Neural Tube Defects

Background: Folic acid (FA), which in its chemical form is pteroylglutamic acid, is the fully oxidised, water-soluble, monoglutamic form of vitamin B9. This compound is part of the folate group but with higher bioavailability, and it is found in vitamin supplements and fortified foods and drugs. Folate metabolism is complex and associated with various metabolic pathways, all of which confer protection on the cell and allow its survival. Methods: We conducted a non-systematic search of articles published in English and Spanish including controlled trials, cohort studies, systematic re-views, and meta-analyses were included, as well as key studies in animal models related to pharmacokinetic studies. Search terms encompassed: "folic acid", "folates", "5-metyltetrahydrofolate", "5-MTHF", "neural tube defects", "supplementation", "fortification", AND "homocysteine" Results: A crucial role demonstrated for FA is to help prevent neural tube defects (NTDs). However, more studies are definitely still needed to establish 5-MTHF as a safe and effective therapeutic approach comparable with FA. Moreover, there is a lack of clinical studies that evaluate the efficacy of 5-MTHF supplementation in the prevention of NTDs. The present evidence-based narrative review discusses differences between FA and 5-MTHF in terms of structure, metabolism, bioavailability, clinical efficacy, and safety. Conclusions: Despite the potential value of 5-MTHF as an alternative to FA, clinical studies would be urgently needed to support the efficacy, dosage, timing, and/or safety of its use as a supplement.

BackgroundNeural tube defects (NTDs) are complex multifactorial disorders in the neurulation of the brain and spinal cord that develop in humans between 21 and 28 days of conception. Neonates with NTDs may experience morbidity and mortality, with severe social and economic consequences. Therefore, the aim of this systematic review and meta-analysis is to assess the pooled prevalence and determinants for neural tube defects among newborns in Ethiopia.MethodsThe protocol of this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42023407095). We systematically searched the databases PubMed, Science Direct, Cochrane Library, Google Scholar and Research Gate. Grey literature was searched on Google. Heterogeneity among studies was assessed using the I2 test statistic and the Cochran Q test statistic. A random effects model was used to estimate the birth prevalence of neural tube defects.ResultTwenty-five articles were included in the meta-analysis to estimate the prevalence and determinants of neural tube defects in Ethiopia. A total of 611,354 newborns were included in the analysis. The pooled birth prevalence of neural tube defects was 83.40 (95% CI: 60.78, 106.02) per 10,000 births. The highest and lowest prevalence rates were 130.9 (95% CI: 113.52, 148.29) in Tigray and 28.60 (95% CI: 18.70, 38.50) per 10,000 births in Amhara regional states. Women's intake of folic acid supplements and planned pregnancy were identified as protective factors for NTDs, while stillbirth history, use of any drugs during pregnancy, exposure to radiation, and pesticides during pregnancy were risk factors for neural tube defects.ConclusionThe pooled birth prevalence of neural tube defects in Ethiopia was found to be high. Effective prevention interventions, especially focusing on periconceptional folic acid supplementation as well as folate fortification, should be prioritized alongside nutrition education, maternal health care, and environmental safety measures.

Integrated biochemical and biophysical signals regulate embryonic development. Correct neural tube formation is critical for the development of central nervous system. However, the role of microgravity in neurodevelopment and its underlying molecular mechanisms remain unclear. In this study, the effects of stimulated microgravity (SMG) on the development of human brain organoids are investigated. SMG impairs N-cadherin-based adherens junction formation, leading to neural tube defects associated with dysregulated self-renewal capacity and neuroepithelial disorganization in human brain organoids. Bulk gene expression analyses reveal that SMG alters Hippo and BMP signaling in brain organoids. The neuropathological deficits in SMG-treated organoids can be rescued by regulating YAP/BMP/ID1 axis. Furthermore, sing-cell RNA sequencing data show that SMG results in perturbations in the number and function of neural stem and progenitor cell subpopulations. One of these subpopulations senses SMG cues and transmits BMP signals to the subpopulation responsible for tube morphogenesis, ultimately affecting the proliferating cell population. Finally, SMG intervention leads to persistent neurologic damage even after returning to normal gravity conditions. Collectively, this study reveals molecular and cellular abnormalities associated with SMG during human brain development, providing opportunities for countermeasures to maintain normal neurodevelopment in space.

PurposeSurgical untethering for spinal dysraphism carries the risk of neural damage affecting sphincter control. Whilst anal sphincter motor-evoked potentials (MEP) are commonly used, they assess efferent pathways and do not directly reflect bladder innervation. The bulbocavernosus reflex (BCR) evaluates both afferent and efferent components of the sacral reflex arc, potentially serving as a better intraoperative predictor of urinary function. This study aimed to (1) assess the correlation between baseline BCR and preoperative urinary continence and (2) determine whether intraoperative BCR loss predicts postoperative urinary outcomes at one year.MethodsA retrospective observational study was conducted on children (aged 4-18 years) undergoing spinal cord untethering with intraoperative BCR monitoring. Preoperative and 1-year postoperative urological assessments included continence status, clean intermittent catheterisation (CIC) dependency, recurrent urinary tract infections (UTI), post-void residual volume (PVR), and vesicoureteral reflux (VUR). Sensitivity, specificity, and predictive values were calculated for both baseline and intraoperative BCR changes relative to urological outcomes.ResultsFifty patients met the inclusion criteria. Preoperative absence of BCR correlated with preoperative incontinence with 34.5% sensitivity and 90.5% specificity. Intraoperative BCR loss predicted postoperative incontinence with 14.8% sensitivity and 82.6% specificity. CIC dependency and recurrent UTIs were unchanged postoperatively, whilst increased PVR decreased from 20 to 12%.ConclusionBaseline BCR has high specificity but limited sensitivity for preoperative continence. Intraoperative BCR loss is a specific but insensitive predictor of postoperative urinary dysfunction. Whilst BCR monitoring aids intraoperative decision-making, further studies are needed to optimise its role in predicting long-term bladder outcomes.