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This article is from Iranian Journal of Public Health , volume 39 . Abstract Background:: Neural tube defects (NTD) are one of the leading causes of infant mortality worldwide. This study was designed to determine the prevalence of NTDs among native Fars ethnic groups during 1998–2005, and to identify maternal and demographic factors associated with NTDs. Methods:: We performed a descriptive cross-sectional hospital-based study in Dezyani Hospital, Gorgan, North of Iran, since January 1998 until December 2005. The design was based on a sample of 30,639 births of native Fars ethnic groups. Data were analyzed by using spss V13.5 software and were compared with the chi-square test. Results:: The prevalence of NTDs in Native Fars during the 8-year period was 25.4 per 10000 births (95% confidence interval: 20.1–31.8). The prevalence of NTDs was 20.6/10000 and 30.6/10000 in males and females respectively but this difference was not significant. The prevalence of spina bifida, anencephaly and encephalocele were 12.7, 11.4 and 1.3 per 10000 respectively. The rate of NTD was 48.9/10000 in newborns with mothers aged > 35 years. The highest rate of NTDs and spina bifida was in 2002. The highest and lowest rate of anencephaly was in 2005 and 2003 respectively. Twenty eight percent of the parents had consanguineous marriages. Degree relatedness 3, 4, 5 and 6 of consanguineous marriages were 12.8%, 9%, 3.8%, 2.5%, respectively. Also 47.5% of the parents resided in rural areas. Conclusion:: This investigation showed that the rate of NTDs in Native Fars was higher in Iran. In addition, this rate is higher than the Canada and Ukraine and lower than Chinese people.

This article is from Frontiers in Genetics , volume 4 . Abstract Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19 bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (“risk genotypes”) and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p = 0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic mechanisms.

This article is from Journal of Global Health , volume 4 . Abstract Background: To provide an estimate for the burden of neural tube defects (NTD) in low– and middle–income countries (LMIC) and explore potential public health policies that may be implemented. Although effective interventions are available to prevent NTD, there is still considerable childhood morbidity and mortality present in LMIC. Methods: A search of Medline, EMBASE, Global Health Library and PubMed identified 37 relevant studies that provided estimates of the burden of NTD in LMIC. Information on burden of total NTD and specific NTD types was separated according to the denominator into two groups: (i) estimates based on the number of live births only; and (ii) live births, stillbirths and terminations. The data was then extracted and analysed. Results: The search retrieved NTD burden from 18 countries in 6 WHO regions. The overall burden calculated using the median from studies based on livebirths was 1.67/1000 (IQR = 0.98–3.49) for total NTD burden, 1.13/1000 (IQR = 0.75–1.73) for spina bifida, 0.25/1000 (IQR = 0.08–1.07) for anencephaly and 0.15/1000 (IQR = 0.08–0.23) for encephalocele. Corresponding estimates based on all pregnancies resulting in live births, still births and terminations were 2.55/1000 (IQR = 1.56–3.91) for total NTD burden, 1.04/1000 (IQR = 0.67–2.48) for spina bifida, 1.03/1000 (IQR = 0.67–1.60) for anencephaly and 0.21 (IQR = 0.16–0.28) for encephalocele. This translates into about 190 000neonates who are born each year with NTD in LMIC. Conclusion: Limited available data on NTD in LMIC indicates the need for additional research that would improve the estimated burden of NTD and recommend suitable aid policies through maternal education on folic acid supplementation or food fortification.

This article is from International Journal of Environmental Research and Public Health , volume 10 . Abstract Objective: A significant decline in the prevalence of neural tube defects (NTD) through food fortification has been reported. Questions remain, however, about the effectiveness of this intervention in reducing the gap in prevalence across socioeconomic status (SES). Study Design: Using health number and through record linkage, children born in Ontario hospitals between 1994 and 2009 were followed for the diagnosis of congenital anomalies. SES quintiles were assigned to each child using census information at the time of birth. Adjusted rates and multivariate models were used to compare trends among children born in different SES groups. Results: Children born in low SES areas had significantly higher rates of NTDs (RR = 1.25, CI: 1.14–1.37). Prevalence of NTDs among children born in low and high SES areas declined since food fortification began in 1999 although has started rising again since 2006. While the crude decline was greater in low SES areas, after adjustment for maternal age, the slope of decline and SES gap in prevalence rates remained unchanged overtime. Conclusions: While food fortification is successful in reducing the prevalence of NTDs, it was not associated with removing the gap between high and low SES groups.

This article is from Surgical Neurology International , volume 3 . Abstract Background:: The presence of multiple neural tube defects (NTDs) is a rare entity. Published literature shows not more than 10 case reports. Such cases contradict the well-established “zipper model” of neural tube closure and support “multi-site closure model.” Case Description:: We are reporting a unique case of multiple NTDs in a 5-month-o ld female child. Occipital encephalocele, dorsal meningomyelocele, Split cord malformation (SCM), and tethered cord were present in this case. Conclusion:: This case report further substantiate the “multisite closure model,” however, more research work on human neuro-embryology is needed to overcome the controversies of neural tube closure.

This article is from Surgical Neurology International , volume 3 . Abstract Background:: The presence of multiple neural tube defects (NTDs) is a rare entity. Published literature shows not more than 10 case reports. Such cases contradict the well-established “zipper model” of neural tube closure and support “multi-site closure model.” Case Description:: We are reporting a unique case of multiple NTDs in a 5-month-o ld female child. Occipital encephalocele, dorsal meningomyelocele, Split cord malformation (SCM), and tethered cord were present in this case. Conclusion:: This case report further substantiate the “multisite closure model,” however, more research work on human neuro-embryology is needed to overcome the controversies of neural tube closure.

This article is from Iranian Journal of Pediatrics , volume 22 . Abstract Objective: The purpose of this study was to identify the relationship of neurotoxic inorganic elements in the hair of patients with the diagnosis of Neural Tube Defects. Our initial hypothesis was that neurotoxic inorganic elements were associated with Neural Tube Defects. Methods: Twenty-three samples of hair from newborns were obtained from the General Hospital, “Aurelio Valdivieso” in the city of Oaxaca, Mexico. The study group included 8 newborn infants with neural tube pathology. The control group was composed of 15 newborns without this pathology. The presence of inorganic elements in the hair samples was determined by inductively-coupled plasma spectroscopy (spectroscopic emission of the plasma). Findings: The population of newborns with Neural Tube Defects showed significantly higher values of the following elements than the control group: Aluminium, Neural Tube Defects 152.77±51.06 µg/g, control group 76.24±27.89 µg/g; Silver, Neural Tube Defects 1.45±0.76, control group 0.25±0.53 µg/g; Potassium, Neural Tube Defects 553.87±77.91 µg/g, control group 341.13±205.90 µg/g. Association was found at 75 percentile between aluminium plus silver, aluminium plus potassium, silver plus potassium, and potassium plus sodium. Conclusion: In the hair of newborns with Neural Tube Defects, the following metals were increased: aluminium, silver. Given the neurotoxicity of the same, and association of Neural Tube Defects with aluminum and silver, one may infer that they may be participating as factors in the development of Neural Tube Defects.

This article is from Iranian Journal of Pediatrics , volume 22 . Abstract Objective: The purpose of this study was to identify the relationship of neurotoxic inorganic elements in the hair of patients with the diagnosis of Neural Tube Defects. Our initial hypothesis was that neurotoxic inorganic elements were associated with Neural Tube Defects. Methods: Twenty-three samples of hair from newborns were obtained from the General Hospital, “Aurelio Valdivieso” in the city of Oaxaca, Mexico. The study group included 8 newborn infants with neural tube pathology. The control group was composed of 15 newborns without this pathology. The presence of inorganic elements in the hair samples was determined by inductively-coupled plasma spectroscopy (spectroscopic emission of the plasma). Findings: The population of newborns with Neural Tube Defects showed significantly higher values of the following elements than the control group: Aluminium, Neural Tube Defects 152.77±51.06 µg/g, control group 76.24±27.89 µg/g; Silver, Neural Tube Defects 1.45±0.76, control group 0.25±0.53 µg/g; Potassium, Neural Tube Defects 553.87±77.91 µg/g, control group 341.13±205.90 µg/g. Association was found at 75 percentile between aluminium plus silver, aluminium plus potassium, silver plus potassium, and potassium plus sodium. Conclusion: In the hair of newborns with Neural Tube Defects, the following metals were increased: aluminium, silver. Given the neurotoxicity of the same, and association of Neural Tube Defects with aluminum and silver, one may infer that they may be participating as factors in the development of Neural Tube Defects.

Focus: Neural Tube Defects, January 1996, Vol. 29, No. 11; birth defects; prenatal care; Missouri Provisional Statistics; 

Focus: Neural Tube Defects and Folic Acid Awareness, March 2002, Vol. 36, No. 1; birth defects; pregnancy; Missouri Monthly Vital Statistics: Provisional Statistics From the Missouri Department of Health & Senior Services, Center for Health Information & Evaluation; 

Artykuł w: Annales Universitatis Mariae Curie-Skłodowska, Sectio D, Medicina. Vol. 61, N2, nr 110 (2006), strony 636-639

This article is from Iranian Journal of Pediatrics , volume 20 . Abstract Objective: This study was conducted to determine the serum level of folic acid and vitamin B12 in neural tube defects pregnancies (NTD) and healthy controls in Northern Iran. Methods: This case-control study was performed on women with neural tube defects pregnancies and controls with unaffected pregnancies in Northern Iran during 2006. Twenty three pregnant women whose pregnancies were diagnosed as NTD by a second-trimester ultrasonographic examination were recruited as cases. The control group (n=23) consisted of women who were selected among socio-economic status (SES) matched women who had a normal targeted ultrasound during the second trimester with documented normal fet al outcome. Fetal NTD was suspected with targeted second-trimester ultrasound during the 16th week of gestation and confirmed with high maternal serum α-fetoprotein levels. Folate, vitamin B12, homocysteine and alpha fetoprotein were evaluated after target ultrasonography. Findings: Serum alpha fetoprotein level (mean±SD) in cases and controls was 120.2±64.1 and 50±33.5 iu/ml, respectively (P

Downloaded from Centers for Disease Control and Prevention (CDC) Youtube channel on 2025-02-02 17:28:13 https://youtube.com/watch?v=6QZOetzZngE -------- Neural tube defects are serious birth defects of the brain and spine. Fortifying grains with folic acid could prevent these defects. Comments on this video are allowed in accordance with our comment policy: http://www.cdc.gov/SocialMedia/Tools/CommentPolicy.html This video can also be viewed at https://www.cdc.gov/video/phgr/btd/2017/BtdNeuralTubeDefects.wmv

Downloaded from Centers for Disease Control and Prevention (CDC) Youtube channel on 2025-02-01 20:00:12 https://youtube.com/watch?v=TCAt1qFyvWk -------- During this webinar, CDC experts will describe the sustained impact of folic acid on the prevention of NTDs, address different forms of folate and why folic acid is the only form proven for NTD prevention, and provide recommendations for people with MTHFR gene variants. CDC will be joined by Shannon Clark, MD, MMS, FACOG, for an interactive discussion in which she will share her experiences counseling patients about NTD prevention. She will also describe how she addresses misinformation about folic acid and how healthcare professionals can improve collaboration within the healthcare team to improve folic acid intake to prevent NTDs. This video can also be viewed at https://www.cdc.gov/ncbddd/folicacid/videos/prevent-neural-tube-defects-webinar/folic-acid-webinar-september-2022-low-res.mp4

Downloaded from Centers for Disease Control and Prevention (CDC) Youtube channel on 2025-02-02 17:27:40 https://youtube.com/watch?v=OezK3hpF-cA -------- Neural tube defects are serious birth defects of the brain and spine. Fortifying grains with folic acid could prevent these defects. Comments on this video are allowed in accordance with our comment policy: http://www.cdc.gov/SocialMedia/Tools/CommentPolicy.html This video can also be viewed at https://www.cdc.gov/video/phgr/2017/GR_10-17-2017.mp4

Downloaded from Centers for Disease Control and Prevention (CDC) Youtube channel on 2025-02-02 17:27:40 https://youtube.com/watch?v=OezK3hpF-cA -------- Neural tube defects are serious birth defects of the brain and spine. Fortifying grains with folic acid could prevent these defects. Comments on this video are allowed in accordance with our comment policy: http://www.cdc.gov/SocialMedia/Tools/CommentPolicy.html This video can also be viewed at https://www.cdc.gov/video/phgr/2017/GR_10-17-2017.mp4

This article is from Indian Journal of Human Genetics , volume 17 . Abstract Neural tube defects (NTDs) are the second most common severely disabling human congenital defects. Worldwide, NTDs incidence is approximately one per 1000 live births and varies between 0.78 and 12 per 1000 births in general populations. NTDs causation involves multiple genes, nutritional and environmental factors. Research in the next stage should include bigger populations and bigger studies that would be suitable to detect significant links and conclusions with relatively minor risk factors; analysis of multiple candidate genes to detect potential gene-gene interactions; detailed analysis of patient samples stratified by phenotype.

This article is from Human Molecular Genetics , volume 21 . Abstract Neural tube defects (NTDs), including spina bifida and anencephaly, are common birth defects of the central nervous system. The complex multigenic causation of human NTDs, together with the large number of possible candidate genes, has hampered efforts to delineate their molecular basis. Function of folate one-carbon metabolism (FOCM) has been implicated as a key determinant of susceptibility to NTDs. The glycine cleavage system (GCS) is a multi-enzyme component of mitochondrial folate metabolism, and GCS-encoding genes therefore represent candidates for involvement in NTDs. To investigate this possibility, we sequenced the coding regions of the GCS genes: AMT, GCSH and GLDC in NTD patients and controls. Two unique non-synonymous changes were identified in the AMT gene that were absent from controls. We also identified a splice acceptor site mutation and five different non-synonymous variants in GLDC, which were found to significantly impair enzymatic activity and represent putative causative mutations. In order to functionally test the requirement for GCS activity in neural tube closure, we generated mice that lack GCS activity, through mutation of AMT. Homozygous Amt−/− mice developed NTDs at high frequency. Although these NTDs were not preventable by supplemental folic acid, there was a partial rescue by methionine. Overall, our findings suggest that loss-of-function mutations in GCS genes predispose to NTDs in mice and humans. These data highlight the importance of adequate function of mitochondrial folate metabolism in neural tube closure.

This article is from Iranian Red Crescent Medical Journal , volume 16 . Abstract Background:: Neural tube defects (NTDs) including spina bifida and anencephaly are the second most common birth defects with 2.8 per 1000 births in northern Iran. Objectives:: This study was conducted to determine the risk factors of neural tube defects in Gorgan, north of Iran. Patients and Methods:: This hospital-based, case-control study was carried out on all NTD-affected pregnancies (n = 59) during February 2007 - August 2010, and 160 healthy pregnancies were selected via convenient sampling method in three hospitals in Gorgan, north of Iran. Risk factors including maternal body mass index (BMI), season of birth, gender of the newborn, mother’s age, ethnicity, consanguineous marriage, folic acid consumption, nutrition, habitat, and education, were assessed through interviews with mothers. Univariate and multivariate logistic regression analyses were used to estimate the risks by odds ratios (ORs) and 95% confidence intervals. Results:: The multivariate analysis showed that maternal BMI (normal/underweight OR: 0.23, overweight/underweight OR: 0.15, obese/underweight OR: 0.13) and maternal ethnicity (Fars/Sistani OR: 3.49) and maternal nutrition (good/poor OR: 0.46) were significantly correlated with NTDs in the newborns. Conclusions:: This study showed that maternal ethnicity, insufficient nutrition, and BMI, were the main risk factors of NTDs in northern Iran.

This article is from Iranian Red Crescent Medical Journal , volume 16 . Abstract Background:: Neural tube defects (NTDs) including spina bifida and anencephaly are the second most common birth defects with 2.8 per 1000 births in northern Iran. Objectives:: This study was conducted to determine the risk factors of neural tube defects in Gorgan, north of Iran. Patients and Methods:: This hospital-based, case-control study was carried out on all NTD-affected pregnancies (n = 59) during February 2007 - August 2010, and 160 healthy pregnancies were selected via convenient sampling method in three hospitals in Gorgan, north of Iran. Risk factors including maternal body mass index (BMI), season of birth, gender of the newborn, mother’s age, ethnicity, consanguineous marriage, folic acid consumption, nutrition, habitat, and education, were assessed through interviews with mothers. Univariate and multivariate logistic regression analyses were used to estimate the risks by odds ratios (ORs) and 95% confidence intervals. Results:: The multivariate analysis showed that maternal BMI (normal/underweight OR: 0.23, overweight/underweight OR: 0.15, obese/underweight OR: 0.13) and maternal ethnicity (Fars/Sistani OR: 3.49) and maternal nutrition (good/poor OR: 0.46) were significantly correlated with NTDs in the newborns. Conclusions:: This study showed that maternal ethnicity, insufficient nutrition, and BMI, were the main risk factors of NTDs in northern Iran.

This article is from Iranian Red Crescent Medical Journal , volume 16 . Abstract Background:: Neural tube defects (NTDs) including spina bifida and anencephaly are the second most common birth defects with 2.8 per 1000 births in northern Iran. Objectives:: This study was conducted to determine the risk factors of neural tube defects in Gorgan, north of Iran. Patients and Methods:: This hospital-based, case-control study was carried out on all NTD-affected pregnancies (n = 59) during February 2007 - August 2010, and 160 healthy pregnancies were selected via convenient sampling method in three hospitals in Gorgan, north of Iran. Risk factors including maternal body mass index (BMI), season of birth, gender of the newborn, mother’s age, ethnicity, consanguineous marriage, folic acid consumption, nutrition, habitat, and education, were assessed through interviews with mothers. Univariate and multivariate logistic regression analyses were used to estimate the risks by odds ratios (ORs) and 95% confidence intervals. Results:: The multivariate analysis showed that maternal BMI (normal/underweight OR: 0.23, overweight/underweight OR: 0.15, obese/underweight OR: 0.13) and maternal ethnicity (Fars/Sistani OR: 3.49) and maternal nutrition (good/poor OR: 0.46) were significantly correlated with NTDs in the newborns. Conclusions:: This study showed that maternal ethnicity, insufficient nutrition, and BMI, were the main risk factors of NTDs in northern Iran.

This article is from Indian Journal of Human Genetics , volume 18 . Abstract CONTEXT:: Tumor protein 53 (tp53) is one of the candidate gene proposed for neural tube defects, which affects central nervous system during early embryonic development, on the basis of mouse models. AIMS:: The present study is an attempt to unfold the possible role of tp53 G412C polymorphism in the incidence of neural tube defect (NTDs) in humans. SETTINGS AND DESIGN:: Case-control study was carried out in government hospitals of Delhi, India. MATERIALS AND METHODS:: Subjects comprised of 100 mothers of NTD children and 100 matched control mothers. Information on some environmental exposures was collected along with blood samples. After DNA extraction, the genotyping of tp53 G412C polymorphism was carried out by PCR-RFLP method. Statistical Analysys:: Fisher Exact or Chi square test, binary logistic model, and odds ratio (95% confidence interval) calculations were used to evaluate effect of risk factors on NTDs using SPSS v17.0. RESULTS:: The ‘CC’ genotype of tp53 G412C showed protective effect towards the development of anencephaly and/or encephalocele (OR: 0.44; 95% CI: 0.19-1.00); however, no significant difference among overall NTD cases and controls was observed (P>0.05). Further segregation of all subjects based on 2 different communities, Hindus and Muslims, the association of ‘CC’ genotype of the polymorphism with reduced NTD risk was observed among Hindu community (OR: 0.33; 95% CI: 0.13-0.79). CONCLUSION:: The study highlights the selective advantage provided by maternal ‘CC’ genotype, thereby reducing risk of cephalic NTDs, probably due to the lower apoptotic activity of the protein, however, more specifically in the presence of community-specific microenvironment.

This article is from PLoS ONE , volume 9 . Abstract Background: Taking folic acid supplements before pregnancy to reduce the risk of a neural tube defect (NTD) is especially important in countries without universal folic acid fortification. The extent of folic acid supplementation among women who had antenatal screening for Down’s syndrome and NTDs at the Wolfson Institute of Preventive Medicine, London between 1999 and 2012 was assessed. Methods and Findings: 466,860 women screened provided details on folic acid supplementation. The proportion of women who took folic acid supplements before pregnancy was determined according to year and characteristics of the women. The proportion of women taking folic acid supplements before pregnancy declined from 35% (95% CI 34%–35%) in 1999–2001 to 31% (30%–31%) in 2011–2012. 6% (5%–6%) of women aged under 20 took folic acid supplements before pregnancy compared with 40% of women aged between 35 and 39. Non-Caucasian women were less likely to take folic acid supplements before pregnancy than Caucasian women; Afro-Caribbean 17% (16%–17%), Oriental 25% (24%–25%) and South Asian 20% (20%–21%) compared with 35% (35%–35%) for Caucasian women. 51% (48%–55%) of women who previously had an NTD pregnancy took folic acid supplements before the current pregnancy. Conclusions: The policy of folic acid supplementation is failing and has led to health inequalities. This study demonstrates the need to fortify flour and other cereal grain with folic acid in all countries of the world.

This article is from Human Mutation , volume 33 . Abstract Neural tube defects (NTDs) are severe malformations of the central nervous system, affecting 1 of 1,000 live births. Mouse models were instrumental in defining the signaling pathways defective in NTDs, including the planar cell polarity (PCP), also called noncanonical Frizzled/Disheveled pathway. Based on the highly penetrant occurrence of NTDs in double Fzd3/Fzd6−/− mutant mice, we investigated the role of the human orthologues, FZD3 and FZD6, by resequencing a cohort of 473 NTDs patients and 639 ethnically matched controls. While we could not demonstrate a significant contribution of FZD3 gene, we identified five rare FZD6 variants that were absent in all controls and predicted to have a functional effect by computational analysis: one de novo frameshift mutation (c.1843_1844insA), three missense changes (p.Arg405Gln, p.Arg511Cys p.Arg511His), and one substitution (c.*20C>T) affecting the 3′-untranslated region (UTR) of the gene. The overall rate of predicted deleterious variants of FZD6 was 5.1-fold higher in cases compared to controls, resulting in a significantly increased NTDs mutation burden. This study demonstrates that rare nonsynonymous variants in FZD6 may contribute to NTDs in humans and enlarges the spectrum of mutations that link PCP pathway to NTDs. Hum Mutat 33:384–390, 2012. © 2011 Wiley Periodicals, Inc.

This article is from Human Mutation , volume 33 . Abstract Neural tube defects (NTDs) are severe malformations of the central nervous system, affecting 1 of 1,000 live births. Mouse models were instrumental in defining the signaling pathways defective in NTDs, including the planar cell polarity (PCP), also called noncanonical Frizzled/Disheveled pathway. Based on the highly penetrant occurrence of NTDs in double Fzd3/Fzd6−/− mutant mice, we investigated the role of the human orthologues, FZD3 and FZD6, by resequencing a cohort of 473 NTDs patients and 639 ethnically matched controls. While we could not demonstrate a significant contribution of FZD3 gene, we identified five rare FZD6 variants that were absent in all controls and predicted to have a functional effect by computational analysis: one de novo frameshift mutation (c.1843_1844insA), three missense changes (p.Arg405Gln, p.Arg511Cys p.Arg511His), and one substitution (c.*20C>T) affecting the 3′-untranslated region (UTR) of the gene. The overall rate of predicted deleterious variants of FZD6 was 5.1-fold higher in cases compared to controls, resulting in a significantly increased NTDs mutation burden. This study demonstrates that rare nonsynonymous variants in FZD6 may contribute to NTDs in humans and enlarges the spectrum of mutations that link PCP pathway to NTDs. Hum Mutat 33:384–390, 2012. © 2011 Wiley Periodicals, Inc.

This article is from Birth Defects Research. Part A, Clinical and Molecular Teratology , volume 97 . Abstract BACKGROUND: It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.).METHODS: A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council’s Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians.RESULTS: Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians.CONCLUSION: From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid–preventable NTDs across different ethnic groups. Birth Defects Research (Part A) 97:444–451, 2013. © 2013 Wiley Periodicals, Inc.

This article is from PLoS ONE , volume 9 . Abstract Objectives: The methylenetetrahydrofolate dehydrogenase (MTHFD1) gene, as one of the key genes involved in the folate pathway, has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). However, the results of published studies are contradictory and inconclusive. Thus, this meta-analysis aimed to evaluate the effect of the common polymorphism in the MTHFD1 gene, the G1958A (R653Q, dbSNP ID: rs2236225) variant, on the risk of NTDs in all eligible studies. Methods: Relevant literature published before January 3, 2014 was retrieved from the MEDLINE, EMBASE, Cochrane Library, and CBM databases. Pooled crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the MTHFD1 G1958A polymorphism and NTDs risk. Results: We performed a meta-analysis of nine studies with a total of 4,302 NTDs patients and 4,238 healthy controls. Our results demonstrated a significant correlation between the MTHFD1 G1958A polymorphism and NTDs in an overall meta-analysis. For family-based studies, the study subjects were classified as NTD cases, mothers with NTDs offspring, and fathers with NTDs offspring. We found no association between any of the fathers’ genotypes and NTDs, whereas there was a clear excess of the 1958A allele in the mothers of children with NTDs compared with controls individuals. Conclusions: In summary, our meta-analysis strongly suggests that the MTHFD1 G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations. However, the evidence of this association should be interpreted with caution due to the selective nature of publication of genetic association studies.

This article is from BMJ : British Medical Journal , volume 349 . Abstract Objective To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects.Design Bayesian model.Setting Data from two population based studies in China.Participants 247 831 participants in a prospective community intervention project in China (1993-95) to prevent neural tube defects with 400 μg/day folic acid supplementation and 1194 participants in a population based randomized trial (2003-05) to evaluate the effect of folic acid supplementation on blood folate concentration among Chinese women of reproductive age.Intervention Folic acid supplementation (400 μg/day).Main outcome measures Estimated RBC folate concentration at time of neural tube closure (day 28 of gestation) and risk of neural tube defects.Results Risk of neural tube defects was high at the lowest estimated RBC folate concentrations (for example, 25.4 (95% uncertainty interval 20.8 to 31.2) neural tube defects per 10 000 births at 500 nmol/L) and decreased as estimated RBC folate concentration increased. Risk of neural tube defects was substantially attenuated at estimated RBC folate concentrations above about 1000 nmol/L (for example, 6 neural tube defects per 10 000 births at 1180 (1050 to 1340) nmol/L). The modeled dose-response relation was consistent with the existing literature. In addition, neural tube defect risk estimates developed using the proposed model and population level RBC information were consistent with the prevalence of neural tube defects in the US population before and after food fortification with folic acid.Conclusions A threshold for “optimal” population RBC folate concentration for the prevention of neural tube defects could be defined (for example, approximately 1000 nmol/L). Population based RBC folate concentrations, as a biomarker for risk of neural tube defects, can be used to facilitate evaluation of prevention programs as well as to identify subpopulations at elevated risk for a neural tube defect affected pregnancy due to folate insufficiency.

This article is from BMJ : British Medical Journal , volume 349 . Abstract Objective To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects.Design Bayesian model.Setting Data from two population based studies in China.Participants 247 831 participants in a prospective community intervention project in China (1993-95) to prevent neural tube defects with 400 μg/day folic acid supplementation and 1194 participants in a population based randomized trial (2003-05) to evaluate the effect of folic acid supplementation on blood folate concentration among Chinese women of reproductive age.Intervention Folic acid supplementation (400 μg/day).Main outcome measures Estimated RBC folate concentration at time of neural tube closure (day 28 of gestation) and risk of neural tube defects.Results Risk of neural tube defects was high at the lowest estimated RBC folate concentrations (for example, 25.4 (95% uncertainty interval 20.8 to 31.2) neural tube defects per 10 000 births at 500 nmol/L) and decreased as estimated RBC folate concentration increased. Risk of neural tube defects was substantially attenuated at estimated RBC folate concentrations above about 1000 nmol/L (for example, 6 neural tube defects per 10 000 births at 1180 (1050 to 1340) nmol/L). The modeled dose-response relation was consistent with the existing literature. In addition, neural tube defect risk estimates developed using the proposed model and population level RBC information were consistent with the prevalence of neural tube defects in the US population before and after food fortification with folic acid.Conclusions A threshold for “optimal” population RBC folate concentration for the prevention of neural tube defects could be defined (for example, approximately 1000 nmol/L). Population based RBC folate concentrations, as a biomarker for risk of neural tube defects, can be used to facilitate evaluation of prevention programs as well as to identify subpopulations at elevated risk for a neural tube defect affected pregnancy due to folate insufficiency.

This article is from BMC Public Health , volume 12 . Abstract Background: Environmental exposure may play an important role in the incidences of neural tube defects (NTD) of birth defects. Their influence on NTD may likely be non-linear; few studies have considered spatial autocorrelation of residuals in the estimation of NTD risk. We aimed to develop a spatial model based on generalized additive model (GAM) plus cokriging to examine and model the expected incidences of NTD and make the inference of the incidence risk. Methods: We developed a spatial model to predict the expected incidences of NTD at village level in Heshun County, Shanxi Province, China, a region with high NTD cases. GAM was used to establish linear and non-linear relationships between local covariates and the expected NTD incidences. We examined the following village-level covariates in the model: projected coordinates, soil types, lithodological classes, distance to watershed, rivers, faults and major roads, annual average fertilizer uses, fruit and vegetable production, gross domestic product, and the number of doctors. The residuals from GAM were assumed to be spatially auto-correlative and cokriged with regional residuals to improve the prediction. Our approach was compared with three other models, universal kriging, generalized linear regression and GAM. Cross validation was conducted for validation. Results: Our model predicted the expected incidences of NTD well, with a good CV R2 of 0.80. Important predictive factors included the fertilizer uses, locations of the centroid of each village, the shortest distance to rivers and faults and lithological classes with significant spatial autocorrelation of residuals. Our model out-performed the other three methods by 16% or more in term of R2. Conclusions: The variance explained by our model was approximately 80%. This modeling approach is useful for NTD epidemiological studies and intervention planning.

This article is from Neural Regeneration Research , volume 8 . Abstract In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an important role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

This article is from Birth Defects Research. Part A, Clinical and Molecular Teratology , volume 97 . Abstract BACKGROUND: Lamins are intermediate filament proteins that form a major component of the nuclear lamina, a protein complex at the surface of the inner nuclear membrane. Numerous clinically diverse conditions, termed laminopathies, have been found to result from mutation of LMNA. In contrast, coding or loss of function mutations of LMNB1, encoding lamin B1, have not been identified in human disease. In mice, polymorphism in Lmnb1 has been shown to modify risk of neural tube defects (NTDs), malformations of the central nervous system that result from incomplete closure of the neural folds. METHODS: Mutation analysis by DNA sequencing was performed on all exons of LMNB1 in 239 samples from patients with NTDs from the United Kingdom, Sweden, and United States. Possible functional effects of missense variants were analyzed by bioinformatics prediction and fluorescence in photobleaching. RESULTS: In NTD patients, we identified two unique missense variants that were predicted to disrupt protein structure/function and represent putative contributory mutations. Fluorescence loss in photobleaching analysis showed that the A436T variant compromised stability of lamin B1 interaction within the lamina. CONCLUSION: The genetic basis of human NTDs appears highly heterogenous with possible involvement of multiple predisposing genes. We hypothesize that rare variants of LMNB1 may contribute to susceptibility to NTDs. Birth Defects Research (Part A) 97:398–402, 2013. © 2013 Wiley Periodicals, Inc.

This article is from PLoS ONE , volume 9 . Abstract Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection.