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Lancet (London, England) Nov 2021
Topics: Folic Acid; Humans; Neural Tube Defects; United Kingdom
PubMed: 34838169
DOI: 10.1016/S0140-6736(21)02447-8 -
Birth Defects Research Jan 2021Mandatory folic acid fortification of staples is a proven intervention to prevent spina bifida and anencephaly, two life-threatening and disabling neural tube defects....
BACKGROUND
Mandatory folic acid fortification of staples is a proven intervention to prevent spina bifida and anencephaly, two life-threatening and disabling neural tube defects. We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) prevented through mandatory folic acid fortification of wheat and/or maize flour in 2019.
METHODS
Using data from the Global Fortification Data Exchange, we identified countries with mandatory fortification policies that required at least 1.0 ppm folic acid be added to wheat and/or maize flour and had information on percentage of industrially milled flour that is fortified. We built FAP SBA prevention models assuming mandatory folic acid fortification at 200 μg/day of folic acid fully protects against FAP SBA and would lower the prevalence neural tube defects to 0.5 per 1,000 live births.
RESULTS
In 2019, 56 countries met our criteria for mandatory folic acid fortification of wheat (n = 56 countries) and/or maize (n = 15 countries) flour and with complete data for our modeling. Overall, our prevention model estimated that 65,380 FAP SBA cases were prevented in 2019 through folic acid fortification of wheat and/or maize flour. We estimated the current global prevention proportion of all preventable FAP SBA cases worldwide to be at 23% of total possible prevention.
CONCLUSION
Global prevention efforts for FAP SBA are slow and have stalled. Mandatory fortification should be urgently implemented in all countries to prevent epidemics of FAP SBA, and to achieve health-related Sustainable Development Goals for year 2030 by reducing child mortality due to preventable FAP SBA.
Topics: Anencephaly; Child; Folic Acid; Food, Fortified; Humans; Neural Tube Defects; Spinal Dysraphism
PubMed: 33124747
DOI: 10.1002/bdr2.1835 -
Annals of the New York Academy of... Sep 2022Neural tube defects (NTDs) are a heterogeneous set of malformations attributed to disruption in normal neural tube closure during early embryogenesis. An in-depth... (Review)
Review
Neural tube defects (NTDs) are a heterogeneous set of malformations attributed to disruption in normal neural tube closure during early embryogenesis. An in-depth understanding of NTD etiology and mechanisms remains elusive, however. Among the proposed mechanisms, epigenetic changes are thought to play an important role in the formation of NTDs. Epigenomics covers a wide spectrum of genomic DNA sequence modifications that can be investigated via high-throughput techniques. Recent advances in epigenomic technologies have enabled epigenetic studies of congenital malformations and facilitated the integration of big data into the understanding of NTDs. Herein, we review clinical epigenomic data that focuses on DNA methylation, histone modification, and miRNA alterations in human neural tissues, placental tissues, and leukocytes to explore potential mechanisms by which candidate genes affect human NTD pathogenesis. We discuss the links between epigenomics and gene regulatory mechanisms, and the effects of epigenetic alterations in human tissues on neural tube closure.
Topics: DNA Methylation; Epigenomics; Female; Humans; MicroRNAs; Neural Tube Defects; Placenta; Pregnancy
PubMed: 35666948
DOI: 10.1111/nyas.14802 -
WIREs Mechanisms of Disease Sep 2022Neural tube closure (NTC) is crucial for proper development of the brain and spinal cord and requires precise morphogenesis from a sheet of cells to an intact... (Review)
Review
Neural tube closure (NTC) is crucial for proper development of the brain and spinal cord and requires precise morphogenesis from a sheet of cells to an intact three-dimensional structure. NTC is dependent on successful regulation of hundreds of genes, a myriad of signaling pathways, concentration gradients, and is influenced by epigenetic and environmental cues. Failure of NTC is termed a neural tube defect (NTD) and is a leading class of congenital defects in the United States and worldwide. Though NTDs are all defined as incomplete closure of the neural tube, the pathogenesis of an NTD determines the type, severity, positioning, and accompanying phenotypes. In this review, we survey pathogenesis of NTDs relating to disruption of cellular processes arising from genetic mutations, altered epigenetic regulation, and environmental influences by micronutrients and maternal condition. This article is categorized under: Congenital Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Stem Cells and Development.
Topics: Epigenesis, Genetic; Folic Acid; Humans; Neural Tube; Neural Tube Defects; Neurulation
PubMed: 35504597
DOI: 10.1002/wsbm.1559 -
Birth Defects Research Nov 2023Fetal deaths are a major source of information on the epidemiology of neural tube defects (NTDs; anencephaly and myelomeningocele). We analyzed NTDs prevalence and...
BACKGROUND
Fetal deaths are a major source of information on the epidemiology of neural tube defects (NTDs; anencephaly and myelomeningocele). We analyzed NTDs prevalence and secular trend using fetal death records between 1994 and 2019 in Argentina.
MATERIALS AND METHODS
Data were obtained from the Department of Statistics and Information of the Ministry of Health (DEIS). Using the number of fetal deaths due to anencephaly and myelomeningocele, we estimated the proportion of all fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) during pre- and post-fortification period in Argentina. We also estimated the ratio of fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) to 10,000 live births. Secular trend in the outcomes was analyzed using a Poisson model and Joinpoint regression analysis.
RESULTS
In the entire period analyzed, the NTD proportion on fetal deaths was 1.32. In 1994, NTDs accounted for 34.7% of congenital malformations fetal deaths (CM) and 1.7% of all fetal deaths, whereas in 2019, these percentages were 9.4% and 0.5%, respectively. NTDs present a negative secular trend (p < .05). The risk of fetal death due to anencephaly and myelomeningocele decreases between 2005 and 2019 by 67% and 51% respectively (p < .05) in comparison to the period between 1994 and 2004 before the effective fortification of wheat flour used in the food industry destined for the domestic market.
DISCUSSION AND CONCLUSION
We found a significant decrease in the risk of all fetal deaths due to NTDs, particularly anencephaly, in Argentina over the study period, with most reduction observed during the mandatory flour fortification era (introduced in Argentina in 2002). The inclusion of fetal deaths in NTD surveillance, coupled or uncoupled with other pregnancy outcomes, is essential for monitoring preventive supplementation measures.
Topics: Pregnancy; Female; Humans; Anencephaly; Folic Acid; Meningomyelocele; Prevalence; Flour; Argentina; Triticum; Neural Tube Defects; Fetal Death
PubMed: 37715338
DOI: 10.1002/bdr2.2248 -
Child's Nervous System : ChNS :... Apr 2021To date, the description of the natural course of concurrent tethered cord syndrome with a low-lying conus medullaris and split cord malformation is lacking in the... (Review)
Review
PURPOSE
To date, the description of the natural course of concurrent tethered cord syndrome with a low-lying conus medullaris and split cord malformation is lacking in the literature. We report a cohort of adult and pediatric patients with concurrent malformations and long-term follow-up.
METHODS
Patients with concurrent diagnoses of split cord malformation and tethered cord (radiographic evidence supporting clinical symptomatology) were identified between 2000 and 2020. Patients without sufficient documentation or at least 6-month follow-up were excluded.
RESULTS
Nine patients were identified with an average of 8.9 years follow-up (range 2-31 years). The most common symptoms were radiating leg pain and lower extremity paresthesias, occurring in 44% of patients; and bladder/bowel dysfunction, worsening scoliosis, and acute motor deterioration were less common. Two patients were successfully treated conservatively for mild leg pain and paresthesias. For those who underwent surgery, all experienced symptomatic relief upon first follow-up. Two had late symptomatic recurrence; one 4 and 8 years after initial surgery; and the other, 11, 26, and 31 years after initial surgery.
CONCLUSION
The rarity of concurrent split cord and tethered cord syndrome with a low-lying conus makes management difficult to formulate. This series supplements our knowledge of the long-term outcomes and lessons learned from the management of these patients. Approximately 25% of patients were managed conservatively and had symptomatic improvement. For surgically managed patients, with intractable pain or worsening neurological function, symptoms can still recur over a decade after intervention. Reoperation, however, can still be beneficial, can provide years of relief, and should be considered.
Topics: Adult; Child; Follow-Up Studies; Humans; Neural Tube Defects; Pain; Retrospective Studies; Spinal Cord; Treatment Outcome
PubMed: 33242106
DOI: 10.1007/s00381-020-04978-9 -
BMJ Case Reports Apr 2022Craniorachischisis totalis (anencephaly with total open spina bifida) is the most severe form of neural tube defects. The exact aetiology of neural tube defects remains...
Craniorachischisis totalis (anencephaly with total open spina bifida) is the most severe form of neural tube defects. The exact aetiology of neural tube defects remains poorly understood. We report a case of a primigravida in her 20s with a fetus in which craniorachischisis totalis was diagnosed during the first-trimester ultrasound at 11 weeks of gestation. The parents opted for pregnancy termination and the diagnosis was confirmed postnatally. Besides the lack of folic acid supplementation during preconception, no other risk factor was found. This case highlights the importance of the first-trimester ultrasound in the diagnosis of severe malformations. The right diagnosis is crucial for future prenatal counselling, yet investigation is still required to better understand the aetiology behind neural tube defects and assess the possibility of underlying genetic features, thus enabling better counselling.
Topics: Abortion, Induced; Anencephaly; Female; Fetus; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis
PubMed: 35470163
DOI: 10.1136/bcr-2021-244682 -
The Pan African Medical Journal 2023
Topics: Humans; Spinal Dysraphism; Neural Tube Defects; Magnetic Resonance Imaging
PubMed: 37900200
DOI: 10.11604/pamj.2023.45.168.40974 -
Child's Nervous System : ChNS :... Jan 2021Adults rarely present with tethered cord syndrome, and this review examines whether it is justifiable to perform surgical intervention in this group. (Review)
Review
INTRODUCTION
Adults rarely present with tethered cord syndrome, and this review examines whether it is justifiable to perform surgical intervention in this group.
METHODS
Between 2003 and 2017, we performed surgical intervention in 32 adults with tethered cord syndrome. The age range varied from 22 to 65 years. Twenty-six had pain, 20 had motor deficits, and 18 had sensory deficits, whereas 17 presented with sphincter disturbances. Three had undergone surgery for meningomyelocele as infants. Six patients had major spinal deformity in the shape of kyphosis or scoliosis. All patients underwent digital radiographs and MR scans of the whole spine. The oldest with a leaking open meningocele was 41 years old.
RESULTS
The mean follow-up was 3.2 years. Twenty-one out of 26 patients presenting with pain had their VAS scores improve significantly; 14 had motor deficits which improved. However, sensory deficits got better in only 7 out of 18 patients, and sphincter improvement was documented (via urodynamics studies and bladder ultrasound) in only 4 out of 17 patients. In 15 cases, surgery was performed under neurophysiological monitoring, and overall improvement was documented in 11 of these patients compared with 7 of the remaining 17 patients. Surgery for spinal deformity was performed in 6 patients, and deformity correction as well as pain reduction was achieved in all.
CONCLUSION
Surgery leads to significant reduction of pain by untethering and in those with spinal deformity by correction of the same. Improvement in sensory changes and sphincter problems occurred in few patients. Neuromonitoring certainly has improved our results.
Topics: Adult; Aged; Humans; Infant; Meningomyelocele; Middle Aged; Neural Tube Defects; Retrospective Studies; Scoliosis; Treatment Outcome; Young Adult
PubMed: 32642975
DOI: 10.1007/s00381-020-04774-5 -
Brain : a Journal of Neurology Aug 2023Neural tube defects are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying...
Neural tube defects are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying molecular mechanisms remain elusive. Retinoic acid, an active derivative of vitamin A, is critical for neural system development, and retinoic acid receptor (RAR) signalling malfunctions have been observed in human neural tube defects. However, retinoic acid-retinoic acid receptor signalling regulation and mechanisms in neural tube defects are not fully understood. The mRNA expression of RARs and retinoid X receptors in the different human neural tube defect phenotypes, including 11 pairs of anencephaly foetuses, 10 pairs of hydrocephalus foetuses and nine pairs of encephalocele foetuses, was investigated by NanoString nCounter technology. Immunoprecipitation-mass spectrometry was performed to screen the potential interacting targets of retinoic acid receptor γ. The interactions between proteins were confirmed by co-immunoprecipitation and immunofluorescence laser confocal microscopy. Luciferase and chromatin immunoprecipitation with quantitative real-time polymerase chain reaction assays were used to clarify the underlying mechanism. Moreover, a neural tube defect animal model, constructed using excess retinoic acid, was used for further analysis with established molecular biology technologies. We report that level of retinoic acid receptor γ (RARγ) mRNA was significantly upregulated in the brain tissues of human foetuses with anencephaly. To further understand the actions of retinoic acid receptor γ in neural tube defects, methylenetetrahydrofolate dehydrogenase 1 was identified as a specific retinoic acid receptor γ target from IP-MS screening. Additionally, methylenetetrahydrofolate dehydrogenase 1 negatively regulated retinoic acid receptor γ transcription factor activity. Furthermore, low expression of methylenetetrahydrofolate dehydrogenase 1 and activation of retinoic acid receptor signalling were further determined in human anencephaly and a retinoic acid-induced neural tube defect mouse model. This study reveals that methylenetetrahydrofolate dehydrogenase 1, the rate-determining enzyme in the one-carbon cycle, might be a specific regulator of retinoic acid receptors; these findings provide new insights into the functional linkage between nuclear folate metabolism and retinoic acid receptor signalling in neural tube defect pathology.
Topics: Mice; Pregnancy; Animals; Female; Humans; Anencephaly; Methylenetetrahydrofolate Dehydrogenase (NADP); Receptors, Retinoic Acid; Tretinoin; Neural Tube Defects; RNA, Messenger; Minor Histocompatibility Antigens
PubMed: 36928982
DOI: 10.1093/brain/awad084