OBJECTIVES: The risk of neural tube defects (NTDs) is decreased in women who take folic acid during the periconceptional period. The main objective of our study was to evaluate the awareness of the need for folic acid supplementation and also the actual intake during the periconceptional period to prevent neural tube defects in a Mediterranean area. STUDY DESIGN: A retrospective study was performed from 1 July to 30 November 2000. One thousand consecutive women who delivered in our hospital were interviewed during the immediate postpartum period about their knowledge of neural tube defects and folic acid intake before and during pregnancy. RESULTS: Most women (85.7%) referred not having been specifically informed about the need to take folic acid to prevent neural tube defects although approximately half of the women (50.6%) were in fact, aware of the need for folic acid intake. Eight percent (8.1%) of the women took folic acid before conception but only 6.9% did so during the effective period from 4 weeks before conception to 4 weeks after conception. Logistic regression analysis showed that awareness of the need to take folic acid together with having had preconceptional counselling and knowledge of NTDs were the strongest variables related to the fact of having taken folic acid during the correct period. CONCLUSIONS: Although the population is aware of the need to take folic acid, the real impact of the present recommendations is almost negligible. Information in primary care and preconceptional counselling to specifically inform patients about the need to take folic acid to prevent NTDs seem to be crucial to improve the final intake of folic acid during the protective period.     

Greater maternal weight and the ongoing risk of neural tube defects after folic acid flour fortification

OBJECTIVE: Maternal obesity is likely a risk factor for neural tube defects (NTDs). By late 1997, it became mandatory in Canada that all refined wheat flour be fortified with folic acid. Because overweight women may consume greater quantities of refined wheat flour, we questioned whether their risk of NTD changed after flour fortification. METHODS: A retrospective population-based study was conducted between 1994 and late 2000. We included all Ontarian women who underwent antenatal maternal screening at 15 to 20 weeks of gestation. Self-declared maternal date of birth, ethnicity, current weight, and the presence of pregestational diabetes mellitus were recorded in a standardized fashion on the maternal screening requisition sheet. The presence of NTDs was systematically detected both antenatally and postnatally. The risk of open NTD was evaluated across maternal weight quartiles and deciles, and an interaction between greater maternal weight and the presence of flour fortification was tested using multiple logistic regression analysis. RESULTS: A total of 292 open NTDs were detected among 420,362 women. The adjusted odds ratio (OR) for NTD was 1.2 (95% confidence interval [CI] 1.1-1.3) per 10-kg incremental rise in maternal weight. Comparing the highest with the lowest quartile of maternal weight, the adjusted OR for NTD was 2.6 (95% CI 1.8-4.0). A similar finding was observed for the highest compared with lowest weight deciles (adjusted OR 3.3, 95% CI 1.7-6.2). The interaction between elevated maternal weight and the presence of folic acid flour fortification was of borderline significance (P = .09). Before fortification, greater maternal weight was associated with a modestly increased risk of NTD (adjusted OR 1.4, 95% CI 1.0-1.8); after flour fortification, this effect was more pronounced (adjusted OR 2.8, 95% CI 1.2-6.6). CONCLUSION: These data emphasize the higher risk of NTD associated with increased maternal weight, even after universal folic acid flour fortification. Beyond periconceptional folic acid use, consideration should be given to testing whether prepregnancy weight reduction is an independent means of preventing NTD. LEVEL OF EVIDENCE: II-2.     

A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

Background  

Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention.     

The regional campaign for women on awareness of neural tube defects and folic acid in Narlidere,Izmir: a community-based intervention

Objectives To create an awareness among women and to update the knowledge of health personnel about neural tube defects (NTDs) and folate in order to reduce the incidence of NTD in Narlidere, ?zmir.

Methods In 2006, a regional campaign was organized in Narlidere, Izmir that aimed at informing women of child-bearing age on folic acid and prevention of NTD. Nearly 4400 women participated in the study. By means of questionnaires the level of knowledge before and after the intervention was evaluated.

Results Before the campaign was carried out, 18% of women had heard of folic acid. Their level of knowledge increased after the campaign (p < 0.0001). Post-intervention scores of high school and university graduates and women with high or middle income, as well as those having a friend or kin with spina bifida were found to have significantly improved.

Conclusions The pilot community-based training programme was very successful. Similar programmes, integrated within routine health care services, promoting the use of folic acid will be fostered in the whole country.