Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh.

BACKGROUND: Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neural tube defect (myelomeningocele) among a highly exposed population in rural Bangladesh. METHODS: We performed a case-control study that recruited physician-confirmed cases from community health clinics served by Dhaka Community Hospital in Bangladesh, as well as local health facilities that treat children with myelomeningocele. Controls were selected from pregnancy registries in the same areas. Maternal arsenic exposure was estimated from drinking water samples taken from wells used during the first trimester of pregnancy. Periconceptional folic acid use was ascertained by self-report, and maternal folate status was further assessed by plasma folate levels measured at the time of the study visit. RESULTS: Fifty-seven cases of myelomeningocele were identified along with 55 controls. A significant interaction was observed between drinking water inorganic arsenic and periconceptional folic acid use. As drinking water inorganic arsenic concentrations increased from 1 to 25 µg/L, the estimated protective effect of folic acid use declined (OR 0.22 to 1.03), and was not protective at higher concentrations of arsenic. No main effect of arsenic exposure on myelomeningocele risk was identified. CONCLUSIONS: Our study found a significant interaction between drinking water inorganic arsenic concentration from wells used during the first trimester of pregnancy and reported intake of periconceptional folic acid supplements. Results suggest that environmental arsenic exposure reduces the effectiveness of folic acid supplementation in preventing myelomeningocele.

Prevention of myelomeningocele: African perspectives.

BACKGROUND: The prevention of neural tube defects (NTDs) is now an issue of major public health concern. Myelomeningocele, the most common NTD, often results in severe disabilities and may be life threatening. In Africa, there is little awareness of the NTDs, and most African countries lag behind in the global efforts at preventing them. PURPOSE: Following a review of global literature, we discuss the burden of myelomeningocele on the society and the current state of its prevention with an emphasis on Africa within the global context. The realization that folate supplementation reduces the occurrence of NTDs by as much as 85 % offers an opportunity to promote global reduction in the incidence of NTDs through (1) effective folate supplementation strategies combined with (2) secondary prevention using prenatal detection and termination of NTD pregnancies within respective national legal frameworks. We call attention to the poor state of understanding of NTDs in Africa and the alarming rarity of policies to prevent the condition in the continent. CONCLUSIONS: The understanding of the contributions of folate deficiency to the causation of NTDs has enabled appropriate, though still inadequate, preventive measures to be taken in several countries. We call on African governments and the international community to rapidly promote policies aimed at making fortification of wheat (and or other substitute staple foods) with folic acid universally available.

Risk factors associated with lipomyelomeningocele: a case-control study.

BACKGROUND: In general, it seems that both genetic and environmental factors play important roles in the induction of neural tube defects. Lipomyelomeningocele (LipoMMC) is a rather common type of closed neural tube defect, but only limited studies have investigated the potential risk factors of this anomaly. Therefore, the purpose of this case-control study was to investigate the risk factors involved in LipoMMC formation. MATERIAL AND METHOD: Various risk factors were evaluated in 35 children between 1 month and 10 years of age with LipoMMC in a hospital-based case-control study. The 2 control arms consisted of 35 children with myelomeningocele (MMC group) and 35 children with congenital anomalies other than central nervous system problems (control group). All groups were matched for age and visited the same hospital. A structured questionnaire was used for the collection of all data, including the mothers' weight and height during pregnancy, education, reproductive history, previous abortions, and socioeconomic status, as well as the parents' consanguinity and family history of the same anomalies. RESULTS: Univariate analysis of the children with LipoMMC compared to the control group showed that the use of periconceptional folic acid supplementation was significantly lower in the MMC and LipoMMC groups compared to the control group. In addition, comparison of the MMC and control groups revealed statistically significant differences regarding the use of folic acid and maternal obesity. In multivariate analysis, use of folic acid in the periconceptional period and during the first trimester was an independent risk factor for LipoMMC and MMC. Furthermore, maternal obesity was a significantly positive risk factor for MMC. CONCLUSION: The probable risk factors for LipoMMC were investigated in this case-control study. Consumption of folic acid in the periconceptional period and during the first trimester is an independent protective factor against LipoMMC. It seems that larger studies are needed to examine other possible risk factors.

Decreased incidence of myelomeningocele at birth: effect of folic acid recommendations or prenatal diagnostics?

PURPOSE: In Denmark, prevention to reduce the spina bifida birth rate has focused on two areas: folic acid supplementation (1997) and changes in the national ultrasonography screening programme (2004). Myelomeningocele (MMC) is the most severe malformation among the spina bifidas. Taking into consideration the potential negative effect of high-dose folic acid consumption, we found a need to look into the effectiveness of these two strategies in our complete MMC population. METHODS: All spina bifida patients born in the western part of Denmark are differentiated into proper subgroups based on MR imaging, giving us a unique chance to study a true MMC population. The total number of the group of MMC children since 1983 is 121. One hundred and eight (89%) parents answered a questionnaire. RESULTS: Following the changes in the prenatal ultrasonography screening programme in 2004, a significant decline of 60% live birth MMC per year was noted, incidence rate ratio (IRR) = 40% (22-73%), p = 0.3%. We found no change in MMC birth rate after introduction of folic acid supplementation, IRR = 121% (81-181%), p = 36%. CONCLUSION: Our findings demonstrate no effect of folic acid recommendation due to lack of compliance among women of reproductive age in Denmark. However, we found an improved early detection rate of prenatal MMC by high-quality ultrasonography. Subsequent early termination of pregnancy has led to a significant reduction of birth rate of babies with MMC.

[Prenatal techniques to prevent central nervous system malformations in the surgically induced model of myelomeningocele]. / El modelo de mielomeningocele en oveja presenta alteraciones cerebrales semejantes a las del humano y estas pueden ser prevenidas mediante cirugía fetal abierta.

AIM: To describe central nervous system malformations in the surgically induced model of Myelomeningocele (MMC) and their prevention using different prenatal treatments. METHODS: MMC was surgically created in 33 fetal lambs. Fifteen did not undergo fetal repair (group A). Of the lambs that did undergo repair, 10 were repaired with open two layer surgical closure (group B), 5 with fetoscopic coverage using bioglue (group C) and 3 fetoscopically using a patch (group D). All procedures were recorded and lamb brains and spinal cords were examined grossly and microscopically in coronal sections for structural organization anomalies. Histopathological changes were assessed using HE and S-100 neural marker. RESULTS: Hydrocephalus, Arnold-Chiari type II (AC-II) malformation and some neuronal migration disorders were observed in group A. Brains from group B and D were not hydrocephalic and had neither cell migration disorders nor hindbrain herniation. Group C presents mild degrees of hydrocephalus and AC-II. In group C lumbar lesion was covered by fibrous tissue. CONCLUSIONS: Some of the central nervous system abnormalities observed in human disease are present in the surgically induced model of MMC. In this model avoidance of fluid drainage using open fetal surgery limits malformation severity.

Understanding the Mothers of Children with Spina Bifida and Hydrocephalus in Tanzania.

OBJECTIVE: To identify if there are cultural, medical, educational, economic, nutritional and geographic barriers to the prevention and treatment of spina bifida and hydrocephalus. METHODS: The mothers of infants with spina bifida and hydrocephalus admitted to Muhimbilli Orthopaedic Institute, Dar Es Salaam, Tanzania, between 2013 and 2014 were asked to complete a questionnaire. A total of 299 infants were identified: 65 with myelomeningoceles, 19 with encephaloceles, and 215 with isolated hydrocephalus. The questionnaire was completed by 294 of the mothers. RESULTS: There was a high variation in the geographic origin of the mothers. Approximately 85% traveled from outside of Dar Es Salaam. The mean age was 29 (15-45) years old with a parity of 3 (1-10). The rates of consanguinity, obesity, antiepileptic medication, HIV seropositivity, and family history were 2%, 13%, 0%, 2%, and 2%, respectively. A maize-based diet was found in 84%, and only 3% of woman took folic acid supplementation, despite 61% of mothers stating that they wished to conceive another baby. Unemployment was high (77%), a low level of education was common (76% not attended any school or obtaining a primary level only), and 20% were single mothers. Hospital only was the preferred method of treatment for 94% of the mothers, and 85% of the babies were born in a hospital. CONCLUSIONS: Our study highlights some of the cultural, educational, geographic, nutritional, and economic difficulties in the prevention and management of spina bifida and hydrocephalus in Tanzania.

Myelomeningocoele in dizygotic twins.

BACKGROUND: Periconceptional use of folic acid can reduce a woman's risk of having a baby with a neural-tube defect and other congenital abnormalities. METHOD: Case reports of babies OO both males, who were delivered at term by emergency caesarean section by a 21 year old woman. At birth, both twins had neural tube defects, bilateral talipes equinovarusdeformity, bladder and bowel dysfunction. Twin one in addition had hydrocephalus and a ventriculoseptal heart defect (VSD). CONCLUSION: We advocate comprehensive neural tube defect (NTD) surveillance, a folic acidsupplementation program for high-risk women who have had a NTD-affectedpregnancy and a national folic acid education campaign for allwomen of reproductive age preconceptionally.

Impact of folic acid food fortification on the birth prevalence of lipomyelomeningocele in Canada.

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.

Myelomeningocele: a review of the epidemiology, genetics, risk factors for conception, prenatal diagnosis, and prognosis for affected individuals.

UNLABELLED: 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.

Prenatal folic acid use associated with decreased risk of myelomeningocele: A case-control study offers further support for folic acid fortification in Bangladesh.

Neural tube defects contribute to severe morbidity and mortality in children and adults; however, they are largely preventable through maternal intake of folic acid before and during early pregnancy. We examined the association between maternal prenatal folic acid supplement intake and risk of myelomeningocele (a severe and common type of neural tube defect) in the offspring. We performed secondary analysis using data from a case-control study conducted at Dhaka Community Hospital, Bangladesh between April and November of 2013. Cases and controls included children with and without myelomeningocele, respectively, and their mothers. Cases were identified from local hospitals and rural health clinics served by Dhaka Community Hospital. Controls were selected from pregnancy registries located in the same region as the cases, and matched (1:1) to cases by age and sex. Myelomeningocele in the offspring was confirmed by a pediatrician with expertise in classifying neural tube defects. Maternal prenatal folic acid supplement intake was the main exposure of interest. We estimated crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression analysis. There were 53 pairs of matched cases and controls in our study. Overall, 51% of case mothers reported using folic acid supplements during pregnancy compared to 72% of control mothers (p = 0.03). Median plasma folate concentrations at the time of study visit were 2.79 ng/mL and 2.86 ng/mL among case and control mothers, respectively (p = 0.85). Maternal prenatal folic acid use significantly decreased the odds of myelomeningocele in the offspring (unadjusted OR = 0.42, 95% CI = 0.18-0.96). The association was slightly attenuated after adjusting for maternal age at the time of pregnancy (adjusted OR = 0.43, 95% CI = 0.18-1.02). Our study confirms the protective association between maternal prenatal folic acid supplement use and myelomeningocele among children born in Bangladesh. Our findings point to an overall low folic acid supplement use and low plasma folate concentrations among women of reproductive age in Bangladesh. Mandatory fortification of staple foods with folic acid can address low folate status among women of child-bearing age, and prevent child morbidity and mortality associated with myelomeningocele in Bangladesh.

Research: Prevalence of neural tube defects Khartoum, Sudan August 2014-July 2015.

BACKGROUND: Neural tube defects (NTDs) are birth defects that results from failure of the neural tube to develop properly during early pregnancy. METHODS: We studied the prevalence of neural tube defects in newborns admitted to the NICU in Soba University and Omdurman Maternity hospitals, during the period 1st August 2014 to 31st July 2015. A cross-sectional hospital based study, involved all newborns with any type of neural tube defect admitted to the NICU in the study area during the study period. Data was collected using a questionnaire reviewing the medical, social history and clinical examination. RESULTS: Out of the 36,785 delivered newborns during the study period, the prevalence of NTDs was 2.8:1000. Females were 56 (54.4%) predominated males 47 (45.6%). History of neural tube defects was found in 11 (10.7%) of the affected newborns siblings. Sixty-eight (66%) of the studied mothers received folic acid during pregnancy with the current child, of those who received folic acid 66 (97.1%) started folic acid after conception, 36 (54.5%) in the first trimester and 39 (57.4%) had no regular intake of the folic acid. The types of NTDs include myelomeningocele 49 (47.6%), anencephaly 18 (17.5%), encephalocele 14 (13.6%), myelomeningocele and hydrocephalus 11 (10.7%) and meningocele 8 (7.8%). CONCLUSION: The prevalence of neural tube defects is 2.8:1000. Myelomeningocele is the commonest encountered NTD. The use of preconception folic acid needs to be advocated.

Spina bifida.

Spina bifida is a birth defect in which the vertebral column is open, often with spinal cord involvement. The most clinically significant subtype is myelomeningocele (open spina bifida), which is a condition characterized by failure of the lumbosacral spinal neural tube to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with the level of the lesion. Occurring in approximately 1 per 1,000 births worldwide, myelomeningocele is one of the most common congenital malformations, but its cause is largely unknown. The genetic component is estimated at 60-70%, but few causative genes have been identified to date, despite much information from mouse models. Non-genetic maternal risk factors include reduced folate intake, anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by periconceptional supplementation with folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is achieved by ultrasonography, enabling women to seek termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II brain malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of myelomeningocele has been associated with improved early neurological outcome compared with postnatal operation. Myelomeningocele affects quality of life during childhood, adolescence and adulthood, posing a challenge for individuals, families and society as a whole. For an illustrated summary of this Primer, visit: http://go.nature.com/fK9XNa.

Ineffectiveness of dietary folic acid supplementation on the incidence of lipomyelomeningocele: pathogenetic implications.

OBJECT: Periconceptual folic acid supplementation is effective in myelomeningocele prevention. The relationship between folic acid and lipomyelomeningocele (LMM) and the overall incidence of this occult form of spina bifida has never been studied. The objectives of this study were to determine the impact of dietary folic acid supplementation on the incidence of LMM and to measure its overall incidence. METHODS: In a retrospective population-based study the authors calculated the incidence of LMM in Nova Scotia between 1985 and 2001. Because of changes in public policy during this period, there are three intervals defined in relation to the treatment of the food supply with folic acid: 1) prior to folic acid fortification (1985-1994); 2) postsupplementation but prefortification (1995-1998); and 3) postfortification. The overall incidence of LMM in Nova Scotia between 1985 and 2001 was 16 per 100,000 live births or one case per 6121 live births. Its incidence between 1985 and 1994 was 15 per 100,000 live births, and between 1995 and 1998 it was 12 per 100.000 live births (relative risk [RR] 0.82, 95% confidence interval [CI] 0.31-2.22; p = 0.7). Between 1999 and 2001, the incidence of LMM was 29 per 100,000 live births, which was not significantly different from that between 1995 and 1998 (RR 2.41. 95% CI 0.79-7.36; p = 0.11) or between 1985 and 1994 (RR 1.98, 95% CI 0.86-4.56; p = 0.1). CONCLUSIONS: The overall incidence of LMM between 1985 and 2001 in Nova Scotia was 16 per 100,000 live births and has not been reduced by dietary folic acid supplementation. This finding provides epidemiological evidence that the embryogenesis of LMM is fundamentally different from that of myelomeningocele.

Myelomeningocele: the medical aspects.

Recent advances in treatment and care for children with myelomeningocele offer new hope for both survival and success. Achieving these goals requires careful attention to both technical areas and to the basics of health care and human interactions. The latter area is one for which the primary care physician should be ideally suited. Although specialty care by neurosurgeons, orthopedists, and urologists is necessary, none of these specialists offer the broad scope and understanding of the child and the family that the primary care physician should be able to provide. Managing a child with this disorder is challenging, can be satisfying, and appears to be cost effective. The goals, however, must be clearly visualized and accepted, and the value of health maintenance and care rather than cure must be recognized.

Myelomeningocele: current concepts of management.

Care of an infant with myelomeningocele may begin with prenatal diagnosis, which allows for optimal perinatal care. In the newborn period, the decision for surgical treatment of myelomeningocele must be made promptly, but only after rational discussion with, and consent by, the affected child's family. Advances in newborn care and in surgical techniques, and an improved ability to both detect and treat hydrocephalus and CSF infections, have resulted in better outcomes for these children. Recent insights into the pathogenesis of myelomeningocele suggest that prevention of most of these congenital malformations may be possible through periconceptual vitamin supplementation.

Reduction in neural injury with earlier delivery in a mouse model of congenital myelomeningocele: laboratory investigation.

OBJECT: The authors undertook this study to assess the effect of preterm delivery with respect to neural protection in a congenital myelomeningocele (MMC) mouse model. METHODS: After confirmation of pregnancy in 15 female mice, a congenital MMC model was produced by administration of retinoic acid on the 7th day of gestation. The pregnant mice underwent cesarean sections on Days 15 (n = 5, Group E15), 17 (n = 5, Group E17), and 19 (n = 5, Group E19). Histological analyses were conducted on the lumbar defect and on the craniocervical junction in all fetuses with MMC. RESULTS: Fetuses in Group E19 showed the most significant injury to neural tissue of the spinal cord at the MMC area followed by those in Group E17, with Group E15 being the least affected. All groups exhibited a degree of Chiari malformation; Group E19 was the most affected, followed by Group E17, and Group E15 was the least affected. CONCLUSIONS: Development of both Chiari malformation and exposed spinal cord injury are progressive during gestation. Preterm delivery in this mouse model of congenital MMC may minimize the degree of injury to the spinal cord neural tissue and the degree of Chiari malformation.