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.     

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.     

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.     

Effects of folic acid supplementation during different pregnancy periods and relationship with the other primary prevention measures to neural tube defects

Objective: To find out the prevention effects of folic acid supplements during different pregnancy periods on neural tube defects (NTDs) and the relationship of folic acid supplements with the other NTDs’ primary preventive measures.

Methods: A 1:1 case-control study was conducted. Four hundred and fifty-nine women who delivered or gestate infants/fetuses with NTDs in the last two years were randomly selected as cases and were matched with women who delivered babies without obvious birth defects as controls.

Results: For anencephaly, folic acid supplementation during the periconceptional period and preconceptional period has a 57–83% reduction in risk of NTDs(ORs ranged from 0.17 to 0.43). For spina bifida, folic acid supplementation during the periconceptional period has a 79% reduction in risk of NTDs (OR?=?0.21). For encephalocele, folic acid supplementation during the periconceptional period has a 67% reduction in risk of NTDs (OR?=?0.33). The prevention effects on NTDs were significant when these preventive measures combined with folic acid supplements during the periconceptional period, with OR 0.04, 0.07, 0.10 and 0.11.

Conclusion: The specific effects of folic acid supplementation during different periods show the reduction in the risk of NTDs, anencephaly, spina bifida, encephalocele. During periconceptional period, folic acid supplements have preventive effects on all NTDs’ subtypes.     

Preventing neural tube defects: The importance of periconceptional folic acid supplements

Objective: To inform the obstetrician-gynecologist of recent scientific evidence regarding the use of supplemental folic acid for prevention of neural tube defects (NTDs).Data Sources: We selected English language articles via MEDLINE published from January 1990 through February 1997, using the search terms “folic acid” and “neural tube defect.” Additional sources were identified through cross-referencing and through searching selected journals published from March through October 1997.Methods of Study Selection: Articles were selected on the basis of their relevance to the relationship between folate intake and NTD incidence, mechanisms of folate responsive NTD formation, and folate provision strategy. We referenced 55 papers in total.Tabulation, Integration, and Results: The majority of evidence demonstrates a decreased incidence of NTDs with increased folic acid consumption. The most convincing trials were performed in Europe among women who were planning pregnancy by using multivitamin or folic acid supplements. Some studies suggest that the protective effect of folate is explained, in many cases, not through correction of dietary deficiencies, but through correction of metabolic defects. Other evidence implies that it reduces NTDs by causing abortion of affected conceptuses. Supplemental folic acid tablets are the most proven means of improving an individual’s folate status, but ensuring compliance with a strategy using vitamin tablets is problematic.Conclusion: Women of reproductive age should be advised to take multivitamin supplements containing 0.4 mg folic acid daily. Women with previously affected offspring who intend to become pregnant should take daily supplementation containing 4 mg of folic acid in the periconceptional period to reduce the risk of recurrence.     

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.     

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.     

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.     

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.     

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.     

Screening for neural tube defects

Neural tube defects are separated into two main categories: (1) abnormalities of the skull and brain (anencephaly, acrania, and encephalocele) and (2) malformations of the spine (meningomyelocele or spina bifida). The cause of neural tube defects is not always clear, and include chromosomal abnormalities, single gene mutations, maternal disease, or maternal exposure to teratogens. Mostly the disorder emerges as a multifactorial trait. Routine screening for neural tube defects was introduced in the United Kingdom in the mid-1970s and the United States in the mid-1980s. The use of screening has resulted in a marked decline in the frequency of neural tube defects diagnosed at birth.