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.

A global update on the status of prevention of folic acid-preventable spina bifida and anencephaly in year 2022.

BACKGROUND: Mandatory fortification of staple foods with folic acid is an effective public health strategy to prevent folic acid-preventable spina bifida and anencephaly (FAP SBA). We estimated the global proportion of FAP SBA prevented through mandatory folic acid fortification of cereal grains (i.e., wheat flour, maize flour, and rice). METHODS: We used year 2022 data from the Food Fortification Initiative to identify countries (n = 69) with mandatory fortification of grains that includes folic acid. Sixty-eight countries were eligible for analysis with complete data. Proportion of FAP SBA prevention was modeled assuming >150 mcg/day of folic acid fortification protects against FAP SBA, reducing post-fortification prevalence to a lowest achievable level of 0.5 cases per 1000 births. RESULTS: Our analysis found that a total of 63,520 cases of FAP SBA were prevented in the year 2022 in 68 countries implementing mandatory folic acid fortification of grains with folic acid. This translated to a 23.7% prevention of all possible FAP SBA prevention globally. An excess of 204,430 cases of FAPSBA still occurred in over 100 countries where mandatory staple food fortification with folic acid is not implemented. CONCLUSION: Our study showed that only a quarter of all FAP SBA cases were averted through mandatory folic acid fortification in the year 2022; many countries are not implementing the policy, resulting in a large proportion of FAP SBA cases that can be prevented. Fortification will help countries with achieving 2030 Sustainable Development Goals on neonatal- and under-five mortality, disability, stillbirths, and elective terminations prevention, from FAP SBA.

Comparison of induction-to-expulsion interval during second-trimester medication abortion in pregnancies with anencephaly and other congenital anomalies compared to those without anomalies: A retrospective cohort study.

OBJECTIVES: To investigate whether the induction-to-expulsion interval during second-trimester medication abortion in pregnancies complicated by anencephaly or other fetal anomalies is prolonged compared to pregnancies without fetal anomalies STUDY DESIGN: This was a retrospective cohort study of women who had second-trimester medication abortion at St. Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia). We assigned subjects to one of three groups based on fetal diagnosis: 1) anencephaly group, 2) other congenital anomaly group, and 3) no anomaly group. Data were collected by reviewing patients' charts. We used SPSS version 23 to analyze the data. Simple descriptive analysis and χ2 test were performed as appropriate. RESULTS: A total of 303 women had second-trimester medication at 14-28 weeks, of which 58 had anencephaly, 19 had congenital anomalies other than anencephaly, and the remaining 226 had no fetal anomalies. The mean induction-to-expulsion interval was 18.4 hours in the anencephaly group versus 19.4 hours in the other congenital anomaly group versus 19.2 hours in those without anomaly (p-value = 0.924). The 24-hour nonexpulsion rate was also comparable among the groups, with 5.25% rate of nonexpulsion in the anencephaly group versus 15.8% in the other congenital anomaly group versus 11.15% in the no anomaly group (p-value = 0.594). In multivariable regression analysis after controlling for parity, the 24-hour nonexpulsion rate was not significantly different. CONCLUSIONS: In this study, pregnancies undergoing second-trimester medication abortion for fetal anomalies had comparable induction-to-expulsion interval and 24-hour expulsion rates compared to those who had the same procedure for other or no anomalies. IMPLICATIONS: Second-trimester medication abortion procedure length in pregnancies complicated by anencephaly is similar to those pregnancies without anomalies.

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.

Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study.

OBJECTIVES: To determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000-2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour to be monitored. DESIGN: Population-based, observational study using congenital anomaly (CA) registration data for England curated by the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). SETTING: Regions of England with active registration in the time period. PARTICIPANTS: Babies that were liveborn or stillborn and pregnancies that resulted in a termination of pregnancy or a late miscarriage (20-23 weeks' gestation) with an NTD. MAIN OUTCOME MEASURES: Total birth prevalence of anencephaly, spina bifida and all NTDs in England. Poisson regression analysis was used to evaluate time trends with regional register as a random effect. The progress of national registration across England was assessed. RESULTS: There were 4541 NTD pregnancies out of 3 637 842 births in England; 1982 anencephaly and 2127 spina bifida. NTD prevalence was 12.5 (95% CI 12.1 to 12.9) per 10 000 total births. NTD prevalence per 10 000 total births was significantly higher in 2015-2019 (13.6, 95% CI 12.9 to 14.4) compared with 2010-2014 (12.1, 95% CI 11.7 to 12.5). An increasing trend in NTDs overall was detected (incidence rate ratio (IRR) 1.01, 1.00 to 1.02), although further analysis determined this effect was confined to 2015-2019 (compared against 2000-2004, IRR 1.14, 1.04 to 1.24). The birth prevalence of anencephaly reflected this pattern. The prevalence of spina bifida remained relatively stable over time. CONCLUSIONS: Baseline NTD prevalence for England has been established. National and standardised CA registration is in place, facilitating the systematic and consistent monitoring of pre-fortification and post-fortification NTD trends and evaluating the impact of fortification on NTD prevalence.

Malformación completa del sistema nervioso central y otras malformaciones asociadas. A propósito de un caso / Complete malformation of the central nervous system and other associated malformations. A case report

La anencefalia es una anomalía gestacional que produce la ausencia de gran parte del cerebro y del cráneo; aunque se desconoce el motivo principal de su aparición, puede estar relacionado con toxinas ambientales, y pobre ingesta de ácido fólico durante el embarazo. Los fetos que padecen de esta malformación, en su mayoría, no llegan a nacer vivos o mueren a las pocas horas. Se presentó una paciente recibida en emergencia en el Centro de Atención Integral Materno Infantil, municipio Ixchiguan, departamento de San Marcos, Guatemala con embarazo a término, según refirió la paciente, sin atención prenatal, dolor en hipogastrio y pérdida de líquido amniótico de un día de evolución. Siendo este un defecto genético multifactorial, para el cual no existe tratamiento, el único recurso para su prevención fue brindar una atención prenatal pormenorizada con énfasis especial en el programa de genética para la detección precoz de anomalías congénitas.

Anencephaly is a gestational anomaly that produces the absence of a large part of the brain and skull; although the main reason for its appearance is unknown, it may be related to environmental toxins and poor intake of folic acid during pregnancy. Most of the fetuses that suffer from this malformation are not born alive or die within a few hours. We present a female patient who was received in the emergency service of the Comprehensive Maternal and Child Care Center in Ixchiguan municipality, San Marcos department, Guatemala, with a full-term pregnancy, as reported by the patient, without prenatal care, hypogastric pain and loss of amniotic fluid of one day of evolution. Since there is no treatment for this multifactorial genetic defect, the only resource for its prevention was to provide detailed prenatal care with special emphasis on the genetics program for the early detection of congenital anomalies.

"Prevalence and secular trend of neural tube defects in fetal deaths in Argentina, 1994-2019".

BACKGROUND: Fetal deaths are a major source of information on the epidemiology of neural tube defects (NTDs; anencephaly and myelomeningocele). We analyzed NTDs prevalence and secular trend using fetal death records between 1994 and 2019 in Argentina. MATERIALS AND METHODS: Data were obtained from the Department of Statistics and Information of the Ministry of Health (DEIS). Using the number of fetal deaths due to anencephaly and myelomeningocele, we estimated the proportion of all fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) during pre- and post-fortification period in Argentina. We also estimated the ratio of fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) to 10,000 live births. Secular trend in the outcomes was analyzed using a Poisson model and Joinpoint regression analysis. RESULTS: In the entire period analyzed, the NTD proportion on fetal deaths was 1.32. In 1994, NTDs accounted for 34.7% of congenital malformations fetal deaths (CM) and 1.7% of all fetal deaths, whereas in 2019, these percentages were 9.4% and 0.5%, respectively. NTDs present a negative secular trend (p < .05). The risk of fetal death due to anencephaly and myelomeningocele decreases between 2005 and 2019 by 67% and 51% respectively (p < .05) in comparison to the period between 1994 and 2004 before the effective fortification of wheat flour used in the food industry destined for the domestic market. DISCUSSION AND CONCLUSION: We found a significant decrease in the risk of all fetal deaths due to NTDs, particularly anencephaly, in Argentina over the study period, with most reduction observed during the mandatory flour fortification era (introduced in Argentina in 2002). The inclusion of fetal deaths in NTD surveillance, coupled or uncoupled with other pregnancy outcomes, is essential for monitoring preventive supplementation measures.

A Shared Pathogenic Mechanism for Valproic Acid and SHROOM3 Knockout in a Brain Organoid Model of Neural Tube Defects.

Neural tube defects (NTDs), including anencephaly and spina bifida, are common major malformations of fetal development resulting from incomplete closure of the neural tube. These conditions lead to either universal death (anencephaly) or severe lifelong complications (spina bifida). Despite hundreds of genetic mouse models of neural tube defect phenotypes, the genetics of human NTDs are poorly understood. Furthermore, pharmaceuticals, such as antiseizure medications, have been found clinically to increase the risk of NTDs when administered during pregnancy. Therefore, a model that recapitulates human neurodevelopment would be of immense benefit to understand the genetics underlying NTDs and identify teratogenic mechanisms. Using our self-organizing single rosette cortical organoid (SOSR-COs) system, we have developed a high-throughput image analysis pipeline for evaluating the SOSR-CO structure for NTD-like phenotypes. Similar to small molecule inhibition of apical constriction, the antiseizure medication valproic acid (VPA), a known cause of NTDs, increases the apical lumen size and apical cell surface area in a dose-responsive manner. GSK3ß and HDAC inhibitors caused similar lumen expansion; however, RNA sequencing suggests VPA does not inhibit GSK3ß at these concentrations. The knockout of SHROOM3, a well-known NTD-related gene, also caused expansion of the lumen, as well as reduced f-actin polarization. The increased lumen sizes were caused by reduced cell apical constriction, suggesting that impingement of this process is a shared mechanism for VPA treatment and SHROOM3-KO, two well-known causes of NTDs. Our system allows the rapid identification of NTD-like phenotypes for both compounds and genetic variants and should prove useful for understanding specific NTD mechanisms and predicting drug teratogenicity.

Post-cesarean section laparoscopic cholecystectomy: a case report.

BACKGROUND: Laparoscopic cholecystectomy at the time of cesarean section is novel in medicine. It is safe, feasible, and cost-effective. CASE PRESENTATION: A 29-year-old G3P2 + 0 woman had two previous cesarean sections. She was pregnant at 32 weeks. The fetus had anencephaly. She had acute cholecystitis. Laparoscopic cholecystectomy done at the time of termination of pregnancy by cesarean section. CONCLUSIONS: In a critical period, such as acute cholecystitis, the combination of laparoscopic cholecystectomy immediately post cesarean section is effective if the surgeon is highly qualified and experienced.

Transitioning care for adolescents with spina bifida in the US: challenges for management.

Open spina bifida (OSB) is a common neural tube defect. Medical and surgical care involves addressing the baseline orthopedic, urologic, and neurological dysfunction as well as the changes or declines that may occur as the patient ages. Given the complexity of this disease, coordinated, multidisciplinary care involving specialists in neurosurgery, orthopedics, urology, rehabilitation and physical medicine, pediatrics, and psychology is necessary to establish and optimize baseline function. Traditionally in the US, pediatric multispecialty spina bifida clinics have provided the patient with a coordinated medical support system. Unfortunately, this coordinated, medical home has been difficult to establish during the transition from pediatric to adult care. Medical professionals must have a strong understanding of OSB to properly manage the disease and detect and prevent associated complications. In this manuscript, we (1) describe the changing needs and challenges of people living with OSB over a lifespan, (2) delineate current practices in the transition of care for people with OSB from childhood to adulthood, and (3) provide recommendations for best practices in navigating the transition process for clinicians who provide care for those afflicted with this most complex congenital abnormality of the nervous system compatible with long term survival.

Neural tube defects: Prevalence, mortality, and maternal characteristics in two departmental hospitals in the northwestern region of Nicaragua, 2006-2018.

BACKGROUND: Congenital anomalies are the fifth most common cause of neonatal mortality in Nicaragua, and neural tube defects (NTDs) are the most common of all cases of lethality associated with a birth defect. Prevalence and mortality estimates are needed to propose effective intervention strategies that prevent NTDs over time. METHODS: A cross-sectional study was carried out in northwestern Nicaragua from January 2006 to December 2018. All cases of NTDs (anencephaly, spina bifida, and encephalocele) were registered in hospital surveillance systems, and the medical histories of the mothers and newborns were reviewed. Prevalence was calculated by considering the number of live births and stillbirths older than 20 weeks of gestation with NTDs, divided by the total number of live births and stillbirths in each study year. Neonatal mortality rate (NMR) for NTD, and case fatality for spina bifida was calculated. RESULTS: Two hundred fifty cases of NTDs were identified from 178,498 deliveries (177,316 live births and 1,182 stillbirths). The prevalence of NTDs during this time period was 14.01 (95% CI: 12.27-15.74) per 10,000 births. The prevalence of spina bifida (n = 140), anencephaly (n = 97), and encephalocele (n = 13) was 7.84, (95% CI: 6.54-9.14), 5.43 (95% CI: 4.30-6.45), and 0.73 (95% CI: 0.33-1.12) per 10,000 births, respectively. Mothers with fetus or newborns affected with NTDs did not use folic acid prior to conception, and 11% experienced periods of hyperthermia during the first trimester of pregnancy. NMR for NTDs was 0.55 per 1.000 livebirths. Case fatality for all NTDs and for spina bifida were 55% and 18%, respectively. CONCLUSION: The prevalence and mortality of NTDs in the northwestern region of Nicaragua present peaks and troughs during the study period. Spina bifida was the most frequent type of NTD. We believe that these findings could be of use by health policy makers to strengthen the primary prevention of NTDs in the region through the monitoring of the food fortification policy and folic acid supplementation to women of childbearing age. Additional etiologic studies of NTDs should be considered to identify additional prevention measures.

First report of surgery for anencephaly in twin pregnancies: Technical notes and postoperative management.

Anencephaly, the most severe form of neural tube defect, has no known cure, and in most cases, patients die before or shortly after birth. To date, no surgical intervention has been reported in the management of anencephaly. This study presents a case of dichorionic-diamniotic twin pregnancy in which 1 twin was anencephalic and describes the surgical management of this complex case. We aimed to share the problems experienced during the follow up of a patient who survived for a long time after surgery. We also aimed to highlight several clinical issues, including the challenges of managing anencephaly in twin pregnancies, problems experienced during the follow up process in our case, diagnosis of brain death in anencephaly cases, and ethical dilemmas related to organ donation. This case is notable because of the challenging nature of the surgical procedure and complexity of postoperative care. By highlighting the difficulties encountered during the follow up period, we hope to provide insights to health professionals that can inform the management of similar cases in the future.

MTHFD1 is critical for the negative regulation of retinoic acid receptor signalling in anencephaly.

Neural tube defects are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying molecular mechanisms remain elusive. Retinoic acid, an active derivative of vitamin A, is critical for neural system development, and retinoic acid receptor (RAR) signalling malfunctions have been observed in human neural tube defects. However, retinoic acid-retinoic acid receptor signalling regulation and mechanisms in neural tube defects are not fully understood. The mRNA expression of RARs and retinoid X receptors in the different human neural tube defect phenotypes, including 11 pairs of anencephaly foetuses, 10 pairs of hydrocephalus foetuses and nine pairs of encephalocele foetuses, was investigated by NanoString nCounter technology. Immunoprecipitation-mass spectrometry was performed to screen the potential interacting targets of retinoic acid receptor γ. The interactions between proteins were confirmed by co-immunoprecipitation and immunofluorescence laser confocal microscopy. Luciferase and chromatin immunoprecipitation with quantitative real-time polymerase chain reaction assays were used to clarify the underlying mechanism. Moreover, a neural tube defect animal model, constructed using excess retinoic acid, was used for further analysis with established molecular biology technologies. We report that level of retinoic acid receptor γ (RARγ) mRNA was significantly upregulated in the brain tissues of human foetuses with anencephaly. To further understand the actions of retinoic acid receptor γ in neural tube defects, methylenetetrahydrofolate dehydrogenase 1 was identified as a specific retinoic acid receptor γ target from IP-MS screening. Additionally, methylenetetrahydrofolate dehydrogenase 1 negatively regulated retinoic acid receptor γ transcription factor activity. Furthermore, low expression of methylenetetrahydrofolate dehydrogenase 1 and activation of retinoic acid receptor signalling were further determined in human anencephaly and a retinoic acid-induced neural tube defect mouse model. This study reveals that methylenetetrahydrofolate dehydrogenase 1, the rate-determining enzyme in the one-carbon cycle, might be a specific regulator of retinoic acid receptors; these findings provide new insights into the functional linkage between nuclear folate metabolism and retinoic acid receptor signalling in neural tube defect pathology.

The role of neurosurgeons in global public health: the case of folic acid fortification of staple foods to prevent spina bifida.

OBJECTIVE: The global neurosurgery movement arose at the crossroads of unmet neurosurgical needs and public health to address the global burden of neurosurgical disease. The case of folic acid fortification (FAF) of staple foods for the prevention of spina bifida and anencephaly (SBA) represents an example of a new neurosurgical paradigm focused on public health intervention in addition to the treatment of individual cases. The Global Alliance for the Prevention of Spina Bifida-F (GAPSBiF), a multidisciplinary coalition of neurosurgeons, pediatricians, geneticists, epidemiologists, food scientists, and fortification policy experts, was formed to advocate for FAF of staple foods worldwide. This paper serves as a review of the work of GAPSBiF thus far in advocating for universal FAF of commonly consumed staple foods to equitably prevent SBA caused by folic acid insufficiency. METHODS: A narrative review was performed using the PubMed and Google Scholar databases. RESULTS: In this review, the authors describe the impact of SBA on patients, caregivers, and health systems, as well as characterize the multifaceted requirements for proper spina bifida care, including multidisciplinary clinics and the transition of care, while highlighting the role of neurosurgeons. Then they discuss prevention policy approaches, including supplementation, fortification, and hybrid efforts with folic acid. Next, they use the example of FAF of staple foods as a model for neurosurgeons' involvement in global public health through clinical practice, research, education and training, and advocacy. Last, they describe mechanisms for involvement in the above initiatives as a potential academic tenure track, including institutional partnerships, organized neurosurgery, neurosurgical expert groups, nongovernmental organizations, national or international governments, and multidisciplinary coalitions. CONCLUSIONS: The role of neurosurgeons in caring for children with spina bifida extends beyond treating patients in clinical practice and includes research, education and training, and advocacy initiatives to promote context-specific, evidence-based initiatives to public health problems. Promoting and championing FAF serves as an example of the far-reaching, impactful role that neurosurgeons worldwide may play at the intersection of neurosurgery and public health.

Assessing associations between residential proximity to greenspace and birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Residential proximity to greenspace is associated with various health outcomes. OBJECTIVES: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors. METHODS: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100 m and 500 m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income. RESULTS: After multivariable adjustment, for the 500 m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lip ± cleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100 m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81). DISCUSSION: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods.