January 2007 – June 2007
Dunlevy LP, Chitty LS, Burren KA, Doudney K, Stojilkovic-Mikic T, Stanier P, Scott R, Copp AJ, Greene ND. Abnormal folate metabolism in foetuses affected by neural tube defects. Brain 2007 Apr;130(Pt 4):1043-9.
Abstract: Folic acid supplementation can prevent many cases of neural tube defects (NTDs), whereas suboptimal maternal folate status is a risk factor, suggesting that folate metabolism is a key determinant of susceptibility to NTDs. Despite extensive genetic analysis of folate cycle enzymes, and quantification of metabolites in maternal blood, neither the protective mechanism nor the relationship between maternal folate status and susceptibility are understood in most cases. In order to investigate potential abnormalities in folate metabolism in the embryo itself, we derived primary fibroblastic cell lines from foetuses affected by NTDs and subjected them to the dU suppression test, a sensitive metabolic test of folate metabolism. Significantly, a subset of NTD cases exhibited low scores in this test, indicative of abnormalities in folate cycling that may be causally linked to the defect. Susceptibility to NTDs may be increased by suppression of the methylation cycle, which is interlinked with the folate cycle. However, reduced efficacy in the dU suppression test was not associated with altered abundance of the methylation cycle intermediates, s-adenosylmethionine and s-adenosylhomocysteine, suggesting that a methylation cycle defect is unlikely to be responsible for the observed abnormality of folate metabolism. Genotyping of samples for known polymorphisms in genes encoding folate-associated enzymes did not reveal any correlation between specific genotypes and the observed abnormalities in folate metabolism. These data suggest that as yet unrecognized genetic variants result in embryonic abnormalities of folate cycling that may be causally related to NTDs
[We still do not clearly understand the link between folic acid and neural tube defects in the developing embryo. For instance, one study has suggested that the placenta may block the uptake of folic acid in some pregnancies. This study suggests that in some embryos, the handling of the folic acid molecule may be impaired. This is not the final word. The answer to this question will be critical in our ability to prevent more occurrences of neural tube defects.]
Llanos A, Hertrampf E, Cortes F, Pardo A, Grosse SD , Uauy R. Cost-effectiveness of a folic acid fortification program in Chile . Health Policy 2007 Mar 13.
Abstract: OBJECTIVE: Periconceptional intake of folic acid reduces the risk of neural tube defects (NTDs), a frequent birth defect that can cause significant infant mortality and disability. In Chile , fortification of wheat flour with folic acid has resulted in significant reduction in the risk of anencephaly and spina bifida. We investigated the cost-effectiveness implications of this policy. METHODS: We conducted an ex-post economic analysis of this intervention. Estimates of the effect of fortification in decreasing NTDs and deaths were derived from a prospective evaluation. The costs of fortification and provision of medical care to children with spina bifida in Chile were based on primary data collection. FINDINGS: The intervention costs per NTD case and infant death averted were I$ 1200 and 11,000, respectively. The cost per DALY averted was I$ 89, 0.8% of Chile ‘s GDP per capita. Taking into account averted costs of care, fortification resulted in net cost savings of I$ 2.3 million. CONCLUSION: Fortification of wheat flour with folic acid is a cost-effective intervention in Chile , a middle income country in the post-epidemiological transition. This result supports the continuation of the Chile fortification program and constitutes valuable information for policy makers in other countries to consider
[This article shows that not only does fortification of flour with folic acid prevent neural tube defects, but that the cost of fortification is outweighed by the benefits (at least in Chile ).]
Mosley BS, Hobbs CA , Flowers BS, Smith V, Robbins JM. Folic acid and the decline in neural tube defects in Arkansas . J.Ark.Med.Soc. 2007 Apr;103(10):247-50.
Abstract: Folic acid has been shown to reduce the risk of pregnancies affected by neural tube defects (NTDs) by as much as 70%. Cereal grains sold in the U.S. have been fortified with folic acid since 1998. The Arkansas Reproductive Health Monitoring System and the Arkansas Folic Acid Coalition have encouraged use of folic acid and monitored the impact of increased consumption of folic acid among Arkansans. NTDs in Arkansas have declined 40% since intervention programs were implemented. The greatest decline has been observed among white and Hispanic women. Efforts to encourage folic acid consumption should continue to target Arkansas women. NTDs include anencephaly and spina bifida. These birth defects result from incomplete closure of the fetal neural tube during the first month of pregnancy. Infants with anencephaly are born without all or most of their brain and die within a few days of life. Infants with spina bifida have varying degrees of impairment ranging from little noticeable disability to severe, lifelong disability. Folic acid, when taken in supplement form has been shown to reduce the risk of a pregnancy affected by a neural tube defect by as much as 70%. As a result of this finding, the U.S. Federal Drug Administration mandated that cereal grains sold in this country be fortified with at least 140 mcg of folic acid per 100 grams of grain by January 1, 1998. Prior to mandatory fortification, the March of Dimes and the U.S. Public Health Service released statements encouraging all women of reproductive age who are capable of becoming pregnant to take 400 mcg ‘of synthetic folic acid daily. The Arkansas Reproductive Health Monitoring System (ARHMS) has monitored rates of NTDs in Arkansas since 1980. ARHMS is the lead agency of the Arkansas Folic Acid Coalition whose mission is to encourage folic acid use among all Arkansas women of reproductive age. In this report, we summarize efforts by ARHMS and the Arkansas Folic Acid Coalition to increase the awareness and use of folic acid in Arkansas , show how the rates of NTDs in the state have declined over the past 10 years, and estimate the direct health care and productivity cost savings to Arkansans over that time
[This article documents the reduction in neural tube defects in Arkansas over the past 10 years. It generally is attributed to folic acid supplementation-both in wheat and during pregnancy.]
O’Rourke KM, Roddy ME. A multivitamin supplementation and education intervention as an effective means of increasing multivitamin use among postpartum women of Mexican origin. Paediatr.Perinat.Epidemiol. 2007 May;21(3):248-55.
Abstract: Postpartum Hispanic women in the USA are at elevated risk for neural tube defects in subsequent pregnancies from the combined effects of ethnicity, folate depletion from the prior pregnancy and lactation, and high parity rates with short inter-birth intervals. This study evaluated an education programme and distribution of a 3-month starter package of multivitamins among Hispanic women attending nutrition clinics for low-income women in El Paso , Texas . At 1-6 weeks postpartum, 329 subjects were selected to receive education only, multivitamins only, education and multivitamins, or no intervention. Multivariable regression obtained odds ratios (OR) and 95% confidence intervals [CI] to measure the association between intervention status and self-reported multivitamin use at least four times per week at 6 and 12 months postpartum, while controlling for potential confounding variables. Multivitamin distribution was related to consumption at both 6 months (OR = 3.5 [95% CI 1.1, 11.2]) and 12 months (OR = 6.5 [95% CI 1.5, 28.3]). Multivitamins plus education was most effective in increasing multivitamin use at both periods: 6 months (OR = 4.0 [95% CI 1.53, 11.7]) and 12 months (OR = 6.4 [95% CI 1.7, 24.2]). At enrolment, 66% of women regularly took vitamins, and approximately 35% took them at both 6 and 12 months postpartum. The education intervention alone was not associated with multivitamin use at either 6 months (OR = 0.79 [95% CI 0.3, 2.4]) or 12 months (OR = 3.1 [95% CI 0.8, 12.1]). Multivitamin use declines precipitously during postpartum at the time Hispanic women may be susceptible to a subsequent pregnancy. This study provides evidence that multivitamin starter packs sustain multivitamin usage up to 1 year postpartum for a specific high-risk group, but the effect of educational intervention alone should be further studied
[Folic acid and vitamin supplementation decrease the occurrence of neural tube defects. However, getting women to take vitamins is challenging. In this study packages of multivitamins were given to women after they had their babies in order to insure that subsequent pregnancies were covered. This study confirmed that education alone (without the startup packages) was not an effective strategy.]
Ray JG, Wyatt PR, Thompson MD, Vermeulen MJ, Meier C, Wong PY, Farrell SA, Cole DE. Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population. Epidemiology 2007 May;18(3):362-6.
Abstract: BACKGROUND: Low maternal vitamin B(12) status may be a risk factor for neural tube defects (NTDs). Prior studies used relatively insensitive measures of B(12), did not adjust for folate levels, and were conducted in countries without folic acid food fortification. In Canada , flour has been fortified with folic acid since mid-1997. METHODS: We completed a population-based case-control study in Ontario . We measured serum holotranscobalamin (holoTC), a sensitive indicator of B(12) status, at 15 to 20 weeks’ gestation. There were 89 women with an NTD and 422 unaffected pregnant controls. A low serum holoTC was defined as less than 55.3 pmol/L, the bottom quartile value in the controls. RESULTS: The geometric mean serum holoTC levels were 67.8 pmol/L in cases and 81.2 pmol/L in controls. There was a trend of increasing risk with lower levels of holoTC, reaching an adjusted odds ratio of 2.9 (95% confidence interval = 1.2-6.9) when comparing the lowest versus highest quartile. CONCLUSIONS: There was almost a tripling in the risk for NTD in the presence of low maternal B(12) status, measured by holoTC. The benefits of adding synthetic B(12) to current recommendations for periconceptional folic acid tablet supplements or folic-acid-fortified foods need to be considered. It remains to be determined what fraction of NTD cases in a universally folate-fortified environment might be prevented by higher periconceptional intake of B(12)
[There is some evidence that adding Vitamin B-12 to folic acid may further decrease the risk of developing a neural tube defect. In this study from Canada , lower levels of maternal Vitamin B-12 were linked with higher levels of neural tube defects. We still recommend healthy diets and multivitamins as well as folic acid in women just before and during pregnancy.]
Vilaiphan P, Suphapeetiporn K, Phupong V, Shotelersuk V. An exceptionally low percentage of Thai expectant mothers and medical personnel with folic acid knowledge and peri-conceptional consumption urges an urgent education program and/or food fortification. Int.J.Food Sci.Nutr. 2007 Jun;58(4):297-303.
Abstract: It has been widely accepted that peri-conceptional consumption of folic acid (FA) can prevent many congenital anomalies, including more than one-half of all neural tube defects. In several developed countries, educational campaigns and/or food fortification with FA have been launched, resulting in lower incidences of some anomalies. In Thailand , congenital anomalies preventable by FA are still an important public health problem. However, there have been no recommendations on the use of FA supplementations from the health authorities. In order to achieve a goal of reducing the diseases’ incidences, our initial effort is to assess knowledge and use of peri-conceptional FA. We conducted a questionnaire survey of 500 pregnant women and 500 child-bearing-age female medical personnel in the King Chulalongkorn Memorial Hospital from June 2003 through December 2003. Of the 383 pregnant women who completed the survey, 23.5% (90/383) knew that FA helped to prevent birth defects, 3.4% (13/383) knew that FA should be taken before pregnancy, and only 0.3% (1/383) reported taking FA before pregnancy. Among the 422 female medical personnel who completed the survey, 84.4% (356/422) knew that FA could prevent birth defects, whereas 40.0% (169/422) knew that FA should be taken prior to pregnancy. This study provided strong evidence that educational campaigns and/or food fortification are urgently needed
[Although folic acid has been shown to decrease the occurrence of neural tube defects, that knowledge is not widespread in many areas. In this study from Thailand , very few women took folic acid or knew that it should be started before you become pregnant.]
June 2007 – January 2008
Shaer CM, Chescheir N, Schulkin J. Myelomeningocele: a review of the epidemiology, genetics, risk factors for conception, prenatal diagnosis, and prognosis for affected individuals. Obstet.Gynecol.Surv. 2007 Jul;62(7):471-9.
Abstract: Although the use of folic acid before conception decreases the chance that a fetus will have an open neural tube defect, this condition still affects 0.5-1.0/1000 pregnancies in the United States . Results of a recent survey suggest that there are gaps in obstetrician-gynecologists’ knowledge of risk factors for conception, strategies for prenatal diagnosis, and prognosis for affected individuals. To address these gaps this paper reviews the epidemiology, genetics, risk factors for conception, prenatal diagnosis, and prognosis for affected individuals, presents current information, and makes suggestions for expanding obstetrician-gynecologists’ knowledge of myelomeningocele. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that despite a large amount of professional and public education on the use of folic acid in prevention of open neural tube defects (ONTDs) the incidence still affects 0.5-1.0/1000 pregnancies and recall that a recent survey conducted by the ACOG shows substantial misunderstanding and misinformation on major categories of neural tube birth defects.
[This article reviews what is known about folic acid and the prevention of neural tube defects. It was developed to help physicians in practice better understand the issues associated with the use of folic acid.]
January 2008 – June 2008
De WP, Van Allen MI, Lowry RB, Evans JA, Van den Hof MC, Crowley M, Tairou F, Uh SH, Sibbald B, Zimmer P, et al. Impact of folic acid food fortification on the birth prevalence of lipomyelomeningocele in Canada. Birth Defects Res.A Clin.Mol.Teratol. 2008 Feb;82(2):106-9.
Abstract: BACKGROUND: Recent studies reported no reduction in the frequency of lipomeningomyelocele (LMMC) in Hawaii and Nova Scotia after the implementation of a folic acid food fortification policy in 1998, while a marked reduction in the prevalence of other NTDs was observed. This study was performed to assess the prevalence of LMMC in Canada in relation to the timing of food fortification. METHODS: The study population included livebirths, stillbirths, and terminations of pregnancies because of fetal anomaly to women residing in seven Canadian provinces, from 1993 to 2002. In each province, the ascertainment of NTD cases relied on multiple sources, and in addition all medical charts were reviewed. The study period was divided into pre-, partial, and full fortification periods, based on results of red cell folate tests published in the literature. RESULTS: A total of 86 LMMC cases were recorded among approximately 1.9 million live births. The average birth prevalence rate was 0.05/1,000, ranging from a minimum of 0.01/1,000 in 2002 to a maximum of 0.08/1,000 in 1999. There was statistical heterogeneity between years (p = .01), but no pattern compatible with a decrease following fortification. Comparing the full fortification period with the prefortification period, there was a slight but not statistically significant decrease in LMMC birth prevalence. CONCLUSIONS: LMMC seems to be pathogenically distinct from myelomeningocele and more studies are needed to understand the embryologic mechanisms leading to this condition, and the environmental and genetic factors involved in its etiology.
[Folic acid can prevent many occurrences of neural tube defects, including spina bifida. However, this study documents that lipomeningomyelocele, which is a type of meningomyelocele associated with a fatty tumor (lipoma), may not be prevented by prenatal folic acid.]
Tedstone A, Browne M, Harrop L, Vernon C, Page V, Swindells J, Hayward W, Croft J, Harris F, Stockley L. Fortification of selected foodstuffs with folic acid in the UK : consumer research carried out to inform policy recommendations. J.Public Health (Oxf) 2008 Mar;30(1):23-9.
Abstract: BACKGROUND: The UK Food Standards Agency Board identified four options to increase folate intake in women of reproductive age in order to reduce the risk of neural tube defect (NTD) affected pregnancies; these ranged from continuing with current policy, to mandatory fortification of bread or flour with folic acid. In order to appraise these options, the agency carried out a consultation, and also commissioned four pieces of research. This paper provides detailed information about two of the research studies, which used qualitative research approaches to gather consumer evidence. METHODS: Study 1: This was carried out with people from a wide range of demographic backgrounds. A ‘reconvened group’ methodology was used, with five groups convened twice, in five geographical locations. In addition paired, in depth face-to-face interviews were conducted with female black and ethnic minority consumers. Study 2: This was carried out with young mothers living in deprived communities. The approach used for this study was in depth face-to-face interviews (n = 24). In addition, discussions were held in seven friendship groups. RESULTS: Study 1: only a minority of participants knew about a link between spina bifida and folic acid, and these tended to be women with young families. After the provision of some information about the causes and impacts of NTDs, the majority were in favour of action to tackle the issue. Support for mandatory fortification increased considerably during the study, and at the final discussion, this option was most preferred. Study 2: In this group, there was a fatalistic approach to pregnancy and to health. The women were less likely to change established habits if this required effort, money or doing something unfamiliar. They tended to actively avoid thinking about risks, by rationalizing them. Mandatory fortification was preferred by the majority of respondents. CONCLUSIONS: In this research, mandatory fortification was the preferred option. There were outstanding concerns about risk, and the maintenance of consumer choice, which would need to be addressed in policy recommendations.
[Although the link between folic acid and spina bifida is clear, getting pregnant women to take folic acid remains a problem. In this study of consumers in Great Britain , the researchers found that only a minority of women knew about a link between spina bifida and folic acid! Women preferred to have their food fortified with folic acid (rather than take it as a supplement), which would decrease their costs and efforts.]
January 2010 to January 2011
CDC Grand Rounds: additional opportunities to prevent neural tube defects with folic acid fortification. MMWR Morb Mortal Wkly Rep 2010 August 13;59(31):980-4.
Abstract: Neural tube defects (NTDs) are serious birth defects that result from the failure of the neural tube to close in the cranial region (anencephaly) or more caudally along the spine (spina bifida) by the 28th day of gestation. Infants born with anencephaly usually die within a few days of birth, and those with spina bifida have life-long disabilities with varying degrees of paralysis. Currently, identified risk factors for NTDs include a mother who previously had an NTD-affected pregnancy, maternal diabetes, obesity, hyperthermia, certain antiseizure medications, genetic variants, race/ethnicity, and nutrition (particularly folic acid insufficiency). In the United States, during 1995-1996, approximately 4,000 pregnancies were affected by an NTD. This number declined to 3,000 pregnancies in 1999-2000 after fortification of enriched cereal grain products with folic acid was mandated. Worldwide, in 1998, approximately 300,000 births were affected by an NTD.
[Although grains in the USA have been fortified with folic acid and obstetricians and other health care providers should be recommending folic acid periconceptually (before pregnancy and through the first trimester), many women still do not receive adequate amounts of folic acid to prevent an NTD.]
Alasfoor D, Elsayed MK, Mohammed AJ. Spina bifida and birth outcome before and after fortification of flour with iron and folic acid in Oman. East Mediterr Health J 2010 May;16(5):533-8.
Abstract: This paper presents the trend of spina bifida and other neural tube defects in Oman after the nationwide implementation of folate supplementation of pregnant women in 1990 and the fortification of wheat flour with iron and folate in 1996. The annual incidence of spina bifida fluctuated from 2.34 to 4.03 per 1000 deliveries between 1991 and 1996, but fell sharply to 2.11 per 1000 deliveries in 1997, after which the downward trend continued, reaching 0.29 per 1000 deliveries by 2006. The rate of other neural tube defects remained almost constant. The reduction in spina bifida rates in Oman could be linked to the start of flour fortification but not the supplementation programme.
[In Oman, a country in the Middle East, flour was fortified with folic acid in 1996. The birth prevalence of spina bifida fell significantly after that. This is another example of the effectiveness of folic acid fortification of food as part of a primary prevention strategy.]
Amarin ZO, Obeidat AZ. Effect of folic acid fortification on the incidence of neural tube defects. Paediatr Perinat Epidemiol 2010 July 1;24(4):349-51.
Abstract: In a few countries enriched cereal grains have been fortified with folic acid to reduce the incidence of neural tube defects. The objective of this study was to analyse the effect of folic acid fortified foods on the incidence of neural tube defects in live newborns at Princess Badea Teaching Hospital, in the north of Jordan, before and after the national food fortification with folic acid was implemented. For the 7-year period from 1 January 2000 to 31 December 2006, we retrospectively extracted the total number of births at Princess Badea Hospital, as well as the number of pregnancies affected by spina bifida and anencephaly, per 1000 births during the periods before (2000-01), during (2002-04) and after (2005-06) folic acid fortification of grain products, was implemented. Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD-10): anencephaly, encephalocele and spina bifida. A total of 78 subjects with neural tube defects were recorded among 61 447 births during the study period. The incidence of neural tube defects decreased from 1.85 per 1000 births before fortification [95% confidence interval (CI) 1.2, 2.4] to 1.07 per 1000 births during the fortification period [95% CI 0.7, 1.5], and 0.95 after full fortification [95% CI 0.5, 1.5], a 49% reduction. The difference between incidence of neural tube defects in the periods before and after food fortification with folic acid was statistically significant. We conclude that food fortification with folic acid was associated with a significant reduction in the rate of neural tube defects in north Jordan.
[This study from Jordan documents a 49% decrease in the birth prevalence of NTDs since the fortification of grain with folic acid.]
Carmichael SL, Yang W, Shaw GM. Periconceptional nutrient intakes and risks of neural tube defects in California. Birth Defects Res A Clin Mol Teratol 2010 August;88(8):670-8.
Abstract: BACKGROUND: This study investigated the association of neural tube defects (NTDs) with maternal periconceptional intake of folic acid-containing supplements and dietary nutrients, including folate, among deliveries that occurred after folic acid fortification in selected California counties. METHODS: The population-based case-control study included fetuses and live born infants with spina bifida (189) or anencephaly (141) and 625 nonmalformed, live born controls delivered from 1999 to 2003. Mothers reported supplement use during telephone interviews, which included a 107-item food frequency questionnaire. For dietary nutrients, intakes <25th, 25th to <75th (reference), and > or =75th percentile were compared, based on control distributions. RESULTS: After adjustment for potential confounders, any versus no supplement intake resulted in ORs of 0.8 (95% CI, 0.5-1.3) for anencephaly and 0.8 (95% CI, 0.6-1.2) for spina bifida. After stratification by maternal intake of vitamin supplements, most factors in the glycemic pathway were not associated with either NTD, with the exception of low levels of fructose and glucose that were significantly associated with anencephaly. Some nutrients that contribute to one-carbon metabolism showed lowered risks (folate, riboflavin, vitamins B(6) and B(12)); others did not (choline, methionine, zinc). Antioxidant nutrients tended to be associated with lowered risks (vitamins C, E, A, beta-carotene, lutein). CONCLUSIONS: Mothers’ intake of vitamin supplements was modestly if at all associated with a lowered risk of NTDs. Dietary intake of several nutrients contributing to one-carbon metabolism and oxidative stress were associated with reduced NTD risk.
[This study from California kept track of the diets of pregnant women and linked them with the occurrence of a neural tube defect (NTD). They found that most vitamin supplements were not associated with risk. A few food-based nutrients like folate, riboflavin, vitamins B6 and B12 were associated with slightly lower risk. The best advice to give women who are planning to get pregnant is (1) take folic acid periconceptionally [before the pregnancy occurs and through the first trimester], (2) eat a balanced diet that includes fresh fruits and vegetables, (3) don’t gain too much or tool little weight, and (4) take only those medications prescribed by the healthcare practitioner who is monitoring the pregnancy.]
Cech I, Burau KD. Serological differences in folate/vitamin B12 in pregnancies affected by neural tube defects. South Med J 2010 May;103(5):419-24.
Abstract: BACKGROUND: Laboratory evidence is presented of significant associations between reduced maternal serum folate and vitamin B12 levels and neural tube birth defects (NTD) compared to referents. METHODS: This was an incident case-control study. Cases of neural tube defects (including anencephaly and open spina bifida) diagnosed in residents within 100 miles of the US-Mexico border from January 1993 to October 2000 were eligible. Most cases were diagnosed in utero upon visits to clinics, obstetrical or genetic expert offices. Cases identified upon hospital admission or at delivery were also eligible. Cases identified after discharge were not. Controls were matched on geographic region, maternal age, race/ethnicity, gestational age, and type of health insurance (including none). RESULTS: Three hundred eighty-two border area residents (107 cases and 275 individually matched controls) provided biological specimens. Median folate concentrations for case mothers were 36% lower than controls (9.8 ng/mL vs. 15 ng/mL). Maternal serum folate concentrations in quartiles above 9.5 ng/mL indicated significantly reduced risk (OR = 0.4, OR = 0.3, and OR = 0.2). Likewise, the risk for NTD decreased (OR = 0.4, OR = 0.3, and OR = 0.2) in quartiles of sera B12 concentrations above 246 pg/mL. CONCLUSIONS: Physician attention is invited to significantly lower concentrations of serum folate and vitamin B12 in women with NTD-affected pregnancies. This study assayed sera samples from women while still pregnant or immediately after delivery. The confounding effect of reduced folate and B12 levels with other biological and chemical exposures will be addressed in subsequent communications.
[In this study low levels of Vitamin B12 as well as folic acid were linked with the birth of a baby with a neural tube defect. Whether or not supplementation during pregnancy with B12 (at levels higher than those found in prenatal vitamins) will make a difference is uncertain.]
Claude KM, Juvenal KL, Hawkes M. Applying a knowledge-to-action framework for primary prevention of spina bifida in tropical Africa. Matern Child Nutr 2010 November 9.
Abstract: Maternal periconceptual folate supplementation reduces the incidence of neural tube defects; however, in settings where population-level food fortification is not available, it is not clear how best to promote this prevention strategy. Guided by a knowledge-to-action methodology, we used mixed quantitative and qualitative methods to define the local disease burden, then designed, implemented and evaluated a culturally tailored educational intervention in eastern Democratic Republic of Congo, where resource limitations and threats to human security contribute to restricted capacity for the prevention and management of congenital malformations. A descriptive case series of 27 patients undergoing surgery for spina bifida demonstrated a short-term mortality of 15% and long-term disability in survivors. A survey of knowledge, attitudes and practices demonstrated a low level of folate awareness (53%) among women of reproductive age. Focus group discussions revealed exotic aetiologic views, significant gender issues and several barriers to folate use. A culturally tailored radio broadcast and an educational video were designed and produced locally based on qualitative and quantitative findings. Evaluation of the video documented high levels of viewer satisfaction and unequivocal knowledge gain (P
[In this study from the Democratic Republic of Congo children born with spina bifida had a very high mortality of 15% as well as long term disability. The authors found that knowledge of folic acid prevention was sorely lacking. They designed a culturally tailored radio broadcast and an educational video to promote knowledge and increase the use of folic acid. Time will tell with regard to its effectiveness.]
Jentink J, Bakker MK, Nijenhuis CM, Wilffert B, de Jong-van den Berg LT. Does folic acid use decrease the risk for spina bifida after in utero exposure to valproic acid? Pharmacoepidemiol Drug Saf 2010 August;19(8):803-7.
Abstract: PURPOSE: Women with child wish are advised to take folic acid supplements to reduce the risk for spina bifida. However, there is less evidence for this protective effect in women using valproic acid (VPA). We investigated the effect of folic acid in women exposed to VPA in the first trimester of pregnancy. METHODS: A case-control study was performed with data from a population-based registry of congenital malformations. Our cases were spina bifida registrations and all other malformed registrations (excluding folic acid sensitive malformations) were used as controls. RESULTS: The ORs for the effect of correct folic acid use were calculated among antiepileptic drug (AED) unexposed pregnancies 0.5 [95%CI: 0.3-0.7] and among VPA exposed pregnancies 1.0 [95%CI: 0.1-7.6]. DISCUSSION: Due to power-reasons, we cannot conclude that folic acid has no effect on the risk for spina bifida among VPA exposed pregnancies. Although for AED unexposed pregnancies we found a decreased risk. Results from (animal) studies support a biologically plausible association between VPA, folic acid and spina bifida. While folic acid might not be able to reduce the risk for lower spina bifida lesions caused by VPA, the use of folic acid might be important to reduce the risk for higher, folic acid sensitive spina bifida lesions. Further research is needed to get more insight in the most effective form and dose of FA in women that use VPA to reduce the risk for (higher forms of) spina bifida.
[Mothers who take valproic acid during pregnancy are more likely to have babies with neural tube defects (NTDs) including spina bifida. Mothers who take folic acid during pregnancy are less likely to have NTDs. It is, however, not clear whether taking folic acid will decrease the adverse effects of valproic acid. Unfortunately, this study, which tried to answer that question, was unable to do so because the number of patients was too small.]
Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, de Jong-van den Berg LT. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 2010 June 10;362(23):2185-93.
Abstract: BACKGROUND: The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited. METHODS: We first combined data from eight published cohort studies (1565 pregnancies in which the women were exposed to valproic acid, among which 118 major malformations were observed) and identified 14 malformations that were significantly more common among the offspring of women who had received valproic acid during the first trimester. We then assessed the associations between use of valproic acid during the first trimester and these 14 malformations by performing a case-control study with the use of the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic-study database, which is derived from population-based congenital-anomaly registries. Registrations (i.e., pregnancy outcomes with malformations included in EUROCAT) with any of these 14 malformations were compared with two control groups, one consisting of infants with malformations not previously linked to valproic acid use (control group 1), and one consisting of infants with chromosomal abnormalities (control group 2). The data set included 98,075 live births, stillbirths, or terminations with malformations among 3.8 million births in 14 European countries from 1995 through 2005. RESULTS: Exposure to valproic acid monotherapy was recorded for a total of 180 registrations, with 122 registrations in the case group, 45 in control group 1, and 13 in control group 2. As compared with no use of an antiepileptic drug during the first trimester (control group 1), use of valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations under consideration; the adjusted odds ratios were as follows: spina bifida, 12.7 (95% confidence interval [CI], 7.7 to 20.7); atrial septal defect, 2.5 (95% CI, 1.4 to 4.4); cleft palate, 5.2 (95% CI, 2.8 to 9.9); hypospadias, 4.8 (95% CI, 2.9 to 8.1); polydactyly, 2.2 (95% CI, 1.0 to 4.5); and craniosynostosis, 6.8 (95% CI, 1.8 to 18.8). Results for exposure to valproic acid were similar to results for exposure to other antiepileptic drugs. CONCLUSIONS: The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs.
[This study found that mothers who took valproic acid during the first trimester of pregnancy had a 12-fold increased chance of having a baby with spina bifida.]
Lopez-Camelo JS, Castilla EE, Orioli IM. Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries. Am J Med Genet A 2010 October;152A(10):2444-58.
Abstract: The aim of the present investigation was to search for a reduction in birth prevalence estimates of 52 selected types of congenital anomalies, associated with folic acid fortification programs in Chile, Argentina, and Brazil. The material included 3,347,559 total births in 77 hospitals of the three countries during the 1982-2007 period: 596,704 births (17 hospitals) in Chile, 1,643,341 (41 hospitals) in Argentina, and 1,107,514 (19 hospitals) in Brazil. We compared pre- and post-fortification rates within each hospital and the resulting Prevalence Rate Ratios (PRRs) were pooled by country. Statistically significant reductions in birth prevalence estimates after fortification were observed for neural tube defects (NTDs), septal heart defects, transverse limb deficiencies, and subluxation of the hip. However, only the reduction of NTDs appeared to be associated with folic acid fortification and not due to other factors, because of its consistency among the three countries, as well as with previously published reports, and its strong statistical significance. Among the NTDs, the maximum prevalence reduction was observed for isolated cephalic (cervical-thoracic) spina bifida, followed by caudal (lumbo-sacral) spina bifida, anencephaly, and cephalocele. This observation suggests etiologic and pathogenetic heterogeneity among different levels of spina bifida, as well as among different NTD subtypes. We concluded that food fortification with folic acid prevents NTDs but not other types of congenital anomalies.
[This study from South America documents the reduction of neural tube defects related to the fortification of food with folic acid. The birth prevalences of the other birth defects that they studied were not affected.]
Prue CE, Hamner HC, Flores AL. Effects of folic acid awareness on knowledge and consumption for the prevention of birth defects among Hispanic women in several U.S. Communities. J Womens Health (Larchmt ) 2010 April;19(4):689-98.
Abstract: BACKGROUND: The neural tube defects (NTDs) anencephaly and spina bifida, are serious birth defects of the brain and spine that affect about 3000 pregnancies per year in the United States. Research has found a strong link between periconceptional folic acid consumption and NTD prevention. METHODS: Because Hispanic women have higher rates of NTD-affected births, targeted folic acid promotion efforts were conducted in several major cities from 1999 to 2002. Efforts included paid and unpaid placements of Spanish language public service announcements (PSAs) and community-level education through the use of promotoras. Analyses focused on whether or not women’s reported awareness of folic acid, regardless of promotion type, impacted their knowledge or behavior. RESULTS AND CONCLUSIONS: Women who reported awareness of folic acid had greater folic acid knowledge and use of vitamins containing folic acid than those not aware. Analyses also examined the use of vitamins containing folic acid by pregnancy intention among women who reported awareness of folic acid. The results were varied. Pregnancy wanters were most likely to use vitamins containing folic acid daily. For this group, however, awareness did not play as large a role in whether they reported consuming a vitamin containing folic acid or not, as it did for pregnancy waiters and avoiders.
[This study evaluated Latina women regarding folic acid knowledge and use after folic acid promotion efforts targeted specifically to Latina women were conducted in several major cities from 1999 to 2002. They divided the women into three categories: Pregnancy Wanters (those who planned to become pregnant in the next year), Pregnancy Waiters (those who planned to become pregnant some time in the future but not in the next year), and Pregnancy Avoiders (those who planned not to become pregnant at any time in the future). Pregnancy wanters were most likely to take a vitamin containing folic acid. However, for this group, awareness of folic acid did not seem to be as important a factor as for the pregnancy waiters and avoiders (who were less likely to be taking folic acid). These findings are somewhat surprising. Yet efforts to increase the use of folic acid need to be continued, including for Spanish-speaking women.]