-
Environmental Health Perspectives Aug 2023Neural tube defects (NTDs) affect pregnancies worldwide annually. Few nongenetic factors, other than folate deficiency, have been identified that may provide... (Review)
Review
BACKGROUND
Neural tube defects (NTDs) affect pregnancies worldwide annually. Few nongenetic factors, other than folate deficiency, have been identified that may provide intervenable solutions to reduce the burden of NTDs. Prenatal exposure to toxic metals [arsenic (As), cadmium (Cd), mercury (Hg), manganese (Mn) and lead (Pb)] may increase the risk of NTDs. Although a growing epidemiologic literature has examined associations, to our knowledge no systematic review has been conducted to date.
OBJECTIVE
Through adaptation of the Navigation Guide systematic review methodology, we aimed to answer the question "does exposure to As, Cd, Hg, Mn, or Pb during gestation increase the risk of NTDs?" and to assess challenges to evaluating this question given the current evidence.
METHODS
We selected available evidence on prenatal As, Cd, Hg, Mn, or Pb exposure and risk of specific NTDs (e.g., spina bifida, anencephaly) or all NTDs via a comprehensive search across MEDLINE, Embase, Web of Science, and TOXLINE databases and applied inclusion/exclusion criteria. We rated the quality and strength of the evidence for each metal. We applied a customized risk of bias protocol and evaluated the sufficiency of evidence of an effect of each metal on NTDs.
RESULTS
We identified 30 studies that met our criteria. Risk of bias for confounding and selection was high in most studies, but low for missing data. We determined that, although the evidence was limited, the literature supported an association between prenatal exposure to Hg or Mn and increased risk of NTDs. For the remaining metals, the evidence was inadequate to establish or rule out an effect.
CONCLUSION
The role of gestational As, Cd, or Pb exposure in the etiology of NTDs remains unclear and warrants further investigation in high-quality studies, with a particular focus on controlling confounding, mitigating selection bias, and improving exposure assessment. https://doi.org/10.1289/EHP11872.
Topics: Female; Pregnancy; Humans; Cadmium; Lead; Prenatal Exposure Delayed Effects; Neural Tube Defects; Mercury; Manganese; Arsenic
PubMed: 37647124
DOI: 10.1289/EHP11872 -
BMC Pregnancy and Childbirth Apr 2022The aim of this study is to determine the frequency of neural tube defects (NTDs) and to examine the epidemiological characteristics of NTD related deaths in Turkey.
OBJECTIVE
The aim of this study is to determine the frequency of neural tube defects (NTDs) and to examine the epidemiological characteristics of NTD related deaths in Turkey.
METHODS
This nationwide descriptive study was included NTD related infant deaths, termination of pregnancy for fetal anomaly (ToPFA) and stillbirth cases registered in Death Notification System between 2014 and 2019, and patients diagnosed with NTD in the 2018 birth cohort.
FINDINGS
In the 2018 birth cohort, there were 3475 cases of NTD at birth (27.5 per 10,000). The fatality rates for live-born babies with NTD in this cohort were 13.5% at first year, and 15.6% at the end of March, 2022. NTDs were associated with 11.7% of ToPFA cases, 2.5% of stillbirths and 2.8% of infant deaths in 2014-2019. NTD related stillbirth rate was 1.74 per 10,000 births, while NTD related ToPFA rate and infant mortality rate were 0.61 and 2.70 per 10,000 live births respectively. NTD-related stillbirth and infant mortality rate were highest in the Eastern region (3.64 per 10,000 births; 4.65 per 10,000 live births respectively), while ToPFA rate was highest in the North and West regions (1.17 and 0.79 per 10,000 live births respectively) (p < 0.05). Prematurity and low birth weight were the variables with the highest NTD related rates for stillbirths (11.26 and 16.80 per 10,000 birth), ToPFA (9.25 and 12.74) per 10,000 live birth), and infant deaths (13.91 and 20.11 per 10,000 live birth) (p < 0.05).
CONCLUSION
NTDs are common and have an important place among the mortality causes in Turkey. Primary prevention through mandatory folic acid fortification should be considered both to reduce the frequency of NTD and related mortality rates.
Topics: Female; Folic Acid; Humans; Infant; Infant Death; Infant, Newborn; Neural Tube Defects; Pregnancy; Prevalence; Stillbirth; Turkey
PubMed: 35439969
DOI: 10.1186/s12884-022-04678-z -
Archives of Endocrinology and Metabolism Nov 2022Congenital malformations are more frequently found among children born to mothers with diabetes than in the background population. There are several complex mechanisms... (Review)
Review
Congenital malformations are more frequently found among children born to mothers with diabetes than in the background population. There are several complex mechanisms involved in the development of congenital malformations in the offspring of mothers with hyperglycemia, such as the overexpression of glucose transporters (GLUTs) 1 and 2, the increased activity of the hexosamine biosynthetic pathway and the reduced expression of the PAX3 gene with a consequent increase in p53 protein expression. These alterations can lead to increased glucose and free radical concentrations in the embryo, thus promoting the process of apoptosis and causing malformation. The most frequent malformations found in the offspring of mothers with diabetes are heart and neural tube defects, urinary tract and kidney malformations, and cleft lip with or without cleft palate. Strict glycemic control should be obtained before and during pregnancy, aiming to avoid or minimize the risk of congenital malformations in the offspring. Beyond hyperglycemia, several factors may also be associated with increased risks of malformations in the offspring of these women, such as obesity, multiple pregnancies, advanced maternal age, folic acid deficiency, use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, assisted reproduction techniques, and exposure to different types of environmental pollutants.
Topics: Pregnancy; Child; Humans; Female; Neural Tube Defects; Hyperglycemia; Obesity; Glucose
PubMed: 36191262
DOI: 10.20945/2359-3997000000521 -
Saudi Medical Journal Dec 2014Neural tube defects (NTDs) constitute a major health burden (0.5-2/1000 pregnancies worldwide), and remain a preventable cause of still birth, neonatal, and infant... (Review)
Review
Neural tube defects (NTDs) constitute a major health burden (0.5-2/1000 pregnancies worldwide), and remain a preventable cause of still birth, neonatal, and infant death, or significant lifelong handicaps. The malformations result from failure of the neural folds to fuse in the midline, and form the neural tube between the third and the fourth week of embryonic development. This review article discusses their classification, clinical features, and genetics. Most NTDs are sporadic and both genetic, and non-genetic environmental factors are involved in its etiology. Consanguinity was suggested to contribute to the high incidence of NTDs in several countries, including Saudi Arabia. Syndromes, often associated with chromosomal anomalies, account for <10% of all NTDs; but a higher proportion (20%) has been documented in Saudi Arabia. Genetic predisposition constitutes the major underlying risk factor, with a strong implication of genes that regulate folate one-carbon metabolism and planar cell polarity.
Topics: Consanguinity; Humans; Infant, Newborn; Methylenetetrahydrofolate Reductase (NADPH2); Neural Tube Defects
PubMed: 25551113
DOI: No ID Found -
Journal of Pediatric Rehabilitation... Dec 2017It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes... (Review)
Review
It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes associated with non-syndromic NTDs in humans is especially notable as the "genomic revolution" has led to new tools (e.g., genome-wide genotyping arrays, next-generation sequencing) that are helping to elucidate the full spectrum of genetic variation (from common to rare) contributing to complex traits, including structural birth defects. However, the application of modern genomic approaches to the study of NTDs has lagged behind that of some other common structural birth defects. This may be due to the difficulty of assembling large study cohorts for anencephaly or spina bifida. The purpose of this review is to outline the evolution of genetic studies of NTDs, from studies of familial aggregation to candidate gene and genome-wide association studies, through whole-exome and whole-genome sequencing. Strategies for addressing gaps in NTD genetic research are also explored.
Topics: Europe; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Molecular Epidemiology; Neural Tube Defects; United States; Exome Sequencing; Whole Genome Sequencing
PubMed: 29125517
DOI: 10.3233/PRM-170456 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Nov 2021To review the research progress on etiology and pathogenesis of spina bifida. (Review)
Review
OBJECTIVE
To review the research progress on etiology and pathogenesis of spina bifida.
METHODS
By consulting relevant domestic and foreign research literature on spina bifida, the classification, epidemic trend, pathogenesis, etiology, prevention and treatment of it were analyzed and summarized.
RESULTS
Spina bifida, a common phenotype of neural tube defects, is classified based on the degree and pattern of malformation associated with neuroectodermal involvement and is due to the disturbance of neural tube closure 28 days before embryonic development. The prevalence of spina bifida varies greatly among different ethnic groups and regions, and its etiology is complex. Currently, some spina bifida patients can be prevented by folic acid supplements, and with the improvement of treatment technology, the short-term and long-term survival rate of children with spina bifida has improved.
CONCLUSION
The research on the pathogenesis of spina bifida will be based on the refined individual information on exposure, genetics, and complex phenotype, and will provide a theoretical basis for improving prevention and treatment strategies through multidisciplinary cooperation.
Topics: Female; Folic Acid; Humans; Neural Tube Defects; Pregnancy; Prevalence; Spinal Dysraphism
PubMed: 34779160
DOI: 10.7507/1002-1892.202106052 -
Italian Journal of Pediatrics Aug 2017The Mediterranean diet has been for a very long time the basis of food habits all over the countries of the Mediterranean basin, originally founded on rural models and... (Review)
Review
The Mediterranean diet has been for a very long time the basis of food habits all over the countries of the Mediterranean basin, originally founded on rural models and low consumption of meat products and high-fat/high-processed foods. However, in the modern era, the traditional Mediterranean diet pattern is now progressively eroding due to the widespread dissemination of the Western-type economy, life-style, technology-driven culture, as well as the globalisation of food production, availability and consumption, with consequent homogenisation of food culture and behaviours. This transition process may affect many situations, including pregnancy and offspring's health. The problem of the diet during pregnancy and the proper intake of nutrients are nowadays a very current topic, arousing much debate. The Mediterranean dietary pattern, in particular, has been associated with the highest risk reduction of major congenital anomalies, like the heterogeneous class of neural tube defects (NTDs). NTDs constitute a major health burden (0.5-2/1000 pregnancies worldwide) and still remain a preventable cause of still birth, neonatal and infant death, or significant lifelong disabilities. Many studies support the finding that appropriate folate levels during pregnancy may confer protection against these diseases. In 1991 one randomised controlled trial (RCT) demonstrated for the first time that periconceptional supplementation of folic acid is able to prevent the recurrence of NTDs, finding confirmed by many other subsequent studies. Anyway, the high rate of unplanned/unintended pregnancies and births and other issues hindering the achievement of adequate folate levels in women in childbearing age, induced the US government and many other countries to institute mandatory food fortification with folic acid. The actual strategy adopted by European Countries (including Italy) suggests that women take 0,4 mg folic acid/die before conception. The main question is which intervention, between folic acid supplementation, foods fortification or both, linked to a healthy life-style and diet pattern may represent the best method in preventing NTDs. The aim of this review is to describe the actual situation in NTDs prevention, with a special attention to the Italiancontext concerning this delicate and controversial subject.
Topics: Diet, Mediterranean; Dietary Supplements; Female; Folic Acid; Food, Fortified; Humans; Infant, Newborn; Italy; Male; Neural Tube Defects; Pregnancy; Treatment Outcome; Vitamin B Complex
PubMed: 28818086
DOI: 10.1186/s13052-017-0391-7 -
Revue Medicale de Liege Sep 2020We report a case of a 35-year-old woman with recurrent lumbar pain and left cruralgia in a post-traumatic context, for which the scanner had made possible the fortuitous...
We report a case of a 35-year-old woman with recurrent lumbar pain and left cruralgia in a post-traumatic context, for which the scanner had made possible the fortuitous diagnostic of a congenital anomaly. The diagnosis of diastematomyelia, which is more frequent in utero, is rare in adulthood and results from the implementation of an iconographic assessment. We will present the major malformations that are associated with diastematomyelia and which could evoke the presence of this malformation. The management of the anomaly is still controversial and can lead, if not done properly, to invalidating neurological deteriorations.
Topics: Adult; Female; Humans; Low Back Pain; Neural Tube Defects
PubMed: 32909406
DOI: No ID Found -
International Journal of Molecular... Jan 2023Neural tube defects (NTDs) are complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which is affected by the interaction... (Review)
Review
Neural tube defects (NTDs) are complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which is affected by the interaction of genetic and environmental factors. It is well known that folate deficiency increases the incidence of NTDs; however, the underlying mechanism remains unclear. Folate deficiency not only causes DNA hypomethylation, but also blocks the synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) and increases uracil misincorporation, resulting in genomic instabilities such as base mismatch, DNA breakage, and even chromosome aberration. DNA repair pathways are essential for ensuring normal DNA synthesis, genomic stability and integrity during embryonic neural development. Genomic instability or lack of DNA repair has been implicated in risk of development of NTDs. Here, we reviewed the relationship between folate deficiency, DNA repair pathways and NTDs so as to reveal the role and significance of DNA repair system in the pathogenesis of NTDs and better understand the pathogenesis of NTDs.
Topics: Humans; Folic Acid; Neural Tube Defects; Folic Acid Deficiency; DNA Repair; DNA; Genomic Instability
PubMed: 36768542
DOI: 10.3390/ijms24032220 -
Birth Defects Research Jan 2020Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly...
BACKGROUND
Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly and spina bifida, and affect 0.5-2 per 1,000 pregnancies worldwide in humans. It has been demonstrated that acetylation plays a pivotal role during neural tube closure, as animal models for defective histone acetyltransferase proteins display NTDs. Acetylation represents an important component of the complex network of posttranslational regulatory interactions, suggesting a possible fundamental role during primary neurulation events. This study aimed to assess protein acetylation contribution to early patterning of the central nervous system both in human and murine specimens.
METHODS
We used both human and mouse (Cited2 ) samples to analyze the dynamic acetylation of proteins during embryo development through immunohistochemistry, western blot analysis and quantitative polymerase chain reaction.
RESULTS
We report the dynamic profile of histone and protein acetylation status during neural tube closure. We also report a rescue effect in an animal model by chemical p53 inhibition.
CONCLUSIONS
Our data suggest that the p53-acetylation equilibrium may play a role in primary neurulation in mammals.
Topics: Acetylation; Anencephaly; Animals; Disease Models, Animal; Embryonic Development; Histone Acetyltransferases; Humans; Mammals; Mice; Neural Tube Defects; Neurulation; Repressor Proteins; Spinal Dysraphism; Trans-Activators; Transcription Factors; Tumor Suppressor Protein p53
PubMed: 31758757
DOI: 10.1002/bdr2.1618