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1.
Ann Med Surg (Lond) ; 86(1): 598-601, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38222692

RESUMO

Introduction and importance: Neural tube defect occurs as a result of failure of spontaneous closure of the neural tube between the third and fourth weeks of foetal life. Exencephaly is a rare malformation of the neural tube characterized by a large amount of protruding brain tissue in the absence of the calvarium. Case presentation: The authors report a 29-year-old female, non-compliant to iron, calcium and folic acid tablets due to nauseating and itchy sensation after intake for 2 weeks, was admitted in ward Obstetrics ward in view of twin pregnancy. After proper counselling, she was advised for caesarean section, which revealed gross malformation in the form of cleft lip, cleft palate and exposed brain tissue covered by thin layer of membrane with incompletely formed cranial vault and multiple-haematoma and ulcerations in the exposed brain tissue suggestive of Exencephaly. The deformed baby survived for 2 days after birth while the other baby was grossly healthy. Clinical discussion: Exencephaly is said to be the embryological precursor anomaly of anencephaly. Exencephaly is a type of cranial malformation that characteristically involves a large disorganized mass of brain tissue. The flat bones of calvaria are absent and the brain mass is left uncovered. This condition is incompatible with life. Conclusion: Each and every pregnant lady must be advised to undergo ultrasonography in every trimester, especially second trimester scan (anomaly scan) to diagnose any gross congenital malformations. Each pregnant lady is suggested to take the necessary vitamins (like folic acid) to avoid any Neural tube defects.

2.
Int J Obstet Anesth ; 57: 103932, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37891127

RESUMO

In the changing legal environment of obstetric care in the USA, with laws in many states banning termination at all stages of pregnancy with narrow exemptions, healthcare providers are encountering cases in which risk to maternal safety is increased. This report presents a case of a 28-year-old primigravida with an anencephalic fetus who was legally unable to pursue termination in her home state. She traveled to another state in order to pursue safe and legal abortion of a non-viable fetus. Due to an unrecognized cornual ectopic gestation, the delivery resulted in uterine rupture, the need for hysterectomy, and significant morbidity in a patient with a strong desire for future fertility.


Assuntos
Gravidez Ectópica , Gravidez , Feminino , Humanos , Adulto , Gravidez Ectópica/cirurgia , Aborto Legal , Histerectomia
3.
Contraception ; 130: 110339, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37992851

RESUMO

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.


Assuntos
Aborto Induzido , Anencefalia , Gravidez , Humanos , Feminino , Segundo Trimestre da Gravidez , Aborto Induzido/métodos , Estudos Retrospectivos , Etiópia
4.
Childs Nerv Syst ; 40(1): 163-170, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37452861

RESUMO

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.


Assuntos
Anencefalia , Meningomielocele , Defeitos do Tubo Neural , Gravidez , Masculino , Recém-Nascido , Lactente , Feminino , Criança , Humanos , Unidades de Terapia Intensiva Neonatal , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/cirurgia , Ácido Fólico , Meningomielocele/cirurgia , Anencefalia/diagnóstico , Encefalocele/diagnóstico
5.
Sci Total Environ ; 913: 169317, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38104833

RESUMO

Exposure to pesticides during pregnancy has been associated with several serious congenital malformations, such as neural tube defects, therefore, is a cause for concern in terms of human health. This review aims to gather information related to maternal exposure during pregnancy and the risk of triggering neural tube defects in the offspring. The search strategy for the studies followed the PRISMA guidelines. We conducted a systematic search in the Science Direct, PubMed, Cochrane Library, Embase, Scopus, and Web of Science databases for all epidemiological studies that sought to associate exposure to pesticides during embryonic development with the risk of neural tube defects (NTDs). The keywords used were "pesticide", "herbicide", "congenital" and "neural". Of the 229 articles, 8 eligible ones (7 case-control and 1 cross-sectional) evaluated pesticide exposure in pregnancy. Different methods were used, including analysis of biological samples and questionnaires. The pesticides studied included insecticides, herbicides, fungicides, and nematicides. Insecticides were the most studied, with variations in concentrations between tissues and studies. Distinct levels of pesticides have been detected in maternal serum, placenta, and umbilical cord. Models were statistically adjusted for confounding factors, such as smoking and dietary supplement intakes. Concentrations were measured in different exposure windows (periconception and prenatal), related to NTDs such as anencephaly and spina bifida. Different data collection techniques, types of biological samples, and exposure windows were used, which made comparison difficult. The main pesticides studied included DDT, DDE, HCH, and endosulfan. Maternal serum showed the highest concentrations of pesticides, but detection in placental tissue and umbilical cord confirms embryonic exposure. Confounding variables were adjusted for in the analysis of the articles, but they may still contribute to the risk of NTDs. All the studies analyzed pesticide exposure and the relationship with NTDs. However, a more standardized survey would be ideal for better comparisons.


Assuntos
Herbicidas , Inseticidas , Defeitos do Tubo Neural , Praguicidas , Feminino , Humanos , Gravidez , Praguicidas/toxicidade , Praguicidas/análise , Estudos Transversais , Placenta/química , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Fatores de Risco
6.
Medicentro (Villa Clara) ; 27(4)dic. 2023.
Artigo em Espanhol | LILACS | ID: biblio-1534866

RESUMO

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.


Assuntos
Anormalidades Congênitas , Sistema Nervoso Central , Anencefalia
7.
Animals (Basel) ; 13(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38136919

RESUMO

Anencephaly, a severe neural tube defect characterized by the absence of major parts of the brain and skull, is a rare congenital disorder that has been observed in various species, including cats. Considering the uncommon appearance of anencephaly, this paper aims to present anencephaly in a stillborn male kitten from an accidental inbreeding using various paraclinical methods. Histological examination of tissue samples from the cranial region, where parts of the skull were absent, revealed the presence of atypical nerve tissue with neurons and glial cells organized in clusters, surrounded by an extracellular matrix and with an abundance of blood vessels, which are large, dilated, and filled with blood, not characteristic of nerve tissue structure. In CT scans, the caudal part of the frontal bone, the fronto-temporal limits, and the parietal bone were observed to be missing. CT also revealed that the dorsal tubercle of the atlas, the dorsal neural arch, and the spinal process of the C2-C7 bones were missing. In conclusion, the kitten was affected by multiple congenital malformations, a combination of exencephaly-anencephaly, maxillary brachygnathism, closed cranial spina bifida at the level of cervical vertebrae, kyphoscoliosis, palatoschisis, and partial intestinal atresia. The importance of employing imaging techniques cannot be overstated when it comes to the accurate diagnosis of neural tube defects.

8.
Birth Defects Res ; 115(18): 1737-1745, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37715338

RESUMO

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.


Assuntos
Anencefalia , Meningomielocele , Defeitos do Tubo Neural , Gravidez , Feminino , Humanos , Anencefalia/epidemiologia , Anencefalia/prevenção & controle , Ácido Fólico , Meningomielocele/epidemiologia , Prevalência , Farinha , Argentina/epidemiologia , Triticum , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/prevenção & controle , Morte Fetal/etiologia
9.
Cells ; 12(13)2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37443734

RESUMO

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.


Assuntos
Anencefalia , Defeitos do Tubo Neural , Disrafismo Espinal , Gravidez , Feminino , Humanos , Camundongos , Animais , Ácido Valproico/farmacologia , Anencefalia/complicações , Anencefalia/genética , Glicogênio Sintase Quinase 3 beta/genética , Camundongos Knockout , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/genética , Disrafismo Espinal/genética , Encéfalo/patologia , Proteínas dos Microfilamentos
10.
BMC Pregnancy Childbirth ; 23(1): 452, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37330492

RESUMO

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.


Assuntos
Anencefalia , Colecistectomia Laparoscópica , Colecistite Aguda , Complicações na Gravidez , Gravidez , Humanos , Feminino , Adulto , Cesárea/efeitos adversos , Colecistectomia Laparoscópica/efeitos adversos , Colecistite Aguda/etiologia , Colecistite Aguda/cirurgia , Complicações na Gravidez/cirurgia
11.
Childs Nerv Syst ; 39(7): 1805-1812, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37209199

RESUMO

BACKGROUND: Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and disease burden to individuals living with these conditions. Mandatory food fortification with folic acid is, by far, one of the most efficacious, safe, and cost-effective interventions to prevent neural tube defects. However, most countries fail to effectively fortify staple foods with folic acid, impacting public health and healthcare systems and generating dismal disparities. AIM: This article discusses the main barriers and facilitators for implementing mandatory food fortification as an evidence-based policy to prevent neural tube defects worldwide. METHODS: A comprehensive review of the scientific literature allowed the identification of the determinant factors acting as barriers or facilitators for the reach, adoption, implementation, and scaling up of mandatory food fortification with folic acid as an evidence-based policy. RESULTS: We identified eight barriers and seven facilitators as determinant factors for food fortification policies. The identified factors were classified as individual, contextual, and external, inspired by the Consolidated Framework for Implementation of Research (CFIR). We discuss mechanisms to overcome obstacles and seize the opportunities to approach this public health intervention safely and effectively. CONCLUSIONS: Several determinant factors acting as barriers or facilitators influence the implementation of mandatory food fortification as an evidence-based policy worldwide. Notoriously, policymakers in many countries may lack knowledge of the benefits of scaling up their policies to prevent folic acid-sensitive neural tube defects, improve the health status of their communities, and promote the protection of many children from these disabling but preventable conditions. Not addressing this problem negatively affects four levels: public health, society, family, and individuals. Science-driven advocacy and partnerships with essential stakeholders can help overcome the barriers and leverage the facilitators for safe and effective food fortification.


Assuntos
Ácido Fólico , Defeitos do Tubo Neural , Criança , Humanos , Ácido Fólico/uso terapêutico , Alimentos Fortificados , Defeitos do Tubo Neural/prevenção & controle , Saúde Pública , Políticas
12.
Childs Nerv Syst ; 39(11): 3123-3130, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37099139

RESUMO

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.


Assuntos
Anencefalia , Espinha Bífida Cística , Disrafismo Espinal , Transição para Assistência do Adulto , Adulto , Humanos , Adolescente , Criança , Adulto Jovem , Ácido Fólico , Anencefalia/prevenção & controle , Alimentos Fortificados , Disrafismo Espinal/terapia
13.
Pan Afr Med J ; 44: 24, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37013212
14.
Pan Afr Med J ; 44: 41, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37070027
15.
Birth Defects Res ; 115(9): 945-953, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37025002

RESUMO

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.


Assuntos
Anencefalia , Defeitos do Tubo Neural , Disrafismo Espinal , Gravidez , Feminino , Recém-Nascido , Humanos , Anencefalia/epidemiologia , Anencefalia/prevenção & controle , Encefalocele/epidemiologia , Natimorto , Prevalência , Estudos Transversais , Nicarágua/epidemiologia , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/prevenção & controle , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/prevenção & controle , Ácido Fólico
17.
Brain ; 146(8): 3455-3469, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36928982

RESUMO

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.


Assuntos
Anencefalia , Defeitos do Tubo Neural , Camundongos , Gravidez , Animais , Feminino , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/efeitos adversos , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Tretinoína/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , RNA Mensageiro , Antígenos de Histocompatibilidade Menor
18.
Childs Nerv Syst ; 39(7): 1703-1710, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882610

RESUMO

Neural tube defects (NTDs) are common birth defects and contribute to life-long disabilities, high medical care costs, and perinatal and child mortality. This review is a primer on prevalence, causes, and evidence-based prevention strategies for NTDs. The estimated average global prevalence of NTDs is two cases per 1000 births, amounting to approximately 214,000-322,000 affected pregnancies worldwide annually. Prevalence and associated adverse outcomes are disproportionately high in developing countries. NTDs have multiple risk factors including genetic and non-genetic (i.e., maternal nutritional status, pre-pregnancy diabetes, early pregnancy exposure to valproic acid (anti-epileptic medication), and a previous pregnancy affected by a NTD) factors. Maternal folate insufficiency before and during early pregnancy is the most common risk factor and is preventable. Folic acid (vitamin B9) is required for formation of the neural tube early in pregnancy, around 28 days after conception, when most women are unaware of their pregnancies. Current guidelines recommend that all women planning or capable of pregnancy take a daily supplement containing 400-800 µg of folic acid. Mandatory folic acid fortification of staple foods (e.g., wheat flour, maize flour, rice) is safe, economical, and the effective intervention for primary prevention of NTDs. Currently, about 60 countries are implementing mandatory folic acid fortification of staple foods, preventing just a quarter of all preventable NTD cases worldwide. There is an urgent need for active champions, including neurosurgeons and other healthcare providers, to generate political will and promote effective mandatory food fortification with folic acid, and reach equitable primary prevention of NTDs in all countries.


Assuntos
Farinha , Defeitos do Tubo Neural , Gravidez , Criança , Feminino , Humanos , Prevalência , Alimentos Fortificados , Triticum , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/prevenção & controle , Ácido Fólico/uso terapêutico , Prevenção Primária
19.
Ann Med Surg (Lond) ; 85(2): 252-256, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36845789

RESUMO

Holoprosencephaly is a rare and possibly fatal neural tube defect represented by complete or partial forebrain noncleavage. It can be classified into four types: alobar, semilobar, lobar, and middle interhemispheric fusion variant. It is usually diagnosed through prenatal ultrasound or after birth by visually observing the morphological abnormalities and/or through neurological screening. Potential causes include maternal diabetes, alcoholism, infections during pregnancy, drugs, and genetic causes. Case presentation: Herein, we report two cases of holoprosencephaly's rarest manifestations, albeit cebocephaly in the first case, and cyclopia with a probocis in the second. Cebocephaly, (hypotelorism with a single nostril and a blind-ended nose) was present in the first case; a Syrian newborn girl for a 41-year-old mother who works in collecting Capparis spinosa, and cyclopia with skull vault absence and posterior encephalocele in the second case; a Syrian newborn girl for a 26-year-old mother, the parents here where second-degree relatives. Conclusions: Early diagnosis through ultrasound is preferred in such cases and management options should be assessed and discussed with the parents due to poor prognosis. Adherence to pregnancy follow-up programs is essential to detect malformations and disorders as early as possible, especially when risk factors exist. Also, this paper may suggest a potential correlation between C. spinosa and holoprosencephaly. Therefore, we suggest that more research should be done.

20.
HEC Forum ; 35(4): 389-406, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35212854

RESUMO

The central concern of this article is whether early induction of labor for an anencephalic fetus can ever be morally justified, particularly by a Catholic healthcare ethics committee. By revisiting and refining arguments in articles by Drane (1992) and Bole (1992) published in this journal, a revised argument - consistent with the Catholic moral tradition - can seemingly be constructed that a Catholic healthcare ethics committee might use to justify early induction of labor in some pregnancies involving an anencephalic fetus. Such a revised argument depends upon two central claims; first, that the anencephalic fetus in question is necessarily in the process of dying when early induction of labor occurs, and second, that the fetus is judged to be undergoing extraordinary or disproportionate means of preserving their life as a result of receiving ongoing maternal support of a mother's womb. The revised argument developed in this article aims to utilize the doctrine of double effect in conjunction with these two central claims to justify early induction of labor for anencephalic fetal persons in some circumstances. Unfortunately, the revised argument - if successful - would be at odds with a stance taken in the United States Conference of Catholic Bishops (USCCB) 1996 statement "Moral Principles Concerning Infants with Anencephaly." However, there is reason to believe the revised argument offered in this article is well aligned with other guidance from the USCCB, contained in the publication Ethical and Religious Directives for Catholic Healthcare Services (2018). This article concludes by noting some important limitations of the argument and offering hope that consideration of the argument ultimately helps to strengthen the Catholic moral tradition.


Assuntos
Anencefalia , Gravidez , Feminino , Humanos , Estados Unidos , Pessoalidade , Princípios Morais , Catolicismo , Trabalho de Parto Induzido
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