Occurrence Of Neural Tube Defects Research Articles

Inhibition of NRF2 signaling and increased reactive oxygen species during embryogenesis in a rat model of retinoic acid-induced neural tube defects

Exposure to retinoic acid (RA) during pregnancy increases the risk of serious neural tube defects (NTDs) in the developing fetus. The precise molecular mechanism for this process is unclear; however, RA is associated with oxidative stress mediated by reactive oxygen species. Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of oxidative stress that directs the expression of antioxidant genes and detoxifying proteins to maintain redox homeostasis. We established a rat model of NTDs in which pregnant dams were administered all-trans (at)RA on gestational day 10, and oxidative stress levels and the spatiotemporal expression of NRF2 and its downstream targets were examined in the resulting embryos and in maternal blood. In the NTD group, total antioxidative capacity decreased and 8-hydroxy-2′-deoxyguanosine increased in maternal serum and fetal spinal cord tissues. Plasma GSH content, the GSH/GSSG ratio, and glutathione peroxidase activity in fetal spinal cords were lower in the NTD group relative to controls. We detected NRF2 protein reduction and concomitant upregulation of Kelch-like ECH-associated protein 1 (KEAP1) - a cytoplasmic inhibitor of NRF2 - in the NTD group. The mRNA and protein levels of downstream targets of NRF2 were downregulated in the spinal cords of NTD embryos. These data demonstrate substantial oxidative stress and NRF2 signaling pathway disruption in a model of NTDs induced by atRA. The inhibitory effects of atRA on NRF2 signaling may lower cellular defenses against RA-induced oxidative stress and could play important roles in NTD occurrence during embryonic development.

Maternal risk factors associated with neural tube defects in Tigray regional state of Ethiopia

IntroductionUnlike developing countries, including Ethiopia the identification of the risk factors in decreasing the burden of neural tube defects (NTDs) is well established in the developed world. Hence, we sought to determine the factors associated with NTDs in Tigray – Ethiopia. MethodsWe undergo a case-control analysis where all NTDs cases were compared to a group of controls derived randomly from the same hospitals where cases were recruited from. The NTDs survey tool which contains a standard questionnaire was prepared. Parental socio-demographic and clinical information such, maternal age, obstetric history, illnesses, drug intake, radiation, occupation, education, history of congenital anomalies, residence, exposure to pollutants such as smoking, chemicals, paternal history, and folic acid utilization was collected and analyzed using SPSS version 20. ResultThis study has shown the maternal age, and residency, birth order 3 and 4, unplanned pregnancy, history of breastfeeding above 2 years, history of stillbirths, history of male gender predominance were found to have a strong association with an occurrence of NTDs (p = 0.0001). Though the binary logistic regression analysis showed no significant association in some of the risk factors such as maternal health and drug history, the frequency analysis showed they may have an impact on the incidence of NTDs. ConclusionThis study has shown the majority of the maternal risk factors and other lifestyle patterns had a significant impact on the occurrence of NTDs. Therefore, efficient monitoring of NTDs in Ethiopia is vital, so our study could be groundwork information in Ethiopia for future programs.

Preconception folic acid supplementation use and the occurrence of neural tube defects in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study.

We evaluated the relationship between preconception folic acid supplementation and the occurrence of neural tube defects (NTDs) in offspring, using data from the Japan Environment and Children's Study (a nationwide prospective birth cohort study) database. Of 92 269 participants with single pregnancies, 74 cases (offspring or fetuses) had NTDs, including 32 cases of spina bifida, 24 cases of anencephaly, and 19 cases of encephalocele. A total of 7634 participants (8.27%) used preconception folic acid supplementation, and of these, 621 (0.67%) also took in dietary folic acid at ≥480 μg/day. Multivariate logistic regression analyses demonstrated no association between preconception folic acid supplementation and NTDs in offspring or fetuses (odds ratio [OR] 0.622; 95% confidence interval [CI]: 0.226-1.713). Moreover, the participants who combined preconception folic acid supplement use with dietary folic acid intake ≥480 μg/day demonstrated no incidence of NTDs in offspring or fetuses. Our analysis is limited by the absence of the data on the daily amount of supplementary folic acid intake, requiring careful attention to the interpretation. Additional surveys are required in Japan to resolve those limitations for further comprehensive assessment.

Relationship Between INPP5E Gene Expression and Embryonic Neural Development in a Mouse Model of Neural Tube Defect.

BackgroundThe INPP5E gene encodes for the inositol polyphosphate-5-phosphatase (INPP5E) 72 kDa protein that regulates the phosphoinositide signaling pathway and other cellular activities, but the functional role of this gene in embryonic neurodevelopment and neural tube defect (NTD) remains unclear. The aim of this study was to use a mouse model of NTD to investigate the expression levels of the INPP5E gene during neural development and the occurrence of NTD.Material/MethodsIn an established NTD mouse model, stereoscopy was used to look for morphological defects. Transcription and expression levels of the INPP5E gene in neural tissues were detected using real-time fluorescence quantitative polymerase chain reaction (PCR) and Western blotting in the NTD mouse embryos and compared with control mouse embryos.ResultsThe expression levels of the INPP5E gene decreased as embryonic development progressed in the neural tissue of control mice embryos, but showed no obvious trend in the neural tissues of the NTD mouse embryos. The expression levels of the INPP5E gene in NTD mouse embryos were significantly lower compared with control embryos, at the time of neural tube closure (gestational day 11.5).ConclusionsThe INPP5E gene regulates the process of embryonic neural development. Abnormal levels of expression of the INPP5E gene may contribute to NTDs. Increased knowledge of the expression pattern of the INPP5E gene may lead to an advanced understanding of the molecular mechanism of embryonic neurodevelopment and identify more specific directions to explore potential treatments for NTDs associated with abnormalities in INPP5E gene expression levels.

The critical chemical and mechanical regulation of folic acid on neural engineering

The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in 1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects. Consequently, folic acid holds great potential as a critical and convenient therapeutic intervention for neural engineering, regenerative medicine, medical prosthetics, and drug delivery.

Hypomethylation of GRHL3 gene is associated with the occurrence of neural tube defects.

To investigate the relationship between GRHL3 methylation and the etiology of neural tube defects (NTDs). Analyze data from a genome-wide DNA methylation array. Targeted DNA methylation analysis was performed for 46 cases and 23 controls. At last, grhl3 overexpression and gene depletion experiments were conducted in zebrafish. Five hypomethylated CpGs were discovered in the methylation arrays performed on NTD cases. In a validation study, 15 hypomethylated CpGs were found and the overall methylation levels decreased in brain/spinal cord tissue from NTD cases. The knockdown and overexpression of grhl3 in zebrafish damaged embryonic convergent extension processes. Hypomethylation of GRHL3 in central nervous tissue is associated with NTDs, further supporting the importance of GRHL3 and methylation in proper neural tube closure.

No evidence for association of MTHFR 677C>T and 1298A>C variants with placental DNA methylation

Background5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one-carbon metabolism that ensures the availability of methyl groups for methylation reactions. Two single-nucleotide polymorphisms (SNPs) in the MTHFR gene, 677C>T and 1298A>C, result in a thermolabile enzyme with reduced function. These variants, in both the maternal and/or fetal genes, have been associated with pregnancy complications including miscarriage, neural tube defects (NTDs), and preeclampsia (PE), perhaps due to altered capacity for DNA methylation (DNAm). In this study, we assessed the association between MTHFR 677TT and 1298CC genotypes and risk of NTDs, PE, or normotensive intrauterine growth restriction (nIUGR). Additionally, we assessed whether these high-risk genotypes are associated with altered DNAm in the placenta.ResultsIn 303 placentas screened for this study, we observed no significant association between the occurrence of NTDs (N = 55), PE (early-onset: N = 28, late-onset: N = 20), or nIUGR (N = 21) and placental (fetal) MTHFR 677TT or 1298CC genotypes compared to healthy pregnancies (N = 179), though a trend of increased 677TT genotype in PE/IUGR together was observed (OR 2.53, p = 0.048). DNAm was profiled in 10 high-risk 677 (677TT + 1298AA), 10 high-risk 1298 (677CC + 1298CC), and 10 reference (677CC + 1298AA) genotype placentas. Linear modeling identified no significantly differentially methylated sites between high-risk 677 or 1298 and reference placentas at a false discovery rate < 0.05 and Δβ ≥ 0.05 using the Illumina Infinium HumanMethylation450 BeadChip. Using a differentially methylated region analysis or separating cytosine-guanine dinucleotides (CpGs) by CpG density to reduce multiple comparisons also did not identify differential methylation. Additionally, there was no consistent evidence for altered methylation of repetitive DNA between high-risk and reference placentas.ConclusionsWe conclude that large-scale, genome-wide disruption in DNAm does not occur in placentas with the high-risk MTHFR 677TT or 1298CC genotypes. Furthermore, there was no evidence for an association of the 1298CC genotype and only a tendency to higher 677TT in pregnancy complications of PE/IUGR. This may be due to small sample sizes or folate repletion in our Canadian population attenuating effects of the high-risk MTHFR variants. However, given our results and the conflicting results in the literature, investigations into alternative mechanisms that may explain the link between MTHFR variants and pregnancy complications, or in populations at risk of folate deficiencies, are warranted.

Acid folic and pregnancy: A mandatory supplementation

Neural tube defects (NTD) occur in 0.5 to 2 per 1000 pregnancies with various handicaps for the affected child. It is now well established that folic acid deficiency (absolute or relative) is a predisposing factor to this type of malformation. Several randomized controlled trials showed that high-dose folic acid (4mg) is an essential factor for prevention of neural tube defects recurrence and significantly prevents the first occurrence of neural tube defects with a lower dose (0.4mg). Other etiologies can favor the occurrence of NTD such as MTHFR polymorphism, some antiepileptic therapies, obesity and pregestational mellitus diabetes. Necessity of a preconception folic acid supplementation or at least folate nutritional status evaluation should be known for all of us including patients and public.

Inhibition of thymidylate synthase affects neural tube development in mice

Thymidylate synthase (TYMS) is a key enzyme in the de novo synthesis of 2′-deoxythymidine-5′-monophosphate (dTMP) from 2′-deoxyuridine-5′-monophosphate (dUMP). Our aim was to investigate the role of dTMP dysmetabolism via inhibition of TYMS by an inhibitor, 5-fluorouracil (5-FU) in the occurrence of neural tube defects (NTDs). We found that a high incidence of NTDs occurred after treatment with 5-FU at 12.5 mg/kg body weight. TYMS activity was significantly inhibited with decreased dTMP and accumulation of dUMP after 5-FU injection. The proliferation of neuroepithelial cells were markedly inhibited in NTDs compared with control. Expressions of proliferating cell nuclear antigen and phosphohistone H3 were significantly decreased in NTDs, while phosphorylated replication protein A2, P53 and Caspase3 were significantly increased in NTDs compared with control. These results indicated that inhibition of TYMS affected the balance between proliferation and apoptosis in neuroepithelial cells, which might shed some lights on the mechanisms involved in NTDs.

Association of neural tube defects with gene polymorphisms in one-carbon metabolic pathway.

Neural tube defects (NTDs) are common congenital malformations. In this study, we aimed to explore the association between single nucleotide polymorphisms (SNPs) related to one-carbon metabolism (OCM) and NTDs in Han population of Northern China. A case-control study was conducted in 152 children with NTDs and 169 controls. Twenty-nine SNPs in five genes were genotyped by Sequenom MassARRAY technology, and haplotype analysis was done by Haploview4.2 software. The allele frequency of rs3733890 in betaine-homocysteine methyltransferase (BHMT) gene was statistically different between NTDs and control groups (P=0.041), and the children with A allele had higher risk for NTDs than G allele (OR=1.408, 95%CI 1.013-1.956). In addition, there was a statistical difference in the allele and genotype frequencies of rs1051266 in reduced folate carrier1 (RFC1) gene between cases and controls (P=0.013, 0.034), and the risk for NTDs was also higher in children with G allele and GG genotype, compared with A allele and AA genotype, respectively (OR=1.492, 95%CI 1.089-2.044; OR=2.020, 95%CI 1.081-3.780). The statistical significant difference was also found in allele frequency of rs1805087 in methionine synthetase (MTR) gene between cases and controls (P=0.031), and the children with G allele were associated with an increased NTDs risk, compared with A allele (OR=1.664, 95%CI 1.045-2.647). Meanwhile, haplotype analysis showed C-A-A-A haplotype of BHMT, and G-G-G-T haplotype of RFC1 was correlated with an increased risk of NTDs, but C-G-A-A haplotype of BHMT and G-G-C-A haplotype of MTR might decrease the risk of NTDs. The BHMT gene rs3733890, RFC1 gene rs1051266 and MTR gene rs1805087 were associated with the occurrence of NTDs in Han population of Northern China. It was confirmed that the gene variation related to OCM was one of the susceptibility factors for NTDs.

Transcriptomic profile analysis of mouse neural tube development by RNA-Seq.

The neural tube is the primordium of the central nervous system (CNS) in which its development is not entirely clear. Understanding the cellular and molecular basis of neural tube development could, therefore, provide vital clues to the mechanism of neural tube defects (NTDs). Here, we investigated the gene expression profiles of three different time points (embryonic day (E) 8.5, 9.5 and 10.5) of mouse neural tube by using RNA-seq approach. About 391 differentially expressed genes (DEGs) were screened during mouse neural tube development, including 45 DEGs involved in CNS development, among which Bmp2, Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles. Of 45 DEGs, Foxp2, Eomes, Hoxb3, Gpr56, Hap1, Nkx2-1, Sez6l2, Wnt7b, Tbx20, Nfib, Cntn1 and Dcx had different isoforms, and the opposite expression pattern of different isoforms was observed for Gpr56, Nkx2-1 and Sez6l2. In addition, alternative splicing, such as mutually exclusive exon, retained intron, skipped exon and alternative 3' splice site was identified in 10 neural related differentially splicing genes, including Ngrn, Ddr1, Dctn1, Dnmt3b, Ect2, Map2, Mbnl1, Meis2, Vcan and App. Moreover, seven neural splicing factors, such as Nova1/2, nSR100/Srrm4, Elavl3/4, Celf3 and Rbfox1 were differentially expressed during mouse neural tube development. Interestingly, nine DEGs identified above were dysregulated in retinoic acid-induced NTDs model, indicating the possible important role of these genes in NTDs. Taken together, our study provides more comprehensive information on mouse neural tube development, which might provide new insights on NTDs occurrence. © 2017 IUBMB Life, 69(9):706-719, 2017.

Knowledge, attitude and practice regarding folic acid among pregnant women in Benghazi, Libya

Periconceptional folic acid supplementation has been shown to decrease the occurrence of neural tube defects (NTD’s). In a cross-sectional study, the knowledge attitude and practice regarding the peri-conceptional use of folic acid were assessed among the pregnant women in Benghazi, Libya. 131 women attending antenatal clinics in three main polyclinics were interviewed through three polyclinics. Seventy-three percent of the participants had heard about folic acid, and only 37% could correctly identify the effect of folic acid when used periconceptionally. 27% of the pregnant women did not take folic acid during their present pregnancy. Only 6% of the women who took folic acid were taking it consistently before pregnancy with the aim of preventing NTDs. This study shows that the interviewed pregnant women reveal high positive attitude (88%) toward retaking folic acid supplements in their next pregnancy. The overall knowledge regarding the periconceptional use of folic acid was relatively low when compared to other studies worldwide. Health education regarding the periconceptional use of folic acid among newly married couples is recommended.

Folate receptors and neural tube closure

Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5-8.0/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1-kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1-kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.

High Ratios of C20:4n-6/C20:5n-3 and Thromboxane B2 /6-Keto-Prostaglandin F1α in Placenta Are Potential Risk Contributors for Neural Tube Defects: A Case-Control Study in Shanxi Province, China.

Neural tube defects (NTDs) are severe congenital malformations. Folate supplementation can reduce the risk, but cannot prevent all NTDs, suggesting other reasons for folate-resistant NTDs. The present study assesses placental fatty acid composition, eicosanoids, and cytokines as risk factors for NTDs in a Chinese population with highly incident NTDs. Seventy-seven aborted fetuses with NTDs during the third trimester were cases and 142 healthy newborns were controls. Placental fatty acid composition, eicosanoids, and cytokines were determined by standard methods. The placental C20:4n-6/C20:5n-3 and thromboxane B2 (TXB2 )/6-keto-prostaglandin F1α (6-keto-PGF1α ) ratios were significantly higher for cases than controls (p < 0.001 and 0.05, respectively). For the top versus the lowest tertiles of placental C20:4n-6/C20:5n-3 and TXB2 /6-keto-PGF1α , odds ratios for NTD occurrence were 3.79 (95% confidence interval, 1.60-8.96) (p for trend < 0.01) and 5.52 (95% confidence interval, 2.07-14.74) (p for trend < 0.001), respectively, adjusted for fetal sex as well as maternal age, occupation, parity, smoking, passive smoking, periconceptional folate supplementation, conception season, and tea drinking. The C20:4n-6/C20:5n-3 and TXB2 /6-keto-PGF1α ratios were positively correlated (r = 0.14; p < 0.05). The proportions of C18:2n-6, C18:3n-6, C20:3n-6, C18:3n-3, C20:3n-3, C20:5n-3, and C22:5n-3 were significantly lower in cases than controls, and all negatively associated with NTD occurrence (tertile-specific odds ratios); after adjustment for the potential confounders, these associations remained significant (p for trend < 0.05) except for C20:3n-3. High placental ratios of C20:4n-6/C20:5n-3 and TXB2 /6-keto-PGF1α are risk factors for neural tube defects.Birth Defects Research 109:550-563, 2017.© 2017 Wiley Periodicals, Inc.

Prevalence of neural tube defects in a rural area of north india from 2001 to 2014: A population-based survey.

Neural tube defects (NTDs) are one of the commonest birth defects. There was paucity of community-based data on occurrence of NTDs in India, especially from rural parts of the country. Against this background, the current study was carried out with main objectives to determine the prevalence of NTDs and its specific types (anencephaly, spina bifida and encephalocele) in a rural community setting over the time period 2001 to 2014. This was a community-based cross-sectional study carried out in 28 villages of Ballabgarh Tehsil of Faridabad district in north India (population ∼ 96,000). A household survey was undertaken by trained multi-purpose workers who enquired ever-married women about history of conception with outcome as NTD during the study period. The probable case of NTD was determined using a colored pictorial card with photographs of different types of NTDs. These cases were confirmed by doctors. A total of 26,946 live births occurred during the years 2001 to 2014. A total of 140 confirmed cases of NTDs were identified. The live birth prevalence of NTDs was 24.1 per 10,000 live births (95% confidence interval, 18.8-30.6). The birth prevalence of NTDs for the years 2008 to 2014 was 50.8 (95% confidence interval, 39.9-63.8) per 10,000 live and stillbirths. The most common type of NTD was found to be spina bifida followed by anencephaly and encephalocele. We found high prevalence of NTDs in rural community settings from north India for years 2001 to 2014.Birth Defects Research 109:203-210, 2017.© 2016 Wiley Periodicals, Inc.

Myoinositol: The Bridge (PONTI) to Reach a Healthy Pregnancy.

The use of folic acid in the periconceptional period can prevent about 70% of neural tube defects (NTDs). In the remaining cases, no medical prevention is available, and those conditions should be defined as folate-resistant NTDs. Rodent models suggest that some folate-resistant NTDs can be prevented by inositol (myoinositol and chiroinositol) supplementation prior to pregnancy. Should folic acid be combined with myoinositol periconceptional supplementation to reduce the overall risk of NTDs even in humans? Hereafter, we discuss the results from the PONTI study that strongly support both the effectiveness and safety of myoinositol periconceptional supplementation in preventing human NTDs. We further report on the largest case series of pregnancies treated with myoinositol and folic acid. At our institution, a sequential study during 12 years involved mothers at risk of fetal NTDs, and 29 babies from 27 pregnancies were born after periconceptional combined myoinositol and folic acid supplementation. No case of NTDs was observed, despite the high recurrence risk in the mothers. Taken together, those data suggest that periconceptional folic acid plus myoinositol can reduce both the occurrence and recurrence risks of NTDs in a greater number of cases than folic acid alone.

Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele.

Myelomeningocele (MMC) is a severe type of neural tube defect (NTD), in which the backbone and spinal canal do not close completely during early embryonic development. This condition results in serious morbidity and increased mortality after birth. Folic acid significantly reduces, and conversely, folate antagonist methotrexate (MTX) and valproic acid (VPA) increase the occurrence of NTDs, including MMC. How these pharmacological agents exactly influence the early neurulation process is still largely unclear. Here, we characterized human amniotic fluid-derived stem cells (AFSCs) from prenatally diagnosed MMC and observed an effect of MTX and VPA administration on the early neural differentiation process. We found that MMC-derived AFSCs highly expressed early neural and radial glial genes that were negatively affected by MTX and VPA exposure. In conclusion, we setup a human cell model of MMC to study early neurogenesis and for drug screening purposes. We also proposed the detection of early neural gene expression in AFSCs as an additional MMC diagnostic tool.

The association and significance of H3K27me3 and a folate metabolic gene ACat2 in neural tube defects.

AimTo study the association between the expression of H3K27me3 and ACat2 (a folate metabolic protein), in order to elucidate the protective mechanism of folic acid (FA) in neural tube defects (NTDs).MethodsEighteen female SD rats were randomly divided into normal, NTD and FA group. NTD group was induced by all-trans retinoic acid (ATRA) at E10d. FA group was fed with FA supplementation since 2 weeks before pregnancy, followed by ATRA induction. At E15d, FA level in the embryonic neural tube was determined by ELISA. Neural stem cells (NSCs) were isolated. Cell proliferation was compared by CCK-8 assay. The differentiation potency was assessed by immunocytochemical staining. H3K27me3 expression was measured by immunofluorescence method and Western blot. ACat2 mRNA expression was detected by qRT-PCR.ResultsCultured NSCs formed numerous Nestin-positive neurospheres. After 5 days, they differentiated into NSE-positive neurons and GFAP-positive astrocytes. When compared with controls, the FA level in NTD group was significantly lower, the ability of cell proliferation and differentiation was significantly reduced, H3K27me3 expression was increased, and ACat2 mRNA expression was decreased (P <0.05). The intervention of FA notably reversed these changes (P <0.05). H3K27me3 expression was negatively correlated with the FA level (rs = −0.908, P <0.01) and ACat2 level (rs = −0.879, P <0.01) in the neural tube.ConclusionThe increased H3K27me3 expression might cause a disorder of folate metabolic pathway by silencing ACat2 expression, leading to reduced proliferation and differentiation of NSCs, and ultimately the occurrence of NTD. FA supplementation may reverse this process.

A novel mutation in PAX3 gene associated with neural tube defect

To assess the efficacy of folic acid (FA) supplementation and fortification in preventing neural tube defects (NTDs) in a high prevalence region of the United States.Active and passive surveillance methods were used to identify all fetuses/infants affected with an NTD in South Carolina. Prevalence rates were compared with FA intake to determine the effects of increased intake on NTD occurrence and recurrence.From 1992 to 2009, 916 NTD cases occurred in South Carolina, with isolated defects comprising 79% of cases. The NTD rate decreased 58% during this period. There was one NTD-affected pregnancy in 418 subsequent pregnancies (0.2%) in mothers with earlier NTD-affected pregnancies who consumed periconceptional FA supplements, and there were 4 NTDs in 66 pregnancies (6.1%) in which the mother did not take FA supplements. FA supplementation increased from 8% to 35% from 1992 to 2007, and knowledge of the protective benefits of FA increased from 8% to 65% in women of childbearing age.Increased periconceptional intake of FA appeared to reduce NTDs in a high-prevalence region. The rate of spina bifida and anencephaly in South Carolina is now essentially the same (0.69 cases per 1000 live births and fetal deaths) as the 1998 to 2005 US rate (0.69).

Electrochemical determination of folic acid: A short review

Folic acid (FA) is an electroactive compound of biological origin. It helps our body to produce and maintain healthy cells. It can significantly reduce the occurrence of neural tube defects and also prevents change in DNA structure. FA deficiency can lead to various health risks. Therefore, a sensitive, specific, and reproducible way of FA detection is essential. A number of analytical methods are in practice for the quantification of FA. However, electroanalytical methods are attracting much attention because of their advantage over conventional methods, as they are fast, simple, sensitive, and cost effective. Moreover, modification of electrodes offers control over size and morphology which allows miniaturization for applicability in portable electrochemical devices.