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Background: Congenital anomalies pose a significant challenge to global health and result in considerable morbidity and mortality in early childhood. With the decline of other causes of death among children under five, the burden of congenital anomalies is rising, emphasizing the need for improved prenatal care, screening, and nutrition for pregnant women. This systematic review and meta-analysis aim to estimate the pooled effect of folic acid intake on congenital anomalies. Methods: To identify relevant research published up until December 30/2023, we conducted electronic searches of PubMed/Medline, PubMed Central, Hinary, Google, African Journals Online, Web of Science, Science Direct, and Google Scholar databases using predefined eligibility criteria. We used Excel to extract data and evaluated the studies using the JBI appraisal checklist. We computed the pooled effect size with 95% confidence intervals for maternal folic acid intake on congenital anomalies using STATA version 17 and the DerSimonian and Laird random effects meta-analysis model. We assessed statistical heterogeneity using Cochran's Q-test, I 2 statistic, and visual examination of the funnel plot. Results: The review included 16 case-control, cohort, and cross-sectional studies. According to the results of this systematic review and meta-analysis, maternal folic acid intake significantly lowers the incidence of congenital anomalies (odds ratio (OR), 0.23; confidence interval (CI), 0.16, 0.32). Among the included studies, both the Cochrane Q-test statistic (χ2 = 118.82, p < 0.001) and I 2 test statistic (I 2 = 87.38%, p < 0.001) revealed statistically significant heterogeneity. Egger's weighted regression (p < 0.001) and funnel plot show evidence of publication bias in this meta-analysis. Conclusion: The results of the recent meta-analysis and systematic review have demonstrated a significant association between maternal folic acid intake and the risk of congenital anomalies. Specifically, children whose mothers received periconceptional folic acid supplementation had a 77% reduced risk of congenital anomalies. To further investigate the correlation between maternal folic acid supplementation and the occurrence of various congenital anomalies, particularly in developing countries, it is recommended that a comprehensive prospective study be conducted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42024511508).

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(1) Background: The interaction between single nucleotide variants (SNVs) associated with congenital heart diseases (CHDs) and their gene methylation status has not been well researched. The aim of the present study was to determine if there is a relationship between the methy lation status (MS) of genes and the allelic variants associated with CHDs. (2) Methods: Seven SNVs of the genes AXIN1, TBX1, TBX20, and MTHFR were selected from the literature. DNA extraction, genotyping, and a methylation analysis were performed on healthy subjects and subjects with CHDs. (3) Results: Twenty-two subjects with CHDs were selected as the case group (15 with ventricular septal defects (VSDs) and 7 with atrial septal defects (ASDs)), and 44 healthy subjects comprised the control group. The MTHFR and AXIN1 genes were hypermethylated in the control group when compared to the case group. When analyzed separately, those with atrial septum defects exhibited greater methylation, except for the gene MTHFR where there were no differences. Only the alternate alleles of MTHFR showed a significantly different methylation status in those without cardiopathy. (4) Conclusions: The MTHFR and AXIN genes were hypermethylated in the control group; however, only the alternate alleles of MTHFR (rs1801133 and rs1801131) showed a significantly different methylation status.

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BACKGROUND: DNA methylation is the best epigenetic mechanism for explaining the interactions between nutrients and genes involved in intrauterine growth and development programming. A possible contributor of methylation abnormalities to congenital heart disease is the folate methylation regulatory pathway; however, the mechanisms and methylation patterns of VSD-associated genes are not fully understood. OBJECTIVE: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). METHODS: Prospective case-control study; 48 mothers and their children were evaluated. The mothers' dietary variables were collected through a food frequency questionnaire focusing on FA and the consumption of supplements with FA. The MS of promoters of genes was determined in the children. RESULTS: The intake of FA supplements was significantly higher in the control mothers. In terms of maternal folic acid consumption, significant differences were found in the first trimester of pregnancy. Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. CONCLUSIONS: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation.

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BACKGROUND: Iron-folic acid (IFA) intake for the recommended period during pregnancy reduces the risk of anemia and congenital anomalies. However, IFA intake for the recommended period is still very low in low-income countries including Ethiopia. Thus, the aim of this study was to assess both individual-and community-level determinants of IFA intake for the recommended period among pregnant women in Ethiopia. METHODS: Data were retrieved from the Demographic and Health Survey program's official database website (http://dhsprogram.com). A two-stage stratified cluster sampling technique was employed to conduct the 2016 Ethiopian Demographic and Health Survey. A sample of 3088 pregnant women who had received at least one dose of IFA in Ethiopia were included in this study. A multivariable multilevel logistic regression analysis model was fitted to identify the determinants of IFA intake below the recommended period [< 90 days] during pregnancy. Akaike's Information Criterion (AIC) was used during the model selection procedure. RESULTS: This study revealed that 87.6% [95% CI; 86.3%, 88.6%] of the women took IFA below the recommended period during the index pregnancy. After adjusting for the covariates: living in rural areas [AOR = 1.74: 95% CI 1.37, 2.50], and women's illiterate proportion [AOR = 1.43: 95% CI 1.06, 1.70] were community level factors. Whereas, primary education level [AOR = 0.63: 95% CI 0.40, 0.78], poorer wealth index [AOR = 1.53: 95% CI 1.08, 3.09], 4 + antenatal care visits [AOR = 0.43: 95% CI 0.31, 0.69], and receive nutritional counseling during pregnancy [AOR = 0.63: 95% CI 0.37, 0.84] were the individual-level factors of IFA intake below the recommended period during pregnancy. CONCLUSIONS: In this study, nearly nine out of ten pregnant women did not take IFA for the recommended period. Thus, promoting recommended ANC visits, enhancing the quality of nutritional counseling, strengthening the expansion of media, and educate rural women towards the importance of optimal intake of IFA during pregnancy. Besides, the policymakers should design essential strategies based on identified barriers to improve the IFA intake for the recommended period.

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Objective: This study aimed to analyze the effect of folic acid supplements on infant and child allergic diseases through systematic review and meta-analysis. Design: PubMed, The Cochrane Library and references of related articles published before January 1, 2020 were searched. Setting: Meta-analysis was used to explore the influence of folic acid on skin allergies (eczema, and atopic dermatitis) and respiratory allergies (asthma, wheezing, and allergic rhinitis). Participants: Data were collected from 15 studies with 244,018 individual participants from five different countries for meta-analysis. Results: Folic acid was confirmed as a risk factor for allergic diseases in infant and child. The risk of allergic diseases dramatically increased when maternal folic acid intake <400 µg/day (RR = 1.050; 95% CI = 1.027-1.073) during pregnancy. Stratified analyses revealed that the association was significant only for respiratory allergy (RR = 1.067; 95% CI = 1.028-1.108) and pregnant women who only used folic acid supplements (RR = 1.070; 95% CI = 1.030-1.112) and that countries without folic acid fortification (RR = 1.046; 95% CI = 1.026-1.067). Conclusions: This study suggested that folic acid intake can be a risk factor for allergic diseases, especially respiratory tract allergies among infants and young children. Furthermore, pregnant women should pay attention to supplementation of folic acid from both folic acid supplements and fortified foods with folic acid during pregnancy.

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BACKGROUND: A number of studies have explored the link of antenatal folic acid (FA) intake with autism spectrum disorder (ASD) in children, with inconsistent findings. Therefore, we conducted a systematic review and meta-analysis of relevant studies to elucidate the actual association between maternal FA intake during the prenatal period and the risk of ASD in offspring. METHODS: PubMed, EMBASE, PsycINFO, Scopus, Web of Science, and Cochrane Library were searched up to June 7, 2018, without language restriction. The random-effects model was applied to summarize results. The adjusted odds ratios (ORs) and hazard ratios (HRs) were pooled separately. RESULTS: Eight observational studies (a total of 13 reports; 840,776 children and 7127 cases) were included. FA intake was mainly estimated from self-report of mothers or available databases. The results of overall analysis from 6 studies (9 reports) combined by OR and 2 studies (4 reports) presenting HR showed that the likelihoods of ASD in offspring whose mothers were prenatally exposed to FA did not vary significantly compared with those in offspring of mothers without such exposure (OR = 0.91, 95% CI: 0.73-1.13 and HR = 0.66, 95% CI: 0.38-1.17, respectively). Further analysis revealed that the primary outcome of the meta-analysis was stable regardless of the study design, and not unduly affected by any single report. Additionally, no publication bias was observed, and the findings of overall analysis were in agreement with those of subgroup analyses. CONCLUSIONS: This study does not provide support for the association between maternal FA intake during the prenatal period and the reduced risk of ASD in children. However, in view of the types and limited number of studies in the literature, more investigation is needed to confirm the findings of this meta-analysis.

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SCOPE: Mild folate deficiency and subsequently elevated plasma level of homocysteine are associated with an increased risk for vascular diseases in adults. Conversely, high intakes of folic acid (FA) may have beneficial effects on vascular function, presumably in part through homocysteine lowering. However, these effects have not yet been translated in terms of prevention or treatment of vascular pathologies. Besides, the complex biologic perturbation induced by variations of the folate supply is still not fully deciphered. We thus carried out a proteomic analysis of the aorta of adult rats after a dietary FA depletion or supplementation. METHODS AND RESULTS: Nine month-old rats were fed a FA-depleted, FA-supplemented or control diet for 8 weeks. Total proteins from adventitia-free aortas were separated by 2DE and differentially expressed proteins were identified by MS. FA depletion or supplementation resulted in significantly changed abundance of 29 spots (p < 0.05), of which 20 proteins were identified. Bioinformatic analysis revealed that most of these proteins are involved in cytoskeleton-related processes important to cell function/maintenance, assembly/organization, and movement. CONCLUSION: Our proteomic study supports that expression of proteins essential to vascular structure and, presumably, function is modulated by high intake as well as deprivation of FA.

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