-
Journal of Medical Genetics Nov 2023Congenital vertebral malformations (CVMs) and neural tube defects (NTDs) are common birth defects affecting the spine and nervous system, respectively, due to defects in... (Review)
Review
Congenital vertebral malformations (CVMs) and neural tube defects (NTDs) are common birth defects affecting the spine and nervous system, respectively, due to defects in somitogenesis and neurulation. Somitogenesis and neurulation rely on factors secreted from neighbouring tissues and the integrity of the axial structure. Crucial signalling pathways like Wnt, Notch and planar cell polarity regulate somitogenesis and neurulation with significant crosstalk. While previous studies suggest an association between CVMs and NTDs, the exact mechanism underlying this relationship remains unclear. In this review, we explore embryonic development, signalling pathways and clinical phenotypes involved in the association between CVMs and NTDs. Moreover, we provide a summary of syndromes that exhibit occurrences of both CVMs and NTDs. We aim to provide insights into the potential mechanisms underlying the association between CVMs and NTDs, thereby facilitating clinical diagnosis and management of these anomalies.
Topics: Female; Pregnancy; Humans; Neural Tube Defects; Spine; Embryonic Development; Neurulation; Signal Transduction
PubMed: 37775263
DOI: 10.1136/jmg-2023-109501 -
Clinics in Perinatology Dec 2022Myelomeningocele is the most common congenital neurologic defect, and the only nonlethal disease addressed by fetal surgery. A randomized control trial has established... (Review)
Review
Myelomeningocele is the most common congenital neurologic defect, and the only nonlethal disease addressed by fetal surgery. A randomized control trial has established amelioration of the Arnold-Chiari II malformation, reduced ventriculoperitoneal shunt rate, and improvement in distal neurologic function in patients that receive in utero repair. Long-term follow-up of these school-age children demonstrates the persistence of these effects. The use of stem cells in fetal repair is being investigated to further improve distal motor function.
Topics: Pregnancy; Child; Female; Humans; Meningomyelocele; Neural Tube Defects; Fetus; Fetal Therapies; Prenatal Care; Randomized Controlled Trials as Topic
PubMed: 36328602
DOI: 10.1016/j.clp.2022.06.004 -
Fetal and Pediatric Pathology Oct 2021Neural tube defects can be as mild as spina bifida, to as severe as anencephaly, with only a fraction of these cases presenting as both craniorachischisis and...
Neural tube defects can be as mild as spina bifida, to as severe as anencephaly, with only a fraction of these cases presenting as both craniorachischisis and exencephaly. The G3, P1011 mother was 25-years old, who at an estimated fetal gestational age of 17 weeks had a fetal diagnosis of anencephaly based on a sonogram, resulting in elective pregnancy termination. The female fetus had an open neural tube defect, consisting of craniorachischisis and exencephaly. No abnormalities were noted in any other organs. Although mostly associated with anencephaly, craniorachischisis can also be associated with exencephaly in early pregnancy.
Topics: Adult; Anencephaly; Female; Fetus; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Spinal Dysraphism
PubMed: 31986946
DOI: 10.1080/15513815.2020.1716282 -
Advances and Technical Standards in... 2023Split cord malformation (SCM) is a rare form of closed spinal dysraphism, in which two hemi-cords are present, instead of a single spinal cord. SCM is categorised into...
Split cord malformation (SCM) is a rare form of closed spinal dysraphism, in which two hemi-cords are present, instead of a single spinal cord. SCM is categorised into type 1 and type 2. Type 1 SCM is defined by the presence of a bony or osseocartilaginous spur between the hemi-cords, whereas type 2 SCM has no bony spur, and the two hemi-cords are contained within a single dura. In this chapter, we present the putative mechanisms by which SCM arises, including gastrulation defects and Pang's unified theory. The typical and rare clinical presentations and variations are described. Finally, we outline the step-by-step surgical approach to both SCM 1 and 2 and the overall prognosis of both conditions.
Topics: Humans; Gastrulation; Cone-Rod Dystrophies; Dura Mater; Neural Tube Defects; Osteophyte
PubMed: 37640870
DOI: 10.1007/978-3-031-34981-2_1 -
The American Journal of Clinical... Dec 2023Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD)....
BACKGROUND
Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD). Following concern around folate status in the United Kingdom, the United Kingdom government announced in 2021 the intention to introduce mandatory folic acid fortification.
OBJECTIVE
This study aimed to describe folate status in the United Kingdom population prior to the implementation of mandatory folic acid fortification of non-whole wheat (non-wholemeal) flour and to assess trends in folate status, including in females of reproductive age (FRA).
METHODS
Data were from the United Kingdom National Diet and Nutrition Survey Rolling Program (2008-2019), a cross-sectional, nationally representative survey of children and adults aged 1.5+ (n = 5792 with folate result). Serum folate concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and red blood cell (RBC) folate concentration by microbiological assay. Concentration data were compared against method-specific cut-offs and thresholds, and relationships were explored against demographic and lifestyle characteristics.
RESULTS
RBC and serum folate concentration significantly decreased by ∼3 percentage points per year between 2008 and 2019 in all age/sex groups. Prevalence of deficiency (RBC folate < 305 nmol/L) was highest in children aged 11 to 18 y (17% in 2016-2019). The proportion of FRA below the cut-off for increased risk of NTD (RBC folate < 748 nmol/L) increased from 69% to 89% between 2008 and 2019. Ethnicity, smoking status, and income were significant determinants of RBC and serum folate concentrations.
CONCLUSIONS
These data reveal a decline in population folate status in the United Kingdom between 2008 and 2019 and a high prevalence of folate deficiency. A high proportion of FRA had RBC folate concentrations below the cut-off for increased risk of NTD. These data provide information on folate status in a population not currently exposed to mandatory folic acid fortification and are essential to model and assess its impact.
Topics: Adult; Child; Female; Humans; Folic Acid; Cross-Sectional Studies; Chromatography, Liquid; Tandem Mass Spectrometry; Neural Tube Defects; Diet; Nutrition Surveys; Erythrocytes; Food, Fortified
PubMed: 37839706
DOI: 10.1016/j.ajcnut.2023.10.006 -
Epilepsy & Behavior : E&B Jul 2020Increasing awareness of the congenital and developmental risks associated with the use of sodium valproate (VPA) has led to recent European guidelines designed to avoid... (Review)
Review
Increasing awareness of the congenital and developmental risks associated with the use of sodium valproate (VPA) has led to recent European guidelines designed to avoid the use of this drug in pregnancy if effective alternative treatments are available. In the general population, it is well established that periconceptual folic acid reduces the risk of neural tube defects (NTDs) and possibly other congenital abnormalities. We here review the evidence 1) that VPA interferes with one-carbon metabolism, including the transport of methylfolate into the brain and the placenta by targeting folate receptors; 2) that VPA effects on the folate metabolic system contribute to congenital and developmental problems associated with VPA exposure; and 3) that genetic factors, notably polymorphisms related to one-carbon metabolism, contribute to the vulnerability to these VPA-induced risks. Based on these facts, we propose that the standard periconceptual use of 400 μg of folic acid may not adequately protect against VPA or other antiepileptic drug (AED)-induced congenital or developmental risks. Pending definitive studies to determine appropriate dose, we recommend up to 5 mg of folic acid periconceptually in at-risk women with the caveat that the addition of supplementary vitamin B12 may also be prudent because vitamin B12 deficiency is common in pregnancy in some countries and is an additional risk factor for developmental abnormalities.
Topics: Anticonvulsants; Brain; Female; Folic Acid; Humans; Nervous System Malformations; Neural Tube Defects; Neurodevelopmental Disorders; Pregnancy; Valproic Acid; Vitamin B Complex
PubMed: 32375098
DOI: 10.1016/j.yebeh.2020.107068 -
American Journal of Medical Genetics.... May 2023Tethered cord syndrome (TCS) is characterized by leg pain and weakness, bladder and bowel dysfunction, orthopedic malformations such as scoliosis, and motor deficits...
Tethered cord syndrome (TCS) is characterized by leg pain and weakness, bladder and bowel dysfunction, orthopedic malformations such as scoliosis, and motor deficits caused by the fixation of the spinal cord to surrounding tissues. TCS is surgically treatable and often found in conjunction with other syndromic conditions. KBG syndrome is caused by variants in the ANKRD11 gene and is characterized by short stature, developmental delay, macrodontia, and a triangular face. The current study explores the prevalence of TCS in pediatric KBG patients and their associated signs and symptoms. Patients with KBG were surveyed for signs and symptoms associated with TCS and asked if they had been diagnosed with the syndrome. We found a high proportion of patients diagnosed with (11%) or being investigated for TCS (24%), emphasizing the need to further characterize the comorbid syndromes. No signs or symptoms clearly emerged as indicative of TCS in KBG patients, but some the prevalence of some signs and symptoms varied by sex. Male KBG patients with diagnosed TCS were more likely to have coordination issues and global delay/brain fog than their female counterparts. Understanding the presentation of TCS in KBG patients is critical for timely diagnosis and treatment.
Topics: Humans; Male; Child; Female; Abnormalities, Multiple; Intellectual Disability; Bone Diseases, Developmental; Tooth Abnormalities; Facies; Phenotype; Repressor Proteins; Neural Tube Defects; Syndrome
PubMed: 36722669
DOI: 10.1002/ajmg.a.63128 -
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 -
Child's Nervous System : ChNS :... Nov 2023Neural tube defects (NTD), such as spina bifida, are surgically treatable and primarily preventable non-communicable diseases. How incidence, mortality and... (Review)
Review
BACKGROUND
Neural tube defects (NTD), such as spina bifida, are surgically treatable and primarily preventable non-communicable diseases. How incidence, mortality and disability-adjusted life year (DALYs) rates of NTD have modulated over time is not well defined. Correspondingly, the aim of this study was to quantitively define the global, regional, and national epidemiological trends in these.
METHODS
A retrospective review of data from the Global Burden of Disease Study 2019 Database was performed. Global, regional, and national outcomes for NTD were collected for incidence, mortality, and DALY rates and their age-standardized metrics analyzed. There were 7 regions at a regional level, and 204 countries and territories at a national level.
RESULTS
Globally, the latest age-standardized rates of incidence, mortality, and DALYs of NTD were 2.1 per 100,000 population, 1.3 per 1000,000, and 117 per 100,000 respectively. All rates demonstrated decreases in the last two decades to now. Regionally, sub-Saharan Africa and North America demonstrated the highest and lowest age-standardized rates of incidence (4.0 vs 0.5 per 100,000), mortality (3.0 vs 0.4 per 100,000), and DALYs (266 vs 33 per 100,000), respectively. Similar to global trends, all regions demonstrated decrease in these rates over the last two decades. Nationally, the highest age-standardized rates were reported in African countries, Central African Republic, with highest incidence rate (7.6 per 100,000), and Burkina Faso with highest mortality rate (5.8 per 100,000) and DALY rate (518 per 100,000). India was the country with the highest number of new NTD cases (22,000 per country) in the most recent year of study. Between 1990 and 2019, 182/204 (89%), 188/204 (92%), and 188/204 (92%) countries and territories demonstrated a decrease in age-standardized incidence, mortality, and DALY rates respectively, with the greatest decreases seen in Saudi Arabia for all statistics.
CONCLUSIONS
Between 1990 and 2019, overall trends in incidence, mortality, and DALY rates of NTD have been favorably downtrending globally. Regionally, these rates in the highest sub-Saharan Africa were 8 times greater compared to the lowest North America. Nationally, although the majority of countries showed decreases in these rates, a small number of countries demonstrated uptrending rates of NTD. Understanding the mechanics behind these trends will allow future public health endeavors for both prevention and neurosurgical treatment to be targeted appropriately.
Topics: Humans; Quality-Adjusted Life Years; Global Health; Africa South of the Sahara; Saudi Arabia; Incidence; Neural Tube Defects
PubMed: 37178370
DOI: 10.1007/s00381-023-05985-2 -
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