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Annual Review of Neuroscience 2014Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development... (Review)
Review
Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies.
Topics: Animals; Folic Acid; Genetic Predisposition to Disease; Humans; Neural Tube Defects; Neurulation; Risk Factors
PubMed: 25032496
DOI: 10.1146/annurev-neuro-062012-170354 -
Birth Defects Research Nov 2019Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD... (Review)
Review
Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD pathogenesis has not yet been fully elucidated, many risk factors, both genetic and environmental, have been extensively reported. Classically divided in two main sub-groups (open and closed defects) NTDs present extremely variable prognosis mainly depending on the site of the lesion. Herein, we review the literature on the histological and pathological features, epidemiology, prenatal diagnosis, and prognosis, based on the type of defect, with the aim of providing important information based on NTDs classification for clinicians and scientists.
Topics: Anencephaly; Female; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 30421543
DOI: 10.1002/bdr2.1380 -
Trends in Neurosciences Jul 2020Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of... (Review)
Review
Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of the CNS. Following mandatory folic acid fortification of dietary grains, a dramatic reduction in the incidence of NTDs was observed in areas where the policy was implemented, yet the genetic drivers of NTDs in humans, and the mechanisms by which folic acid prevents disease, remain disputed. Here, we discuss current understanding of human NTD genetics, recent advances regarding potential mechanisms by which folic acid might modify risk through effects on the epigenome and transcriptome, and new approaches to study refined phenotypes for a greater appreciation of the developmental and genetic causes of NTDs.
Topics: Folic Acid; Humans; Neural Tube Defects
PubMed: 32423763
DOI: 10.1016/j.tins.2020.04.009 -
Journal of Clinical Pharmacology Feb 2016During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other... (Review)
Review
During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester.
Topics: Anencephaly; Dietary Supplements; Dose-Response Relationship, Drug; Female; Folic Acid; Humans; Pregnancy; Vitamins
PubMed: 26272218
DOI: 10.1002/jcph.616 -
The Pan African Medical Journal 2023
Topics: Humans; Neural Tube Defects
PubMed: 37013212
DOI: 10.11604/pamj.2023.44.24.35962 -
Romanian Journal of Morphology and... 2020Anencephaly is a severe malformation of the central nervous system (CNS), being one of the most common types of neural tube defects. It is defined as total or partial... (Review)
Review
Anencephaly is a severe malformation of the central nervous system (CNS), being one of the most common types of neural tube defects. It is defined as total or partial absence of the calvarium, with absence of the brain. Anencephaly has an incidence of 1 to 5 in every 1000 births, and the mortality rate is 100% during intrauterine life or within hours or days after birth. The etiology of anencephaly remains unclear, but various maternal-related environmental and genetic risk factors have been reported, which include diabetes, obesity, exposure to different drugs or toxins, genetic polymorphisms and mutations, as well as positive family history for neural tube defects. One of the most important nutritional factors in the development of anencephaly is folate deficiency. Methylenetetrahydrofolate reductase (MTHFR) gene codes the enzyme involved in the intracellular metabolism of folic acid; the 677C-T polymorphism of this gene causes the thermolability of the enzyme and decreased enzymatic activity, which is also dependent of folate plasmatic level. Etiopathogenesis of anencephaly includes several mutations in various other genes, such as: platelet-derived growth factor receptor alpha (PDGFRA), cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1), Vang-like 1 (VANGL1) and Vang-like 2 (VANGL2), the last two being involved in the process of neurulation. Screening tests include maternal serum alpha-fetoprotein level and ultrasound (US) examination. During the first trimester US screening, anencephaly is now detected in all cases, but in order to decrease the complication rate of pregnancy termination, the diagnosis should be established as soon as possible, during the pregnancy confirmation US. We conclude that given that anencephaly is a severe malformation of the CNS, morphological characterization could improve the screening by US that is mandatory in the first trimester in order to plan the best, safe and early management.
Topics: Anencephaly; Female; Humans; Male; Polymorphism, Genetic
PubMed: 33544785
DOI: 10.47162/RJME.61.2.03 -
Journal of Clinical and Diagnostic... Sep 2014Anencephaly is a serious neural tube defect in which parts of the brain and skull are not developed. But apart from this it is also associated with other malformations...
INTRODUCTION
Anencephaly is a serious neural tube defect in which parts of the brain and skull are not developed. But apart from this it is also associated with other malformations which are not related to neural tube in development.
AIM
The present study was undertaken to find the associated congenital malformations in western region of India and establish a aetiological correlation.
MATERIALS AND METHODS
The study was conducted using 20 anencephalic fetuses.
RESULTS
Nearly 80% of fetuses had associated malformations. Spina bifida was seen in 9 fetuses and cleft palate in 8. Female fetus with cleft palate had other severe associated gastrointestinal and skeletal malformation.
CONCLUSION
In cases of anencephaly other associated malfor-mations like spina bifida and cleft palate are commonly seen.
PubMed: 25386414
DOI: 10.7860/JCDR/2014/10402.4885 -
Scientific Reports Dec 2021Anencephaly is a severe anomaly of the brain that results from the failure of the cephalic part of the neural tube to close during the fourth week. It occurs at least in... (Meta-Analysis)
Meta-Analysis
Anencephaly is a severe anomaly of the brain that results from the failure of the cephalic part of the neural tube to close during the fourth week. It occurs at least in one per thousand births and is the major cause of fetal loss and disabilities in newborns. The objective of this review is to determine the birth prevalence of anencephaly in Africa. We identified relevant studies via a search of databases like PubMed Central, PubMed/Medline, Science Direct, Joanna Briggs Institute, African Journals Online, Embase, Google Scholar, Web of Science, and Cochrane Library. After examining the heterogeneity of studies via the Cochran Q test and I test (and Forest plot for visual inspection), the prevalence of anencephaly was estimated using the random-effect meta-analysis model. Consequently, we carried out subgroup, sensitivity, meta-regression, trim and fill, time-trend, and meta-cumulative analyses. In this systematic review and meta-analysis, the twenty-four studies reported a total of 4,963,266 births. The pooled birth prevalence of anencephaly in Africa was 0.14% (95% CI: 0.12, 0.15%). Higher burden of anencephaly was detected in Ethiopia (0.37%, CI: 0.15, 0.58%), Algeria (0.24%, CI: 0.24, 0.25%), and Eritrea (0.19%, CI: 0.19, 0.19%). The higher pooled prevalence of anencephaly was observed in the studies that included both live births and stillbirths (0.16%) and in studies done after the year 2010 (0.25%) whereas, the lower burden was detected among countries that had a mandatory folic acid fortification (0.05%). High birth prevalence of anencephaly was detected in Africa. Strong prevention and control measures should be the priority because of an increment in the magnitude of anencephaly. Helping in prevention programs, which should be the ultimate contribution of this study to the field.
Topics: Africa; Anencephaly; Disease Susceptibility; Female; Humans; Male; Population Surveillance; Prevalence
PubMed: 34887455
DOI: 10.1038/s41598-021-02966-w