Overview of Neural Tube Defects: Gene–Environment Interactions, Preventative Approaches and Future Perspectives

Abstract

Neural tube defects (NTDs) are the second most common congenital malformations of humans, characterized by impaired development of the central nervous system. Even though the etiology of most birth defects remains undetermined, genetic and environmental risk factors in the background of NTDs have been identified and extensively reported. On top of genetic and nutritional risks which include mutations in both coding and non-coding regions and maternal folate status, respectively, recent years have seen a rise in the identification of a variety of teratogens that could be implicated in NTD development. These include polycyclic aromatic hydrocarbons, arsenic, pesticides, maternal hyperthermia and antibiotics as well as pain and seizure medication. With an increase in understanding of teratogens leading to NTD formation, preventative and treatment approaches have witnessed great advances throughout the years. While the most common preventative approach includes folic acid food fortification as well as suggested inositol supplementation, treatment and management approaches differ greatly depending on the developmental stage and the site of the lesion and include prenatal surgery, stem cell transplantation and postnatal surgery. Because NTDs still represent a large health and financial burden for the patient and society as a whole, it is crucial to investigate potential risk factors and develop novel approaches in order to fully prevent this category of disorders.

A quest for genetic causes underlying signaling pathways associated with neural tube defects

“…Previous studies demonstrated the relationship between Zn and neural tube defects ( 46 , 47 ). The status of folate may also affect the gene expression associated with neurodevelopment as they influence histone modification and DNA methylation ( 48 ). Folate of maternal plasma affects the differential methylation of DNA in the newborn, leading to alterations of gene expression that eventually culminate in neural tube defects ( 49 ).…”

“… Arsenic (As): Globally, the level of arsenic has increased due to metalworking industries, the combustion of coal, and the production of pesticides, resulting in contamination of inorganic arsenic in air, water, and soil. Approximately 95% of Arsenic absorption among Europeans is due to the consumption of arsenic-contaminated foods ( 48 ). Several lines of evidence reported the teratogenic and toxic properties of arsenic and found that it is an utmost risk for the development of neural tube defects ( 78 – 80 ).…”

“…DNA methylation is a crucial process during the developmental period and is influenced by arsenic poisoning. Studies based on arsenic poisoning showed that it inhibits DNA methylation by reducing the activity of DNA methylase (1 and 3b) and S-adenosyl methionine (SAM) ( 48 , 83 , 84 ). Folate interacts with arsenic resulting in a reduction of arsenic in blood as well as an extensive efflux of folate ( 79 ).…”

Birth prevalence and risk factors of neural tube defects in Ethiopia: a systematic review and meta-analysis

“…In general, the formation of NTDs could stem from hereditary origins to environmental factors, although the mechanism of NTDs pathogenesis has not been well elucidated 26 27. A history of NTDs, family history of NTDs and consanguineous marriages specifically with first-degree relatives are identified as hereditary factors that contribute to NTDs 28–32.…”

Antibiotic impregnated and non antibiotic impregnated ventriculoperitoneal shunts in neonatal myelomeningocele associated with hydrocephalus, Is there a valuable difference?

“…Myelomeningocele (MMC) is a congenital defect of the central nervous system characterized by protrusion of the meninges and spinal cord through open vertebral arches leaving the underlying neural tissue susceptible to damage. It is the most common and severe form of spina bifida that results from failure of neural tube closure during embryonic development genetic and micronutrient causes (Isakovid et al, 2022).…”