Neural tube defects: is a decreasing prevalence associated with a decrease in severity?

OBJECTIVE: Severe neural tube defects (NTDs) tend to occur with disproportionate frequency in areas of high prevalence. The objective of our study was to determine the birth prevalence of NTDs during a 25-year period at a single institution based in an area of high prevalence for NTDs and to investigate if a decreasing prevalence resulted in a change in the type of NTDs. STUDY DESIGN: All cases of NTD affected births born at the Coombe Women's Hospital during the interval 1975-1999 were reviewed. There were 171,260 births at the Coombe Women's Hospital between 1975 and 1999. During this interval, there were 522 NTD affected births. RESULTS: From 1975 until 1999 the prevalence of NTDs significantly decreased (P < 0.0001). This transition from high to low prevalence was associated with a significant decrease in severe forms of NTDs (P < 0.0001). This decreasing trend in rate and severity of NTD affected births was most dramatic prior to either food fortification or periconceptual folic acid supplementation. CONCLUSIONS: Our transition from high to low prevalence for NTDs has been associated with a significant decrease in severe forms of NTDs.     

Periconceptual folic acid intake by Sicilian couples at a risk of recurrence of NTD

BACKGROUND AND AIM: The authors aimed to evaluate the frequency with which pregnant Sicilian women with a high risk of recurring neural tube defects (NTD) attending the Ultrasonography and Prenatal Diagnosis Clinic in the Department of Diagnosis and Treatment at Ospedale S. Bambino in Catania were aware of the preventive effect of folic acid supplements during the periconceptional period and whether they therefore took folic acid supplements before the next pregnancy. METHODS: All pregnant women undergoing ultrasonography between January 1997 and December 1998 were interviewed. It was noted whether any earlier offspring had suffered from NTD or whether relatives (sisters, brothers, parents) had also suffered from the same experience. They were also asked whether they knew about the preventive effect of periconceptional folic acid supplements on the development of NTD, whether their pregnancy was planned and whether they had taken periconceptional folic acid supplements and, if so, at what dose. RESULTS: Eighteen couples were identified as being at risk for recurring NTD, in 3 cases owing to an earlier pregnancy resulting in NTD (2 cases of spina bifida and 1 case of anencephaly) with a negative family history for NTD; a further 15 couples showed a positive family history for NTD. None of the women were aware of the preventive effect of acid folic supplements during the periconceptional period on the development of NTD. Out of 11 programmed pregnancies, none of the pregnant women took folic acid during the periconceptional phase. CONCLUSIONS: Pregnant Sicilian women at risk for recurring NTD interviewed by the authors were not aware of the possible prevention of NTD using folic acid supplements during the periconceptional phase.     

Folate consumption in the preconception period of Sicilian pregnant women and their knowledge about the prevention of neural tube defect by folate supplementation]

BACKGROUND AND AIMS: To define the frequency of Sicilian pregnant women taking folic acid during the periconceptional period (three months before and two months after conception) and how many are familiar with the preventive effects of folic acid on NTD. METHODS: 987 pregnant women from eastern Sicily, mainly with low incomes and low levels of education, most with secondary school certificates, underwent biochemical screening for Down's syndrome and NTD in the second trimester of pregnancy. RESULTS: An anencephalous fetus was diagnosed (frequency 0.1%) in a non-risk couple who had not taken folic acid during the periconceptional period: 4.1% (41 cases) of pregnant women reported having taken folic acid before pregnancy and 12.3% (122) during the first two months of pregnancy: five (0.5%) took folic acid during the periconceptional period (three months before conception and two months after). None of the 5 patients with a positive family history of NTD had taken folic acid. In all 122 cases the intake of folic acid supplements during pregnancy started after the positive results of the pregnancy test or echographic evidence of pregnancy, namely between the fifth and eighth week of pregnancy. Only the 5 pregnant women (0.5%) who took folic acid during the periconceptional period were aware of the possibility of preventing NTD through supplements of this vitamin. CONCLUSIONS: Greater efforts must be made to increase periconceptional use of folic acid for the prevention of NTD in pregnant women in Sicily.     

Periconceptional use of folic acid supplements in Oslo

BACKGROUND: Periconceptional supplementation with folic acid has been shown to decrease the occurrence of neural tube defects (NTD). A daily supplement of 400 micro g folic acid from the month before pregnancy and the first 2 to 3 months of pregnancy is recommended in Norway. We wanted to evaluate the use of folic acid supplements among pregnant women in Oslo, and to explore demographic factors that were associated with periconceptional intake. METHODS: All women attending antenatal ultrasound screening at the two main obstetric departments in Oslo during 3 months in 2001 were invited to answer questions regarding folic acid supplementation before and during their present pregnancy. RESULTS: A total of 1541 women (91, 5%) participated in the study, of which 26% were nonwestern immigrants. Only 17% of all women had started the folic acid supplementation preconceptionally (22% of the nonimmigrant vs. 2% of the immigrant population). Folic acid had been used by 58% at some time during the present pregnancy (73% of the nonimmigrant vs. 19% of the immigrant population). Regression analysis demonstrated that the difference in periconceptional use of folic acid between the two population groups could not be explained by registered demographic factors other than immigrant status. CONCLUSIONS: Most pregnant women in Oslo do not use folic acid as recommended and a dramatically low usage is seen among the immigrant population, indicating that more widespread information is necessary. Furthermore, fortification of cereals with folic acid should be considered to secure a sufficient intake of folic acid in all fertile women.     

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.     

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.     

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.     

Trends and predictors of folic acid awareness and periconceptional use in pregnant women

OBJECTIVE: The purpose of this study was to describe recent trends in folic acid awareness and use in the periconceptional period among pregnant women in relation to maternal sociodemographic and other relevant factors. STUDY DESIGN: From 1988 to 2002, 16,555 women from the Slone Epidemiology Center Birth Defects Study were interviewed about medication use before and during pregnancy (which included multivitamins and folic acid), about whether they were aware of any vitamins that might decrease the risk of birth defects, and about sociodemographic and medical factors. RESULTS: Awareness of folic acid benefits increased from 0 in 1988 to 50% in 1996 and thereafter. The use of folic acid in the periconceptional period increased from 15% in 1988 to 40% in the last few years. Maternal education was a strong independent predictor of both awareness and use as were ethnicity, whether the pregnancy was wanted, family income, and whether a health care provider was consulted before planning. CONCLUSION: Promoting the use of folic acid supplements, particularly among these disadvantaged groups, is essential to further decrease the prevalence of neural tube defects.     

Trends in twinning rates in metropolitan Atlanta before and after folic acid fortification

OBJECTIVE: To examine whether trends in rates of twinning in metropolitan Atlanta increased after folic acid fortification. STUDY DESIGN: Live births to residents of 5 metropolitan Atlanta counties during the period 1990-2001 were identified from the state of Georgia's vital records. Rates of twinning and rate ratios were computed for the periods before and after fortification with folic acid. RESULTS: Of the 510,000 singleton and twin births in metropolitan Atlanta during the study period, 7168 (1.43%) represented twin pregnancies. Overall, the rate of twinning increased 18% (P < .001)from the prefortification to postfortification period. As compared with the rate of twinning during the prefortification period, that during the postfortification period increased by 23% (OR 1.23, 95% CI 1.7, 1.28) among women over 30 years but showed no increase among women <30 years of age (OR 1.02, CI 0.94, 1.10). Among women >30, there was an increasing rate of twinning throughout the prefortification period (4.9%). There was no upward trend in twinning rates among women younger than 30 years prior to fortification. CONCLUSION: Increasing trends of twinning were observed only in women older than 30 years, but these trends began prior to folic acid fortification and reached a plateau in recent years. Further elucidation of the possible relationship between folic acid and twinning will need to account for the use of fertility treatments by older women.     

Periconceptional folic acid/multivitamin supplementation and twin pregnancy

OBJECTIVE: Results of our previous randomized controlled trial suggested an increase of twin pregnancies that was associated with the use of a multivitamin that contained folic acid during the periconceptional period. These findings were confirmed by US and Swedish studies, but not in the Chinese population. The aim of this analysis is to evaluate this possible association in a population-based data set. STUDY DESIGN: The population-based large control data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-1996) was evaluated. Control pregnant women were differentiated according to pre- and postconceptional supplementation of folic acid (in general 6 mg), multivitamins that contained 0.1 to 1.0 mg folic acid, folic acid plus multivitamin, and the prevalence of twin pregnancies was compared with the prevalence of twin pregnancies in the women who did not received supplements as referent. RESULTS: Of 38,151 women, 395 women gave birth to twins. The prevalence of twin births was 0.78% in the unsupplemented group; the rate of twin pregnancies was 1.52% after the preconceptional supplementation (adjusted odds ratio, 1.80; 95% CI, 1.14-2.85). The proportions of twin pregnancies were 1.14%, 1.45%, and 2.00% after the postconceptional folic acid, multivitamin, and folic acid plus multivitamin supplementation, respectively. CONCLUSION: Our findings suggest that both pre- and postconceptional supplementation of a high dose of folic acid and multivitamins are associated with a slight increase of the incidence of twin pregnancies.     

Periconceptional folic acid use among women giving birth at Queen Mary Maternity Hospital in Dunedin

BACKGROUND: The New Zealand Ministry of Health advises that all women planning a pregnancy take a folic acid supplement to reduce the risk of having a neural tube defect (NTD)-affected pregnancy. There is little information available to determine if women are following this advice. OBJECTIVE: The purpose of this study was to determine periconceptional folic acid use among women in the postnatal ward of Queen Mary Maternity Hospital in Dunedin. METHODS: A questionnaire was administered to women in the postnatal ward between 14 November and 22 December 2004. RESULTS: One hundred and six women were interviewed during the study period. Forty women (39%) used folic acid supplements before conception. Sixty-seven women (64%) planned their pregnancy. The proportion of women (P<0.001) who planned their pregnancy (53%) and used folic acid before conception was higher than those who did not (11%). The proportion of women 30 years of age (55%) who took folic acid supplements before conception was higher than women aged 17 to <25 years (10%). CONCLUSION: Despite a lack of a public health campaign in New Zealand, a high proportion of participants, especially those who planned their pregnancy, took folic acid during the periconceptional period. A comprehensive public health campaign is needed to increase folic acid use. Fortification may be required to reach those women who do not plan their pregnancies.     

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.     

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.     

Preconceptional and prenatal predictors of folic acid intake in Hungarian pregnant women

Objective

The purpose of the study was to determine demographic, obstetric and pregnancy care related factors of folic acid intake during preconceptional and prenatal period of pregnancy.

Study design

A questionnaire-based retrospective study was delivered at the Department of Obstetrics and Gynecology and Pregnancy Care Centre. The frequency of folic acid intake was measured before and during pregnancy in 349 pregnant women.

Results

Factors influencing preconceptional folic acid consumption were planning of pregnancy, previous infertility therapy, multivitamin intake before pregnancy, and folic acid intake during pregnancy. Probability of taking folic acid during pregnancy increased with age, and decreased with gestational age. Earlier detection of pregnancy corresponded to a higher chance of folic acid intake. Prenatal folic acid intake significantly related to the earlier intake of folic acid, and prenatal multivitamin medication.

Conclusion

It is important to target women who are less likely to take periconceptional folic acid as well as to increase awareness of women of childbearing age in general through an intensive campaign and improved education.     

An evaluation of the recording of folic acid use in the South West Congenital Anomaly Register

OBJECTIVE: Some congenital anomaly registers are collecting data on risk factors for pregnancies affected by anomalies; yet the quality of that information is rarely assessed. We assessed the quality of the risk factor data in the South West Congenital Anomaly Register (SWCAR) through a review of the data held on folic acid use, in cases of neural tube defect (NTD). METHODS: We reviewed all cases of NTD reported to SWCAR over 2 years and compared information held in the register with that in handwritten and computerised prenatal records, where available. RESULTS: Data on folic acid use was recorded in only 41 (36.9%) of the prenatal records of the 111 cases of NTDs reviewed. Information on any folic acid use in the prenatal records was transferred to the register in all instances where it existed. Information on the time of taking folic acid or not taking folic acid was rarely recorded in prenatal records. CONCLUSION: Incomplete recording of folic acid use and timing in prenatal records has limited the ability of SWCAR to collect accurate information on folic acid use in cases of NTDs. Minimal recording information on folic acid use in prenatal records is suggested.     

Prevalence and determinants of inadequate use of folic acid supplementation in Japanese pregnant women: the Japan Environment and Children’s Study (JECS)

Objective: The aim of the study was to clarify the prevalence and determinants of inadequate use of folic acid supplementation in pregnant Japanese women.

Methods: This study was part of the Japan Environment and Children’s Study, a nationwide and government-funded birth cohort study. We collected information on the use of folic acid supplementation before and during pregnancy and characteristics of participants using self-administered questionnaire.

Results: Among 9849 women who completed the data collection for this study, the prevalence of inadequate users was 92.6% of the total population and varied from 84.5% to 96.2% among regions. On the basis of multivariate logistic regression analysis, younger age, not married, lower family income, multipara, natural conception and no history of spontaneous abortion were found to be determinants for inadequate users of folic acid supplementation.

Conclusion: Most Japanese pregnant women show inadequate folic acid supplementation use. Japanese women of child-bearing age need to be specifically informed about the need for periconceptional intake of folic acid to prevent neural tube defects.     

Randomized trial of a physician-based intervention to increase the use of folic acid supplements among women

OBJECTIVE: Fewer than one third of American women take folic acid daily, although many women report that they would take folic acid if their physicians advised them to do so. This study determined the impact of a physician intervention during routine gynecologic visits on folic acid supplementation. STUDY DESIGN: Patients were assigned randomly to receive brief folic acid counseling, a reminder phone call, and 30 folic acid tablets (n = 162 women; intervention group) or to receive counseling about other preventive health behaviors and a folic acid informational pamphlet (n = 160 women; control group). Self-reported folic acid use was compared at baseline and at 2 months. RESULTS: Of the 279 patients who completed the study, weekly folic acid intake increased in the intervention group by 68%, compared with 20% in the control group ( P =.008). No significant differences were found in daily intake. The women who were most influenced by the intervention were black and lower income and not planning pregnancies. CONCLUSION: With little effort expended to encourage folic acid use, gynecologists could potentially reduce the risk of folate-preventable birth defects among their patients by as much as 11%.     

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.     

Awareness of the role of folic acid, dietary folate intake and plasma folate concentration in Japan

AIM: To investigate awareness of the role of folic acid in the prevention of neural tube defects, dietary intake of folate, and plasma folate concentration. METHODS: Postal questionnaires were collected from 1190 lay female subjects in three different groups and from seven groups of 3067 health-care providers. Dietary folate was investigated by assessing food frequency charts that were kept for 3 days by 245 women, and plasma folate was assessed by analyzing the blood serum of 194 women. RESULTS: Less than 15% of citizens and mothers who had live births knew that there was a link between folic acid and neural tube defects. The exception was with myelodysplastic families, in which awareness was 92%. Awareness among health-care professionals was generally low. The highest level was found in obstetricians-gynecologists (76%) and the lowest in nurses (12%). Dietary folate intake and plasma concentration were highest in pregnant women (356 microg/day and 11.9 ng/mL) and the lowest in student nurses (217 microg/day and 6.8 ng/mL). When the recommended dietary allowance of folate in Japan is taken into consideration, 22% of the non-pregnant women and 71% of the pregnant women did not fulfill the recommended dietary allowance. CONCLUSIONS: Information on the role of periconceptional intake of folic acid is not sufficiently disseminated to young women and health-care professionals alike. Pregnant women should be repeatedly recommended to take folic acid supplements of 400 microg/day.     

Periconceptional intake of folic acid and food folate and risks of preterm delivery

We investigated multiple sources of folate and folic acid to determine whether their periconceptional intakes were associated with preterm delivery. Studied were controls from the National Birth Defects Prevention Study delivered September 1998 to December 2005. Telephone interviews were conducted with 5952 (68% of eligible) mothers. Women were queried about intake of vitamin supplements in the 12 weeks before conception through delivery. A version of the Nurse's Health Study food frequency questionnaire was used to assess food sources. Eight percent of infants ( N?=?487) were preterm (<37 weeks). Compared with women who began intake of supplements with folic acid before pregnancy, those who began any time during pregnancy had an ~20% lowered risk of preterm delivery. Lower dietary intakes showed a modest increased risk of preterm delivery: odds ratios were 1.44 (1.01 to 2.04) for lowest quartile intake of folate and 1.27 (0.95 to 1.69) for lowest quartile intake of folic acid compared with the highest. Findings suggest some evidence that folates influenced risks; however, an interpretation of results was also consistent with no association between intake of folates and preterm delivery.