The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review

Abstract

Neural tube defects (NTDs) are birth defects that arise during embryogenesis when normal neural tube closure fails to occur. According to the World Health Organization, NTDs are detected annually in approximately 300,000 neonates worldwide. The exact etiology of NTDs remains complex and poorly understood. It is generally agreed that most NTD cases are of multifactorial origin, having a combination of multiple genes and a number of environmental risk factors. The role of folic acid, vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs, has also been extensively studied. This knowledge synthesis brings together different types of evidence to update the role of vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs. Following a PubMed search and screening for relevant articles, we included 40 studies in our review (30 case–control studies, 3 cross‐sectional studies, 5 cohort studies, and 2 case reports). The available data showed that vitamin B12 levels were decreased in mothers and infants in NTD groups compared with control groups. Holo‐transcobalamin, the active form of vitamin B12, was also found in lower levels in mothers with NTD‐affected infants. Several studies reported elevated homocysteine levels in mothers and infants in NTD groups. Additionally, numerous studies reported links between genetic variants and increased NTD risk. These genes include GIF, LRP2, CUBN, TCb1R, MTHFR, and others. Several maternal factors have also been linked with significant NTD risk such as BMI, maternal diet, air pollutants, low maternal age, and many others. The majority of studies on NTDs have focused on the role of folic acid, hence there is a need for well‐designed studies on the role of other risk factors like vitamin B12 deficiency in the etiology of NTDs.

Assessment of Outcomes of Myelomeningocele Repair and Early Post-Operative Complications

“…18 The anatomical position of myelomeningocele varies in literature however it has often present at 22.3% to 55.7% lumbosacral, cervical 1.8% to 5.6%, cervicothoracic 0.9%, thoracic 4.2%, lumbar 16.8% to 55.7%, sacral 16% to 34.5% and in 0.9% cervical, 5.6% thoracolumbar, and 16% sacral injuries were reported. [19][20] Age of pediatric patients was not statistically significant in our study which was found to be similar to the Lillegard J.B. et al, study results i.e., with two groups of OMFS (open maternal-fetal surgery) for fMMC (fetal myelomeningocele) closure compared with fetal and maternal outcomes (anterior and posterior placental locations) and found insignificance in gestational age at the time of delivery (p = 0.583). 21 In the Management of Myelomeningocele Study (MOMS) on 161 cohort patients, the children's average age at the time of the study visit was 7.8 years (range 5.9 -10.3).…”

Surgical outcomes of myelomeningocele repair: A 20-year experience from a single center in a middle-income country

“…Genetics, maternal diminished folate status, maternal obesity, ambient air pollution, smoking, and maternal alcohol use are among the most important risk factor for NTDs 3,4,9,15,21,27,28 .…”

Homocysteine Metabolism in Pregnancy and Developmental Impacts

“…Indeed, the early phase of pregnancy represents a period of high embryonic developmental vulnerability that is critically dependent on the adequate provision of interacting nutrients involved in one-carbon metabolism, as most clearly exemplified in the case of NTDs, a group of congenital malformations of the central nervous system that arise from a failure of neural tube closure during embryogenesis. Sensitivity of neural tube closure to one-carbon metabolism is signified by the lowering of NTD risk associated with higher maternal folate ( MRC Vitamin Study Research Group, 1991 ; Czeizel et al, 2011 ; De-Regil et al, 2015 ; Yadav et al, 2021 ), vitamin B 12 ( Ray et al, 2007 ; Gu et al, 2012 ; Molloy, 2018 ; Wahbeh and Manyama 2021 ; Yadav et al, 2021 ), vitamin B 6 ( Candito et al, 2008 ), choline ( Shaw et al, 2004 ; Shaw et al, 2009 ), betaine ( Shaw et al, 2004 ), and methionine ( Shaw et al, 1997 ; Shaw et al, 2004 ) status.…”