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BACKGROUND: Direct potable reuse (DPR) involves adding purified wastewater that has not passed through an environmental buffer into a water distribution system. DPR may help address water shortages and is approved or is under consideration as a source of drinking water for several water-stressed population centers in the United States, however, there are no studies of health outcomes in populations who receive DPR drinking water. Our objective was to determine whether the introduction of DPR for certain public water systems in Texas was associated with changes in birth defect prevalence. METHODS: We obtained data on maternal characteristics for all live births and birth defects cases regardless of pregnancy outcome in Texas from 2003 to 2017 from the Texas Birth Defects Registry and birth and fetal death records. The ridge augmented synthetic control method was used to model changes in birth defect prevalence (per 10,000 live births) following the adoption of DPR by four Texas counties in mid-2013, with county-level data on maternal age, percent women without a high school diploma, percent who identified as Hispanic/Latina or non-Hispanic/Latina Black, and rural-urban continuum code as covariates. RESULTS: There were nonstatistically significant increases in prevalence of all birth defects collectively (average treatment effect in the treated = 53.6) and congenital heart disease (average treatment effect in the treated = 287.3) since June 2013. The estimated prevalence of neural tube defects was unchanged. CONCLUSIONS: We estimated nonstatistically significant increases in birth defect prevalence following the implementation of DPR in four West Texas counties. Further research is warranted to inform water policy decisions.

PURPOSE: Tethered cord syndrome (TCS) is characterized by abnormal attachment of the spinal cord neural elements to surrounding tissues. The most common symptoms include pain, motor or sensory dysfunction, and urologic deficits. Although TCS is common in children, there is a significant heterogeneity in outcomes reporting. We systematically reviewed surgical indications and postoperative outcomes to assess the need for a grading/classification system. METHODS: PubMed and EMBASE searches identified pediatric TCS literature published between 1950 and 2023. Studies reporting surgical interventions, ≥ 6-month follow-up, and ≥ 5 patients were included. RESULTS: Fifty-five studies representing 3798 patients were included. The most commonly reported non-urologic symptoms were nonspecific lower-extremity motor disturbances (36.4% of studies), lower-extremity/back pain (32.7%), nonspecific lower-extremity sensory disturbances (29.1%), gait abnormalities (29.1%), and nonspecific bowel dysfunction/fecal incontinence (25.5%). Urologic symptoms were most commonly reported as nonspecific complaints (40.0%). After detethering surgery, retethering was the most widely reported non-urologic outcome (40.0%), followed by other nonspecific findings: motor deficits (32.7%), lower-extremity/back/perianal pain (18.2%), gait/ambulation function (18.2%), sensory deficits (12.7%), and bowel deficits/fecal incontinence (12.7%). Commonly reported urologic outcomes included nonspecific bladder/urinary deficits (27.3%), bladder capacity (20.0%), bladder compliance (18.2%), urinary incontinence/enuresis/neurogenic bladder (18.2%), and nonspecific urodynamics/urodynamics score change (16.4%). CONCLUSION: TCS surgical literature is highly variable regarding surgical indications and reporting of postsurgical outcomes. The lack of common data elements and consistent quantitative measures inhibits higher-level analysis. The development and validation of a standardized outcomes measurement tool-ideally encompassing both patient-reported outcome and objective measures-would significantly benefit future TCS research and surgical management.

Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids. FOLR1 knockdown in neural organoids and in Xenopus laevis embryos leads to NTDs that are rescued by pteroate, a folate precursor that is unable to participate in metabolism. We demonstrate that FOLR1 interacts with and opposes the function of CD2-associated protein, molecule essential for apical endocytosis and turnover of C-cadherin in neural plate cells. In addition, folates increase Ca2+ transient frequency, suggesting that folate and FOLR1 signal intracellularly to regulate neural plate folding. This study identifies a mechanism of action of folate distinct from its vitamin function during neural tube formation.

Objective: Myelomeningocele (MMC), a congenital neural tube defect, is the most common developmental anomaly of the central nervous system (CNS). Spasticity is among the main disabling factors in these patients, affecting up to 1/5 of children. The purpose of this article is to review the current knowledge regarding spasticity in MMC patients, mainly focusing on its manifestations and management. Methods: A literature search was conducted using the PubMed database for the terms "myelomeningocele" and "spasticity." Data were collected by 5 independent investigators and then synthesized in a scoping format. Results: Causes of spasticity in these patients include hydrocephalus, tethered cord syndrome (TCS), syringomyelia, CNS infection, and associated congenital brain and spine anomalies. Clinical manifestations include limb spasticity and neurogenic bladder. Spasticity primarily affects muscles below the neurological level and contributes to gait impairment. Besides walking ability, spasticity also severely affects functional mobility in general, self-care, and quality of life. The majority of MMC patients experience neurogenic bladder. Treatment of spasticity can be symptomatic or target its cause. Medical and surgical options are available for both limb and bladder spasticity. Regular physiotherapy and orthotics are used to prevent contractures and the early introduction of orthoses is the cornerstone of a gait training program. Neurosurgical treatment options for spasticity include nonablative and ablative procedures such as selective dorsal rhizototmy. The urodynamic pattern guides treatment strategies, with intermittent catheterization being the best treatment option for patients with underactive detrusor and overactive sphincter muscles. Conclusion: Given the particularities of spasticity in MMC patients, a multidisciplinary team approach and early rehabilitation programs are keys for their optimal management. [ABSTRACT FROM AUTHOR]

Background: One of the most common and serious congenital defects is neural tube defect (NTD) in India. The data about the NTDs in India is lacking. The objective of this meta-analysis is to provide an estimate of NTDs in India with regional variations. Method: This study was conducted by doing a literature search using PubMed (Medline) and Embase databases for studies published from their inception to 1 October 2023 by using relevant keywords. We have prepared our study protocol by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, and our study is registered in PROSPERO. Pooled prevalence was calculated by using the Der Simonian-Liard method and random effect model to find out the burden of NTD in India. Additionally, subgroup and sensitivity analyses were also performed. NHLBI (National Heart, Lung, and Blood Institute) tool was used for assessing the study quality. Results: A total of 1129 articles were identified by using the predefined keywords in which 27 articles were selected which were fitting the selection criteria defined in our study. The prevalence of NTDs in our meta-analysis was found to be 9.46 per 1000 births with a 95% confidence interval of 8.01 to 10.91 per 1000 births with significant heterogeneity with I2 of 99.15%. Conclusion: Our study highlights the increasing trend of NTDs over the past decades, with significant regional variation in India. There is an urgent need for comprehensive prevention strategies such as advocacy and awareness, antenatal screening for NTDs, folic acid supplementation, and food fortification. Future research is required for identification and implementation for a target-based approach for region specific. [ABSTRACT FROM AUTHOR]

Purpose: To document the pre-operative rate of clinical deterioration in a cohort of patients with split cord malformation type 1 (SCM 1) and the early- and long-term surgical outcome in these patients. Methods: Data from 41 patients with SCM 1 operated upon by the same surgeon (VR) between January 2008 to June 2023 were retrospectively reviewed with respect to history of clinical deterioration prior to surgery and early and long-term surgical outcomes. Results: The mean age of the patients at presentation was 79.3 months and the male to female ratio was 1:1.93. Twelve (29%) patients had congenital deficits whereas 4 (10%) patients had no neurological deficits. Twenty-six (63%) patients had kyphoscoliosis and 25 (61%) patients had motor dysfunction. Thirty-three (81%) patients (8/12 (67%) with congenital deficits) had clinical deterioration prior to surgery. By the age of 2 years, 56% of patients had clinical deterioration. After surgery, 18 (55%) patients with progressive symptoms had improvement in one or more of their symptoms on long-term follow-up (mean, 63.4 months). There were no predictors of surgical outcome. Conclusions: Since over half of our patients with SCM 1 developed progression of congenital deficits or developed deficits by the age of 2 years, surgery should be performed as soon as possible in these children. On long-term follow-up after surgery, improvement can be expected in over half the patients. [ABSTRACT FROM AUTHOR]

Purpose: Encephaloceles are neural tube closure defects characterized by herniation of intracranial contents through the skull, with a mortality rate of 33.3%. Approximately 50% of patients who survived have some degree of neuropsychomotor developmental impairment or seizures. This study aimed to analyze the relationship between good neuropsychomotor development (NPMD) in patients undergoing fetal occipital encephalocele correction and the reversal of microcephaly, comparing these outcomes with those observed in patients who underwent postnatal surgery. Methods: The 22 participants were categorized into two groups: 10 in the fetal group (FG) and 12 in the postnatal group (PNG). During the study, 1 patient was excluded from the FG and 2 patients were excluded from the PNG, totaling 19 patients in the study. All patients were diagnosed, evaluated, and monitored by the same healthcare service between July 2012 and July 2018. All participants were subjected to a careful developmental assessment using the Bayley Scale of Infant Development, Second Edition (BSID-II), up to 2 years and 11 months of age. Additionally, CP measurements were taken during the first year of life to monitor their progress. The relationship between microcephaly reversal and NPMD was studied. Results: The CP adjusted for gestational age showed a tendency toward the reversal of progressive microcephaly after correction of encephaloceles in the FG. We found a statistically significant difference in the median BSID-II score between the PNG and FG. Patients in the FG maintained normal CP development in the first year of life, whereas those in the PNG remained microcephalic. Conclusion: The reversal of microcephaly in the FG directly influences good NPMD and can be considered a protective factor. [ABSTRACT FROM AUTHOR]

Introduction: For many therapeutic drugs, including antiretroviral drugs used to treat people living with HIV-1 (PLWH), we have little data on the potential effects on the developing human brain due to limited access to tissue and historical constraints on the inclusion of pregnant populations in clinical trials. Human induced pluripotent stem cells (iPSCs) offer a new avenue to gain insight on how drugs may impact human cell types representative of the developing central nervous system. To prevent vertical transmission of HIV and promote the health of pregnant PLWH, antiretroviral therapy must be initiated and/or maintained throughout pregnancy. However, many antiretroviral drugs are approved for widespread use following clinical testing only in non-pregnant populations and there may be limited information on potential teratogenicity until pregnancy outcomes are evaluated. The integrase strand transfer inhibitor dolutegravir (DTG) is a frontline antiretroviral drug that is effective in viral suppression of HIV but was previously reported to be associated with a slight increase in the risk for neural tube defects in one study, although this has not been replicated in other cohorts. Methods: To directly investigate the potential impact of DTG on human cortical neurogenesis, we measured the effects of daily drug exposure on the early stages of corticogenesis in a human iPSC-based forebrain organoid model. We quantified organoid size and structure and analyzed gene and protein expression to evaluate the impact of several doses of DTG on organoid development. Results: We observed deficits in organoid structure and impaired neurogenesis in DTG-treated organoids compared to vehicle-treated control organoids after 20 or 40 days in culture. Our highest dose of DTG (10 μM) resulted in significantly smaller organoids with a reduced density of neural rosette structures compared to vehicle-treated controls. Mechanistically, RNA-sequencing and immunohistological analysis suggests dysregulated amino acid transport and activation of the integrated stress response in the DTG-treated organoids, and functionally, a small molecule integrated stress response inhibitor (ISRIB) could partially rescue increased expression of proteins related to cell cycle regulation. Discussion: Together, these results illustrate the potential for human iPSC-based strategies to reveal biological processes during neurogenesis that may be affected by therapeutic drugs and provide complementary data in relevant human cell types to augment preclinical investigations of drug safety during pregnancy. [ABSTRACT FROM AUTHOR]

(1) Background: Fetal surgery for meningomyelocele (MMC) should reduce the occurrence of Arnold–Chiari malformations, hydrocephalus, the associated need for craniocervical decompression, and the need for cerebrospinal fluid shunt insertion. Fetal surgery should improve ambulatory status. (2) Methods: We used retrospective analysis of the documentation and descriptive statistics to summarize the clinical data and measured MRI parameters. The neurosurgical results are presented as the frequency of findings in percentages and compared with the results of the Management of Myelomeningocele Study (MOMS). (3) Results: A total of eight patients who underwent prenatal correction of MMC between 2016 and 2020 participated. MRI detected Chiari II malformation in all patients during prenatal imaging and in 87.5% of the patients at the age of 12 months. Craniocervical decompression was used in 25% of the patients. Shunt-dependent hydrocephalus occurred in 50% of the cases. In 87.5% of the cases, the functional level exceeded the expected ambulatory status. (4) Conclusions: We present the clinical status of our patients. Analysis of the complete cohort confirmed that prenatal surgery is associated with a reduced occurrence of Chiari malformations and reduced associated occurrence of hydrocephalus. Specific lesion levels are not associated with the need for craniocervical decompression. The results of our study are valuable in prenatal counseling and important for treatment planning. [ABSTRACT FROM AUTHOR]

The adverse outcome pathway (AOP) concept has gained attention as a way to explore the mechanism of chemical toxicity. In this study, quantitative structure–activity relationship (QSAR) models were developed to predict compound activity toward protein targets relevant to molecular initiating events (MIE) upstream of organ-specific toxicities, namely liver steatosis, cholestasis, nephrotoxicity, neural tube closure defects, and cognitive functional defects. Utilizing bioactivity data from the ChEMBL 33 database, various machine learning algorithms, chemical features and methods to assess prediction reliability were compared and applied to develop robust models to predict compound activity. The results demonstrate high predictive performance across multiple targets, with balanced accuracy exceeding 0.80 for the majority of models. Furthermore, stability checks confirmed the consistency of predictive performance across multiple training-test splits. The results obtained by using QSAR predictions to identify known markers of adversities highlighted the utility of the models for risk assessment and for prioritizing compounds for further experimental evaluation. Scientific contribution The work describes the development of QSAR models as tools for screening chemicals with potential systemic toxicity, thus contributing to resource savings and providing indications for further better-targeted testing. This study provides advances in the field of computational modeling of MIEs and information from AOP which is still relatively young and unexplored. The comprehensive modeling procedure is highly generalizable, and offers a robust framework for predicting a wide range of toxicological endpoints. [ABSTRACT FROM AUTHOR]

Spina bifida is a congenital neural tube closure defect, with myelomeningocele being the most clinically significant open neural tube defect occurring in one in 1000 births worldwide as reported by Phillips LA et al. (Curr Probl Pediatr Adolesc Health Care 47(7):173–177, 2017) and Zerah M and Kulkarni AV (Handb Clin Neurol 112:975–991, 2013). With advances in fetal surgery, this condition can be corrected in utero. Despite such precision surgery, many complications may still arise, with consequent spinal cord tethering being a major one. When the roots of the spinal cord adhere to the spinal canal instead of floating freely within the dural sleeve within the canal, it is termed as "tethering" as discussed by Martínez-Lage JF et al. (Neurocirugia (Astur) 18(4):312–319, 2007). Tethering has a variety of complications, which are best avoided by analyzing the outcomes of the different dural substitutes and improving surgical techniques. This literature review evaluates the use of different dural substitutes in fetal and postnatal surgery, with their effects on spinal cord tethering. Finding a significant difference in spinal cord adherence outcomes between these two groups can help one introspect on the impact of ideal surgical techniques to be implemented, thus reducing subsequent tethering and other future surgical interventions. [ABSTRACT FROM AUTHOR]

The primary purpose of this study was to enhance the understanding of diastematomyelia, with a particular focus on adult-onset cases, which are infrequent and not fully elucidated. Additionally, the study sought to analyse the clinical features, diagnostic characteristics, and surgical interventions employed to manage the condition. This retrospective case series aimed to investigate diastematomyelia, a rare congenital deformation affecting the spinal cord. The study included 16 patients diagnosed with diastematomyelia, consisting of 13 pediatric cases (mean age: 7.6 years, age range: 5 months to 13 years) and 3 adult cases (mean age: 36 years, age range: 26 to 48 years). Among the paediatric cases, 9 were females, and 4 were males, while the adult cohort comprised 2 males and 1 female. The study design involved a thorough review of medical records, imaging reports, and surgical outcomes without specific inclusion or exclusion criteria. Surgical intervention emerged as the primary treatment modality for all cases, except one. Following surgical intervention, significant improvements were observed in pain management, motor function, and bladder control. Furthermore, additional findings indicated the presence of Dural Ectasia and Vertebral segmentation defects among the study population. This retrospective case series sheds light on the clinical features and surgical outcomes of diastematomyelia in both pediatric and adult patients. The findings underscore the importance of surgical intervention in alleviating symptoms and enhancing motor coordination and bladder control. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the prevalence of tethered cord among patients in the postoperative period of open and occult spina bifida. To identify warning signs for its early diagnosis, as well as outcomes after the new surgical approach. Methods: Retrospective study of patients followed at the Pediatric Neurosurgery Department of the Federal University of São Paulo with spinal dysraphism. Signs and symptoms indicating reoperation were collected, and postoperative results were classified as improved, unchanged, or worsened. Results: 222 medical records of patients diagnosed with spinal dysraphism were evaluated. Symptomatic Tethered Cord Syndrome (STCS) was identified in 30 patients (13.51%), with clinical manifestations related to orthopedic deformities (66.7%), neurological deficits (56.7%), urological dysfunction (50%), and intestinal dysfunction (40%). 20 cases underwent surgery for tethered cord release. The mean age at the time of surgery was 7.7 ± 4.9 years, with 13 female patients (65%). In the postoperative evaluation, improvement in low back pain (90.9%), urological pattern, and urinary tract infection episodes (45.4%) were particularly noteworthy. 3 patients (33.3%) with constipation showed improvement, and one worsened (11.1%). Improvement in ambulation was seen in two cases (16.7%). Low back pain was the first symptom to improve after surgery, with an average time of 1.3 months, followed by changes in the urological pattern at 15.6 months. Improvement in constipation was observed in the first month in 2 cases (66.7%), positive changes in ambulation were observed around 7 months after surgery, and only one case showed improvement in clubfoot correction. Conclusions: The prevalence of tethered cord recurrence after primary correction surgery for open or occult neural tube closure defects was similar to that found in the literature. The results were encouraging, with good postoperative evolution of patients, especially in the improvement of low back pain and urological symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Myelomeningocele (MMC) is a prevalent neural tube closure defect often associated with hydrocephalus, necessitating surgical intervention in a significant proportion of cases. While ventriculoperitoneal shunting (VPS) has been a standard treatment approach, endoscopic third ventriculostomy (ETV) has emerged as a promising alternative. However, factors influencing the success of ETV in MMC patients remain uncertain. This retrospective observational study aimed to identify clinical and radiological factors correlating with a higher success rate of ETV in MMC patients. Methods: Medical records of MMC patients who underwent ETV at a tertiary care center between 2015 and 2021 were reviewed. Demographic, clinical, and radiological data were analyzed. ETV success was defined as the absence of further hydrocephalus treatment during follow-up. Results: Of 131 MMC patients, 21 met inclusion criteria and underwent ETV. The overall success rate of ETV was 57.1%, with a six-month success rate of 61.9%. Age ≤ 6 months was significantly associated with lower ETV success (25%) compared to older patients (76.9%) (OR: 0.1; 95% CI 0.005–2.006; p = 0.019). Radiological factors, including posterior fossa dimensions and linear indices, did not exhibit statistically significant associations with ETV success. Conclusion: Age emerged as a significant factor affecting ETV success in MMC patients, with younger patients exhibiting lower success rates. Radiological variables did not significantly influence ETV outcomes in this study. Identifying predictors of ETV success in MMC patients is crucial for optimizing treatment strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Spinal arteriovenous shunts and spinal dysraphism both have a different underlying cause, disease spectrum and developmental process; hence, these entities rarely coexist in a patient. Here, we reported four cases of coexistence of adult-onset spinal arteriovenous shunt and spinal dysraphism in the same patient along with their therapeutic embolisation. Additionally, we conducted an extensive literature review to explore the potential theories and explanations for this coexistence. Methods: We retrospectively searched our imaging database from January 2015 to December 2023 to identify instances of spinal arteriovenous shunts occurring in patients with spinal dysraphism or neural tube defect disorders. MRI and angiographic imaging, clinical presentation, treatment and follow-up were analysed. Results: Four patients with arteriovenous fistula/shunt and spinal dysraphism were included in the study. The mean age of presentation was 35.5 years. The most common symptoms were sensory disturbance and motor weakness. Arteriovenous fistula or shunt was located at the lumber region in one patient and at the sacral region in three cases. Two patients have a prior history of surgery in first decade. Two patients were treated with glue embolisation. The internal iliac artery was a common feeder in all cases. Conclusions: The rare coexistence of neural tube defects with spinal vascular abnormalities should be considered when assessing a middle-aged patient with neural tube defect and myelopathy. Correct diagnosis can help in treatment planning and thereby improve prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Myelomeningocele (MMC) is the most common neural tube defect, but rarely seen in premature infants. Most centers advocate for closure of MMC within 24 h of birth. However, this is not always possible in severely premature infants. Given the rarity of this patient population, we aimed to share our institutional experience and outcomes of severely premature infants with MMC. Methods: We performed a retrospective, observational review of premature infants (≤ 32 weeks gestational age) identified through our multidisciplinary spina bifida clinic (1995–2021) and surgical logs. Descriptive statistics were compiled about this sample including timing of MMC closure and incidence of adverse events such as sepsis, CSF diversion, meningitis, and death. Results: Eight patients were identified (50% male) with MMC who were born ≤ 32 weeks gestational age. Mean gestational age of the population was 27.3 weeks (SD 3.5). Median time to MMC closure was 1.5 days (IQR = 1—80.8). Five patients were taken for surgery within the recommended 48 h of birth; 2 patients underwent significantly delayed closure (107 and 139 days); and one patient's defect epithelized without surgical intervention. Six of eight patients required permanent cerebrospinal fluid (CSF) diversion (2 patients were treated with ventriculoperitoneal shunting (VPS), three were treated with endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) and 1 patient treated with ETV; mean of 3 years after birth, ranging from 1 day to 16 years). Two patients required more than one permanent CSF diversion procedure. Two patients developed sepsis (defined as meeting at least 2/4 SIRS criteria). In both cases of sepsis, patients developed signs and symptoms more than 72 h after birth. Notably, both instances of sepsis occurred unrelated to operative intervention as they occurred before permanent MMC closure. Two patients had intraventricular hemorrhage (both grade III). No patients developed meningitis (defined as positive CSF cultures) prior to MMC closure. Median follow up duration was 9.7 years. During this time epoch, 3 patients died: Two before 2 years of age of causes unrelated to surgical intervention. One of the two patients with grade III IVH died within 24 h of MMC closure. Conclusions: In our institutional experience with premature infants with MMC, some patients underwent delayed MMC closure. The overall rate of meningitis, sepsis, and mortality for preterm children with MMC was similar to MMC patients born at term. [ABSTRACT FROM AUTHOR]

CONTEXT: Tethered cord syndrome is associated with motor and sensory deficits. OBJECTIVE: Our objective was to summarize evidence regarding the diagnosis, prophylactic surgery, symptomatic treatment, and repeat surgery of tethered spinal cord in a systematic review (CRD42023461296). DATA SOURCES AND STUDY SELECTION: We searched 13 databases, reference-mined reviews, and contacted authors to identify diagnostic accuracy studies and treatment studies published until March 2024. DATA EXTRACTION: One reviewer abstracted data, and a content expert checked the data for accuracy. We assessed the risk of bias, strength of evidence (SoE), and applicability. RESULTS: The evidence base includes 103 controlled studies, many with risk of bias and applicability concerns, and 355 case series providing additional clinical information. We found moderate SoE form RI diagnosing tethered spinal cord, with medium to high diagnostic sensitivity and specificity. A small number of prophylactic surgery studies suggested motor function benefits and stability of neurologic status over time, but also complications such as surgical site infection (low SoE). A larger body of evidence documents treatments for symptomatic patients; studies revealed improvement in neurologic status after surgical detethering (low SoE), but also postoperative complications such as cerebrospinal fluid leakage (moderate SoE). A small body of evidence exists for retethering treatment (low or insufficient SoE for all outcomes). LIMITATIONS: There was insufficient evidence for key outcomes (eg, over- or undertreatment, clinical impact of diagnostic modalities, ambulation, quality of life). CONCLUSIONS: This comprehensive overview informs difficult clinical decisions that parents and their children with tethered spinal cords, as well as their health care providers, face. [ABSTRACT FROM AUTHOR]

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Potential associations between periconception dolutegravir (DTG) exposure and neural tube defects (NTDs) reported in 2018 caused shifting international and national antiretroviral treatment (ART) guidelines. They sometimes required women to use contraception prior to initiating DTG. To better understand the tensions between ART and family planning (FP) choices, and explore the decision-making processes of women living with HIV (WLHIV) and their healthcare providers (HCPs) employed, we conducted interviews with WLHIV exposed to DTG and their providers in western Kenya from July 2019 to August 2020. For the interviews with WLHIV, we sampled women at varying ages who either continued using DTG, switched to a different ART, or became pregnant while using DTG. We utilized inductive coding and thematic analysis. We conducted 44 interviews with WLHIV and 10 with providers. We found four dominant themes: (1) a range of attitudes about birth defects, (2) nuanced knowledge of DTG and its potential risk of birth defects, (3) significant tensions at the intersection of DTG and FP use with varying priorities amongst WLHIV and their providers for navigating the tensions, and (4) WLHIV desiring autonomy, and provider support for this, in such decision-making. Variations in beliefs were noted between WLHIV and HCPs. WLHIV highlighted the impact of community and social beliefs when discussing their attitudes while HCPs generally reported more medicalized views towards DTG utilization, potential adverse outcomes, and FP selection. Decisions pertaining to ART and FP selection are complex, and HIV treatment guidelines need to better support women's agency and reproductive health justice. [ABSTRACT FROM AUTHOR]

Introduction: Congenital anomalies are one of the major causes of the global burden of diseases, and low- and middle-income countries (LMICs) are disproportionately affected. This review assesses the prenatal and postnatal screening methods and compares the prevalence of major congenital anomalies in LMICs. Methodology: We conducted a systematic search in MEDLINE/PubMed, CINAHL, Cochrane databases of systematic reviews, clinical trials.gov for relevant studies using Medical Subject Headings and keywords. We categorized the studies into different systems and screening methods depending on the time the tests were conducted (prenatal or postnatal). The studies were then subjected to detailed descriptive analysis. Results: A total of 59 studies were selected for analysis; these focused on screening methods for congenital anomalies and compared their prevalence with regards to different systems. The most common screening techniques both prenatal and postnatal included antenatal ultrasound, fetal echocardiography, pulse oximetry, and clinical examination. The most common congenital abnormalities involved the central nervous system (neural tube defects) and musculoskeletal (clubfoot), followed by gastrointestinal (omphalocele and gastroschisis) and cardiovascular (structural heart defect). Overall, different systems had varying prevalences of different birth defects, ranging from 0.28 to 8.5%. In contrast, the prevalence of musculoskeletal system disorders varied from 1.01% to 3.96%, in the cardiovascular system from 0.57% to 10.4%, and in the urogenital group from 0.83% to 5.9%. Conclusion: The review highlights the lack of screening programs and studies, especially in the primary and secondary care settings in LMICs, and limited studies do indicate a high burden of various congenital anomalies. There is a need for guidelines and programs in global maternal and child health programs to include timely screening and management of common birth defects in LMICs. [ABSTRACT FROM AUTHOR]

Introduction: Genetic and environmental factors influence the risk of neural tube defects (NTD), congenital malformations characterized by abnormal brain and spine formation. Mouse embryos deficient in Scavenger Receptor Class B Type 1 (SR-B1), which is involved in the bidirectional transfer of lipids between lipoproteins and cells, exhibit a high prevalence of exencephaly, preventable by maternal vitamin E supplementation. SR-B1 knock-out (KO) embryos are severely deficient in vitamin E and show elevated reactive oxygen species levels during neurulation. Methods: We fed SR-B1 heterozygous female mice a high-fat/high-sugar (HFHS) diet and evaluated the vitamin E and oxidative status in dams and embryos from heterozygous intercrosses. We also determined the incidence of NTD. Results and discussion: HFHS-fed SR-B1 HET females exhibited altered glucose metabolism and excess circulating lipids, along with a higher incidence of embryos with developmental delay and NTD. Vitamin E supplementation partially mitigated HFHS-induced maternal metabolic abnormalities and completely prevented embryonic malformations, likely through indirect mechanisms involving the reduction of oxidative stress and improved lipid handling by the parietal yolk sac. [ABSTRACT FROM AUTHOR]

S‐adenosylmethionine (SAM) as a major methyl donor plays a key role in methylation modification in vivo, and its disorder was closely related to neural tube defects (NTDs). However, the exact mechanism between SAM deficiency and NTDs remained unclearly. Hence, we investigated the association between histone methylation modification and cell differentiation in NTDs mice induced by SAM deficiency. The levels of SAM and SAH (S‐adenosylhomocysteine) were determined by enzyme linked immunosorbent assay (ELISA). The level of histone methylation, β‐catenin were analyzed by Western blot, reversing transcription and quantitative PCR (RT‐qPCR) and immunofluorescence. The results showed that the incidence rate of NTDs induced by ethionine were 46.2%. Post treatment of ethionine combined with SAM, the incidence rate of NTDs was reduced to 26.2%. The level of SAM was significantly decreased (p < 0.05) and a reduction in the SAM/SAH ratio was observed after entionine treatment. The SAM deficiency caused the reduction of H3K27me3 modifications and the elevated UTX activity (p < 0.05), and inhibited the expressions of β‐catenin. The differentiations of NSCs into neurons and oligodendrocytes were inhibited under SAM deficiency (p < 0.05). These results indicated that the SAM deficiency led to reduce H3K27me3 modifications, prevented the β‐catenin signaling pathway and NSCs differentiation, which provided an understanding of the novel function of epigenetic regulation in NTDs. [ABSTRACT FROM AUTHOR]

Neural tube defects (NTDs), such as spina bifida and anencephaly, are severe congenital anomalies affecting the development of the brain and spine. These conditions are often linked to folic acid deficiency during early pregnancy, a modifiable risk factor. While high-income countries have implemented mandatory folic acid fortification in staple foods, resulting in significant reductions in NTD prevalence, low- and middle-income countries (LMICs) continue to experience disproportionately high rates of these birth defects. Folic acid supplementation and fortification are proven interventions for preventing NTDs, but many LMICs face political, financial, and logistical barriers to implementing these programs. This paper highlights the importance of mandatory folic acid fortification as a cost-effective public health intervention and advocates for its expansion in LMICs. It reviews the successes of fortification programs in high-income countries, explores alternative food vehicles like rice for regions with different dietary staples, and discusses the potential of multi-nutrient fortification strategies. Additionally, this paper emphasizes the need for global collaboration, enhanced monitoring and evaluation, and public health education campaigns to ensure that women of reproductive age, especially in LMICs, receive adequate folic acid. By addressing these challenges, the global health community can significantly reduce the incidence of NTDs, improve maternal and child health, and promote health equity worldwide. The time to act is now, as the benefits of folic acid fortification far outweigh the costs of inaction. [ABSTRACT FROM AUTHOR]

(1) Background: Neural tube defects are a prevalent cause of congenital malformations, myelomeningocele (MMC) being the most severe form. This study evaluates the clinical outcome and postoperative-associated complications following MMC surgical closures, focusing on the following three techniques: direct suture (DS); VY advancement flap (VYF); and Limberg flap (LF). (2) Methods: A retrospective observational study was conducted from March 2015 to February 2023, and the inclusion criteria were newborns who underwent lumbosacral MMC within 24 h of birth. (3) Results: Out of 20 cases, 45% underwent DS closure; 25% underwent VY-F closure; 15% underwent LF closure, and 15% (n = 3) underwent combined flap closure. A significant statistical correlation was observed between intracranial hypertension (IH), the need for external ventricular drainage (EVD), and DS closure type. In the DS group, 60% of patients required EVD (p = 0.041), and 90% had IH (p = 0.027). CSF fistula was present in 40% of LF cases and 30% of DS cases, while wound dehiscence was observed in 60% of LF cases and 30% of DS cases. (4) Conclusions: Our study demonstrated that DS was linked to higher rates of complications. The VY-F is the safest method for closing MMC defects. [ABSTRACT FROM AUTHOR]

Ultrasound (USG) plays a pivotal role in the early detection and diagnosis of fetal malformations, significantly enhancing prenatal care and the management of pregnancies. As a non-invasive, widely available, and cost-effective imaging modality, ultrasound allows for the real-time visualization of fetal anatomy and development. It serves as the primary tool for screening and diagnosing congenital anomalies, including structural abnormalities of the brain, heart, spine, abdomen, and limbs, which may indicate genetic disorders or developmental defects. The early diagnosis of fetal malformations, typically during the second trimester anomaly scan, is crucial for guiding clinical decisions regarding pregnancy management. It provides parents and healthcare providers with critical information to prepare for postnatal interventions or, in some cases, enables decisions about pregnancy termination. Ultrasound's ability to detect common abnormalities such as neural tube defects, cardiac anomalies, and abdominal wall defects has made it indispensable in prenatal medicine. In addition to 2D ultrasound, advanced techniques such as 3D and 4D ultrasound further enhance the visualization of fetal malformations, allowing for more accurate assessment of complex anomalies. Doppler ultrasound also plays a role in assessing fetal blood flow, offering additional information on potential circulatory abnormalities. This review highlights the role of USG in diagnosing fetal malformations, its importance in routine prenatal screening, and its impact on clinical outcomes. By identifying abnormalities early, ultrasound helps in providing timely interventions, improving neonatal outcomes, and reducing the emotional and physical burden on parents and families. The continuous advancements in ultrasound technology promise even greater accuracy and earlier detection of fetal malformations, reinforcing its role as a cornerstone of prenatal care. [ABSTRACT FROM AUTHOR]

Background: Obesity rates have significantly increased globally, affecting up to 40% of women of childbearing age in the United States. While prenatal repair of open fetal spina bifida has shown improved outcomes, most fetal surgery centers exclude patients with a body mass index (BMI) ≥ 35 kg/m2 based on criteria from the Management of Myelomeningocele Study (MOMS) trial. This exclusion raises concerns about healthcare equity and highlights a significant knowledge gap regarding the safety and efficacy of fetal spina bifida repair in patients with obesity. Objective: To review the current state of knowledge regarding open fetal surgery for fetal spina bifida in patients with obesity, focusing on safety, efficacy, and clinical considerations. Methods: A comprehensive literature search was conducted using the PubMed and EMBASE databases, covering articles from the inception of the databases to April 2024. Studies discussing fetal surgery for neural tube defects and documenting BMI measurements and their impact on surgical outcomes, published in peer-reviewed journals, and available in English were included. Quantitative data were extracted into an Excel sheet, and data synthesis was conducted using the R programming language (version 4.3.3). Results: Three retrospective studies examining outcomes of prenatal open spina bifida repair in a total of 43 patients with a BMI ≥ 35 kg/m2 were identified. These studies did not report significant adverse maternal or fetal outcomes compared to patients with lower BMIs. Our pooled analysis revealed a perinatal mortality rate of 6.1% (95% CI: 1.76–18.92%), with 28.0% (95% CI: 14.0–48.2%) experiencing the premature rupture of membranes and 82.0% (95% CI: 29.2–98.0%) delivering preterm (<37 weeks). Membrane separation was reported in 10.3% of cases (95% CI: 3.3–27.7%), the mean gestational age at birth was 34.3 weeks (95% CI: 32.3–36.3), and the average birth weight was 2651.5 g (95% CI: 2473.7–2829.4). Additionally, 40.1% (95% CI: 23.1–60.0%) required a ventriculoperitoneal shunt. Conclusion: While current evidence suggests that fetal spina bifida repair may be feasible in patients with obesity, significant limitations in the existing body of research were identified. These include small sample sizes, retrospective designs, and a lack of long-term follow-up data. There is an urgent need for large-scale, prospective, multicenter studies to definitively establish the safety and efficacy of fetal spina bifida repair in patients with obesity. Such research is crucial for developing evidence-based guidelines, improving clinical outcomes, and addressing healthcare disparities in this growing patient population with obesity. [ABSTRACT FROM AUTHOR]

Infant cereals are typically the first foods introduced as complementary foods. Cereals used to elaborate complementary foods, such as wheat, maize and rice, are susceptible to mycotoxin contamination. Among mycotoxins, fumonisins have been epidemiologically associated, in humans, with oesophageal cancer, neural tube defects and stunting. Fumonisins have been found in maize and wheat grains in Argentina. In the present study, a survey was conducted to determine their occurrence in 82 wheat-based and multicereal-based infant cereal items collected from retail stores in Rio Cuarto, Argentina, using HPLC-MS. Of these samples, 84% showed FBs contamination with levels ranging from 0.05 to 992 μg/kg). Although FB1 was the most prevalent fumonisin, FB2 was found at higher levels. Most samples had levels below the limit of 200 μg/kg set for Argentinean cereal products for children. The outcome of this survey provides information on the naturally presence of fumonisin in infant cereal intended for children in Argentina, which can be helpful to consider relevant monitoring programmes. [ABSTRACT FROM AUTHOR]

DNA damage is associated with hyperhomocysteinemia (HHcy) and neural tube defects (NTDs). Additionally, HHcy is a risk factor for NTDs. Therefore, this study examined whether DNA damage is involved in HHcy-induced NTDs and investigated the underlying pathological mechanisms involved. Embryonic day 9 (E9) mouse neuroectoderm cells (NE4C) and homocysteine-thiolactone (HTL, active metabolite of Hcy)-induced NTD chicken embryos were studied by Western blotting, immunofluorescence. RNA interference or gene overexpression techniques were employed to investigate the impact of Menin expression changes on the DNA damage. Chromatin immunoprecipitation-quantitative polymerase chain reaction was used to investigate the epigenetic regulation of histone modifications. An increase in γH2AX (a DNA damage indicator) was detected in HTL-induced NTD chicken embryos and HTL-treated NE4C, accompanied by dysregulation of phospho-Atr-Chk1-nucleotide excision repair (NER) pathway. Further investigation, based on previous research, revealed that disruption of NER was subject to the epigenetic regulation of low-expressed Menin-H3K4me3. Overexpression of Menin or supplementation with folic acid in HTL-treated NE4C reversed the adverse effects caused by high HTL. Additionally, by overexpressing the Mars gene, we tentatively propose a mechanism whereby HTL regulates Menin expression through H3K79hcy, which subsequently influences H3K4me3 modifications, reflecting an interaction between histone modifications. Finally, in 10 human fetal NTDs with HHcy, we detected a decrease in the expression of Menin-H3K4me3 and disorder in the NER pathway, which to some extent validated our proposed mechanism. The present study demonstrated that the decreased expression of Menin in high HTL downregulated H3K4me3 modifications, further weakening the Atr-Chk1-NER pathway, resulting in the occurrence of NTDs. [ABSTRACT FROM AUTHOR]

Myelomeningocele, a severe form of open neural tube defect which is mostly associated with Chiari II malformation remains a cause of adverse neonatal outcomes. Myelomeningocele is mostly detected in the second trimester and subsequently followed up in the third trimester. We present a case of myelomeningocele with associated Chiari II malformation that was diagnosed for the first time in the third trimester in a 32-year-old pregnant woman. Previously performed ultrasound at 12 weeks gestation was unremarkable. Considering the prognosis of the detected anomalies, the patient opted for medical termination of the pregnancy after receiving thorough counselling.Third trimester anomaly screening should be encouraged as part of routine third trimester scans; particularly in women who report late for antenatal care and those who lack periconceptional folate supplementation.

We conducted an umbrella review focusing on maternal risk factors during pregnancy associated with neural tube defects (NTDs).

OBJECTIVE: To identify the genetic markers of spina bifida through a systematic survey of the exome in an Indian cohort. MATERIALS AND METHODS: Three consecutive patients (P1: 1 year, male; P2: 2.8 years, male; and P3: 10 years, female) with spina bifida (lumbosacral meningomyelocele) underwent whole-exome sequencing (libraries: SureSelect Human All Exon V8; sequencing: 2 * 150 bp paired-end run, 100×) with NovaSeq 6000. Data analysis was performed using SMART-One™ (secondary analysis) and SMARTer™ (tertiary analysis) for automated quality check, alignment (GRCh38/hg38), variant calling, annotation (ClinVar, OMIM, avsnp150, 1000 Genomes v5b, ExAC v0.3, gnomAD v4.0, and esp6500vi2all v0.0.25), v0.0.25), interpretation. The pathogenic and likely pathogenic (ClinVar/ InterVar), non-synonymous, exonic markers (read depth ≥ 5) were matched with the Familial Neural Tube Defects (Version 1.10) panel (FNTD panel). Results: Pathogenic variants overlapping with the FNTD panel were MTRR, CC2D2A, and ZIC2 in P1 and P2, TGIF1 in P1 only, and none in P3. Novel pathogenic/likely pathogenic variants common to all three patients were PRUNE1, PKD1, PDZD2, and DAB2 in the homozygous state as well as in the heterozygous state, PLK1 and NLGN2. The possible role of such markers in etiopathogenesis was explored through a literatur search. Conclusions: The genetic landscape of the spina bifida in an Indian cohort is diverse compared to that reported from other parts of the world. A comprehensive catalog of single-nucleotide variants in the etiopathogenesis of the spina bifida on a background of the Familial Neural Tube Defects Panel has been generated.

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. [ABSTRACT FROM AUTHOR]

In humans, loss of heterozygosity for defective alleles of any of the four subunits of mitochondrial tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH, also Complex II of the electron transport chain) can lead to paraganglioma tumors in neuroendocrine cells. With the goal of developing mouse models of this rare disorder, we have developed various SDH conditional loss strategies. Based on recent lineage tracing studies, we hypothesized that conditional SDHC loss in early embryogenesis during migration of primordial neural crest cells that form the susceptible chromaffin cells of the adrenal medulla might induce paraganglioma. We triggered low levels of detectable SDHC loss in Sox10+ cells at E11.5 of mouse development. We report that, rather than developing adrenal medulla paraganglioma (pheochromocytoma), offspring survived with evidence of neural crest cell dysfunction. Phenotypes included mild lower extremity gait anomalies suggestive of neural tube closure defects and patches of unpigmented fur consistent with neural crest‐derived melanocyte dysfunction. These defects were not observed in mice lacking Sdhc knockout. Our results add to existing data suggesting that, unlike humans, even early embryonic (Sox10‐driven) SDHx loss is inadequate to trigger paraganglioma in mice of the genetic backgrounds that have been investigated. Instead, low levels of tricarboxylic acid cycle‐deficient neural crest cells cause mild developmental defects in hind limb and melanocyte function. This new model may be of interest for studies of metabolism during early neural crest cell development. [ABSTRACT FROM AUTHOR]

Introduction: Suture tensile properties have only been tested in extrauterine environments. Amniotic fluid (AF) is a complex milieu of enzymes and inflammatory factors. This study tested the mechanical properties of sutures with a variety of inherent properties, after exposure to AF from patients with conditions prompting fetal intervention. Methods: AF was obtained from 3 patients with twin-twin transfusion syndrome (TTTS), and 3 patients with neural tube defects. Six types of 2-0 sutures were placed on 1.2 N of tension to mimic placement in vivo, and incubated in AF at 37°C (98.6°F). These included ethylene terephthalate (Ethibond), glycomer 631 (V-Loc), poliglecaprone 25 (Monocryl), poly-4-hydroxybutyrate (Monomax), polydioxanone (PDS), and polyglactin 910 (Vicryl). Failure load, stress, strain, and initial modulus were tested after 24 h of incubation and after 4 weeks, and compared with control (unincubated) sutures using t tests, Kruskal-Wallis tests, and stress-strain curves. Results: Poliglecaprone 25 and polyglactin 910 dissolve more quickly in AF compared to outside the uterus, disintegrating at 4 weeks. Ethylene terephthalate and PDS experienced little change across 4 weeks of incubation. Glycomer 631 and poly-4-hydroxybutyrate exhibited interesting behavior in AF: glycomer 631 became more deformable at 24 h but later regained toughness by 4 weeks, while poly-4-hydroxybutyrate became tougher and in some cases stronger with time in AF. As a class, braided sutures act more like rigid materials, and monofilaments act like deformable plastics. Conclusion: These findings along with other suture characteristics such as ease of handling and availability may inform fetal intervention teams as they optimize procedures in a relatively new surgical field. [ABSTRACT FROM AUTHOR]

Diagnostic biomarkers play a critical role in biomedical research, particularly for the diagnosis and prediction of diseases, etc. To enhance diagnostic accuracy, extensive research about combining multiple biomarkers has been developed based on the multivariate normality, which is often not true in practice, as most biomarkers follow distributions that deviate from normality. While the likelihood ratio combination is recognized to be the optimal approach, it is complicated to calculate. To achieve a more accurate and effective combination of biomarkers, especially when these biomarkers deviate from normality, we propose using a receiver operating characteristic (ROC) curve methodology based on the optimal combination of elliptically distributed biomarkers. In this paper, we derive the ROC curve function for the elliptical likelihood ratio combination. Further, proceeding from the derived best combinations of biomarkers, we propose an efficient technique via nonparametric maximum likelihood estimate (NPMLE) to build empirical estimation. Simulation results show that the proposed elliptical combination method consistently provided better performance, demonstrating its robustness in handling various distribution types of biomarkers. We apply the proposed method to two real datasets: Autism/autism spectrum disorder (ASD) and neural tube defects (NTD). In both applications, the elliptical likelihood ratio combination improves the AUC value compared to the multivariate normal likelihood ratio combination and the best linear combination. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Early detection of occult spinal dysraphism, such as diastematomyelia with tethered cord, is vital to prevent neurological damage. Though rarely diagnosed in the neonatal period, cutaneous stigmata can aid early identification. Utilizing neonatal ultrasound enables timely management and multidisciplinary intervention. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fetal spina bifida (fSB) is the most common neural tube defect, and intrauterine repair has become a valid treatment option for selected cases. If fSB repair is offered, the ideal time for surgery is from 24 to 26 gestational weeks (GWs). The preoperative steroids for lung maturation and preoperative tocolytics that are administered are known to increase the prevalence of gestational diabetes (GD), which normally occurs in about 10–15% of all pregnant women. This study assessed the prevalence, possible influencing factors, and consequences on the course of pregnancy regarding GD in this cohort. Methods: Between 2010 and 2022, 184 fSB cases were operated. Those patients operated on after 24 0/7 GWs received steroids before surgery. All the patients received tocolysis, and an oral glucose tolerance test was performed between 26 and 28 GWs at least 7 days after steroid administration. In 2020, we established an early postoperative mobilization protocol. The perioperative management procedures of those patients with and without GD were compared to each other, and also, the patients treated according to the early mobilization protocol were compared to the remaining cohort. Results: Nineteen percent were diagnosed with GD. Corticosteroids were administered in 92%. Neither the corticoid administration nor the interval between the administration and glucose tolerance test was different in patients with or without GD. Further, 99.5% received postoperative tocolytics for at least 48 h. The women with GD had significantly longer administration of tocolytics. The length of stay (LOS) was higher in those patients with GD. The gestational age (GA) at delivery was significantly lower in the cohort with GD. In the early mobilized group, we found a significantly higher GA at delivery (37.1 GWs vs. 36.2 GWs, p = 0.009) and shorter LOS (p < 0.001), and their GD rate was lower (10% vs. 20%), although not statistically significant. Conclusions: The GD incidence in the women after fSB repair was higher than in the usual pregnant population. Early mobilization, rapid tocolytics decrease, and shorter LOS could benefit the pregnancy course after fSB repair and may decrease the risk for GD in this already high-risk cohort without increasing the risk for preterm delivery. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? SUMMARY ANSWER Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (

In 1998, Health Canada mandated folic acid fortification of white flour and enriched grain products to prevent neural tube defects. At the time, neither the Canadian Nutrient File (CNF) nor product labels reflected the actual folate content of foods. We aimed to assess if 20 years post-fortification, the CNF values for total folate and synthetic folic acid accurately reflect amounts determined by direct analysis. Using the 2001 Food Expenditure Survey and ACNielsen Company data, we identified 10–15 of the most purchased fortified foods across seven food categories in Canada. Total folate concentrations were determined by tri-enzyme digestion and microbial assay. Folic acid concentrations were determined using liquid chromatography-tandem mass spectrometry. Except for "cooked pastas", mean total folate content of foods (n = 89) were significantly higher than CNF values across categories (p < 0.05), reflecting 167% ± 54% of CNF values. Similarly, mean folic acid content of foods was higher than CNF values for all categories except "cooked pastas" (p < 0.05), with a mean of 188% ± 94% of CNF values; the latter CNF values included uncooked pasta. In sum, 20 years post-fortification, and 10 years since the last direct measurement, CNF and product label values still underestimate actual total folate and the folic acid content of foods. These findings emphasize that dietary estimates established using the CNF may significantly underestimate actual intakes and thus caution should be exercised when interpreting estimates of nutritional adequacy based on these values. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to explore the effect of intraoperative neurophysiological monitoring (IONM) on tethered spinal cord release in children. Methods: The clinical data of 454 children with tethered cord syndrome who underwent surgery for tethered cord release were retrospectively analyzed. The children were divided into two groups: the non-IONM group and the IONM group. SPSS 26.0 software was used for statistical analysis. The evaluation indices included the effective rate and incidence of new neurological dysfunction. Results: The short-term results showed that the effective rate of the non-IONM group was 14.8%, while that of the IONM group was 15.2%. Additionally, the incidence of new neurological dysfunction was 7.8% in the non-IONM group and 5.6% in the IONM group. However, there was no significant difference between the two groups (P > 0.05). The medium- to long-term follow-up had significant difference (P < 0.05), the response rate was 32.1% in the IONM group and 23.7% in the non-IONM group, and deterioration rates regarding neurological dysfunction were 3.3% in the IONM group and 8.5% in the non-IONM group. Conclusion: This study revealed that the use of IONM does not significantly improve the short-term treatment effect of patients undergoing surgery for tethered cord release or reduce the short-term incidence of postoperative new neurological dysfunction. However, the medium- to long-term prognoses of patients in the IONM group were better than those of patients in the non-IONM group. [ABSTRACT FROM AUTHOR]

Introduction: Myelomeningocele (MMC) is a prevalent form of neural tube defect. Despite advancements in treatment, MMC still poses significant health risks, including complications leading to chronic disability and mortality. Identifying prognostic risk factors for early outcomes is crucial for tailored intervention strategies. Methods: This prospective study involved newborns and infants diagnosed with MMC who underwent surgery between 2020 and 2023 at Urmia University of Medical Sciences. Demographic data and surgical outcomes were collected, and participants were followed up for six months. Statistical analyses were conducted using descriptive statistics, Chi-Square, and independent t-test. Results: The study included 29 MMC cases, with an incidence rate of 1.4 per 10,000 live births. Lesions were predominantly located in the lumbar spine. Although mortality rates appeared to increase with ascending lesion sites, this trend was not statistically significant. Short-term outcomes revealed high morbidity and mortality rates, with neurological deficits being the most prevalent complication. Multivariable analysis identified head circumference as a significant predictor of adverse outcomes (IRR = 1.37, 95% CI = 1.02 to 1.86, p = 0.04). Furthermore, an increase in birth weight was associated with a reduction in the incidence of requiring a ventriculoperitoneal shunt (IRR = 0.99, 95% CI = 0.998 to 0.999, p = 0.02). Conclusion: This prospective study highlights prognostic risk factors for early outcomes in MMC patients, emphasizing the need for personalized intervention strategies. By addressing modifiable risk factors and implementing targeted interventions, healthcare providers can strive to improve outcomes and enhance the quality of life for MMC patients. [ABSTRACT FROM AUTHOR]

Primary cilia are crucial for neurogenesis, and cilium-related genes are involved in the closure of neural tubes. Inositol polyphosphate-5-phosphatase (Inpp5e) was enriched in primary cilia and closely related to the occurrence of neural tube defects (NTDs). However, the role of Inpp5e in the development of NTDs is not well-known. To investigate whether Inpp5e gene is associated with the neural tube closure, we established a mouse model of NTDs by 5-fluorouracil (5-FU) exposure at gestational day 7.5 (GD7.5). The Inpp5e knockdown (Inpp5e-/-) mouse embryonic stem cells (mESCs) were produced by CRISPR/Cas9 system. The expressions of Inpp5e and other cilium-related genes including intraflagellar transport 80 (Ift80), McKusick-Kaufman syndrome (Mkks), and Kirsten rat sarcoma viral oncogene homolog (Kras) were determined, utilizing quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, PCR array, and immunofluorescence staining. The result showed that the incidence of NTDs was 37.10% (23 NTDs/62 total embryos) and significantly higher than that in the control group (P < 0.001). The neuroepithelial cells of neural tubes were obviously disarranged in NTD embryos. The mRNA and protein levels of Inpp5e, Ift80, Mkks, and Kras were significantly decreased in NTD embryonic brain tissues, compared to the control (P < 0.05). Knockdown of the Inpp5e (Inpp5e-/-) reduced the expressions of Ift80, Mkks, and Kras in mESCs. Furthermore, the levels of α-tubulin were significantly reduced in NTD embryonic neural tissue and Inpp5e-/- mESCs. These results suggested that maternal 5-FU exposure inhibited the expression of Inpp5e, which resulted in the downregulation of cilium-related genes (Ift80, Mkks, and Kras), leading to the impairment of primary cilium development, and ultimately disrupted the neural tube closure. [ABSTRACT FROM AUTHOR]