Cycloleucine induces neural tube defects by reducing Pax3 expression and impairing the balance of proliferation and apoptosis in early neurulation.

S-adenosylmethionine (SAM) plays a critical role in the development of neural tube defects (NTDs). Studies have shown that the paired box 3 (Pax3) gene is involved in neural tube closure. However, the exact mechanism between Pax3 and NTDs induced by SAM deficiency remains unclear. Here, The NTD mouse model was induced using cycloleucine (CL), an inhibitor of SAM biosynthesis, to determine the effect of Pax3 on NTDs. The effect of CL on NTD occurrence was assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and Western blot in NTD embryonic brain tissues and immortalized hippocampal neuron cells (HT-22). A high incidence of NTDs was observed when CL was administered at a dose of 200 mg/kg body weight. The levels of SAM and Pax3 were significantly reduced in NTD embryonic brain tissues and HT-22 cells after CL exposure. Decreased proliferation and excessive apoptosis were observed in neuroepithelial cells of NTD embryos and HT-22 cells under SAM deficiency, but these effects were reversed by overexpression of Pax3. These results suggest that decreased expression of Pax3 impairs the dynamic balance between cellular proliferation and apoptosis, contributing to NTDs induced by SAM deficiency, which would provide new insights for clarifying the underlying mechanism of NTDs.

Single-cell transcriptomics reveals the cellular identity of a novel progenitor population crucial for murine neural tube closure.

Neural tube closure in vertebrates is achieved through a highly dynamic and coordinated series of morphogenic events involving neuroepithelium, surface ectoderm, and neural plate border. Failure of this process in the caudal region causes spina bifida. Grainyhead-like 3 (GRHL3) is an indispensable transcription factor for neural tube closure as constitutive inactivation of the Grhl3 gene in mice leads to fully penetrant spina bifida. Here, through single-cell transcriptomics we show that at E8.5, the time-point preceding mouse neural tube closure, co-expression of Grhl3, Tfap2a, and Tfap2c defines a previously unrecognised progenitor population of surface ectoderm integral for neural tube closure. Deletion of Grhl3 expression in this cell population using a Tfap2a-Cre transgene recapitulates the spina bifida observed in Grhl3-null animals. Moreover, conditional inactivation of Tfap2c expression in Grhl3-expressing neural plate border cells also induces spina bifida. These findings indicate that a specific neural plate border cellular cohort is required for the early-stage neurulation.

Antenatally diagnosed myelomeningocele with associated chiari ii malformation in the third trimester. A case report.

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.

Dichorionic Diamniotic Twin Anencephaly and Exencephaly.

We present a rare case of dichorionic diamniotic twin anencephaly and exencephaly discovered in a 35-year-old female at 13.1 weeks of gestation. Anencephaly and exencephaly are neural tube defects (NTD) with devastating consequences caused by the failure of the anterior neural groove closure leading to exencephaly, followed by brain disintegration causing anencephaly. While NTD themselves are common congenital anomalies, their presence in both twins of a dichorionic diamniotic gestation is exceedingly rare and has only been documented in one other instance. The uncertainty surrounding risk factors involved in this specific case underscores the importance of ongoing research to elucidate other potential determinants in the pathogenesis of NTD and to discover novel preventive strategies, particularly in twin pregnancies. Future research endeavors should explore the interplay of genetic, environmental, and other anomalous factors to deepen our understanding and improve clinical outcomes for affected pregnancies.

Fatty acids profile in pregnancies affected by neural tube defects.

This study aimed to determine if maternal fatty acids (FA) levels during pregnancy are associated with the occurrence of neural tube defects (NTDs) and to explore the correlation between FA and maternal vitamin D, homocysteine, vitamin B12, and folate in cases. Plasma FA composition was assessed using capillary gas chromatography. Comparisons between cases and controls were performed by independent samples t-test for continuous variables. Cases had significantly higher levels of heptadecanoic acid, linolelaidic acid, and arachidonic acid (ARA):(eicosapentaenoic acid+docosahexaenoic acid) ratio than controls (p < 0.05). Nervonic acid, ARA, adrenic acid, eicosapentaenoic acid, docosahexaenoic acid, and omega-3 polyunsaturated fatty acids (n-3 PUFA) levels were significantly lower in cases (p < 0.05). Maternal 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with maternal polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids. RBC folate levels were negatively correlated with n-3 PUFA.Further research is required to clarify the association of FA metabolism with NTDs.

[Declining Rate of Neural Tube Defects and Outcomes of Defective Infants in Shaanxi Province from 2003 to 2022].

Objective To evaluate the changes in the incidence of neural tube defects (NTDs) in Shaanxi province from 2003 to 2022,investigate the diagnosis time and outcomes of defective infants,and predict the incidence of NTDs in Shaanxi province from 2023 to 2025,thereby providing a basis for improving the birth defects surveillance system. Methods Data were collected from all the perinatal infants from 28 weeks of gestation to 7 days after birth in all the hospitals with obstetrical department in Shaanxi province during 2003-2022.The changes in the incidence of NTDs from 2003 to 2022 were analyzed based on the birth defects surveillance system. Results A total of 1 106 483 perinatal infants in Shaanxi province from 2003 to 2022 were surveyed,among which NTDs occurred in 848 perinatal infants,with an incidence of 7.66/10 000.The incidence was the highest (48.02/10 000) in 2005 and the lowest (0.57/10 000) in 2022.The NTDs in Shaanxi province were mainly spina bifida (55.90%),which was followed by anencephaly (25.71%) and encephalocele (18.40%).The incidences of the three declined with fluctuations (P<0.001).The results of the Joinpoint analysis showed that the incidence of NTDs decreased slowly with the annual percentage change of -4.04 from 2003 to 2014 and declined rapidly with the annual percentage change of -28.05 from 2014 to 2022.From 2003 to 2022,the average proportion of prenatal diagnosis of NTDs in Shaanxi province was 72.88%.Dead fetus (61.91%) was the main birth outcome,followed by live birth (26.77%),stillbirth (8.73%),and death within seven days after birth (2.59%).The incidence of NTDs in Shaanxi province from 2023 to 2025 were predicted by the GM (1,1) model as 0.49/10 000,0.41/10 000,and 0.35/10 000,respectively. Conclusion The incidence of NTDs in Shaanxi province declined significantly during 2003-2022,especially in a rapid manner after 2014.Dead fetus was the primary outcome of perinatal infants with NTDs,followed by live birth.

Nondysraphic Intradural Spinal Lipoma: A Case Report and Review of Pathogenesis.

Intradural spinal lipomas are rare benign lesions typically located in the lumbosacral region and associated with spinal dysraphism in children. When unassociated with spinal dysraphism, they are most often diagnosed in young children or adolescents following the emergence of neurological symptoms. In their most rare form, intradural spinal lipomas may be found in adults without spinal dysraphism. Here, we present a case of a 42-year-old female with an intradural spinal lipoma without dysraphism at the T10-T11 level, demonstrating the diagnostic challenge of atypical lipomas and the importance of timely assessment and management. We also reviewed the embryopathogenesis of the different types of intradural spinal lipomas and the importance of surgical interventional planning and approach.

Research progress on ultrasound and molecular markers for prenatal diagnosis of neural tube defects.

Neural tube defects (NTDs) are severe congenital anomalies that result from the failure of early neural tube closure during fetal neurogenesis. They are the most common and severe congenital malformations of the central nervous system. Identifying reliable prenatal diagnostic ultrasound and molecular markers that can predict NTDs is of paramount importance. Early diagnosis of NTDs allows embryonic treatment and prevention strategies, which are crucial for reducing the disability rate associated with these malformations, reducing the burden on individuals and on society. The purpose of this comprehensive review was to summarize the ultrasound biomarkers between 11 and 13 weeks of gestation and the molecular biomarkers used in the diagnosis of NTDs, providing additional insights into early screening for NTDs.

Neurosurgical Advocacy in the Prevention of Neural Tube Defects: Impacting Global Fortification Policies Through Leadership, Collaboration, and Stakeholder Engagement.

The G4 Alliance and its member organizations formed a delegation that participated in the 76th World Health Assembly (WHA) in 2023, which unanimously adopted the resolution to address micronutrient deficiencies through safe, effective food fortification to prevent congenital disorders such as spina bifida and anencephaly, the first neurosurgery-led resolution since the founding of the World Health Organization. The WHA included other resolutions and side events by the G4 Alliance and other organizations relevant to neurosurgery. An opportunity exists for neurosurgeons to harness the momentum from this resolution to promote initiatives to prevent neurosurgical disease or expand access to neurosurgical care.

Associations between exposure to extreme ambient heat and neural tube defects in Georgia, USA: A population-based case-control study.

INTRODUCTION: The association between extreme ambient heat exposures during pregnancy and neural tube defects (NTDs) in offspring remains unclear. This study sought to estimate the association between exposure to extreme ambient heat during periconception and NTDs. METHODS: This population-based case-control study in Georgia, USA (1994-2017) included 825 isolated NTD cases (473 anencephaly, 352 spina bifida) and 3,300 controls matched 1:4 on county of residence and time period of delivery. Daily ambient temperature data were linked to fetal death and birth records by county of residence. Extreme ambient heat exposure was defined as the number of consecutive days the daily apparent temperature exceeded the county-specific 95th percentile (derived over 1980-2010) during an eight-week periconception period. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CI) using conditional logistic regression models adjusted for maternal age, education, and ethnicity and month and year of last menstrual period. RESULTS: The aORs for NTDs were 1.09 (95% CI 1.01, 1.17), 1.18 (95% CI 1.03, 1.36), and 1.29 (95% CI 1.04, 1.58) for exposure to 1-2, 3-5, and 6 or more consecutive days with apparent ambient temperatures exceeding the county-specific 95th percentile during periconception, respectively, compared to no days of extreme ambient heat exposure. Weekly analysis of extreme heat exposure indicated consistently elevated odds of offspring NTDs during periconception. These results were largely driven by spina bifida cases. CONCLUSIONS: Our results highlight potential health threats posed by increasing global average temperatures for pregnant people with implications for increased risk of neural tube defects in their offspring.

Folic acid supplement prescribing practice during the protective period and its associated factors among health professionals in selected governmental health centers in Addis Ababa, Ethiopia, 2023: A cross-sectional study.

Background: Supplementing folic acid (FA) before and in the first month of conception is an essential preventive factor, especially for neural tube defects (NTDs) and other congenital anomalies. Aim: The research aimed to assess FA supplement prescribing practice during the protective period and its associated factors among health professionals in selected governmental health centers in Addis Ababa, Ethiopia, in 2023. Methods: An institutionalized cross-sectional survey was carried out in Addis Ababa public health centers with a total sample size of 396 in February 2023. Systematic random sampling methods were used, and after each respondent's signed consent, a row of data was gathered using pretested self-administered questionnaires. The data was coded, interred to Epi Data 4.6.0.6 and transferred to Statistical Package for Social Sciences 27 software. Then a binary and multivariable logistic regression analysis method was used to show the associated variables with FA prescribing practice using a confidence interval (CI) of 95% and a significance value < 0.05. Results: The total prevalence of FA prescribing practice during the periconceptional period was 64.4% [95% CI (59.68-69.12)]. But those prescribed during the protective period were 26.7%. Ever since the birth of a neonate with NTDs, not prescribing a dose of 4 mg of FA for women with NTD, the type of women for whom FA was prescribed were associated with FA prescribing practice during the protective period. Conclusion: The healthcare professional's prescribing practice during the protective period was still low and needs more attention to strengthen FA supplements.

Bibliometric Analysis and a Call for Increased Rigor in Citing Scientific Literature: Folic Acid Fortification and Neural Tube Defect Risk as an Example.

The health benefits of vitamin B9 (folate) are well documented, particularly in regard to neural tube defects during pregnancy; however, much remains to be learned regarding the health effects and risks of consuming folic acid supplements and foods fortified with folic acid. In 2020, our laboratory conducted a population-based analysis of the Food Fortification Initiative (FFI) dataset to determine the strength of the evidence regarding the prevalence of neural tube defects (NTD) at the national level in response to mandatory fortification of cereal grains with folic acid. We found a very weak correlation between the prevalence of NTDs and the level of folic acid fortification irrespective of the cereal grain fortified (wheat, maize, or rice). We found a strong linear relationship between reduced NTDs and higher socioeconomic status (SES). Our paper incited a debate on the proper statistics to employ for population-level data. Subsequently, there has been a large number of erroneous citations to our original work. The objective here was to conduct a bibliometric analysis to quantitate the accuracy of citations to Murphy and Westmark's publication entitled, "Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset". We found a 70% inaccuracy rate. These findings highlight the dire need for increased rigor in citing scientific literature, particularly in regard to biomedical research that directly impacts public health policy.

Dorsal intercostal artery flap; A reliable option for coverage of myelomeningocele defects: A case series.

Meningomyelocele is a common congenital condition and its reconstruction poses a challenge for surgeons. The dorsal intercostal artery (DICA) flap offers a one-stage tension-free closure with adequate results. This study, spanning from January 2019 to September 2022, analyses the outcome of nine DICA flaps for meningomyelocele reconstruction, where the average size of the DICA flap was 6.8 x 4.6 cm for an average defect of 6.33 x 4 cm. Notably, no post-operative blood transfusion was required, nor any complications occurred except for one patient's septic shock-related death. Two had post-operative cerebrospinal fluid (CSF) leak, repaired primarily with one requiring VP shunt. Based on our experience, the DICA flap, with its consistent anatomy, is a reliable option for the reconstruction of meningomyelocele defects.

Association of maternal ABO blood type with lesion level and birthweight of children with spina bifida: a descriptive study.

The etiology of spina bifida, a neural tube birth defect, is largely unknown, but a majority of cases are thought to be genetic in origin. Although maternal blood type was found not to be associated with the occurrence of spina bifida, the analysis was never extended to other aspects of the disorder. The purpose of this descriptive study was to determine if maternal blood type was related to characteristics of children with spina bifida. The blood type of 221 mothers of children with spina bifida enrolled on the Arkansas Spinal Cord Disability Registry from 1995 to 2008 was obtained by mailed questionnaire. All children were community-dwelling and from singleton pregnancies. As expected, analysis of mother-child data showed that the distribution of mothers' blood type was not statistically different from the general population (chi-squared, P = 0.9203). However, the blood type of these mothers was associated with their child's lesion level (chi-squared, P = 0.011). Mothers with blood type A more frequently had children with thoracic lesions; mothers with non-A blood types more frequently had children with lumbar and sacral lesions. In addition, mean birthweight differed by mothers' blood type (analysis of variance, P = 0.025). Children of mothers with blood type A had the highest mean birthweight, while those of mothers with blood type AB had the lowest. Also, hydrocephalus was present more frequently in children with thoracic lesions compared to those with lumbar and sacral lesions (chi-squared, P = 0.001). Interestingly, these results were significant for female children but not for male children. In conclusion, maternal blood type was associated with lesion level and birthweight of children with spina bifida.

Climate Change and Congenital Anomalies: A Population-Based Study of the Effect of Prolonged Extreme Heat Exposure on the Risk of Neural Tube Defects in France.

BACKGROUND: Exposure to long-lasting extreme ambient temperatures in the periconceptional or early pregnancy period might increase the risk of neural tube defects (NTDs). We tested whether prolonged severe heat exposure as experienced during the 2003 extreme heatwave in France, affected the risk of NTDs. METHODS: We retrieved NTD cases spanning from January 1994 to December 2018 from the Paris Registry of Congenital Malformations. The 2003 heatwave was characterized by the long duration and high intensity of nine consecutive days with temperatures ≥35°C. We classified monthly conceptions occurring in August 2003 as "exposed" to prolonged extreme heat around conception (i.e., periconceptional period). We assessed whether the risk of NTDs among cohorts exposed to the prolonged severe heatwave of 2003 in the periconceptional period differed from expected values using Poisson/negative binomial regression. FINDINGS: We identified 1272 NTD cases from January 1994 to December 2018, yielding a monthly mean count of 4.24. Ten NTD cases occurred among births conceived in August 2003. The risk of NTD was increased in the cohort with periconceptional exposure to the August 2003 heatwave (relative risk = 2.14, 95% confidence interval: 1.46 to 3.13), compared to non-exposed cohorts. Sensitivity analyses excluding July and September months or restricting to summer months yielded consistent findings. INTERPRETATION: Evidence from the "natural experiment" of an extreme climate event suggests an elevated risk of NTDs following exposure to prolonged extreme heat during the periconceptional period.

Folate and Vitamin B12 Status in Women of Reproductive Age in Rural Haryana, India: Estimating Population-Based Prevalence for Neural Tube Defects.

BACKGROUND: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs). METHODS: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design. RESULTS: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively. CONCLUSIONS: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared.

Split Cord Malformation Presentation and Management in Pediatric and Adult Cases: a Case Series.

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.

"No One Needs to be Forced": Qualitative Insights on Competing Priorities between Antiretroviral Therapy and Reproductive Health Planning during the Dolutegravir Rollout.

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.

Effect and mechanism of Jinkui Shenqi Pill on preventing neural tube defects in mice based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: jinkui Shenqi Pill (JSP) is a classic traditional Chinese medicine used to treat "Kidney Yang Deficiency" disease. Previous studies indicate a protective effect of JSP on apoptosis in mouse neurons. AIM OF THE STUDY: This research, combining network pharmacology with in vivo experiments, explores the mechanism of JSP in preventing neural tube defects (NTDs) in mice. MATERIALS AND METHODS: Network pharmacology analyzed JSP components and targets, identifying common genes with NTDs and exploring potential pathways. Molecular docking assessed interactions between key JSP components and pathway proteins. In an all-trans retinoic acid (atRA)-induced NTDs mouse model, histopathological changes were observed using HE staining, neuronal apoptosis was detected using TUNEL, and Western Blot assessed changes in the PI3K/AKT signaling pathway and apoptosis-related proteins. RESULTS: Different concentrations of JSP led to varying degrees of reduction in the occurrence of neural tube defects in mouse embryos, with the highest dose showing the most significant decrease. Furthermore, it showed a better reduction in NTDs rates compared to folic acid (FA). Network pharmacology constructed a Drug-Active Ingredient-Gene Target network, suggesting key active ingredients such as Quercetin, Wogonin, Beta-Sitosterol, Kaempferol, and Stigmasterol, possibly acting on the PI3K/Akt signaling pathway. Molecular docking confirmed stable binding structures. Western Blot analysis demonstrated increased expression of p-PI3K, p-Akt, p-Akt1, p-Akt2, p-Akt3, downregulation of cleaved caspase-3 and Bax, and upregulation of Bcl-2, indicating prevention of NTDs through anti-apoptotic effects. CONCLUSION: We have identified an effective dosage of JSP for preventing NTDs, revealing its potential by activating the PI3K/Akt signaling pathway and inhibiting cell apoptosis in atRA-induced mouse embryonic NTDs.

Association between UCP2 gene 3'UTR I/D and A55V polymorphisms and neural tube defects susceptibility: systematic review, meta-analysis, and trial sequential analysis.

Aim: Our study aimed to assess the association between UCP2 gene 3' untranslated region insertion/deletion (3'UTR I/D) and A55V (alanine/valine) polymorphisms and neural tube defects (NTDs) susceptibility. Materials and methods: According to pre-determined inclusion and exclusion criteria, the article search was conducted to search articles published before October 2023. Two authors independently screened the included articles and extracted their basic characteristics. After quality evaluation, the meta-analysis and trial sequential analysis (TSA) were conducted using RevMan 5.4, Stata/MP 17, and TSA 0.9.5.10 Beta. Subgroup analysis was conducted based on country and case group composition. Sensitivity analysis was conducted using a one-by-one exclusion method. Begg's and Egger's tests were used to evaluate publication bias. Results: A total of seven articles were included. Overall meta-analysis revealed significant heterogeneity among the included studies for 3'UTR I/D polymorphism of the UCP2 gene. Significant statistical data indicated that those with the DD genotype and D allele had higher chances of NTD compared to those with the II genotype and the I allele, respectively. The combined result of II vs. ID was not statistically significant. A55V variation showed no statistical significance in the risk of NTD, despite the absence of significant heterogeneity across the included studies. Most of the heterogeneity was resolved after subgrouping, and a higher risk of the ID genotype was found than the II genotype for Chinese people. Genotyping NTD patients or their mothers was not a factor affecting the heterogeneity. Sensitivity analysis and publication bias analysis suggested that positive findings supported our results. Conclusion: The UCP2 gene 3'UTR I/D polymorphism increased the likelihood of developing NTDs in the Chinese population, with the D allele being the risk factor, which contributed to the understanding of the genetic basis of NTDs. TSA indicated that more high-quality original studies were needed in the future for further validation.