Incidence Of Neural Tube Defects Research Articles

PRENATAL DIAGNOSIS OF NEURAL TUBE DEFECTS USING ANTENATAL ULTRASOUND

Objective: To determine the prevalence and causes of neural tube defects (NTDs) using antenatal ultrasound and clinical history. Introduction: NTDs are common congenital malformations affecting the central nervous system, with maternal folic acid deficiency being a key risk factor. NTDs are classified as open or closed, with open spina bifida being the most common compatible with life. Methods: The study included 2730 antenatal patients. Excluded were those with prior NTD diagnoses. Results: Twenty-two cases of NTDs were identified (prevalence: 0.80%). The most common types were anencephaly (63.6%), open spina bifida (13.6%), encephalocele (9.09%), and myelomeningocele (9.09%). Key risk factors included non-use of folic acid (50%) and a history of congenital anomalies (18%). Discussion: NTDs arise from failed neural tube closure, affecting brain and spinal cord development. Early detection via ultrasound, fetal MRI, and maternal screening can improve diagnosis. In cases compatible with life, further renal and neurological evaluations are recommended. Conclusion: Antenatal ultrasound is essential for diagnosing NTDs, with MRI used for confirmation. Prevalence in this study was 0.80%, and anencephaly was the most common defect. Folic acid supplementation is critical for reducing NTD incidence.

A Spectrum of Neural Tube Defects: An Observational Study in the Eastern State of India

Objective: This study aimed to determine the prevalence and types of neural tube defects (NTDs) in eastern India, examine the associated maternal and paternal risk factors, and evaluate the impact of antenatal ultrasonography for early detection and management.Materials and Methods: A four-year observational study was conducted at the IMS and SUM Hospital, SOA University, Bhubaneswar, India, from July 2020 to June 2024. Pregnant women attending the antenatal clinic were screened for NTDs by using high-resolution ultrasonography. Diagnosed cases were further confirmed by postmortem autopsy, when available. Relevant maternal and paternal demographic data, including age, socioeconomic status, consanguinity, body mass index (BMI), hyperthermia, and paternal occupation, were collected. Statistical analysis was performed using Fisher’s exact test to identify significant associations between these factors and NTD occurrence, with significance set at P < 0.05.Results: The incidence of NTDs was 9.12 per 1000 deliveries, with spina bifida (43.4%) being the most prevalent, followed by anencephaly (32.9%), and encephalocele (11.1%). NTDs were significantly associated with maternal age (20-24 years), lower socioeconomic status, consanguinity (12.93% of cases), maternal obesity (BMI ≥30 kg/m²), and hyperthermia (≥100 °F). Fathers engaged in labor-intensive occupations had higher rates of offspring with NTDs (56%). This study highlights the effectiveness of antenatal ultrasonography for early detection and management, particularly in high-risk populations.Conclusion: NTDs continue to pose a significant public health challenge in Eastern India. This study underscores the need for improved prenatal care, genetic counseling, and targeted public health interventions, including folic acid supplementation and lifestyle modifications, to mitigate risk factors. Future research should focus on expanding geographic coverage and integrating genetic analysis to better understand the complex interplay between environmental and genetic factors contributing to NTDs.

Vitamin E supplementation prevents obesogenic diet-induced developmental abnormalities in SR-B1 deficient embryos.

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. 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. 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.

Folate fortification for spina bifida: preventing neural tube defects.

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.

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.

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).

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.

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.

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.

A CASE REPORT OF MYELOMENIGOCELE WITH ARNOLD CHIARI MALFORMATIN II-HIGHLIGHTING THE IMPORTANCE OF ANEMIA MUKTH BHARATH PROGRAMME

Introduction:Neural tube defects are common complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which usually completes by 28 days post conception. Myelomeningocele is almost always associated with Arnold Chiari Malformation II (CM II)and vice versa. Aims &amp;Objectives : As most of the neural tube defects can be prevented by pre-conceptional folate supplements, we would like to high light the importance of proper implementation and utilization of Anemia Mukhth Bharath Programme. Background: Neural tube defects (NTDs) are caused by a combination of multiple genes and multiple environmental factors like folic acid deficiency, insulin dependent diabetes, obesity and certain medications which interfere with folate metabolism.One of the beneficiaries under the Anemia Mukth Bharath programme are women in the reproductive age group in the pre-conception period and up to the first trimester of the pregnancy. They are advised to have400 mcg of Folic Acid tablets, daily, to reduce the incidence of neural tube defects in the fetus. Case report :We present a case of Chiari malformation associated with megaloblastic anemia with an attempt to highlight the importance of proper utilization of national program for prevention of iron and folate deficiency in women of reproductive age group. Clinical relevance : Neural tube defects are largely preventable anomalies by simple and effective management of folate deficiency preconceptionally. Conclusion :Proper utilization of the Anemia Mukth Bharath program which is available to the beneficiaries at their doorstep can not only prevent maternal anemia but also prevent fetal loss due to NTD.

Retrospective Investigation of the Incidence of Patients with Neural Tube Defects During the Pandemic Period, Single Center Study

Objective: Our aim in this study is as a result of the measures taken during the Covid 19 epidemic period; investigate whether factors related to immobilization due to the ban on going outdoors, carbon dioxide retention due to the use of masks, inability to perform appropriate pregnancy vizits on time and stress-related factors on pregnant women during the disease period increase the incidence of neural tube defects in both Turkish society and Syrian refugees living in Turkey. Materials and Methods: The data in the study were obtained from the archive of the single-center Şanlıurfa Research and Training Hospital. In this study, live births in the hospital archive between 01.01.2018-31.12.2019 and 01.01.2020-31.12.2021 and patients who were operated for neural tube defects were examined. Results: In the Turkish population, the incidence of neural tube defects in 2018, 2019, 2020 and 2021 was found to be 0.077%, 0.186%, 0.298% and 0.436%, respectively. There was a statistically significant difference between these years (p&amp;lt;0.001) (2018 and other years). The incidence of neural tube defects in refugees of Syrian origin in 2018, 2019, 2020 and 2021 was found to be 0.148%, 0.145%, 0.483% and 0.603%, respectively. There was a statistically significant difference between the years specified in refugees of Syrian origin (p&amp;lt;0.001) (2019 vs 2020 and 2019 vs. 2021). In 2020, the incidence of neural tube defects in refugees of Syrian origin (0.483%) was found to be significantly higher than the incidence of neural tube defects in the Turkish population (0.298%) (p=0.039). Conclusion: We detected an increase in neural tube defects due to the restrictions brought by the pandemic. The incidence increase between the sexes was similar. Incidence rates were similar in both Turks and Syrians in the years except 2020.

Inpp5e Regulated the Cilium-Related Genes Contributing to the Neural Tube Defects Under 5-Fluorouracil Exposure.

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.

Maternal Smoking during Pregnancy and its effects on Neural Tube Defects.

Maternal smoking is a potent teratogen among congenital malformations, however its role in the development of Neural Tube Defects (NTDs) is still unclear. In this systematic review, we intend to further investigate the interaction of smoking during pregnancy and the incidence of NTDs. This article was written according to PRISMA criteria from February 2015 and August 2022. After examining the four stages of PRISMA criteria, we selected clinical articles. These articles were selected from PubMed, Scopus and Google scholar (for results follow-up) databases. We gathered NTDs effect and types, smoking type and habit of parents, from neonates. Eventually, 8 articles were included by two separated authors, Smoking was associated with an increase NTDs in the population of pregnant mothers and also among children whose fathers smoked. The main side effects that were considered to be the cause of NTDs besides smoking were alcohol and BMI (18.5-24.9). Smoking also affects the level of folic acid as a substance with an essential role that affects the closure of the neural tube. folic acid available to infants changing along with the level of other blood elements such as zinc, that necessary prevent for NTDs condition. Parental smoking can be considered as one of the strong teratogens in the occurrence of NTDs. Smoking, whether active or passive by the mother, or by the father, is associated with the occurrence of NTDs, In order to reduce the prevalence this disorder, we advise pregnant mothers and neonate's fathers to quit smoking.

Effect of sugammadex administration on neural tube development in 48-h chick embryos.

Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. The aim of this study is to investigate the teratogenic effects of sugammadex on neural tube and embryonic development in early chick embryos. In this study, 50 0-day fertile specific non-pathogenic (SPF) eggs were used. Fifty eggs were divided into 5 different groups, each consisting of 10 pieces. While no substance was given to the control group at the 28th hour of the study, 4 different doses of sugammadex were administered to the experimental groups, respectively 2, 4, 8, 16 mg/kg. Cranio-caudal lengths of embryos, somite numbers, average number of argyrophilic nucleolar regulatory regions (AgNOR) per nucleus, total AgNOR area/total nuclear area (TAA/NA) ratios, Caspase-3 H-Score results, and presence of neural tube defect were compared among the groups. While the mean cranio-caudal lengths, somite counts, TAA/NA ratios and AgNOR counts of the embryos were found to be statistically significantly lower than the control group, Caspase-3 H-Score mean results were found to be significantly higher (p < .05). In addition, it was observed that there was an increase in neural tube patency and developmental delay. As a result, sugammadex crossing the placenta was revealed to increase the release of proapopitotic molecules and disrupt the developmental stages of embryos. Thus, it was determined that sugammadex in increased developmental delay and incidence of neural tube defects in early chick embryos with increased dose dependent. Despite these results, the effects of sugammadex on fetal development in in vivo and in vitro environments should be studied with further studies. RESEARCH HIGHLIGHTS: Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. It has been observed that different doses of sugammadex increase the risk of neural tube defect development on chick embryos and slow the embryo development in a dose-dependent manner.

Wuzi Yanzong Pill protects neural tube defects by activating PI3K/Akt signaling pathway.

Neural tube defects (NTDs) are severe congenital malformations that can lead to lifelong disability. Wuzi Yanzong Pill (WYP) is an herbal formula of traditional Chinese medicine (TCM) that has been shown to have a protective effect against NTDs in a rodent model induced by all-trans retinoic acid (atRA), but the mechanism remains unclear. In this study, the neuroprotective effect and mechanism of WYP on NTDs were investigated in vivo using an atRA-induced mouse model and in vitro using cell injury model induced by atRA in Chinese hamster ovary (CHO) cells and Chinese hamster dihydrofolate reductase-deficient (CHO/dhFr) cells. Our findings suggest that WYP has an excellent preventive effect on atRA-induced NTDs in mouse embryos, which may be related to the activation of the PI3K/Akt signaling pathway, improved embryonic antioxidant capacity, and anti-apoptotic effects, and this effect is not dependent on folic acid (FA). Our results demonstrated that WYP significantly reduced the incidence of NTDs induced by atRA; increased the activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and content of glutathione (GSH); decreased the apoptosis of neural tube cells; up-regulated the expression of phosphatidylinositol 3 kinase (PI3K), phospho protein kinase B (p-Akt), nuclear factor erythroid-2 related factor (Nrf2), and b-cell lymphoma-2 (Bcl-2); and down-regulated the expression of bcl-2-associated X protein (Bax). Our in vitro studies suggested that the preventive effect of WYP on atRA-treated NTDs was independent of FA, which might be attributed to the herbal ingredients of WYP. The results suggest that WYP had an excellent prevention effect on atRA-induced NTDs mouse embryos, which may be independent of FA but related to the activation of the PI3K/Akt signaling pathway and improvement of embryonic antioxidant capacity and anti-apoptosis.

Global, regional, and national epidemiological trends in neural tube defects between 1990 and 2019: a summary.

Neural tube defects (NTD), such as spina bifida, are surgically treatable and primarily preventable non-communicable diseases. How incidence, mortality and disability-adjusted life year (DALYs) rates of NTD have modulated over time is not well defined. Correspondingly, the aim of this study was to quantitively define the global, regional, and national epidemiological trends in these. A retrospective review of data from the Global Burden of Disease Study 2019 Database was performed. Global, regional, and national outcomes for NTD were collected for incidence, mortality, and DALY rates and their age-standardized metrics analyzed. There were 7 regions at a regional level, and 204 countries and territories at a national level. Globally, the latest age-standardized rates of incidence, mortality, and DALYs of NTD were 2.1 per 100,000 population, 1.3 per 1000,000, and 117 per 100,000 respectively. All rates demonstrated decreases in the last two decades to now. Regionally, sub-Saharan Africa and North America demonstrated the highest and lowest age-standardized rates of incidence (4.0 vs 0.5 per 100,000), mortality (3.0 vs 0.4 per 100,000), and DALYs (266 vs 33 per 100,000), respectively. Similar to global trends, all regions demonstrated decrease in these rates over the last two decades. Nationally, the highest age-standardized rates were reported in African countries, Central African Republic, with highest incidence rate (7.6 per 100,000), and Burkina Faso with highest mortality rate (5.8 per 100,000) and DALY rate (518 per 100,000). India was the country with the highest number of new NTD cases (22,000 per country) in the most recent year of study. Between 1990 and 2019, 182/204 (89%), 188/204 (92%), and 188/204 (92%) countries and territories demonstrated a decrease in age-standardized incidence, mortality, and DALY rates respectively, with the greatest decreases seen in Saudi Arabia for all statistics. Between 1990 and 2019, overall trends in incidence, mortality, and DALY rates of NTD have been favorably downtrending globally. Regionally, these rates in the highest sub-Saharan Africa were 8 times greater compared to the lowest North America. Nationally, although the majority of countries showed decreases in these rates, a small number of countries demonstrated uptrending rates of NTD. Understanding the mechanics behind these trends will allow future public health endeavors for both prevention and neurosurgical treatment to be targeted appropriately.

Contribution of folic acid to human health and challenges of translating the science into effective policy: a call to action for the implementation of food fortification in Ireland

Over 30 years ago it was proven beyond doubt that folic acid supplementation of mothers in early pregnancy protects against neural tube defects (NTD) in their babies. Such conclusive scientific evidence led to clear recommendations for women worldwide to take 0⋅4 mg/d folic acid before conceiving and in early pregnancy, but implementing these into effective policy has been problematic. As a result, there has been no change in the incidence of NTD in Ireland, the UK or any other European country over the 25-year period that the current strategy, recommending periconceptional folic acid supplements to women, has been in place. Thus preventable NTD are not being prevented. Notably, in September 2021, the UK government announced that starch is to be fortified with folic acid on a mandatory basis. A similar decision is now urgently needed in Ireland, where rates of NTD are among the highest in the world. A policy of mandatory folic acid fortification of food would be highly effective in preventing NTD because it reaches all women, including those who have not planned their pregnancy. International evidence shows that wherever such a policy has been introduced, it has proved to be effective in reducing rates of NTD in that country. Apart from preventing NTD, the driver of policy in the area, other potential health benefits across the lifecycle can be anticipated from folic acid fortification. Urgent action is needed on implementation of mandatory food fortification with folic acid in Ireland so that mothers and their babies can benefit.

An optimal combination of five main monomer components in Wuzi Yanzong Pill that prevents neural tube defects and reduces apoptosis and oxidative stress

Ethnopharmacological relevanceWuzi Yanzong Pill (WYP) is a classic traditional Chinese medicine (TCM) formula that is used for reproductive system diseases. Previous studies showed that WYP had a preventive effect on the development of neural tube defects (NTDs) induced by all-trans retinoic acid (atRA) in mice. Aim of the studyThis study aimed to determine the optimal combination of main monomer components in WYP on preventing NTDs and to understand the underlying mechanism. Materials and methodsAn optimal combination was made from five representative components in WYP including hyperoside, acteoside, schizandrol A, kaempferide and ellagic acid by orthogonal design method. In a mouse model of NTDs induced by intraperitoneal injection of atRA, pathological changes of neural tube tissues were observed by Hematoxylin & Eosin (HE) staining, neural tube epithelial cells apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), protein changes related to apoptosis, anti-apoptosis, and antioxidant factors were detected with Western blot. Potential targets and mechanisms of monomer compatibility group (MCG) acting on NTDs were analyzed by bioinformatics. ResultsTreatment with different combinations of WYP bioactive ingredients resulted in varying decreases in the incidence of NTDs in mice embryos. The combination of MCG15 (200 mg/kg of hyperoside, 100 mg/kg of acteoside, 10 mg/kg of schizandrol A, 100 mg/kg of kaempferide and 1 mg/kg of ellagic acid) showed the most significant reduction in NTD incidence. Mechanistically, MCG15 inhibited apoptosis and oxidative stress, as evidenced by reduced TUNEL-positive cells, downregulation of caspase-9, cleaved caspase-3, Bad, and Bax, and upregulation of Bcl-2, as well as decreased MDA and increased SOD, CAT, GSH, HO-1, and GPX1 levels. Bioinformatics analysis showed that MCG15 acted on the PI3K/Akt signaling pathway, which was confirmed by Western blot analysis showing increased expression of p-PI3K, p-Akt/Akt, and Nrf2 related indicators. ConclusionWe have identified an optimal combination of five bioactive components in WYP (MCG15) that prevented NTDs in mice embryos induced by atRA by activating the PI3K/Akt signaling pathway and inhibiting apoptosis and oxidative stress.

Neural Tube Defects and Folate Deficiency: Is DNA Repair Defective?

Neural tube defects (NTDs) are complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which is affected by the interaction of genetic and environmental factors. It is well known that folate deficiency increases the incidence of NTDs; however, the underlying mechanism remains unclear. Folate deficiency not only causes DNA hypomethylation, but also blocks the synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) and increases uracil misincorporation, resulting in genomic instabilities such as base mismatch, DNA breakage, and even chromosome aberration. DNA repair pathways are essential for ensuring normal DNA synthesis, genomic stability and integrity during embryonic neural development. Genomic instability or lack of DNA repair has been implicated in risk of development of NTDs. Here, we reviewed the relationship between folate deficiency, DNA repair pathways and NTDs so as to reveal the role and significance of DNA repair system in the pathogenesis of NTDs and better understand the pathogenesis of NTDs.

The Effect of Health Education on Knowledge, Attitude and Practice of Folic Acid Supplementation among Periconceptional Women at the Health Clinic in Kuala Lumpur

Background: Neural tube defects (NTDs) are congenital abnormalities of the central nervous system that can be prevented by consuming 400 µg of folic acid daily during conception until the twelfth week of pregnancy. Malaysia is experiencing an increase in NTD cases. Addressing women's knowledge, attitudes, and practices regarding folic acid- and folate-rich foods is crucial to reduce the incidence of NTDs. Objectives: This study aimed to evaluate the impact of a health education program on improving knowledge, attitudes, and practices related to folic acid supplementation among periconceptional women in a community clinic. Methods: A pre- and post-quasi-experimental study was conducted among 114 periconceptional women in two groups. The intervention group received structured Folic Acid supplementation education, while the control group received routine antenatal care. Results: Regarding knowledge, the intervention significantly improved the scores of the intervention group, increasing from 13.40 to 15.39. This improvement was statistically significant, with a mean difference of 1.98 (p &lt; 0.001), large effect size of 0.16, and strong statistical power of 0.89. Meanwhile for attitude, the intervention group experienced a more significant increase in scores, from 25.72 to 27.46. Statistically significant effects were observed (p = 0.031), along with a large effect size 0.26 and relatively high statistical power 0.99. In terms of practice, the intervention group showed a significant improvement, with scores increasing from 27.68 33.16. The findings were significant, with a mean difference of 5.47 (p &lt; 0.001), extreme effect size of 0.74, and strong statistical power of 1.00. Conclusion: A comprehensive health education program for pregnant women can significantly improve their understanding, attitude, and adherence to folic acid supplementation. In addition, it is essential to promote the consumption of folic acid-fortified foods.