Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neural Tube Defects”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1993

Maternal lymphocyte subsets in the cases with neural tube defects.

Neural tube defects (NTDs) are among the most prevalent of congenital malformations. Organ system anomalies and certain changes in the thymus gland have also been reported. Lymphocyte subset changes can be expected in infants with NTD as a result of these thymic anomalies. We investigated lymphocyte subpopulations in twenty-one mothers of NTD cases in order to evaluate the maternal immunological alterations. The mothers of twenty-one healthy infants were chosen as a control group. Pregnancy is known to be associated with a depression in cellular immunity. We found, however, some additional changes in cellular immunity in the mothers of NTDs. The CD4/CD8 ratios were significantly lower than those of control mothers (p = 0.044). This difference was related to the increased percentage of CD8 cells found in mothers of NTDs (p = 0.004). These results suggest that immunosuppression is more evident in the mothers of babies with NTDs.

CD4-CD8 Ratio↗
PubMed1985

Sonography, a complementary examination to alpha-fetoprotein testing for fetal neural tube defects.

Neural tube defects (NTDs) are among the most common congenital anomalies in the United States, with an estimated prevalence of 16 per 10,000 births. The measurement of amniotic fluid alpha-fetoprotein (AF-AFP) concentration has been used to detect NTDs since the early 1970s. When the AF-AFP concentration is elevated, ultrasonography is commonly used to confirm the presence of a NTD. In this study, patient charts, amniocentesis records, and ultrasound reports from a three-year period were reviewed. The 97 fetuses identified as being at high risk for NTDs were divided into four groups: those with high AF-AFP concentrations (Groups 1 and 2, with from 3 to 5 standard deviations (SD) above the mean and with more than 5 SD above the mean, respectively): those referred from other institutions because of suspicious sonographic results (Group 3); and those at risk because of a previous sibling with a NTD (Group 4). Ultrasonography was 100 per cent sensitive and 100 per cent specific in diagnosing NTDs. Thus, in pregnancies with an elevated AF-AFP concentration, ultrasonography can reliably identify normal fetuses as well as differentiate between those with NTDs and those with other congenital anomalies. Also, since AF-AFP concentrations decline after 20 weeks' gestation, ultrasonography may be a better test than a repeat amniocentesis in equivocal cases of AF-AFP elevation.

Adult↗
PubMed2001

Promoter haplotype combinations of the platelet-derived growth factor alpha-receptor gene predispose to human neural tube defects.

Neural tube defects (NTDs), including anencephaly and spina bifida, are multifactorial diseases that occur with an incidence of 1 in 300 births in the United Kingdom. Mouse models have indicated that deregulated expression of the gene encoding the platelet-derived growth factor alpha-receptor (Pdgfra) causes congenital NTDs (refs. 2-4), whereas mutant forms of Pax-1 that have been associated with NTDs cause deregulated activation of the human PDGFRA promoter. There is an increasing awareness that genetic polymorphisms may have an important role in the susceptibility for NTDs (ref. 6). Here we identify five different haplotypes in the human PDGFRA promoter, of which the two most abundant ones, designated H1 and H2 alpha, differ in at least six polymorphic sites. In a transient transfection assay in human bone cells, the five haplotypes differ strongly in their ability to enhance reporter gene activity. In a group of patients with sporadic spina bifida, haplotypes with low transcriptional activity, including H1, were under-represented, whereas those with high transcriptional activity, including H2 alpha, were over-represented. When testing for haplotype combinations, H1 homozygotes were fully absent from the group of sporadic patients, whereas H1/H2 alpha heterozygotes were over-represented in the groups of both sporadic and familial spina bifida patients, but strongly under-represented in unrelated controls. Our data indicate that specific combinations of naturally occurring PDGFRA promoter haplotypes strongly affect NTD genesis.

Genetic Predisposition to Disease↗
PubMed1999

High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects.

Neural tube defects (NTD) are highly prevalent in the Mexican population. According to data from the Registry and Epidemiological Surveillance of External Congenital Malformations (RYVEMCE), at least 1 in 250 conceptions that reach 20 weeks of pregnancy or more has a NTD. This number is three to four times higher than that observed in other related ethnic groups. A common novel mutation (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene is considered an associated risk factor for NTD and other malformations. Studies in different populations agree that the prevalence of the homozygote for the mutated allele is higher in cases of NTD than in controls. In a meta-analysis recently published, the mean prevalence of the homozygote for the mutation was 9.2% for different groups of European controls and 16.4% in NTD cases from the same populations. This prompted us to investigate the frequency of the normal (C) and the mutant (T) alleles and the prevalence of the expected (CC, CT and TT) genotypes in 250 healthy Mexican women from different parts of the country. The proportion of CC (17.6%), CT (47.6%), and TT (34. 8%) genotypes found, and the gene frequencies of 0.414 and 0.586% for the C and T alleles, respectively, confirmed the very high prevalence of the mutant allele and the TT genotype in the sample studied. Comparisons with studies done in Holland, Ireland, the United States, Japan, and other ethnic groups showed highly significant differences, with an average OR of 5.8 (95% Cl 3.4-10.3) for a Mexican being homozygous for the mutation. These findings may explain an important part of the high prevalence of NTD observed in our population.

Alleles↗
PubMed1992

Neural tube defects without neural crest defects in splotch mice.

Homozygous Splotch mutant mice (Sp/Sp) die on day 14 of gestation with neural tube defects, curly tail, and malformations of neural crest derivatives. Sp1H mice, which have a radiation-induced allele of Splotch with a similar phenotype, were used for this study. The neural tube defects are always located in the lumbosacral region and in 50% of the cases also in the region of the hindbrain. In this report, rare cases of neural tube defects and tail defects among the offspring of crosses between Splotch (Sp1H) heterozygotes are presented, which are not associated with a neural crest defect. This suggests that the development of the neural tube and neural crest defects in this mutant is caused by independent mechanisms or is dependent on the dosage of the mutant gene, with different thresholds being pathogenetic in the neural tube and neural crest, respectively.

Abnormalities, Multiple↗
PubMed2000

Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects.

BACKGROUND: Neural tube defects arise during the development of the brain and spinal cord. OBJECTIVES: The objective of this review was to assess the effects of increased consumption of multivitamins or folate on the prevalence of neural tube defects before pregnancy and in the first two months of pregnancy (periconceptionally). SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing periconceptional supplementation by multivitamins with placebo, folate with placebo, or multivitamins with folate; different dosages of multivitamins or folate; prepregnancy dietary advice and counselling in primary care settings to increase the consumption of folate-rich foods, or folate-fortified foods, with standard care; increased intensity of information provision with standard public health dissemination. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. MAIN RESULTS: Four trials involving 6425 women were included. The trials all addressed the question of supplementation and they were of variable quality. No dissemination trials were identified. Periconceptional folate supplementation reduced the incidence of neural tube defects (odds ratio 0.28, 95% confidence interval 0.15 to 0.53). Folate supplementation did not significantly increase spontaneous abortion, ectopic pregnancy or stillbirth, although there was a possible increase in multiple gestation. Multivitamins alone were not associated with prevention of neural tube defects and did not produce preventive effects when given with folate. REVIEWER'S CONCLUSIONS: Periconceptional folate supplementation has a strong protective effect against neural tube defects. Information about folate should be made more widely available throughout the health and education systems. Women whose fetuses or babies have neural tube defects should be offered continuing folate supplementation. The benefits and risks of fortifying basic food stuffs, such as flour, with added folate remain unresolved.

Dietary Supplements↗
PubMed1999

The role of folate transport and metabolism in neural tube defect risk.

Neural tube defects (NTDs) are common congenital malformations in humans. While etiologically heterogeneous, for the most part they are multifactorial in their pathogenesis, having both genetic and environmental factors contributing to their development. In recent years, there has been a great deal of epidemiologic evidence demonstrating that women who received multivitamins containing folic acid periconceptionally had significantly reduced occurrence and recurrence risks for producing infants with such malformations. Unfortunately, the mechanism(s) underlying the beneficial effects of folic acid is not well understood. In this article, we review the fundamental embryological processes involved in closing the neural tube, the relevant epidemiologic data on folic acid supplementation and relative NTD risk, as well as several recent studies of candidate genes for NTD sensitivity that are involved in folate transport and metabolism.

Biological Transport↗
PubMed1999

Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population.

Neural tube defects (NTDs) are a common birth defect, seen in approximately 1/1,000 births in the United States. NTDs are considered a complex trait where several genes, interacting with environmental factors, create the phenotype. Using a Midwestern NTD population consisting of probands, parents, and siblings from Iowa, Minnesota, and Nebraska, we analyzed a range of candidate genes, including 5,10-methylenetetrahydrofolate reductase (MTHFR), folate receptors-alpha (FOLR1; hereafter abbreviated "FR-alpha") and -beta (FOLR2; hereafter, "FR-beta"), methionine synthase (hereinafter, "MS"), T, the human homolog of the murine Brachyury gene, and the paired-box homeotic gene 3 (PAX3), for association with NTDs. We were unable to demonstrate an association using a previously described Ala-->Val mutation in MTHFR and the majority of our NTD populations. However, we discovered a silent polymorphism in exon 6 of MTHFR which conserved a serine residue and which showed significant association with NTDs in our Iowa population. Analysis of exon 7 of MTHFR then demonstrated an Ala-->Glu mutation which was significantly associated with our Iowa NTD population; however, we could not replicate this result either in a combined Minnesota/ Nebraska or in a California NTD population. Using polymorphic markers for MS, FR-beta, T, and PAX3, we were unable to demonstrate linkage disequilibrium with our NTD populations. A mutation search of FR-alpha revealed one proband with a de novo silent mutation of the stop codon. This work provides a new panel of genetic variants for studies of folate metabolism and supports, in some NTD populations, an association between MTHFR and NTDs.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1986

Neural tube defects: a review of human and animal studies on the etiology of neural tube defects.

Although neural tube defects are a common congenital anomaly, their etiology is not known. Human studies have emphasized the pathology and epidemiology of the defects and suggest that in the majority of cases the etiology is multifactorial. Factors which appear possibly to be important are genetic predisposition, maternal illness, and fetal drug exposure. Animal studies have utilized naturally occurring neural tube defects and teratologically induced lesions. No animal model has been convincingly established as the equivalent of human neural tube defects. However, animal models have allowed investigation of the mechanisms of suggested human teratogens and determination of the pathogenesis of naturally occurring animal defects. Their most important contribution has been in furthering the understanding of the normal mechanisms of neural tube closure. It may be through this understanding that the etiology of human neural tube defects will be determined.

Animals↗
PubMed1991

Use of folic acid for prevention of spina bifida and other neural tube defects--1983-1991.

Neural tube defects--including spina bifida, anencephaly, and encephalocele--are common, serious birth defects that are important causes of infant mortality and disability. Women in the United States who have had a pregnancy resulting in an infant or fetus with a neural tube defect have a 2%-3% risk for having another pregnancy resulting in an infant or fetus with a neural tube defect (i.e., a recurrence) The British Medical Research Council (MRC) Vitamin Study Group recently reported the results of a randomized prevention trial that indicated that daily oral supplementation with folic acid before conception and during early pregnancy substantially reduces the recurrence of neural tube defects. This report summarizes the findings of that study and provides recommendations for supplementation with folic acid to prevent the recurrence of neural tube defects.

Anencephaly↗
PubMed1989

The absence of a relation between the periconceptional use of vitamins and neural-tube defects. National Institute of Child Health and Human Development Neural Tube Defects Study Group.

Whether taking multivitamins or folate around the time of conception can reduce a woman's risk of having a child with a neural-tube defect is controversial. To investigate this question, we examined the periconceptional use of vitamin supplements by women who had a conceptus with a neural-tube defect (n = 571), women who had had a stillbirth or a conceptus with another malformation (n = 546), and women who had had a normal conceptus (n = 573). Women with conceptuses with neural-tube defects were identified either prenatally or postnatally and were matched to control mothers for gestational age. To minimize recall bias, we interviewed nearly all the women within five months of the diagnosis of a birth defect or the birth of the infant (mean, 84 days); information on vitamin use was obtained by an interviewer who was unaware of the outcome of pregnancy. The rate of periconceptional multivitamin use among the mothers of infants with neural-tube defects (15.8 percent) was not significantly different from the rate among mothers in either the abnormal or the normal control group (14.1 percent and 15.9 percent, respectively). After adjustment for potential confounding factors, the odds ratio for having an infant with a neural-tube defect among women classified as having had full supplementation with multivitamins was 0.95 as compared with the mothers of the abnormal infants (95 percent confidence interval, 0.78 to 1.14) and 1.00 as compared with the mothers of normal infants (95 percent confidence interval, 0.83 to 1.20). There were no differences among the groups in the use of folate supplements. The adjusted odds ratio for having an infant with a neural-tube defect among those receiving the recommended daily allowance of folate was 0.97 as compared with the mothers of abnormal infants (95 percent confidence interval, 0.79 to 1.18) and 0.98 as compared with the mothers of normal infants (95 percent confidence interval, 0.80 to 1.20). We conclude that the periconceptional use of multivitamins or folate-containing supplements by American women does not decrease the risk of having an infant with a neural-tube defect.

Adult↗
PubMed1986

Strain differences in heat-induced neural tube defects in mice.

Neural tube defects are common congenital anomalies affecting approximately 0.1% of liveborn infants. It is widely accepted that these disorders are of a multifactorial origin, having both a genetic and an environmental component to their development. In a study designed to elucidate the genetic factors involved in a mouse model of hyperthermia-induced neural tube defects, it is apparent that a hierarchy of susceptibility exists among various inbred mouse strains. Female SWV mice were extremely sensitive to a 10-minute hyperthermic treatment on day 8.5 of gestation, with 44.3% of their offspring having exencephaly. The other strains used in these studies (LM/Bc, SWR/J, C57BL/6J, and DBA/2J) all had less than 14% affected offspring. In experimental situations where the environment is held constant and the only difference between the strains is their genotype, it is assumed that the difference in response to a teratogen is genetically mediated. To test the hypothesis that several genes are involved, reciprocal crosses were made between strains of high, moderate, and low sensitivity. When this was done, the high sensitivity of the SWV strain was lost in the F1 hybrid, implying not only that multiple genes are involved, but that it is the embryo's genotype and not the maternal genotype that is the major factor in determining susceptibility to heat-induced neural tube defects.

Animals↗
PubMed1995

[Analyses of the prevalences for neural tube defects and cleft lip and palate in China from 1988 to 1991].

This paper reports the monitoring results of two main categories of birth defects-neural tube defects (NTD) and cleft of lip and palate (CLP) in China during the period of continuous monitoring (1988-1991). The method of hospital-based monitoring was adopted for data collection. From Jan. 1988 to Dec. 1991, a total of 2,750,588 births were monitored, and 28,168 cases of congenital malformations were identified. The prevalence of total birth defects was 102.4 per 10,000. 6885 cases of NTD were identified during this period, the prevalence of NTD being 25.0 per 10,000. The prevalence of NTD varied geographically; it declined gradually from the north to the south of China with the highest rate of NTD in the Taihang Mountain Regions. A total of 4548 cases of CLP were identified, and the provincial prevalence of CLP varied from 11.2 to 25.7 per 10000 with a mean of 16.5 per 10000. The prevalence of NTDs varied seasonally with the peak in winter (January). The sex ratio of NTD was 0.59, the prevalences in female births (32.1 per 10,000) being higher than that in male births (17.4 per 10,000) (P < 0.01). The sex ratio of CLP was 1.33. A significant difference was noted between the sex ratio of cleft palate (0.80) and that of the total cleft lip (1.46) (P < 0.01). The prevalence of NTD in rural areas (44.3 per 10,000) was 3 times as high as that in urban areas (14.4 per 10,000), but no difference in occurrence of CLP was observed between the urban and rural areas (P > 0.05).

China↗
PubMed1999

Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

BACKGROUND AND METHODS: Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. RESULTS: Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). CONCLUSIONS: Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

Adult↗
PubMed2000

Ribonucleotide reductase subunit R1: a gene conferring sensitivity to valproic acid-induced neural tube defects in mice.

Neural tube defects (NTDs), although prevalent and easily diagnosed, are etiologically heterogeneous, rendering mechanistic interpretation problematic. To date, there is evidence that mammalian neural tube closure (NTC) initiates and fuses intermittently at four discrete locations. Disruption of this process at any of these four sites may lead to a region-specific NTDs, possibly arising through closure site-specific genetic mechanisms. Although recent efforts have focused on elucidating the genetic components of NTDs, a void persists regarding gene identification in closure site-specific neural tissue. To this end, experiments were conducted to identify neural tube closure site-specific genes that might confer regional sensitivity to teratogen-induced NTDs. Using an inbred mouse strain (SWV/Fnn) with a high susceptibility to VPA- induced NTDs that specifically targets and disrupts NTC between the prosencephalon and mesencephalon region (future fore/midbrain; neural tube closure site II), we identified a VPA-sensitive closure site II-specific clone. Sequencing of this clone from an SWV neural tube cDNA library confirmed that it encodes the r1 subunit of the cell cycle enzyme ribonucleotide reductase (RNR). The abundance of rnr-r1 mRNA was significantly increased in response to VPA drug treatment. This upregulated expression was accompanied by a significant decrease in cellular proliferation in the closure site II neural tube region of the embryos, as determined by ELISA cellular proliferation assays performed on BrdU-pulsed neuroepithelial cells in vivo. We hypothesize that rnr-r1 plays a critical role in the development of VPA-induced exencephaly.

Animals↗
PubMed1997

[Territorial distribution of neural tube defects in Poland].

Neural tube defects (ntd) remain unresolved therapeutic problems, even for contemporary health services. Prophylactic measures are the best methods for limitation of the problem. In many countries, the number of children born with ntd has been reduced significantly, even in 4-5 folds. Authors found that the situation in Poland remains stable since last 20 years. Epidemiological evaluation of the ntd morbidity in Poland is very difficult. There is no National Register of Inherited Defects. Authors observed and analysed mortality and hospitalisation due to ntd in Poland, in early ninetees, and compared these data with information originated from Regional (Wielkopolska) Inherited Defects Register. It was found that ntd mortality and hospitalisation in Wielkopolska was similar to average in Poland. It has been estimated that the rate of children born with ntd in Poland, in 1995 was 2.68 per 1000 live and stillbriths (in 1972-1974 was 2.04). Especially high rates of ntd's have been found in north-eastern part of Country. Incidence of ntd's was higher in rural, than in urban population of the Country.

Adult↗