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The Pan African Medical Journal 2022
Topics: Female; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Spinal Dysraphism; Ultrasonography, Prenatal
PubMed: 36160275
DOI: 10.11604/pamj.2022.42.146.35644 -
Clinical Nutrition (Edinburgh, Scotland) Apr 2022Neural tube defects (NTDs) are severe congenital malformations and have a complex etiology. This study aimed to explore the association between selected essential trace...
BACKGROUND AND AIMS
Neural tube defects (NTDs) are severe congenital malformations and have a complex etiology. This study aimed to explore the association between selected essential trace elements (ETEs) and metabolic pathway markers in the serum of women and the likelihood of NTDs.
METHODS
The study included 99 mothers of offspring with and 114 mothers of offspring without NTDs. Five ETEs (iron, zinc, selenium [Se], cobalt, and molybdenum) and 106 metabolic pathway markers in maternal serum were quantified. The associations between ETEs and metabolic pathway markers and the chance of NTDs were examined. Mediating effects of the metabolic pathway markers on the association between Se and the likelihood of NTDs were evaluated.
RESULTS
Compared to a Se concentration below the median, a concentration above the median was associated with a decreased chance of NTDs with an odds ratio of 0.29 (95% confidence interval: 0.11-0.66). The concentrations of 32 metabolic pathway markers differed between mothers of offspring with and without NTDs; five of these (asymmetric dimethylarginine, ornithine, glutamate, proline, and phenylalanine) were associated with increased chances of NTDs, with adjusted odds ratios of 3.01 (1.31-7.31), 2.79 (1.18-6.86), 2.38 (1.03-5.75), 2.41 (1.05-5.75), and 2.27 (1.09-5.40), respectively, for the higher interquartile of concentration compared to the lower one. Three arginine pathway metabolic markers (i.e., dimethylarginine, ornithine, and proline) mediated the association between Se and the occurrence of NTDs.
CONCLUSION
This study suggests an association between Se and a reduced chance of NTDs. The arginine pathway may play a role in mediating this association.
Topics: Arginine; Case-Control Studies; Female; Humans; Metabolic Networks and Pathways; Neural Tube Defects; Selenium
PubMed: 35263693
DOI: 10.1016/j.clnu.2022.02.006 -
Epigenetics & Chromatin Dec 2023Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal...
BACKGROUND
Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined.
RESULTS
Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis.
CONCLUSION
Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.
Topics: Mice; Humans; Animals; Histones; Neural Tube Defects; Methylation; Folic Acid; Gene Expression; Hedgehog Proteins; Histone-Lysine N-Methyltransferase
PubMed: 38093377
DOI: 10.1186/s13072-023-00517-3 -
Child's Nervous System : ChNS :... Jul 2023Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and... (Review)
Review
BACKGROUND
Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and disease burden to individuals living with these conditions. Mandatory food fortification with folic acid is, by far, one of the most efficacious, safe, and cost-effective interventions to prevent neural tube defects. However, most countries fail to effectively fortify staple foods with folic acid, impacting public health and healthcare systems and generating dismal disparities.
AIM
This article discusses the main barriers and facilitators for implementing mandatory food fortification as an evidence-based policy to prevent neural tube defects worldwide.
METHODS
A comprehensive review of the scientific literature allowed the identification of the determinant factors acting as barriers or facilitators for the reach, adoption, implementation, and scaling up of mandatory food fortification with folic acid as an evidence-based policy.
RESULTS
We identified eight barriers and seven facilitators as determinant factors for food fortification policies. The identified factors were classified as individual, contextual, and external, inspired by the Consolidated Framework for Implementation of Research (CFIR). We discuss mechanisms to overcome obstacles and seize the opportunities to approach this public health intervention safely and effectively.
CONCLUSIONS
Several determinant factors acting as barriers or facilitators influence the implementation of mandatory food fortification as an evidence-based policy worldwide. Notoriously, policymakers in many countries may lack knowledge of the benefits of scaling up their policies to prevent folic acid-sensitive neural tube defects, improve the health status of their communities, and promote the protection of many children from these disabling but preventable conditions. Not addressing this problem negatively affects four levels: public health, society, family, and individuals. Science-driven advocacy and partnerships with essential stakeholders can help overcome the barriers and leverage the facilitators for safe and effective food fortification.
Topics: Child; Humans; Folic Acid; Food, Fortified; Neural Tube Defects; Public Health; Policy
PubMed: 37209199
DOI: 10.1007/s00381-023-05944-x -
Birth Defects Research Nov 2019The neural tube defects (NTDs) are a heterogeneous group of structural birth defects that arise from a complex array of multiple genetic and environmental factors and... (Review)
Review
BACKGROUND
The neural tube defects (NTDs) are a heterogeneous group of structural birth defects that arise from a complex array of multiple genetic and environmental factors and adversely affect the structure and function of the brain and spinal cord. Spinal NTDs are clinically more common than cranial NTDs. There remains a significant gap in linking the multiple NTD phenotypes to current genomic understanding.
METHODS
This article summarizes the neurosurgical clinical approach to spinal NTDs by correlating each step of embryonic development of the human nervous system with key management concepts for defects that arise at that step.
RESULTS
The NTDs are broadly classified as open or closed. Open defects include myelomeningocele (MMC), encephalocele, and anencephaly. Closed defects are also known as occult spinal dysraphism and are characterized by intact skin over the spinal defect. They are more common and often cause neurologic decline from tethered cord syndrome. Failure of primary neurulation gives rise to open myelomeningocele (MMC). Surgical closure of an open MMC focuses on realigning the tissue layers that failed to separate during neurulation. In utero closure is a promising recent technique. Chronic neurosurgical management largely focuses treating hydrocephalus. The Chiari II malformation is uniformly present in MMC patients and may cause brainstem dysfunction. Tethered spinal cord may progressively impair normal neurologic function but typically responds well to surgical untethering.
CONCLUSIONS
Surgical closure of MMC centers on approximated realignment of embryologically disordered neural tissue. Clinical surgical management decisions in the spinal NTDs remains challenging but standardized principles have emerged.
Topics: Anencephaly; Brain; Ectoderm; Embryo, Mammalian; Embryonic Development; Encephalocele; Female; Gastrulation; Humans; Hydrocephalus; Male; Meningomyelocele; Mesoderm; Neural Tube Defects; Neurulation; Pregnancy; Spinal Cord; Spine
PubMed: 31576681
DOI: 10.1002/bdr2.1588 -
Reproductive Sciences (Thousand Oaks,... Dec 2023Diastematomyelia is a type of closed spinal dysraphism in which there is splitting of the spinal cord. It is a rare entity that accounts for less than 3% of closed... (Review)
Review
Diastematomyelia is a type of closed spinal dysraphism in which there is splitting of the spinal cord. It is a rare entity that accounts for less than 3% of closed spinal dysraphisms and affects females 1.3 to 6 times more frequently than males. Lesions are usually found in the lower thoracic and upper lumbar regions. It is characterised by two hemicords separated by a bony or cartilaginous spur. In most cases, it is an isolated malformation with a favourable prognosis. However, it may be associated with other abnormalities and sonography is the imaging test par excellence for early prenatal diagnosis. We report a case of diastematomyelia diagnosed by prenatal sonography at 24 weeks' gestation. Amniotic fluid alpha-fetoprotein (AF-AFP) was normal, while amniotic fluid acetylcholinesterase (AF-AChE) was positive. After birth, the diagnosis was confirmed with magnetic resonance imaging (MRI). The anomaly was associated with a spinal lipoma, tethered cord and dermal sinus. A review of all the cases described in the literature to date is carried out.
Topics: Pregnancy; Male; Female; Humans; Acetylcholinesterase; Prenatal Diagnosis; Neural Tube Defects; Ultrasonography, Prenatal; Spinal Cord; Magnetic Resonance Imaging
PubMed: 37491555
DOI: 10.1007/s43032-023-01307-8 -
Advances in Nutrition (Bethesda, Md.) Mar 2021Weekly iron and folic acid supplementation (WIFAS) is among the 8 key effective actions for improving adolescent nutrition included by the WHO in the 2018 guidelines.... (Review)
Review
Perspective: Weekly Iron and Folic Acid Supplementation (WIFAS): A Critical Review and Rationale for Inclusion in the Essential Medicines List to Accelerate Anemia and Neural Tube Defects Reduction.
Weekly iron and folic acid supplementation (WIFAS) is among the 8 key effective actions for improving adolescent nutrition included by the WHO in the 2018 guidelines. However, at present WIFAS in the WHO-recommended formulation is not included in the Model Essential Medicines List (MEML), limiting the potential for countries to import, produce, and prioritize this formulation as part of their national supply management and procurement plans for medicines. The WHO WIFAS guideline presents evidence that the formulation reduces anemia, but not that folic acid reduces neural tube defects (NTDs), because sufficient evidence was unavailable at the time of the last review. Recently, a 3-arm, parallel-group, randomized, double-blind, placebo-controlled folic acid efficacy trial on WIFAS was conducted to address this evidence gap. The study population included 331 women (18-45 y old), randomly assigned to 3 treatment groups, including a supplement with 60 mg Fe as ferrous fumarate and either 0 mg, 0.4 mg, or 2.8 mg of folic acid, to be consumed once weekly for 16 wk, followed by a 4-wk washout period. In this article we critically review how the outcomes of this folic acid efficacy trial, and how the evidence generated, could potentially be used to inform WHO WIFAS guidelines for the potential inclusion of this formulation on the MEML, and how this, in turn, may affect product availability. If the new evidence on weekly folic acid is assessed as adequately reducing the risk of NTDs, a guideline revision could be warranted and WIFAS could be presented to the MEML for the dual benefits of anemia reduction and NTD prevention. This inclusion could enable acceleration of implementing policies and programs to contribute to global anemia and NTD reduction efforts.
Topics: Adolescent; Anemia; Dietary Supplements; Female; Folic Acid; Humans; Iron; Neural Tube Defects; Randomized Controlled Trials as Topic
PubMed: 33439978
DOI: 10.1093/advances/nmaa169 -
Child's Nervous System : ChNS :... Jan 2020
Topics: Arnold-Chiari Malformation; Female; Humans; Neural Tube Defects; Spinal Dysraphism
PubMed: 30066163
DOI: 10.1007/s00381-018-3933-4 -
BMJ Open Nov 2023This study aims to estimate the prevalence of neural tube defects (NTDs) and to identify potential risk factors in the Ethiopian context. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to estimate the prevalence of neural tube defects (NTDs) and to identify potential risk factors in the Ethiopian context.
STUDY DESIGN
Systematic review and meta-analysis.
STUDY PARTICIPANTS
A total of 611 064 participants were included in the review obtained from 42 studies.
METHODS
PubMed (Medline), Embase and Cochrane Library databases in combination with other potential sources of literature were systematically searched, whereby studies conducted between January 2010 and December 2022 were targeted in the review process. All observational studies were included and heterogeneity between studies was verified using Cochrane Q test statistics and I test statistics. Small study effects were checked using Egger's statistical test at a 5% significance level.
RESULT
The pooled prevalence of all NTDs per 10 000 births in Ethiopia was 71.48 (95% CI 57.80 to 86.58). The between-study heterogeneity was high (I= 97.49%, p<0.0001). Birth prevalence of spina bifida (33.99 per 10 000) was higher than anencephaly (23.70 per 10 000), and encephalocele (4.22 per 10 000). Unbooked antenatal care (AOR 2.26, 95% CI (1.30 to 3.94)), preconception intake of folic acid (AOR 0.41, 95% CI (0.26 to 0.66)), having chronic medical illness (AOR 2.06, 95% CI (1.42 to 2.99)), drinking alcohol (AOR 2.70, 95% CI (1.89 to 3.85)), smoking cigarette (AOR 2.49, 95% CI (1.51 to 4.11)), chewing khat (AOR 3.30, 95% CI (1.88 to 5.80)), exposure to pesticides (AOR 3.87, 95% CI (2.63 to 5.71)), maternal age ≥35 (AOR 1.90, 95% CI (1.13 to 3.25)), maternal low educational status (AOR 1.60, 95% CI (1.13 to 2.24)), residing in urban areas (AOR 0.75, 95% CI (0.58 to 0.97))and family history of NTDs (AOR 2.51, 95% CI (1.36 to 4.62)) were associated with NTD cases.
CONCLUSION
The prevalence of NTDs in Ethiopia is seven times as high as in other Western countries where prevention measures are put in place. Heredity, maternal and environmental factors are associated with a high prevalence of NTDs. Mandatory fortification of staple food with folic acid should be taken as a priority intervention to curb the burden of NTDs. To smoothen and overlook the pace of implementation of mass fortification, screening, and monitoring surveillance systems should be in place along with awareness-raising measures.
PROSPERO REGISTRATION NUMBER
CRD42023413490.
Topics: Female; Pregnancy; Humans; Prevalence; Ethiopia; Neural Tube Defects; Folic Acid; Risk Factors; Food, Fortified
PubMed: 37940152
DOI: 10.1136/bmjopen-2023-077685 -
The Science of the Total Environment Nov 2023Bisphenol A (BPA) and its analogs such as bisphenol Z (BPZ) are widely used in the production of consumer products, but few studies have investigated the associations...
Bisphenol A (BPA) and its analogs such as bisphenol Z (BPZ) are widely used in the production of consumer products, but few studies have investigated the associations among BPA, its analogs, and chlorinated derivatives (collectively, BPs) and risk for NTDs. This study investigated the associations between concentrations of BPs in the placenta and risk for NTDs. This was a case-control study including 122 NTDs and 164 controls. BPs in the placenta were determined using liquid chromatography-tandem mass spectrometry. The associations between BPs and NTD risk were evaluated using conventional logistic regression and weighted quantile sum regression (WQS) models. In the logistic regression, exposure to higher levels of BPA and BPZ was associated with increased NTD risk (odds ratio [OR] = 3.17, 95 % confidence interval [CI], 1.22-8.22; OR = 3.11, 95 % CI, 1.20-8.09, respectively). Meanwhile, a significant dose-response relationship was found between BPA and BPZ concentrations and NTD risk. In the WQS model, a quartile increase in WQS index resulted in 4.34 (95 % CI: 1.69, 11.20) higher odds for NTDs, and BPA and BPZ accounted for most of the weight index in the joint effects of BPs. In conclusion, high levels of BPs in the placenta are associated with increased risk for NTDs, of which BPA and BPZ are important risk factors.
Topics: Pregnancy; Female; Humans; Case-Control Studies; Phenols; Benzhydryl Compounds; Neural Tube Defects; Placenta
PubMed: 37474044
DOI: 10.1016/j.scitotenv.2023.165586