The range of neural tube defects in southern India.

During a prospective study of 3500 consecutive births from November 1985 to January 1987 at three hospitals, 40 babies were found to have neural tube defects, an extremely high incidence (11.4/1000 births). The defects comprised anencephaly (n = 18), meningomyelocele (n = 11), Arnold-Chiari deformity (n = 3), encephalocele (n = 3), iniencephaly (n = 2), and one each of occipital meningocele, spina bifida occulta, and anencephaly with rachischisis. There were significant differences in incidence between those with consanguineous and nonconsanguineous parents and those whose mothers had previously given birth to malformed infants or who had had miscarriages, and those who had not. Significantly more defects were found among stillborn and low birthweight babies, among girls, and among those whose mothers were aged between 20 and 30 years. Just over a third (14) were breech presentations, and hydramnios was present in 16 (40%).     

Vitamin dificiencies and neural tube defects.

Serum folate, red cell folate, white blood cell vitamin C, riboflavin saturation index, and serum vitamin A were determined during the first trimester of pregnancy in over 900 cases. For each of these there was a social classes I + II showed the highest levels which differed significantly from other classes, except for serum folate. In 6 mothers who gave birth to infants with neural tube defects, first trimester serum folate, red cell folate, white blood cell vitamin C, and riboflavin values were lower than in controls. In spite of small numbers the differences were significant for red cell folate (P less than 0-001) and white blood cell vitamin C (P less than 0-05). These findings are compatible with the hypothesis that nutritional deficiencies are significant in the causation of congenital defects of the neural tube in man.     

Recurrent neural tube defects,risk factors and vitamins.

Data from our trial of periconceptional vitamin supplementation for the prevention of neural tube defects have been analysed to assess the influence of various factors on recurrence rates of neural tube defect. Our data suggest that the risk of recurrence of neural tube defect is influenced by the number of previous neural tube defects, area of residence, immediately prior miscarriage, and interpregnancy interval. None of these factors, however, contributed any significant differential risk between supplemented and unsupplemented mothers. Hence we conclude that the highly significant difference in recurrence rates of neural tube defect between supplemented and unsupplemented mothers was due to vitamin supplementation.     

Spontaneous abortion rates, gravidity and neural tube defects.

Kline and her co-workers [20, 21] suggest that spontaneous abortions show no overall gravidity effect. However, spontaneous abortions seem to show a negative gravidity effect in some sibships (those containing an infant affected by anencephaly or spina bifida) [22]. It is inferred that there is a heterogeneity among spontaneous abortion sibships, and that there are other sibships in which spontaneous abortions show a positive gravidity effect (perhaps as a result of e.g. iso-immunization).     

神经管缺陷畸形的蛋白质学研究进展

神经管缺陷(neural tube defects,NTD)是在胚胎发育过程中,神经管闭合不全所引起的一组缺陷,是环境因素和遗传因素共同作用的结果。目前已发现的与 NTD 相关的蛋白质标志物主要有血清甲胎蛋白、羊水甲胎蛋白、羊水胶质纤维酸性蛋白和 S100蛋白。该文对 NTD 相关的蛋白质标志物的研究进展进行综述。     

Etiology, pathogenesis and prevention of neural tube defects

Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD. A host of suspected teratogens are also available in the literature. The UK and Hungarian studies showed that periconceptional supplementation of women with folate (FA) reduces significantly both the first occurrence and recurrence of NTD in the offspring. This led to mandatory periconceptional FA supplementation in a number of countries. Encouraged by the results of clinical studies, numerous laboratory investigations focused on the genes involved in the FA, vitamin B12 and homocysteine metabolism during neural tube development. As of today no clinical or experimental study has provided unequivocal evidence for a definitive role for any of these genes in the causation of NTD suggesting that a multitude of genes, growth factors and receptors interact in controlling neural tube development by yet unknown mechanisms. Future studies must address issues of gene-gene, gene-nutrient and gene-environment interactions in the pathogenesis of NTD.     

Closed neural tube defects: neurologic, orthopedic, and gait outcomes.

PURPOSE: The purpose of our study was to obtain a clear understanding of the various diagnoses within the closed neural tube defect (NTD) groups included in the large database of clients in our Spina Bifida Clinic and a clear picture of the outcomes for the various NTD groups. METHODS: One hundred and four clients with closed NTD were categorized using a classification system devised by Tortori-Donati et al. Various clinical markers were investigated, including ambulation and the need for orthoses and wheelchairs. RESULTS: Most clients are ambulatory, requiring an orthoses, but not a wheelchair, despite the high incidence of ankle/foot abnormalities. CONCLUSIONS: This classification system has enhanced our knowledge of this group of clients, provided a greater understanding of the varied outcomes of these children and clinical management required.     

The changing picture of hepatitis A in the United States

PURPOSE OF REVIEW: Hepatitis A causes approximately half of the cases of viral hepatitis in the United States. Since 1999, routine hepatitis A immunization of children in areas of the United States with high rates of hepatitis A has been recommended. RECENT FINDINGS: There has been an increasing appreciation of the role of young children with asymptomatic or inapparent infection as the community reservoir of hepatitis A virus. Epidemiologic studies have demonstrated striking geographic variations in the incidence of hepatitis A in the United States. On the basis of this understanding, recommendations for control of hepatitis A were updated in 1999 to include routine vaccination of children living in states, counties, and communities with high rates of hepatitis A. Routine hepatitis A vaccination of children in areas with high rates of hepatitis A is a cost-effective strategy to reduce the incidence of hepatitis A. SUMMARY: Improved understanding of the epidemiology and transmission of hepatitis A combined with the availability of effective hepatitis A vaccines have dramatically reduced the burden of hepatitis A in the United States.     

The changing epidemiology of cerebral palsy.

AIM: To determine the prevalence of cerebral palsy in a specific population. METHODS: Multiple sources of ascertainment were used to create and maintain a register of all cases of cerebral palsy born to mothers resident in the counties of Merseyside and Cheshire in the years 1966 to 1989. Denominator data of infant births and deaths from 1966 to 1981 were obtained from statutory notifications made to health authorities and, for the period 1982-89, from statutory birth and death registrations. Over 1500 cases formed the database for the study. RESULTS: The prevalence of cerebral palsy has increased among all the low birthweight groups with, most recently, an increase in infants weighing < 1000 g at birth. Low birthweight infants now comprise about 50% of all cases of cerebral palsy; in the early years of the study they comprised about 32% of all cases. The proportion of cerebral palsy by clinical type has changed among low birthweight babies, with relatively fewer cases with diplegia and a concomitant increase in the proportion with hemiplegia. An increase in the severity of functional disability, determined by the proportion of children with severe learning, manual, and ambulatory disabilities, was also found. CONCLUSIONS: The change in the epidemiology of cerebral palsy has implications for the aetiology of the condition, and for health, educational, and social service provision.     

Genetic risk factors of neural tube defects

Neural tube defects (NTDs) are a group of diseases caused by a failure of closure of the neural tube. Its aetiology contains both environmental and genetic factors. NTDs have a polygenic background. Genes, which are linked with NTDs occurrence, are both directly and indirectly connected with controlling the process of closure of the neural tube. Ones of those are genes of metabolism of folic acid as MTHFR, MTR, MTRR, CBS, MTHFD, folic acid receptors (FR) regulator genes from PAX family, T, PDGFRA and BRCA1 genes.     

神经管缺陷的表观遗传学研究进展

本综述介绍了NTDs(神经管缺陷)的疾病特点,总结了目前国际及国内范围对该病的病因研究情况,综合近五年的对该病的表观遗传发病机制研究的文章,分别从DNA甲基化、组蛋白修饰、印迹基因、小分子核糖核酸等表观遗传修饰在NTDs病因中的作用进行了详细的描述,并从NTDs发病的相关信号通路入手,总结了不同信号通路中基因组DNA甲基化与NTDs发生的关系.     

Genetic studies in neural tube defects. NTD Collaborative Group

Neural tube defects (NTD) are one of the most common birth defects and are caused by both environmental and genetic factors. The approach to identifying the genes predisposing to NTD, through linkage analysis and candidate gene analysis, is reviewed along with characteristics of a large, nationally ascertained cohort of families. Results from specific assessments of p53, PAX3 and MTHFR failed to suggest that these genes play a major role in NTD development in these families. Advances in genetic laboratory and statistical techniques have made this a prime opportunity for investigation into the causes of complex disorders, such as NTD. However, traditional approaches may prove to be challenging due to the difficulty of ascertaining samplable multiplex families.