[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.

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.

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.

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.

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

BACKGROUND: Our aim was to evaluate the prevalence, mortality, regional and sex distribution of neural tube defects (NTDs) in Finland. METHODS: Data for this population-based study were collected from 1987 to 2018 from the national health and social welfare registers. RESULTS: 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. CONCLUSIONS: 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.

Maternal periconceptional exposure to drinking water disinfection by-products and neural tube defects in offspring.

BACKGROUND: Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. METHODS: Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. RESULTS: Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. CONCLUSIONS: Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

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.

BACKGROUND: Neural 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 Ethiopia, the estimated number of neural tube defect cases was significantly higher. So, identifying factors contributing to it would be significant for planning risk reduction and preventive strategies. Therefore, identifying the possible determinants was aimed at this study. METHODS: A hospital-based, unmatched case-control study was conducted on 104 cases and 208 controls selected from neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, southern Ethiopia from December 2021 to November 2022. All neural tube defect cases were included consecutively and controls were selected by using a simple random sampling method. Data were collected using interviewer-administered semistructured questionnaires. Data analysis was done by using SPSS V.25. Binary logistic regression was used, and variables with a p value less than 0.25 in bivariate analysis were entered into the multivariable logistic regression model. An adjusted OR with a 95% CI was estimated, and finally, variables that show a level of p value less than 0.05 in multivariable analysis were declared statistically significant. RESULT: After controlling confounders, factors such as unplanned pregnancy 2.20 (95% CI 1.20 to 4.041), history of abortions 2.09 (95% CI 1.19 to 3.67), khat chewing 6.67 (95% CI 2.95 to 15.06), antipyretic and analgesic medications 2.87 (95% CI 1.47 to 5.56) and, being a female neonate 2.11 (95% CI 1.21 to 3.67) were significantly associated with a neural tube defect. CONCLUSION: This study has identified some determinants of neural tube defects. Hence, the behavioural, medical and obstetrical conditions of mothers need serious evaluation in the prepregnancy period. So, improving preconception counselling and prenatal care practices would have a significant role in reducing the risk of neural tube defects.

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

OBJECTIVE: To 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 Matritva Abhiyan sessions. DESIGN: A population-based cross-sectional study with a household survey for neural tube defects using pictorial card as well as a hospital-based study for antenatal ultrasonography data. SETTING: The sample population was selected through multistage random sampling. In the first stage, one district from each zone was selected randomly. In the second stage, using simple random sampling, one community health centre and one urban primary health centre were selected from each district. In the third stage, the population from a block and ward were picked from the selected rural and urban settings, respectively. PARTICIPANTS: All married women in the reproductive age group (18-49 years) residing in these cluster villages in the selected districts were enrolled. RESULTS: The study surveyed 49 215 women and recorded 50 196 birth outcomes, including 49 174 live births, 890 stillbirths and 132 medical terminations of pregnancy. A total of 30 neural tube defect cases were detected. The overall prevalence rate of neural tube defect was 0.59 per 1000 birth outcomes. Spina bifida was the most prevalent neural tube defect with the prevalence of, followed by anencephaly and encephalocele. Despite 26 860 mothers receiving antenatal ultrasonography Pradhan Mantri Surakshit Matritva Abhiyan session, data on neural tube defects and other birth defects detected through these scans is unavailable. CONCLUSION: This study found a low prevalence of neural tube defect in Odisha, which is far lower compared with the older studies from India. There is an urgent need to strengthen the quality of antenatal care services provided under Pradhan Mantri Surakshit Matritva Abhiyan through better training regarding anomaly scans and better data keeping at public healthcare facilities. TRIAL REGISTRATION NUMBER: CTRI/2021/06/034487.

Inadvertent antibiotic exposure during pregnancy may increase the risk for neural tube defects in offspring.

BACKGROUND: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. METHODS: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. RESULTS: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01-10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. CONCLUSIONS: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

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.

Prevalence and associated factors of congenital anomalies in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Congenital anomalies represent a significant contributor to infant mortality, morbidity, and enduring disability. With this in mind, the present investigation endeavour to ascertain the pooled prevalence of congenital anomalies and associated determinants among neonates in Ethiopia. METHOD: PubMed, Google Scholar, CINAHAL, Hinari, and Global Health databases were systematically searched. Joanna Briggs Institute (JBI) assessment checklist was used to assess quality of included studies. Data were extracted from database and exported to stataMP-17 for analysis. Pooled prevalence was determined using DerSimonian-Laird random effects model. The degree of heterogeneity and Publication bias were assessed using I2 statistics and Eggers test, respectively. Study protocol was registered under PROSPERO ID CRD42021229140. RESULT: A total of 18 studies with 519,327 participants were included in the study. Pooled prevalence of congenital anomalies in Ethiopia was 2% (95% CI: 0.02, 0.03%). Among affected newborns neural tube defect (48%) was the most common congenital anomaly in Ethiopia, followed by orofacial cleft (19%). Risk factors such as alcohol consumption (pooled OR: 2.28, 95% CI: 1.54, 3.38), lack of folic acid supplement (pooled OR: 2.83, 95% CI: 1.09-7.36), medication during pregnancy (pooled OR: 2.58, 95% CI: 1.03-6.47), khat (Catha edulis) chewing (pooled OR: 2.44, 95% CI: 1.61-3.71), exposure to pesticides (pooled OR: 4.45, 95% CI: 2.44-8.09) and maternal illness (pooled OR:1.79, 95% CI: 1.03, 3.10) had statistically significant association with congenital anomalies in Ethiopia. CONCLUSION: In this review, prevalence of congenital anomalies in Ethiopia was high with considerable regional variation. The most common type of congenital anomaly in Ethiopia was neural tube defects, followed by oro-facial cleft. Alcohol consumption, inadequate intake of folic acid, khat chewing, maternal diseases, exposure to pesticides, and use of medication during pregnancy were identified as potential contributors to congenital abnormalities in Ethiopia.

Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

BACKGROUND: Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. OBJECTIVE: We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. METHODS: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. RESULTS: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. CONCLUSIONS: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

Expanding the Massachusetts Birth Defects Monitoring Program to include additional pregnancy outcomes: Programmatic efforts and impacts on case ascertainment, 2012-2020.

BACKGROUND: Birth defects affect 1 in 33 infants in the United States and are a leading cause of infant mortality. Birth defects surveillance is crucial for informing public health action. The Massachusetts Birth Defects Monitoring Program (MBDMP) began collecting other pregnancy losses (OPLs) in 2011, including miscarriages (<20 weeks gestation) or elective terminations (any gestational age), in addition to live births and stillbirths (≥20 weeks gestation). We describe programmatic changes for adding OPLs and their impact on prevalence estimates. METHODS: Using population-based, statewide, data from the MBDMP (2012-2020), we assessed prevalence per 10,000 live births and 95% confidence intervals (CIs) with and without OPLs overall and for specific birth defects by time period, maternal age, and race/ethnicity. RESULTS: Including OPLs required amending a state statute and promulgating regulations, new data sources, and additional data processing, cleaning, and verification. Overall prevalence with OPLs increased from 257.4 (95% CI: 253.5-261.4) to 333.9 (95% CI: 329.4-338.4) per 10,000; increases were observed in all time periods, age, and race/ethnicity groups. After including OPLs, the prevalence increased for neural tube defects [3.2 (2.7-3.6) to 8.3 (7.6-9.0)], and trisomies 13 [0.5 (0.3-0.7) to 4.1 (3.6-4.6)], 18 [1.5 (1.2-1.9) to 8.2 (7.5-8.9)], and 21 [12.3 (11.4-13.2) to 28.9 (27.6-30.2)]. Cardiovascular defects increased slightly, while prevalence of eye/ear, respiratory, and gastrointestinal defects remained similar. CONCLUSIONS: Adding OPLs required substantial programmatic efforts and resulted in more complete case ascertainment, particularly for certain birth defects. More complete case ascertainment will allow for improved research, screening, and resource allocation.

Incidence of tethered cord syndrome in neurofibromatosis types 1 and 2 pediatric patients: a population-level analysis.

PURPOSE: Tethered spinal cord syndrome (TCS) is characterized by cutaneous attachments on the filum terminale that stretch the spinal cord, leading to musculoskeletal and urogenital sequelae. While the neurocutaneous associations with TCS remain undefined, a recent study reports a high incidence of TCS among a pediatric neurofibromatosis (NF) cohort. This present study utilizes a population-level database to estimate TCS incidence among pediatric patients with neurofibromatosis types 1 and 2 (NF1, NF2). METHODS: The TriNetX Research Network was queried to identify patients diagnosed with NF and/or TCS before the age of 21. Symptomatic TCS requiring surgical intervention was identified using corresponding procedural codes within 12 months following TCS diagnosis. Odds ratios (OR) were calculated to measure the associations of NF1/NF2 with TCS. RESULTS: 19,426 pediatric NF patients were evaluated (NF1: 18,383, NF2: 1042). The average ages of TCS diagnosis among NF1, NF2, and non-NF patients were 12, 16, and 9 years, respectively. The incidence of TCS was 1.2% in NF1 patients and 7.3% in NF2 patients, compared to 0.074% in the general population. The associations of NF incidence with TCS were significantly increased in both NF1 (OR 16.42; 14.38-18.76) and NF2 (OR 105.58; 83.56-133.40) patients compared to the general population. Symptomatic TCS requiring surgical intervention was not significantly associated with NF1/NF2 patients compared to the general TCS population. CONCLUSION: This analysis demonstrates a high incidence of TCS but delayed intervention in pediatric NF patients. Considering TCS counseling, spinal MRI, and earlier intervention may be warranted for NF patients experiencing musculoskeletal symptomatology.

Congenital Malformations in the Moroccan Surveillance System: Contribution to Prevalence Estimation.

Background: Congenital malformations (CMs) are a group of structural or functional anomalies present at birth. These anomalies result in a high rate of mortality, morbidity, and disability in children. CMs are a major public health problem and place a heavy burden on healthcare systems in both developed and developing countries including Morocco, which has had a CMs surveillance system in place since 2011. The aim of this study is to determine the prevalence of CMs in Morocco. Methods: In this study, the epidemiology of CMs in Morocco was assessed retrospectively using the national surveillance system data gathered from case notification forms from 2017 to 2021. Results: The main results showed that the prevalence of CMs in Morocco is 3.91/1000 live births (LBs), and the minimum annual prevalence of CMs was reached in 2017 (3.10/1000 LBs) while the maximum annual prevalence was recorded in 2018 (4.55/1000 LBs). The majority of CMs are unspecified CMs (68.55%), neural tube defects (NTDs) account for (21.13%), and orofacial clefts (OFCs) account for (10.32%). In addition, the majority of CMs (61.73%) were from rural areas. According to region, the Dakhla-Oued Eddahab region recorded the highest prevalence of CMs in Morocco, with 8.81/1000 LBs, while the lowest prevalence was recorded in the Rabat-Sale-Kenitra region, with 2.02/1000 LB. Conclusions: This study reveals that the national prevalence of CMs is high and may be underestimated, as most of the CMS reported is unspecified. The use of a CM registry with detailed reporting of all CMs and the promotion of preventive measures are urgently recommended.

Risk Factors for Neural-Tube Defects Detected in Utero: A Prospective Community-Based Study from Addis Ababa.

BACKGROUND: A recent community-based study from Addis Ababa identifying Neural Tube Defect (NTD) cases by ultrasound examination of pregnant women showed a higher prevalence of 17 per 1000 fetuses. The risk factors behind the high prevalence remain unclear. METHODS: Altogether 891 of the 958 women participated in the ultrasound examination. Thirteen with unaffected twin pregnancies were excluded. Among 878 singleton pregnancies, 15 NTD cases were identified. Serum Folate, vitamin B12, and homocysteine levels were measured in case-mothers and a sub-set of 28 noncase mothers. Because of the modest sample size, exact logistic regression analysis was used to estimate associations between risk factors and NTDs. RESULTS: Serum vitamin status was generally poor for participants in the study. Still, relatively higher values of folate or vitamin B12 in serum, appeared to be protective for NTD (odds ratio [OR] = 0.61 per ng/ml, 95% Confidence interval [CI]: 0.42-0.85 and OR = 0.67 per 100 pg/ml, 95% CI: 0.41-1.02, respectively). High serum homocysteine was associated with higher risk of NTD (OR = 1.3 per µmol/l, 95% CI: 1.02-1.8). Women aged 30 years or more had an OR of 3.5 (95% CI: 1.1-12) for having a NTD child, and families with NTD children had lower household income. Women in the NTD group also had more spontaneous abortions or stillbirths in previous pregnancies. Self-reported intake of folate did not appear to protect against NTDs. CONCLUSIONS: Within this high-prevalence community, poor vitamin status was identified as a risk factor for NTDs detected at ultrasound examination. Improving food security and fortification of foods or food ingredients could be alternative measures.

Periconceptional folic acid usage and its associated factors in eastern Sudan: A cross-sectional study.

BACKGROUND: Several countries poorly adhere to the World Health Organization's recommendation of folic acid supplementation in the periconceptional period, especially in limited-resource settings. OBJECTIVE: The objective of this study was to investigate the prevalence of and the factors associated with folic acid usage in the periconceptional period among pregnant women at Gadarif Maternity Hospital in eastern Sudan. STUDY DESIGN: This is a cross-sectional study. METHODS: This study was conducted in eastern Sudan from April to September 2022. A total of 720 pregnant women in their first trimester were enrolled. The sociodemographic characteristics and clinical and obstetrical data of pregnant women in their first trimester were assessed using a face-to-face questionnaire. In addition, multivariate regression analysis was performed. RESULTS: In this study, the median (interquartile range) of the age and gravidity of the enrolled women was 26.3 (24.14-29.52) years and 2 (1-4), respectively. Of these 720 women, 423 (58.8%) used folic acid during the periconceptional period, while 27 (3.7%) women used folic acid in the preconceptional period. None of the investigated factors (age, residence, education, employment, body mass index, or gravidity) were associated with periconceptional use of folic acid. CONCLUSION: The study revealed a low prevalence of folic acid usage in preconceptional period among pregnant women in eastern Sudan. Additional efforts are needed to promote folic acid usage in the preconceptional period as well as in the first trimester.

ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans.

BACKGROUND: Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II). RESULTS: We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized decrease in mRNA transcription. In neural progenitor cells, ARMC5 knockout only dysregulates 106 genes, some of which are known to be involved in neural tube development. FOLH1, critical in folate uptake and hence neural tube development, is downregulated in the knockout intestine. We also identify nine deleterious mutations in the ARMC5 gene in 511 patients with myelomeningocele, a severe form of spina bifida. These mutations impair the interaction between ARMC5 and Pol II and reduce Pol II ubiquitination. CONCLUSIONS: Mutations in ARMC5 increase the risk of NTDs in mice and humans. ARMC5 is part of an E3 controlling the degradation of all 12 subunits of Pol II under physiological conditions. The Pol II pool size might have effects on NTD pathogenesis, and some of the effects might be via the downregulation of FOLH1. Additional mechanistic work is needed to establish the causal effect of the findings on NTD pathogenesis.

Clinical presentation and outcomes of neonates born with neural tube defects- an experience from a level III B NICU in Western India.

PURPOSE: Neural tube defects (NTDs) are one of the most common congenital anomalies and a cause of chronic disability. The study was done to study outcomes of neural tube defects admitted at a tertiary level neonatal intensive care unit (NICU) from 2018 to 2022, a period of 4 years that also coincided with the COVID pandemic. The secondary outcome was to study the clinical presentation, associated anomalies and epidemiological features. METHODS: It was a retrospective observational study; data of infants was obtained from medical records and analysis was done. RESULTS: Thirty-four neonates were enrolled, of which there were 16 (47%) males and 18 (53%) females. History of pre-pregnancy maternal folate intake was present in 4 (11.7%) cases. 33 (97%) babies were diagnosed with meningomyelocele (MMC) and one each had anencephaly, iniencephaly and encephalocele, of which one had frontal and two had occipital encephalocele. The median age of surgery was 16 days of life with primary repair being the most common procedure followed by MMC repair with VP shunt. Twenty babies (58.8%) were discharged successfully, while 9 (26.5%) expired and 5 (14.7%) were discharged against medical advice; which can be attributed to the financial problems of the patients in a developing country. The overall deaths in our series were four (26.5%) which is slightly higher than other studies which may be due to the fact that this study was conducted during the COVID era with lesser rates of folate supplementation, reduced access to prenatal diagnosis coupled with poor follow-up and compliance of patients post-surgical repair. CONCLUSION: This study emphasizes the importance of periconceptional folic acid supplementation, prenatal diagnosis, early surgery and meticulous follow-up as being pivotal to improving outcomes in children with NTDs.