Neural Tube Defects Cases Research Articles

NEURAL TUBE CLOSURE ANOMALIES: EPIDEMIOLOGICAL STUDIES AND RISK FACTORS AT THE NEONATAL AND NEONATAL RESUSCITATION DEPARTMENT OF MOHAMMED VI UNIVERSITY HOSPITAL, OUJDA

Objective:This studyaims to identify the sociodemographic, maternal, and obstetricriskfactorsassociatedwith neural tube defects (NTDs) and determinetheirprevalenceamongnewbornshospitalized in the neonatology and neonatal intensive care unit at CHU Mohamed VI Oujda. Methods:Weconducted a descriptive retrospectivestudy over an 18-month period, including all newbornshospitalizedwithisolated or associatedNTDs. Incomplete records wereexcludedfrom the analysis. Results:Out of 797 hospitalizednewborns, 66 hadcongenital malformations, including 10 cases of NTDs (1.25%). The types of NTDsidentifiedwereanencephaly (1 case), spina bifida (6 cases), and encephalocele (3 cases). The majority of mothers had an average age of 34.3 years, with 80% coming from a low socioeconomic status and 60% having a history of consanguineous marriages. Additionally, fenugreek consumption during the first trimester of pregnancy was reported in 70% of cases, while only 20% of mothers had taken folic acid.Regarding the newborns, 70% presented with hypotonia, and 60% exhibited weak or absent primitive reflexes. The short-term postoperative mortality rate was 30%. Discussion:The prevalence of neural tube defects (NTDs) observed in this study is significantly higher than the global average, which may be explained by unfavorable socioeconomic conditions and maternal nutritional deficiencies. Fenugreek consumption and low folic acid supplementation were identified as significant risk factors. Conclusion:To reduce the incidence of NTDs, itis essential to Strengthening prenatal care, encouraging folic acid supplementation, and advising against the consumption of fenugreek during pregnancy are essential. A preventive strategy tailored to local specificities could significantly improve newborn health and reduce complications associated with neural tube defects (NTDs).

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.

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. 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. 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. 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.

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

IntroductionThe 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. MethodsThis 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. ResultsThe 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. ConclusionsOur 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.

Association between the MTHFR (rs1801133) gene variation and serum trace elements levels (Copper and Zinc) in individuals diagnosed with neural tube defects

Background and AimsNeural tube defects (NTDs) occur when the neural tube fails to close within 28 days of human embryonic development. This results in central nervous system disorders like anencephaly, spina bifida, and encephalocele. Early diagnosis and treatment are crucial to minimize their impact on an individual’s health and well-being. The present study aims to define the association between prenatal exposure to trace elements (Cu and Zn) and the single nucleotide polymorphism (SNP) of the MTHFR gene involved in folate metabolism pathways in neural tube defects in children and their mothers. Material and MethodsA cross-sectional study involving 331 participants (90 NTD cases, 88 healthy mothers, 85 NTD children, and 68 healthy children) from antenatal check-ups in Obstetrics and Gynaecology and Pediatric Surgery for Neural Tube Defects in the Outpatient Department (OPD) and Inpatient Department (IPD). Assessed Cu and Zn concentrations and their associations. Genomic DNA was extracted, and real-time PCR was used to determine genotypes. Atomic absorption spectrophotometry measured trace elements. Statistical analyses included Chi-Square tests, odds ratios, and Mann-Whitney U tests. ResultsSignificant associations were found between MTHFR C677T genotypes and NTD risk in mothers (p = 0.0491) and children (p = 0.0297). Allelic frequency analysis indicated a T allele association with NTD risk in children (p = 0.0107). Recessive models showed significant associations in mothers (p = 0.0169) and children (p = 0.1678). Cu levels differed significantly between NTD cases and controls (p < 0.0001), with MTHFR genotypes influencing Cu levels. Zinc levels also varied significantly (p < 0.0001). ConclusionThis study reveals complex associations between MTHFR C677T genotypes, trace element concentrations, and NTD risk in mothers and children. This targeted approach allows healthcare providers to identify at-risk pregnancies early, enabling personalised interventions like folic acid supplementation and counselling to moderate neural tube defect (NTD) risk in a future pregnancy.

The prevalence of neural tube defects and their prevention by folic acid supplementation

Background & AimsFolate is crucial for the development of the fetal neurological system. Moroccan Health authorities promote Folic acid (FA) supplementation, before and during pregnancy, as a significant protection against fetal neural tube defects (NTDs). Thus, the current study aims to investigate the effect of FA supplementation guidelines on NTDs prevalence and to assess the health professionals' (HPs) knowledge, attitude, and practice (KAP) regarding FA supplementation in Morocco. MethodsTo assess the prevalence of NTDs, epidemiological data were collected from local and regional medical facilities and enhanced through a literature study. In addition, an auto-administered questionnaire was implemented to evaluate KAP among HPs on the FA supplementation national program. ResultsThe study results showed that from 2017 to 2023, the national prevalence rate of NTDs ranged from 4.26 to 21 per 10,000 live births, according to the region. Lack of information about FA supplementation is evident among HPs; while, 13.7% of the participants confused FA with vitamin B12; merely 50% recognized the significance of FA; and 11.9% had no idea which foods contained the most folate. Consequently, HPs' attitude and practice towards FA supplementation were deemed inadequate. Additionally, only 35.8% of respondents stated that they occasionally inquire about their patients' nutrition, 55.9% do not prescribe FA, and 44.1% are unwilling to report cases of NTDs. ConclusionNTDs remain a serious public health problem in Morocco. Despite the significant incidence of these diseases, HPs' knowledge, attitudes and practices in terms of prevention present gaps and inadequacies. According to the results of this study, the preparation of specific training sessions and the start of preconception consultations constitute an urgent and important issue.

Epidemiology of neural tube defects in Finland: a nationwide register study 1987-2018.

Our aim was to evaluate the prevalence, mortality, regional and sex distribution of neural tube defects (NTDs) in Finland. Data for this population-based study were collected from 1987 to 2018 from the national health and social welfare registers. There were in total 1634 cases of NTDs, of which 511 were live births, 72 pregnancies ended in stillbirth and 1051 were terminations of pregnancy due to fetal anomaly (TOPFA). The total prevalence of NTDs was 8.6 per 10 000 births and it increased slightly annually (OR 1.008; 95% CI: 1.002, 1.013) during the 32-year study period. The birth prevalence of NTDs decreased (OR 0.979; 95% CI: 0.970, 0.987), but the prevalence of TOPFA increased annually (OR 1.024; 95% CI 1.017, 1.031). The perinatal mortality of NTD children was 260.7 per 1000 births and the infant mortality was 184.0 per 1000 live births, whereas these measures in the general population were 4.6 per 1000 births and 3.3 per 1000 live births, respectively. There was no difference in the NTD prevalence between males and females (P-value 0.77). The total prevalence of NTDs varied from 7.1 to 9.4 per 10 000 births in Finland by region. Although the majority of NTDs are preventable with an adequate folic acid supplementation, the total prevalence increased in Finland during the study period when folic acid supplementation was mainly recommended to high-risk families and to women with folic acid deficiency. NTDs remain an important cause of infant morbidity and mortality in Finland.

Determinants of neural tube defect among newborns admitted to neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, Southern Ethiopia: a case–control study

BackgroundNeural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited attention. In...

Chromium levels in placental tissue and neural tube defects: Association and mechanistic study

Human exposure to chromium (Cr) is common but little is known about its adverse effects on pregnancy outcomes. This study aimed to explore the association between Cr exposure and the risk of neural tube defects (NTDs) and the underlying mechanisms of Cr-induced NTDs. 593 controls and 408 NTD cases with placentas were included in this study. Chromium trichloride (Cr(III)) and potassium dichromate (Cr(VI)) were intragastrically administered to pregnant mice and the number of NTDs was recorded. The odds ratio for total NTDs in the highest exposure group in placenta was 4.18 (95% confidence interval (CI), 1.97–8.84). The incidence of fetal NTDs in mice administered with Cr(III) showed a dose-response relationship. Cr(VI) didn't show teratogenicity of NTDs whereas increased the stillbirth rate. Prenatal exposure to Cr(III) increased levels of oxidative stress and apoptosis in fetal mice. RNA-sequencing results indicated significant enrichment of the MAPK pathway. RT-qPCR and Western blot analysis revealed that Cr(III) induced increased expression of p-JNK, p-P38, and Casp3. Toxicological effects can be partly antagonized by antioxidant supplementation. High chromium exposure was associated with increased human NTD risks. Excessive Cr(III) exposure can induce NTDs in fetal mice by increasing apoptosis through upgrading oxidative stress and then activating JNK/P38 MAPK signaling pathway.

Prevalence of neural tube defect and its identification during antenatal period: a cross-sectional study in eastern Indian state

ObjectiveTo estimate the prevalence of neural tube defects among all birth outcomes in Odisha during 2016–2022. Additionally, to estimate the identification rate of neural tube defects during Pradhan Mantri Surakshit...

Incidence of neural tube defects and associated anomalies in a tertiary care hospital

Abstract Background: Neural tube defects (NTDs) are the second most common congenital malformations after cardiac anomalies. The rate of associated malformation is reported to be 17%–80%. NTDs could also be a component of syndromic process. Objective: The objective of the study was to study the incidence of NTDs and associated anomalies. Methods: A hospital-based observational study was carried out among 6934 pregnant women referred for ultrasound. Pregnant women with NTDs were included. Detailed maternal history and clinical data were recorded. All ultrasound examinations were performed transabdominally by a radiologist using a 1–5 MHz convex array transducer (Voluson S8). Results: During this period of study, a total of 6934 pregnant women were screened and 47 cases of NTDs were detected and included, giving an incidence of 6.7 in 1000 conceptions (95% confidence interval = 5.02–8.92). NTDs were more common in mothers of age group 20–30 years. Spina bifida was the most common type of NTD in 53% of the cases. The most common type of spina bifida was meningomyelocele in 56%. The most common associated central nervous system (CNS) anomaly was Chiari II malformation. Conclusion: The most common NTD was spina bifida. CNS anomalies are more commonly associated with NTDs, followed by extremity defects.

Prevalence of Neural Tube Defects Following Flour Fortification with Folic Acid in North Iran

Background: Neural tube defects are prevalent malformations of the central nervous system in infants, often fatal, and considered global medical-social problems. Due to National Laws fortifying wheat flour in the bread industry, 100% of the population of this province has consumed wheat flour enriched with folic acid since June 2007. Objectives: This study aimed to determine the prevalence of neural tube defects following the fortification of flour with folic acid in the north of Iran. Methods: This descriptive-analytical study examined all neural tube defect cases in Golestan province, northern Iran, from March 2016 to March 2018. Data on the parent's age, ethnicity, mother's education, residency, and types of neural tube defects were recorded for each subject. Results: The prevalence rate of NTDs was 1.04 per 1000 births. The highest frequency was observed in the Turkmen ethnic group, with a prevalence rate of 1.251 per 1000 births. Geographically, most cases were in the West of Golestan province, with a prevalence rate of 1.876 per 1000 births. Additionally, the highest prevalence of NTD in Kalaleh City was reported as 1.67 per 1000 births. Among NTD cases, the highest frequency was related to mothers aged less than 35 years (82.72%). Conclusions: The prevalence of neural tube defects during 2016 - 2018 has increased compared to the previous study conducted in this region from 2006 - 2009. Future studies should investigate the reasons behind this increase.

Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects

Neural tube defects (NTDs) are severe malformations of the central nervous system that arise from failure of neural tube closure. HECTD1 is an E3 ubiquitin ligase required for cranial neural tube closure in mouse models. NTDs in the Hectd1 mutant mouse model are due to the failure of cranial mesenchyme morphogenesis during neural fold elevation. Our earlier research has linked increased extracellular heat shock protein 90 (eHSP90) secretion to aberrant cranial mesenchyme morphogenesis in the Hectd1 model. Furthermore, overexpression of HECTD1 suppresses stress-induced eHSP90 secretion in cell lines. In this study, we report the identification of five rare HECTD1 missense sequence variants in NTD cases. The variants were found through targeted next-generation sequencing in a Chinese cohort of 352 NTD cases and 224 ethnically matched controls. We present data showing that HECTD1 is a highly conserved gene, extremely intolerant to loss-of-function mutations and missense changes. To evaluate the functional consequences of NTD-associated missense variants, functional assays in HEK293T cells were performed to examine protein expression and the ability of HECTD1 sequence variants to suppress eHSP90 secretion. One NTD-associated variant (A1084T) had significantly reduced expression in HEK293T cells. All five NTD-associated variants (p.M392V, p.T801I, p.I906V, p.A1084T, and p.P1835L) reduced regulation of eHSP90 secretion by HECTD1, while a putative benign variant (p.P2474L) did not. These findings are the first association of HECTD1 sequence variation with NTDs in humans.

Spina Bifida Prevention: A Narrative Review of Folic Acid Supplements for Childbearing Age Women.

Neural tube defects (NTDs) are malformations that occur during embryonic development, and they account for most central nervous system birth anomalies. Genetic and environmental factors have been shown to play a role in the etiology of NTDs. The different types of NTDs are classified according to anatomic location and severity of the defect, with most of the neural axis anomalies occurring in the caudal spinal or cranial areas. Spina bifida is a type of NTD that is characterized by an opening in the vertebral arch, and the level of severity is determined by the extent to which the neural tissue protrudes through the opened arch(es). Prevention of NTDs by administration of folic acid has been studied and described in the literature, yet there are approximately 300,000 cases of NTDs that occur annually, with 88,000 deaths occurring per year worldwide. A daily intake of at least 400 μg of folic acid is recommended especially for women of childbearing age. To provide the benefits of folic acid, prenatal vitamins are recommended in pregnancy, and many countries have been fortifying foods such as cereal grain products with folic acid; however, not all countries have instituted folic acid fortification programs. The present investigation includes a description of the pharmacology of folic acid, neural tube formation, defects such as spina bifida, and the relevance of folic acid to developing spina bifida. Women's knowledge and awareness of folic acid regarding its importance in the prevention of spina bifida is a major factor in reducing incidence worldwide.

Understanding perspectives on neural tube defect management: insights from Jordanian parents

Introduction Neural tube defects (NTDs) represent a spectrum of heterogeneous birth anomalies characterized by the incomplete closure of the neural tube. In Jordan, NTDs are estimated to occur in approximately one out of every 1000 live births. Timely identification of NTDs during the 18–22 weeks of gestation period offers parents various management options, including intrauterine NTD repair and termination of pregnancy (TOP). This study aims to assess and compare parental knowledge and perceptions of these management modalities between parents of affected children and those with healthy offspring. Materials and methods This retrospective case-control study was conducted at Jordan University Hospital (JUH) using telephone-administered questionnaires. Categorical variables were summarized using counts and percentages, while continuous variables were analyzed using mean and standard deviation. The association between exposure variables and outcomes was explored using binary logistic regression. Data analysis was performed using SPSS for Windows version 26 (SPSS Inc., Chicago, IL). Results The study sample comprised 143 participants, with 49.7% being parents of children with NTDs. The majority of NTD cases were associated with unplanned pregnancies, lack of folic acid supplementation, and postnatal diagnosis. Concerning parental knowledge of TOP in Jordan, 86% believed it to be legally permissible in certain situations. However, there was no statistically significant difference between cases and controls regarding attitudes toward TOP. While the majority of parents with NTD-affected children (88.7%) expressed a willingness to consider intrauterine surgery, this percentage decreased significantly (to 77.6%) after receiving detailed information about the procedure’s risks and benefits (p = .013). Conclusions This study represents the first case-control investigational study in Jordan focusing on parental perspectives regarding TOP versus intrauterine repair of myelomeningocele following a diagnosis of an NTD-affected fetus. Based on our findings, we urge the implementation of a national and international surveillance program for NTDs, assessing the disease burden, facilitating resource allocation toward prevention strategies, and promoting early diagnosis initiatives either by using newly suggested diagnostic biomarkers or early Antenatal ultrasonography.

Role of Autopsy and Genetic Testing in the Diagnosis of Perinatal Deaths due to Congenital Anomalies: A Cross-sectional Study

Introduction: Foetal autopsy is one of the primary modalities for establishing the underlying causative aetiology in congenitally anomalous foetuses. Genetic aetiology is the cause in at least half of the foetuses. A correlative approach including dysmorphological evaluation, histopathology, imaging studies, and genetic testing plays a significant role in establishing the final diagnosis and management of such cases. Aim: To investigate the cause of perinatal death through a correlative approach involving Ultrasonography (USG), cytogenetic analysis, and autopsy in congenitally malformed neonates. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology and Obstetrics and Gynaecology at SCB Medical College, Cuttack, Odisha, India, from June 2018 to June 2020. The study included 19 congenitally malformed foetuses/aborted foetuses/neonates not compatible with life, born in the labour room. Written informed consent was obtained, and cord/cardiac blood/soft tissue samples from congenitally anomalous foetuses were collected in a heparinised vial/sterile container during delivery and sent for cytogenetic testing. The deceased foetuses were weighed, external abnormalities and anthropometry were recorded, and then they were preserved in 10% formalin. Autopsies were performed using Virchow’s method. All internal abnormalities were recorded, and sections were sent for Histopathological (HP) study. All the data was analysed using the Statistical Package for Social Sciences (SPSS) software version 20.0. Results: The study included a total of 19 cases, including 11 (57.8%) cases of Intrauterine Deaths (IUD). The majority were males 8 (42%), in the gestational age group of 20-25 weeks (36.7%). Maternal age ranged from 21 to 30 years, with the majority being nine cases (47.3%), and 13 cases (68.3%) without antenatal check-ups. The study comprised 6 cases (31.57%) of genetic syndromes, including Trisomy 21, 13, 18, and Monosomy X, 5 cases (26.3%) of musculoskeletal defects such as Meckel Gruber syndrome, Heterotaxy syndrome, and Thanatophoric dysplasia, and 5 cases (26.3%) of neural tube defects. Conclusion: Autopsy determined the cause of death in 90% of the cases and, when combined with genetic analysis, established the syndromic diagnosis. Autopsy findings can complement or modify the ultrasonographic findings. Therefore, perinatal autopsy should always be included in the management of deaths due to congenital anomalies.

Flap Closure in Neonatal Neural Tube Defects: Challenges in Flap Design and Lessons Learnt.

Management of neural tube defects (NTDs) is challenging and the outcome is demanding. To analyze the outcomes in operated cases of NTDs closed using various types of flaps. The data between June 2017 and May 2023 were analyzed. The mode of presentation, timing of intervention, type of flap, neurological status after closure, status of the wound, presence of hydrocephalous, flap blackening, flap necrosis, features of sepsis, and the outcome were recorded and analyzed. Covered NTD; closure done using primary closure or 'Z' Plasty (everywhere); incomplete data; lost to follow-up; and not giving consent were excluded from the study. Out of 92 cases, 35 were operated using the rhomboid flap, 33 using dufourmentel modification of limberg flap, and 24 using keystone island flap. The mean age at presentation was 4 days (range: 0-28 days). The mean duration of surgery after presentation was 2 days (range: 1-3 days). Mean operating time was 1.15 h (range: 0.45-3.15 h). A ventriculoperitoneal shunt was required in 62 cases at various stages. The preoperative and the postoperative power were nearly the same in all. Wound infection was seen in 2, 3, and 1 cases in each group. Blackening of the flap was seen in 3, 2, and 1 cases in three groups. Cerebrospinal fluid (CSF) leak was seen in 2, 2, and 0 cases. Wound dehiscence was present in one case in each group and sepsis was present in 2, 3, and 2, respectively. The management of open NTD requires adequate planning. CSF shunting and flap closure are often required.

Risk Factors and Prevalence of Spina Bifida in Children Reported at Children Hospital (Lahore): A Mix Method Analysis

Pakistan is the country with more than 100 million children and spina bifida is a neural tube defect that commonly affects children. Folic acid deficiency during the initial three weeks of pregnancy has been identified as a significant causative factor. However, other factors and their effects vary based on geographic location, maternal pregnancy history, child sex, and race. This cross sectional study aimed to investigate the factors contributing to the incidence rate of spina bifida in Lahore, Pakistan. A total of 200 cases of neural tube defects, including spina bifida, were studied and reported from October 2012 to August 2013 at Children's Hospital Lahore. Various factors were examined, such as the age of mothers, with 50% of babies with neural tube defects born to mothers aged between 26 and 36 years. The incidence of spina bifida was found to be higher in boys (59%) compared to girls (41%). Hydrocephalus, a common complication of spina bifida, was more prevalent in boys (51%) than in girls (14%). Spina bifida cystica, another form of the condition, occurred more frequently in girls (38%) than in boys (33%). In this study group, 161 out of 200 women did not use or properly use folic acid during pregnancy, indicating a lack of awareness regarding its importance. The study also revealed that 119 cases of spina bifida occurred during winter, suggesting a seasonal influence on the condition. In addition to other identified risk factors, this study underscores the critical need for raising awareness about the use of folic acid before conception and during the initial three weeks of pregnancy.

The Aperta type of neural tube defect: The relevant experience in a local community with the diversity of the presentation.

A series of birth defects known as neural tube defects (NTDs) appear when the neural tube fails to fully or partially close during fetal development. In nations without folic acid supplementation, their incidence ranges from 0.5 to 2 per 1,000 births. The purpose of our study is to estimate the prevalence of NTDs and define the workup for newborn infants with an open neural tube in Al-Qadissiyah, Iraq. This 18-year descriptive retrospective analysis included all babies with NTD diagnoses at the Maternity and Child Teaching Hospital in Al-Qadissiyah Governorate, Iraq. Over the research period, 187 cases of NTDs were evaluated. NTDs presented a male predominance and an incidence rate of 9.4 per 1,000 births, with spina bifida (67.9%), encephalocele (24.02%), and anencephaly (8.02%) being the most prevalent defects. The typical gestational age was 36±5, whereas the typical maternal age was 30±5. It should be noted that 29.9% of women did not take folic acid supplements during the first trimester, while one-third of moms did not benefit from medical supervision during pregnancy. In 65.2% of instances, an antenatal diagnosis was made, and cesarean section was the mode of delivery in 87,8% of cases. Other than that, 64.7% of women lived in low socioeconomic conditions, and 67.9% were from rural areas. The relevance of reinforcing and maximizing folic acid measures throughout the periconceptional phase is emphasized by the fact that NTDs require high intensity and advanced care.

Neighborhood Deprivation and Neural Tube Defects.

Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk. The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery. Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity. Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida.

MicroRNA-322 overexpression reduces neural tube defects in diabetic pregnancies

Hyperglycemia from pregestational diabetes mellitus induces neural tube defects in the developing fetus. Folate supplementation is the only effective way to prevent neural tube defects; however, some cases of neural tube defects are resistant to folate. Excess folate has been linked to higher maternal cancer risk and infant allergy. Therefore, additional interventions are needed. Understanding the mechanisms underlying maternal diabetes mellitus-induced neural tube defects can identify potential targets for preventing such defects. Despite not yet being in clinical use, growing evidence suggests that microRNAs are important intermediates in embryonic development and can serve as both biomarkers and drug targets for disease intervention. Our previous studies showed that maternal diabetes mellitus invivo activates the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in the developing embryo and that a high glucose condition invitro reduces microRNA-322 (miR-322) levels. IRE1α is an RNA endonuclease; however, it is unknown whether IRE1α targets and degrades miR-322 specifically or whether miR-322 degradation leads to neural tube defects via apoptosis. We hypothesize that IRE1α can inhibit miR-322 in maternal diabetes mellitus-induced neural tube defects and that restoring miR-322 expression in developing neuroepithelium ameliorates neural tube defects. This study aimed to identify potential targets for preventing maternal diabetes mellitus-induced neural tube defects and to investigate the roles and relationship of a microRNA and an RNA endonuclease in mouse embryos exposed to maternal diabetes mellitus. To determine whether miR-322 reduction is necessary for neural tube defect formation in pregnancies complicated by diabetes mellitus, male mice carrying a transgene expressing miR-322 were mated with nondiabetic or diabetic wide-type female mice to generate embryos with or without miR-322 overexpression. At embryonic day 8.5 when the neural tube is not yet closed, embryos were harvested for the assessment of 3 miR-322 transcripts (primary, precursor, and mature miR-322), tumor necrosis factor receptor-associated factor 3 (TRAF3), and neuroepithelium cell survival. Neural tube defect incidences were determined in embryonic day 10.5 embryos when the neural tube should be closed if there is no neural tube defect formation. To identify which miR-322 transcript is affected by maternal diabetes mellitus and high glucose conditions, 3 miR-322 transcripts were assessed in embryos from dams with or without diabetes mellitus and in C17.2 mouse neural stem cells treated with different concentrations of glucose and at different time points. To determine whether the endonuclease IRE1α targets miR-322, small interfering RNA knockdown of IRE1α or overexpression of inositol-requiring transmembrane kinase/endoribonuclease 1α by DNA plasmid transfection was used to determine the effect of IRE1α deficiency or overexpression on miR-322 expression. RNA immunoprecipitation was performed to reveal the direct targets of inositol-requiring transmembrane kinase/endoribonuclease 1α. Maternal diabetes mellitus suppressed miR-322 expression in the developing neuroepithelium. Restoring miR-322 expression in the neuroepithelium blocked maternal diabetes mellitus-induced caspase-3 and caspase-8 cleavage and cell apoptosis, leading to a neural tube defect reduction. Reversal of maternal diabetes mellitus-inhibited miR-322 via transgenic overexpression prevented TRAF3 up-regulation in embryos exposed to maternal diabetes mellitus. Activated IRE1α acted as an endonuclease and degraded precursor miR-322, resulting in mature miR-322 reduction. This study supports the crucial role of the IRE1α-microRNA-TRAF3 circuit in the induction of neuroepithelial cell apoptosis and neural tube defect formation in pregnancies complicated by diabetes mellitus and identifies IRE1α and miR-322 as potential targets for preventing maternal diabetes mellitus-induced neural tube defects.