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Child's Nervous System : ChNS :... Jul 2023Neural tube defects (NTDs) are common birth defects and contribute to life-long disabilities, high medical care costs, and perinatal and child mortality. This review is... (Review)
Review
Neural tube defects (NTDs) are common birth defects and contribute to life-long disabilities, high medical care costs, and perinatal and child mortality. This review is a primer on prevalence, causes, and evidence-based prevention strategies for NTDs. The estimated average global prevalence of NTDs is two cases per 1000 births, amounting to approximately 214,000-322,000 affected pregnancies worldwide annually. Prevalence and associated adverse outcomes are disproportionately high in developing countries. NTDs have multiple risk factors including genetic and non-genetic (i.e., maternal nutritional status, pre-pregnancy diabetes, early pregnancy exposure to valproic acid (anti-epileptic medication), and a previous pregnancy affected by a NTD) factors. Maternal folate insufficiency before and during early pregnancy is the most common risk factor and is preventable. Folic acid (vitamin B9) is required for formation of the neural tube early in pregnancy, around 28 days after conception, when most women are unaware of their pregnancies. Current guidelines recommend that all women planning or capable of pregnancy take a daily supplement containing 400-800 μg of folic acid. Mandatory folic acid fortification of staple foods (e.g., wheat flour, maize flour, rice) is safe, economical, and the effective intervention for primary prevention of NTDs. Currently, about 60 countries are implementing mandatory folic acid fortification of staple foods, preventing just a quarter of all preventable NTD cases worldwide. There is an urgent need for active champions, including neurosurgeons and other healthcare providers, to generate political will and promote effective mandatory food fortification with folic acid, and reach equitable primary prevention of NTDs in all countries.
Topics: Pregnancy; Child; Female; Humans; Flour; Prevalence; Food, Fortified; Triticum; Neural Tube Defects; Folic Acid; Primary Prevention
PubMed: 36882610
DOI: 10.1007/s00381-023-05910-7 -
Frontiers in Cell and Developmental... 2023Neural rosettes develop from the self-organization of differentiating human pluripotent stem cells. This process mimics the emergence of the embryonic central nervous... (Review)
Review
Neural rosettes develop from the self-organization of differentiating human pluripotent stem cells. This process mimics the emergence of the embryonic central nervous system primordium, i.e., the neural tube, whose formation is under close investigation as errors during such process result in severe diseases like spina bifida and anencephaly. While neural tube formation is recognized as an example of self-organization, we still do not understand the fundamental mechanisms guiding the process. Here, we discuss the different theoretical frameworks that have been proposed to explain self-organization in morphogenesis. We show that an explanation based exclusively on stem cell differentiation cannot describe the emergence of spatial organization, and an explanation based on patterning models cannot explain how different groups of cells can collectively migrate and produce the mechanical transformations required to generate the neural tube. We conclude that neural rosette development is a relevant experimental 2D model of morphogenesis because it is a multi-scale self-organization process that involves both cell differentiation and tissue development. Ultimately, to understand rosette formation, we first need to fully understand the complex interplay between growth, migration, cytoarchitecture organization, and cell type evolution.
PubMed: 37635866
DOI: 10.3389/fcell.2023.1134091 -
Epidemiology (Cambridge, Mass.) Nov 2023Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between...
BACKGROUND
Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk.
METHODS
The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery.
RESULTS
Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity.
CONCLUSIONS
Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida.
Topics: Humans; Educational Status; Ethnicity; Maternal Age; Neural Tube Defects; Odds Ratio; Female
PubMed: 37757869
DOI: 10.1097/EDE.0000000000001655 -
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 -
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