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Ecotoxicology and Environmental Safety Apr 2023Metallic elements play a pivotal role in maternal and fetal health. Metals can cross the placental barrier and be absorbed by fetuses, where they may affect closure of... (Review)
Review
Metallic elements play a pivotal role in maternal and fetal health. Metals can cross the placental barrier and be absorbed by fetuses, where they may affect closure of the neural tube during embryonic development. Neural tube defects (NTDs), which result from aberrant closure of the neural tube three to four weeks post-conception, have a multifactorial and complex etiology that combines genetic variants and environmental exposure. Recent advances in population-level association studies have investigated the link between maternal environmental exposure and NTDs, particularly the influence of metals on the incidence of NTDs. Herein, we present a broad and qualitative review of current literature on the association between maternal and prenatal metal exposure via the maternal peripheral blood, amniotic fluid, placenta, umbilical cord, and maternal hair, and the risk of developing NTDs. Specifically, we identify the various aggravating or attenuating effects of metallic exposure on the risk of NTD formation. This review provides novel insights into the association between environmental metals and NTDs and has important applications for NTD prevention and mitigating environmental exposure to metals.
Topics: Humans; Female; Pregnancy; Prenatal Exposure Delayed Effects; Placenta; Neural Tube Defects; Neural Tube; Fetus
PubMed: 36948008
DOI: 10.1016/j.ecoenv.2023.114815 -
The Science of the Total Environment Feb 2024Exposure to pesticides during pregnancy has been associated with several serious congenital malformations, such as neural tube defects, therefore, is a cause for concern... (Review)
Review
Exposure to pesticides during pregnancy has been associated with several serious congenital malformations, such as neural tube defects, therefore, is a cause for concern in terms of human health. This review aims to gather information related to maternal exposure during pregnancy and the risk of triggering neural tube defects in the offspring. The search strategy for the studies followed the PRISMA guidelines. We conducted a systematic search in the Science Direct, PubMed, Cochrane Library, Embase, Scopus, and Web of Science databases for all epidemiological studies that sought to associate exposure to pesticides during embryonic development with the risk of neural tube defects (NTDs). The keywords used were "pesticide", "herbicide", "congenital" and "neural". Of the 229 articles, 8 eligible ones (7 case-control and 1 cross-sectional) evaluated pesticide exposure in pregnancy. Different methods were used, including analysis of biological samples and questionnaires. The pesticides studied included insecticides, herbicides, fungicides, and nematicides. Insecticides were the most studied, with variations in concentrations between tissues and studies. Distinct levels of pesticides have been detected in maternal serum, placenta, and umbilical cord. Models were statistically adjusted for confounding factors, such as smoking and dietary supplement intakes. Concentrations were measured in different exposure windows (periconception and prenatal), related to NTDs such as anencephaly and spina bifida. Different data collection techniques, types of biological samples, and exposure windows were used, which made comparison difficult. The main pesticides studied included DDT, DDE, HCH, and endosulfan. Maternal serum showed the highest concentrations of pesticides, but detection in placental tissue and umbilical cord confirms embryonic exposure. Confounding variables were adjusted for in the analysis of the articles, but they may still contribute to the risk of NTDs. All the studies analyzed pesticide exposure and the relationship with NTDs. However, a more standardized survey would be ideal for better comparisons.
Topics: Female; Humans; Pregnancy; Pesticides; Insecticides; Cross-Sectional Studies; Placenta; Neural Tube Defects; Herbicides; Risk Factors
PubMed: 38104833
DOI: 10.1016/j.scitotenv.2023.169317 -
Journal of Medicine and Life 2021Spina bifida is a disorder characterized by failure of the neural tube to form during embryological development. The early signs in the head and spine may be detected on...
Spina bifida is a disorder characterized by failure of the neural tube to form during embryological development. The early signs in the head and spine may be detected on ultrasound from 11 weeks of gestation. Diabetes is a well-known teratogen factor that increases the chances of birth defects, such as neural tube defects. We report a 12 weeks case of spina bifida in type 1 diabetes.
Topics: Diabetes Mellitus; Female; Humans; Neural Tube Defects; Pregnancy; Spinal Dysraphism; Ultrasonography
PubMed: 35126760
DOI: 10.25122/jml-2021-0249 -
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 -
Journal of Neurosurgery. Pediatrics Jul 2023The two main objectives of this study were to explore the rate of spinal dysraphism within bladder and cloacal exstrophy and to analyze the relationship between spinal...
OBJECTIVE
The two main objectives of this study were to explore the rate of spinal dysraphism within bladder and cloacal exstrophy and to analyze the relationship between spinal dysraphism surgery, including timing of spinal dysraphism surgery, with urological and neurological outcomes.
METHODS
A prospectively maintained IRB-approved database of pediatric exstrophy patients treated from 1982 to 2021 was retrospectively reviewed for patients with spinal dysraphism. Spinal dysraphism was categorized into the following 7 subtypes: lipoma-based closed defect, myelomeningocele, meningocele, diastematomyelia, myelocystocele, low-lying conus with tethered cord/fatty filum, and sacral bony defect. Other factors assessed included patient demographic characteristics, type of spinal dysraphism procedure, reoperation, complication, presence of other neurological problems (e.g., hydrocephalus, Chiari malformation), neurological status, and urological function.
RESULTS
Analysis revealed that 114/1401 patients had coexisting spinal dysraphism. Of these 114, sufficient records including type of dysraphism were available for 54. Spinal dysraphism was most common within cloacal exstrophy (83.3% [45/54 patients]), followed by cloacal exstrophy variants (9.3% [5/54]), classic bladder exstrophy (3.7% [2/54]), and classic bladder exstrophy variants (3.7% [2/54]). Within spinal dysraphism, lipoma-based closed defects (63.0% [34/54]) and low-lying conus with tethered cord/fatty filum (11.1% [6/54]) were most common. Hydrocephalus and Chiari malformation occurred in 24.1% (13/54) and 11.1% (6/54) of patients. All 13 patients with hydrocephalus underwent shunt placement. Among those who underwent neurosurgical intervention, the complication rate for spinal dysraphism was 14.6% (7/48). Motor function data were available for 41 patients and revealed that motor function declined for 2/41 (4.8%) patients and improved for 6/41 (14.6%) after neurosurgery. There was no statistical difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure.
CONCLUSIONS
The authors have reported the surgical management and outcomes of patients with exstrophy and coexisting spinal dysraphism (n = 54). In 54 patients, spinal dysraphism was most common in the subset of patients with cloacal exstrophy (83.3%). Lipoma-based closed defects (63.0%) and low-lying conus with tethered cord/fatty filum (11.1%) were the most common, and the rates of hydrocephalus and Chiari malformation were 24.1% and 11.1%, respectively. There was no difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure.
Topics: Humans; Child; Bladder Exstrophy; Retrospective Studies; Spinal Dysraphism; Neural Tube Defects; Meningomyelocele; Arnold-Chiari Malformation; Hydrocephalus; Digestive System Abnormalities; Lipoma
PubMed: 37119103
DOI: 10.3171/2023.3.PEDS22447 -
Clinical Genetics Apr 2022Neural tube defects (NTDs) are the most severe birth defects and the main cause of newborn death; posing a great challenge to the affected children, families, and... (Review)
Review
Neural tube defects (NTDs) are the most severe birth defects and the main cause of newborn death; posing a great challenge to the affected children, families, and societies. Presently, the clinical diagnosis of NTDs mainly relies on ultrasound images combined with certain indices, such as alpha-fetoprotein levels in the maternal serum and amniotic fluid. Recently, the discovery of additional biomarkers in maternal tissue has presented new possibilities for prenatal diagnosis. Over the past 20 years, "omics" techniques have provided the premise for the study of biomarkers. This review summarizes recent advances in candidate biomarkers for the prenatal diagnosis of fetal NTDs based on omics techniques using maternal biological specimens of different origins, including amniotic fluid, blood, and urine, which may provide a foundation for the early prenatal diagnosis of NTDs.
Topics: Amniotic Fluid; Biomarkers; Child; Female; Humans; Infant, Newborn; Neural Tube Defects; Pregnancy; Prenatal Diagnosis
PubMed: 34761376
DOI: 10.1111/cge.14087 -
Cells Jun 2023Neural tube defects (NTDs), including anencephaly and spina bifida, are common major malformations of fetal development resulting from incomplete closure of the neural...
Neural tube defects (NTDs), including anencephaly and spina bifida, are common major malformations of fetal development resulting from incomplete closure of the neural tube. These conditions lead to either universal death (anencephaly) or severe lifelong complications (spina bifida). Despite hundreds of genetic mouse models of neural tube defect phenotypes, the genetics of human NTDs are poorly understood. Furthermore, pharmaceuticals, such as antiseizure medications, have been found clinically to increase the risk of NTDs when administered during pregnancy. Therefore, a model that recapitulates human neurodevelopment would be of immense benefit to understand the genetics underlying NTDs and identify teratogenic mechanisms. Using our self-organizing single rosette cortical organoid (SOSR-COs) system, we have developed a high-throughput image analysis pipeline for evaluating the SOSR-CO structure for NTD-like phenotypes. Similar to small molecule inhibition of apical constriction, the antiseizure medication valproic acid (VPA), a known cause of NTDs, increases the apical lumen size and apical cell surface area in a dose-responsive manner. GSK3β and HDAC inhibitors caused similar lumen expansion; however, RNA sequencing suggests VPA does not inhibit GSK3β at these concentrations. The knockout of , a well-known NTD-related gene, also caused expansion of the lumen, as well as reduced f-actin polarization. The increased lumen sizes were caused by reduced cell apical constriction, suggesting that impingement of this process is a shared mechanism for VPA treatment and -KO, two well-known causes of NTDs. Our system allows the rapid identification of NTD-like phenotypes for both compounds and genetic variants and should prove useful for understanding specific NTD mechanisms and predicting drug teratogenicity.
Topics: Pregnancy; Female; Humans; Mice; Animals; Valproic Acid; Anencephaly; Glycogen Synthase Kinase 3 beta; Mice, Knockout; Neural Tube Defects; Spinal Dysraphism; Brain; Microfilament Proteins
PubMed: 37443734
DOI: 10.3390/cells12131697 -
Journal of Pediatric Rehabilitation... 2022Whereas legislation mandates for folic acid fortification have been implemented throughout many nations, divergent neural tube defects (NTDs) prevalence rates still...
Whereas legislation mandates for folic acid fortification have been implemented throughout many nations, divergent neural tube defects (NTDs) prevalence rates still remain among the world's populations. In North America, the prevalence estimate is 39 infants per 100,000 live births. Open spina bifida (SB), also known as myelomeningocele, remains the most complex congenital abnormality of the central nervous system compatible with long term survival; this recognized complexity gives rise to emerging comorbidities and interventions. For example, increasing autism spectrum disorder rates have been reported among individuals with SB utilizing a 31,220 subject population-based birth cohort. Along with new clinical observations, telecommunication platforms such as Zoom® have evolved as clinical and investigational tools. Historically, society meetings, research conferences, and journals have provided opportunities for professional development and dissemination of up-to-date materials. The Journal of Pediatric Rehabilitation Medicine (JPRM) has arisen as an open-access global platform for the dissemination of SB-related inquiry. The journal has also highlighted the research presented at the Spina Bifida Association's previous Spina Bifida World Congresses. At the last congress, which was held in 2017, twenty-three countries were represented; this number is expected to grow by the next convocation in 2023. This congress will provide an opportunity for health care professionals from around the globe to present a broad array of research topics and build collaborations. Concurrently, the JPRM will continue as an open-access platform for SB advocacy, care, education, and investigation, across our fast changing world for the international SB community well into the future.
Topics: Infant; Child; Humans; Autistic Disorder; Autism Spectrum Disorder; Spinal Dysraphism; Neural Tube Defects; Folic Acid; Prevalence
PubMed: 36565077
DOI: 10.3233/PRM-220126 -
JAMA Aug 2023Neural tube defects are among the most common congenital malformations in the US, with an estimated 3000 pregnancies affected each year. Many of these neural tube...
IMPORTANCE
Neural tube defects are among the most common congenital malformations in the US, with an estimated 3000 pregnancies affected each year. Many of these neural tube defects are caused by low folate levels in the body.
OBJECTIVE
The US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on the benefits and harms of folic acid supplementation.
POPULATION
Persons who are planning to or could become pregnant.
EVIDENCE ASSESSMENT
The USPSTF concludes that, for persons who are planning to or could become pregnant, there is high certainty that folic acid supplementation has a substantial net benefit to prevent neural tube defects in their offspring.
RECOMMENDATION
The USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 μg) of folic acid. (A recommendation).
Topics: Female; Humans; Pregnancy; Advisory Committees; Dietary Supplements; Folic Acid; Mass Screening; Neural Tube Defects; Preventive Health Services; Folic Acid Deficiency; Pregnancy Complications; Preconception Care
PubMed: 37526713
DOI: 10.1001/jama.2023.12876 -
Birth Defects Research Mar 2021Neural tube defects (NTDs) are congenital malformations resulting from the improper or incomplete closure of the neural tube during embryonic development. A number of... (Review)
Review
Neural tube defects (NTDs) are congenital malformations resulting from the improper or incomplete closure of the neural tube during embryonic development. A number of similar malformations of the protective coverings surrounding the central nervous system are also often included under this umbrella term, which may not strictly fit this definition. A range of NTD phenotypes exist and have been reported in humans and a wide range of domestic and livestock species. In the veterinary literature, these include cases of anencephaly, encephalocele, dermoid sinus, spina bifida, and craniorachischisis. While environmental factors have a role, genetic predisposition may account for a significant part of the risk of NTDs in these animal cases. Studies of laboratory model species (fish, birds, amphibians, and rodents) have been instrumental in improving our understanding of the neurulation process. In mice, over 200 genes that may be involved in this process have been identified and variant phenotypes investigated. Like laboratory mouse models, domestic animals and livestock species display a wide range of NTD phenotypes. They remain, however, a largely underutilized population and could complement already established laboratory models. Here we review reports of NTDs in companion animals and livestock, and compare these to other animal species and human cases. We aim to highlight the potential of nonlaboratory animal models for mutation discovery as well as general insights into the mechanisms of neurulation and the development of NTDs.
Topics: Anencephaly; Animals; Female; Livestock; Mice; Neural Tube Defects; Pets; Pregnancy; Spinal Dysraphism
PubMed: 33615733
DOI: 10.1002/bdr2.1848