Association of embryonic inositol status with susceptibility to neural tube defects, metabolite profile, and maternal inositol intake.

Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.

Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China.

BACKGROUND: Folic acid supplementation is recommended for reducing the risk of birth defects. We aimed to assess the protective association of periconception folic acid supplements with birth defects in real-world setting. METHODS: This prospective, population-based cohort study utilized national preconception registered data of married Chinese couples planning a pregnancy within 6 months between 2010 and 2012 in Mainland China. Participated women are freely provided folic acid starting 3 months before conception till 3 months after conception. Birth defects were self-reported at 42 days postpartumn followup. R software (v4.0.2) was applied for statistical analyses. RESULTS: Complete data of 567,547 couples with pregnancy outcomes and folic acid supplementation were extracted for final analysis. A total of 74.7% women were with folic acid supplementation, and 599 birth defects were self-reported. The odd of birth defects was lower among women taking folic acid compared to their counterparts not taking (0.102% vs 0.116%, P < 0.001). In the multiple logistic regression analyses, the odd of birth defects was lower among couples with maternal folic acid supplementation (OR = 0.78, 95%CI: 0.66-0.95, P = 0.011), especially decreased odd of neural tube defects (NTDs) (OR = 0.56, 95%CI: 0.39-0.82, P = 0.003). This association was confirmed by 1:4 and 1:10 case control analysis. Odds of birth defects were significantly lower among women with folic acid supplementation more than 3 months before pregnancy (P < 0.001), and moreover, the odds of cleft (P = 0.007) and NTDs (P = 0.007) were of notable decrease. CONCLUSION: This retrospective case cohort study provides programmatic evidence for public health strategy-making to for reducing the risk of NTDs and clefts.

World health assembly resolution for preventing micronutrient deficiencies and associated neural tube defects-A case study of global partnerships for a successful resolution adoption.

BACKGROUND: On May 29, 2023, the 76th World Health Assembly (WHA) unanimously adopted the resolution entitled, "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." The Society for Birth Defects Research and Prevention published their resolution in 2015 supporting mandatory fortification of staple foods with folic acid and recommendations aiming to achieve global total prevention of folate-sensitive spina bifida and anencephaly, setting a goal to achieve by the year 2024. The WHA resolution provides another global push for the cause, with recommendations to member nations for food fortification to be achieved by the year 2030. METHODS: This short communication documents the steps, from inception up to the passage, of the 76th WHA resolution on food fortification, with a narrative on the nature of strategic advocacy efforts by multiple governmental and nongovernmental organizations. RESULTS: WHA resolutions can take many years to be introduced and passed by the assembly; however, this is a case study of the swiftness of the process enabled by powerful global partnership. CONCLUSION: The documentation of this process serves as an example for developing and processing future WHA resolutions aiming to improve global maternal and child health.

The concept of folic acid supplementation and its role in prevention of neural tube defect among pregnant women: PRISMA.

Folic acid is the synthetic form of vitamin B9, found in supplements and fortified foods, while folate occurs naturally in foods. Folic acid and its derivatives are extremely important in the synthesis of nucleic acids (DNA and ribose nucleic acid [RNA]) and different proteins. It acts as a coenzyme for the transfer of 1 carbon in the biosynthesis of purine, pyrimidine, and amino acids. Folic acid is critically important in rapidly proliferating tissues, including fetus and trophoblastic tissue to prevent neural tube defect (NTD). The main objective of this review is to identify the role of folic acid to prevent NTD among pregnancy mothers. Electronic databases including Web of Science, Google Scholar, MEDLINE, Scopus, and Cochrane library used to systematically search without limitation of publication date and status. In pregnancy, the first trimester is a significant time for neural tube closure. Decreased blood folic acid levels inhibit DNA replication, repair, RNA synthesis, histone and DNA methylation, methionine production, and homocysteine remethylation reactions that cause NTDs in pregnancy. Therefore, folic acid supplementation is critically important for childbearing mothers before conception and in the first trimester pregnancy. As a result, women are recommended to take 400 microgram FA/day from preconception until the end of the first trimester to prevent NTD-affected pregnancies. This allows the developing neural tissue to acquire critical mass and provides the preferred rostrocaudal orientation so that these divisions contribute to the elongation of the developing neural tube in embryos.

Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020.

BACKGROUND: Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. RESULTS: The proportion of Hispanic WRA with folic acid usual intakes <400 µg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. CONCLUSIONS: Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions.

Risk of Excess Maternal Folic Acid Supplementation in Offspring.

Folate, also known as vitamin B9, facilitates the transfer of methyl groups among molecules, which is crucial for amino acid metabolism and nucleotide synthesis. Adequate maternal folate supplementation has been widely acknowledged for its pivotal role in promoting cell proliferation and preventing neural tube defects. However, in the post-fortification era, there has been a rising concern regarding an excess maternal intake of folic acid (FA), the synthetic form of folate. In this review, we focused on recent advancements in understanding the influence of excess maternal FA intake on offspring. For human studies, we summarized findings from clinical trials investigating the effects of periconceptional FA intake on neurodevelopment and molecular-level changes in offspring. For studies using mouse models, we compiled the impact of high maternal FA supplementation on gene expression and behavioral changes in offspring. In summary, excessive maternal folate intake could potentially have adverse effects on offspring. Overall, we highlighted concerns regarding elevated maternal folate status in the population, providing a comprehensive perspective on the potential adverse effects of excessive maternal FA supplementation on offspring.

Periconceptional folic acid usage and its associated factors in eastern Sudan: A cross-sectional study.

BACKGROUND: Several countries poorly adhere to the World Health Organization's recommendation of folic acid supplementation in the periconceptional period, especially in limited-resource settings. OBJECTIVE: The objective of this study was to investigate the prevalence of and the factors associated with folic acid usage in the periconceptional period among pregnant women at Gadarif Maternity Hospital in eastern Sudan. STUDY DESIGN: This is a cross-sectional study. METHODS: This study was conducted in eastern Sudan from April to September 2022. A total of 720 pregnant women in their first trimester were enrolled. The sociodemographic characteristics and clinical and obstetrical data of pregnant women in their first trimester were assessed using a face-to-face questionnaire. In addition, multivariate regression analysis was performed. RESULTS: In this study, the median (interquartile range) of the age and gravidity of the enrolled women was 26.3 (24.14-29.52) years and 2 (1-4), respectively. Of these 720 women, 423 (58.8%) used folic acid during the periconceptional period, while 27 (3.7%) women used folic acid in the preconceptional period. None of the investigated factors (age, residence, education, employment, body mass index, or gravidity) were associated with periconceptional use of folic acid. CONCLUSION: The study revealed a low prevalence of folic acid usage in preconceptional period among pregnant women in eastern Sudan. Additional efforts are needed to promote folic acid usage in the preconceptional period as well as in the first trimester.

Expanding Fortification with Folic Acid: Thinking Outside the Cereal-Grain Box.

(1) Background: Fortifying maize and wheat flours with folic acid has effectively reduced neural tube defect-affected births. However, maize and wheat flours may not be widely consumed in all countries; further reduction in neural tube defect-affected births could benefit from the identification of alternative food vehicles. We aimed to use dietary intake or apparent consumption data to determine alternative food vehicles for large-scale fortification with folic acid in low-income and lower-middle-income countries (LILMICs) and identify current research related to examining the technological feasibility of fortifying alternative foods with folic acid. (2) Methods: We identified 81 LILMICs, defined by the World Bank's (WB) 2018 income classifications. To identify dietary intake or apparent consumption, we reviewed WB's Microdata Library and Global Health Data Exchange for national surveys from 1997-2018. We reviewed survey reports for dietary intake or apparent consumption data and analyzed survey datasets for population coverage of foods. We defined alternative food vehicles as those that may cover/be consumed by ≥30% of the population or households; cereal grains (maize and wheat flours and rice) were included as an alternative food vehicle if a country did not have existing mandatory fortification legislation. To identify current research on fortification with folic acid in foods other than cereal grains, we conducted a systematic review of published literature and unpublished theses, and screened for foods or food products. (3) Results: We extracted or analyzed data from 18 national surveys and countries. The alternative foods most represented in the surveys were oil (n = 16), sugar (n = 16), and salt (n = 14). The coverage of oil ranged from 33.2 to 95.7%, sugar from 32.2 to 98.4%, and salt from 49.8 to 99.9%. We found 34 eligible studies describing research on alternative foods. The most studied alternative foods for fortification with folic acid were dairy products (n = 10), salt (n = 6), and various fruit juices (n = 5). (4) Conclusions: Because of their high coverage, oil, sugar, and salt emerge as potential alternative foods for large-scale fortification with folic acid. However, except for salt, there are limited or no studies examining the technological feasibility of fortifying these foods with folic acid.

Determinants of neural tube defect among newborns admitted to neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, Southern Ethiopia: a case-control study.

BACKGROUND: Neural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited attention. In Ethiopia, the estimated number of neural tube defect cases was significantly higher. So, identifying factors contributing to it would be significant for planning risk reduction and preventive strategies. Therefore, identifying the possible determinants was aimed at this study. METHODS: A hospital-based, unmatched case-control study was conducted on 104 cases and 208 controls selected from neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, southern Ethiopia from December 2021 to November 2022. All neural tube defect cases were included consecutively and controls were selected by using a simple random sampling method. Data were collected using interviewer-administered semistructured questionnaires. Data analysis was done by using SPSS V.25. Binary logistic regression was used, and variables with a p value less than 0.25 in bivariate analysis were entered into the multivariable logistic regression model. An adjusted OR with a 95% CI was estimated, and finally, variables that show a level of p value less than 0.05 in multivariable analysis were declared statistically significant. RESULT: After controlling confounders, factors such as unplanned pregnancy 2.20 (95% CI 1.20 to 4.041), history of abortions 2.09 (95% CI 1.19 to 3.67), khat chewing 6.67 (95% CI 2.95 to 15.06), antipyretic and analgesic medications 2.87 (95% CI 1.47 to 5.56) and, being a female neonate 2.11 (95% CI 1.21 to 3.67) were significantly associated with a neural tube defect. CONCLUSION: This study has identified some determinants of neural tube defects. Hence, the behavioural, medical and obstetrical conditions of mothers need serious evaluation in the prepregnancy period. So, improving preconception counselling and prenatal care practices would have a significant role in reducing the risk of neural tube defects.

Bibliometric Analysis and a Call for Increased Rigor in Citing Scientific Literature: Folic Acid Fortification and Neural Tube Defect Risk as an Example.

The health benefits of vitamin B9 (folate) are well documented, particularly in regard to neural tube defects during pregnancy; however, much remains to be learned regarding the health effects and risks of consuming folic acid supplements and foods fortified with folic acid. In 2020, our laboratory conducted a population-based analysis of the Food Fortification Initiative (FFI) dataset to determine the strength of the evidence regarding the prevalence of neural tube defects (NTD) at the national level in response to mandatory fortification of cereal grains with folic acid. We found a very weak correlation between the prevalence of NTDs and the level of folic acid fortification irrespective of the cereal grain fortified (wheat, maize, or rice). We found a strong linear relationship between reduced NTDs and higher socioeconomic status (SES). Our paper incited a debate on the proper statistics to employ for population-level data. Subsequently, there has been a large number of erroneous citations to our original work. The objective here was to conduct a bibliometric analysis to quantitate the accuracy of citations to Murphy and Westmark's publication entitled, "Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset". We found a 70% inaccuracy rate. These findings highlight the dire need for increased rigor in citing scientific literature, particularly in regard to biomedical research that directly impacts public health policy.

Are migrants during the periconception period less likely to be supplementing with folic acid: An Australian cohort study.

BACKGROUND: Folic acid (FA) supplementation before and in early pregnancy is known to improve outcomes such as reducing neural tube defects; however, little is known about groups in Australia at risk of low FA use. AIM: To determine whether differences exist in FA supplementation rates between Australian-born women and migrant women, with a secondary aim of examining the sociodemographic characteristics of women who are not supplementing with FA in early pregnancy. METHODS: A retrospective cohort study from January 2018-July 2022 in a high-migrant population in Western Sydney, Australia. Multivariate logistic regression analysis was conducted adjusting for confounders including place of birth, age, ethnicity, parity, history of diabetes, and type of conception. FINDINGS: There were 48,045 women who met inclusion criteria; 65% of whom were migrants. We identified that 39.4% of the study population did not report FA supplementation by early pregnancy. Women who were migrants were more likely to report FA usage than those born in Australia (aOR 1.24; 95%CI 1.17-1.31). Women least likely to report use of FA were women < 20 years of age (aOR 0.54; 95%CI 0.44-0.67) and multiparous women (aOR 0.84; 95%CI 0.82-0.86). Women with type 1 or type 2 diabetes were more likely to report FA use (aOR 1.66; 95%CI 1.11-2.48, aOR 1.30; 95%CI 1.05-1.61). CONCLUSION: A significant proportion of the population did not report FA supplementation before or during early pregnancy. To increase uptake of FA supplementation, clinicians and public health messaging should target at-risk groups.

Multivitamin Use Among Hispanic Women of Reproductive Age in the United States, 2013-2022.

Background: The U.S. Public Health Service and the Institute of Medicine recommend that all women capable of becoming pregnant consume 400 µg of folic acid daily to help prevent neural tube defects (NTDs). Hispanic women are at higher risk of having babies with NTDs than non-Hispanic White women. This study assessed multivitamin (MV) use, a main source of folic acid, among Hispanic women of reproductive age using a survey of solely U.S. Hispanic adults. Materials and Methods: MV use was assessed as part of Porter Novelli's Estilos survey, fielded annually through the largest online U.S. Hispanic panel, Offerwise's QueOpinas. During the study period of 2013-2022, 9,999 surveys were completed; selection was weighted to match the U.S. Census American Community Survey proportions. Log-binomial regression models were applied to estimate MV use trends by age groups, acculturation levels, and pregnancy intention. Results: Among 3,700 Hispanic women of reproductive age, overall no MV use increased from 39.3% in 2013 to 54.7% in 2022 (p for trend <0.0001), especially among Hispanic women aged 18-34 years and those classified as acculturated. Among women planning to get pregnant, daily MV use was 31.1% in 2013 compared with 18.7% in 2020-2022 (p = 0.04). Conclusions: Given the increase in no MV use among Hispanic women of reproductive age, targeted interventions may help reach at-risk groups for NTDs prevention.

Effect and mechanism of Jinkui Shenqi Pill on preventing neural tube defects in mice based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: jinkui Shenqi Pill (JSP) is a classic traditional Chinese medicine used to treat "Kidney Yang Deficiency" disease. Previous studies indicate a protective effect of JSP on apoptosis in mouse neurons. AIM OF THE STUDY: This research, combining network pharmacology with in vivo experiments, explores the mechanism of JSP in preventing neural tube defects (NTDs) in mice. MATERIALS AND METHODS: Network pharmacology analyzed JSP components and targets, identifying common genes with NTDs and exploring potential pathways. Molecular docking assessed interactions between key JSP components and pathway proteins. In an all-trans retinoic acid (atRA)-induced NTDs mouse model, histopathological changes were observed using HE staining, neuronal apoptosis was detected using TUNEL, and Western Blot assessed changes in the PI3K/AKT signaling pathway and apoptosis-related proteins. RESULTS: Different concentrations of JSP led to varying degrees of reduction in the occurrence of neural tube defects in mouse embryos, with the highest dose showing the most significant decrease. Furthermore, it showed a better reduction in NTDs rates compared to folic acid (FA). Network pharmacology constructed a Drug-Active Ingredient-Gene Target network, suggesting key active ingredients such as Quercetin, Wogonin, Beta-Sitosterol, Kaempferol, and Stigmasterol, possibly acting on the PI3K/Akt signaling pathway. Molecular docking confirmed stable binding structures. Western Blot analysis demonstrated increased expression of p-PI3K, p-Akt, p-Akt1, p-Akt2, p-Akt3, downregulation of cleaved caspase-3 and Bax, and upregulation of Bcl-2, indicating prevention of NTDs through anti-apoptotic effects. CONCLUSION: We have identified an effective dosage of JSP for preventing NTDs, revealing its potential by activating the PI3K/Akt signaling pathway and inhibiting cell apoptosis in atRA-induced mouse embryonic NTDs.

Influence of folic acid knowledge on effective folic acid intake in Chinese pregnant women: a cross-sectional study.

PURPOSE: This study aimed to investigate the current status of effective folic acid intake and the level of folic acid knowledge of Chinese pregnant women and to analyze the relationship between effective folic acid intake and folic acid knowledge. METHODS: From November 2021 to May 2022, 140 pregnant women at Yantai Yuhuangding Hospital in the Chinese province of Shandong, answered questions about their general characteristics, folic acid intake, and folic acid knowledge. The data were analyzed using the t-test, chi-square test, and logistic regression analysis, and were presented with frequency with percentage or mean±standard deviation. RESULTS: Only 16.4% of the pregnant women (n=23) took folic acid effectively, using the following four criteria. Of all pregnant women who took folic acid, 72.2% took folic acid starting 1 month before pregnancy, 70.8% took folic acid up to 3 months after pregnancy, 36.8% took 400 µg every time, and 78.6% took folic acid more than 24 days every month. The score for folic acid knowledge was relatively high (5.61±2.18 on a scale of 0-9). A higher folic acid knowledge score correlated with more effective folic acid intake (t=4.10, p<.001). CONCLUSION: Our study shows that the current recommendations to prevent neural tube defects through effective folic acid intake supplementation are not being fully implemented in China. Furthermore, folic acid knowledge was positively correlated with the effectiveness of its intake. Future education related to effective folic acid intake should emphasize the four methods of effective folic acid intake, especially regarding the recommended dose of 400 µg every time.

Inequities in pre-pregnancy folic acid use in Central and South Auckland: secondary analysis from a postpartum contraception survey.

Introduction In Aotearoa New Zealand (NZ), there is inequity in rates of neural tube defects (NTDs). Among Maaori, NTD occur in 4.58/10 000 live births, and for Pacific peoples, it is 4.09/10 000 live births; this is compared to 2.81/10 000 live births for non-Maaori, non-Pacific peoples. Aim To describe self-reported pre-pregnancy folic acid supplementation and to determine the association between pregnancy intendedness, ethnicity, parity, maternal age, care provider and pre-pregnancy folic acid supplementation. Methods Secondary analysis of postpartum survey data collected at Te Whatu Ora Te Toka Tumai and Counties Manukau birthing facilities in 2020 was conducted. Descriptive analyses explored pregnancy intendedness and self-reported folic acid use by demographic variables. Multivariable logistic regression explored independent associations between demographic variables and folic acid use among intended pregnancies. Results In total, 398 participants completed the survey. The response rate was (140/149) 94% at Counties Manukau and (258/315) 82% at Te Toka Tumai. Pre-pregnancy supplementation was reported by 182 of 398 participants (46%). Use was higher among those who intended their pregnancy (151/262, 58%) compared to those who were 'pregnancy ambivalent' (9/33, 27%) or did not intend to become pregnant (22/103, 21%). Factors independently associated with supplementation among intended pregnancies included: 'Other ethnicity' (European, Middle Eastern, Latin American, African) compared to Maaori (aOR 5.3 (95% CI 1.3, 21.8)), age ≥30 years compared to Discussion Low rates of pre-pregnancy folic acid supplementation exist in Auckland with significant ethnic disparity. Mandatory fortification of non-organic wheat is important, but supplementation is still recommended to maximally reduce risk.

Factors Associated with Neural Tube Defects among Women Who Gave Birth at Adama Hospital Medical College, Adama, Ethiopia: A Case Control Study.

Background: Neural tube defects (NTDs) occur as a result of incomplete closure of the neural tube by the embryonic age of 26 to 28 days. Addressing factors associated with NTDs would help to identify and prioritize high-risk women, which in turn guides the preventive strategy. The study aimed to identify factors associated with NTDs among women who gave birth or had a second-trimester abortion at Adama Hospital Medical College, from January 1st to December 31st, 2019. Methods: Hospital based unmatched case-control study was conducted on 344 women. Data were analyzed with SPSS 20. Descriptive statistics were computed. Binary logistic regression analysis was performed to determine factors associations with NTDs. Results: The odds of having a fetus with NTDs were 2.19 times higher among women who are not in a marital relationship (AOR = 2.19; 95% CI: 1.13, 4.25). Women with a previous history of Abortion or stillbirth had 3 fold increased risk of having a fetus with NTDs (AOR = 3.05; 95% CI: 1.58, 5.88). Inadequate housing condition nearly doubles the odds of having a fetus with NTDs (AOR = 1.91; 95% CI: 1.20, 3.04). Folic acid or multivitamin supplementation early in pregnancy reduced the odds of having a fetus with NTDs by 43% (AOR = 0.57; 95% CI: 0.35, 0.91). Conclusion: Being not in a marital relationship, previous history of abortion or stillbirth, and living in inadequate housing conditions were risk factors for NTDs, while multivitamins or folic acid supplementation was a protective factor.

A importância do metilfolato na prevenção dos defeitos abertos do tubo neural / The importance of methylfolate in the prevention of open neural tube defects

A suplementação periconcepcional com vitamina B9 ou folato é considerada medida efetiva para diminuir a ocorrência e a recorrência de defeitos do tubo neural (DTNs). É recomendada para todas as mulheres que planejam gravidez ou que possam engravidar. O ácido fólico necessita passar por processos enzimáticos necessários à metabolização para a sua forma ativa L-5-metiltetrahidrofolato (L-metilfolato, 5-MTHF) envolvida nos processos biológicos e que circula no plasma. A enzima metilenotetrahidrofolato redutase (MTHFR) é de fundamental importância para fornecer 5-MTHF, forma biologicamente ativa. A presença de polimorfismo do gene da MTHF-redutase promove menor atividade enzimática e menor produção de L-metilfolato.(AU)

Fisuras labio-palatinas y fortificación de la harina con ácido fólico en Chile: an exploratory study / Cleft lip/palate and flour fortification with folic acid in Chile

Background: The effect of food fortification with folic acid on the incidence of lip-palate fissures (FLP) is under discussion. Aim: To calculate the rate of hospital discharges due to cleft lip and palate (CLP) and explore whether they decreased after the start of folic acid fortification in Chile. Material and Methods: The hospital discharge databases published by the Chilean Ministry of Health were analyzed. The trends of discharge rates due to CLP of children of less than one year of life (ICD-10 Q350-379 code) and live births (lb) were calculated from 1986 to 2012. Variables such as incidence of rubella, poverty rate, obesity in pregnant women, and percentage of women who smoked or drank alcohol in the last month were included. The relative risk (RR) of CLP pre-fortification (1986-1999) and post-fortification (2000-2010) was calculated. Mixed and Prais-Winsten models were used to adjust other variables. Results: The hospital discharge rate due to CLP decreased from 1.88 x 1,000 lb during 1986-1996 to 1.68 x 1,000 lb (RR = 1.09 (95% CI 1.05-1.14, p < 0.001). Prais-Winsten and Mixed models, determined that folic acid fortification is the variable explaining this decrease. During 2004-2011, hospital discharge rates for cleft lip decreased but there was an increase in the figures for cleft lip and palate. Conclusions: The 9% decrease in hospital discharge rates for CLP is concomitant with wheat folic acid fortification.

Defectos del tubo neural y del ácido fólico: recorrido histórico de una intervención preventiva altamente efectiva / Neural tube defects and folic acid: a historical overview of a highly successful preventive intervention

Este artículo describe de forma comprehensiva parte del devenir histórico que han tenido, el conocimiento médico de los defectos del tubo neural (DTN) y el descubrimiento de la vitamina B9 o ácido fólico, así como algunos de los acontecimientos investigativos relevantes que a través de varios siglos definieron las relaciones entre la comprensión de la embriología del sistema nervioso central, el descubrimiento de la vitamina, la correlación del ácido fólico con la proliferación celular y finalmente el desarrollo de medidas preventivas de este tipo de defectos. Se pretende, a través de esta narrativa, exponer los conceptos históricamente relevantes que sustentan las acciones de índole clínico y de impacto poblacional que previenen los DTN a través del consumo preconcepcional de ácido fólico.

This article gives a broad overview of part of the historical evolution of medical knowledge about neural tube defects (NTD) and the discovery of vitamin B9 or folic acid, as well as some relevant research events that, over the course of several centuries, defined the relationships between the understanding of central nervous system embryology, the discovery of the vitamin, the correlation between folic acid and cell proliferation and lastly the development of preventive measures for this type of defects. This narrative allows us to examine historically relevant concepts underlying clinical actions with a populational impact that prevent NTDs via folic acid consumption prior to conception.

Folic acid intake by pregnant women from Vale do Jequitinhonha, Brazil, and the contribution of fortified foods / Consumo de ácido fólico por gestantes do Vale do Jequitinhonha, Brasil, e a contribuição dos alimentos fortificados

The folate deficiency can result in irreversible health damage, such as the neural tube defects. The aim of this article is to determine the folate intake of pregnant women in Vale do Jequitinhonha, Minas Gerais state, Brazil, one of the poorest regions in the world. A descriptive, cross-sectional study was done in 2013 with 492 pregnant women attending the basic health units run by the public health service (Sistema Único de Saúde, SUS) in 15 municipalities. A standard questionnaire was used to gather the data, which included socioeconomic indicators and a food frequency questionnaire. The data were analyzed and compared statistically based on prevalence ratios and 95% confidence intervals. The prevalence of inadequate folate intake was associated with some socioeconomic factors: it was higher amongst the low income and less educated women, in younger women and those who had fewer meals per day. The prevalence of inadequate folate intake in the diet was 94.7% when the contribution of food fortification was not considered, 49.2% taking into account fortified foods, and 17.1% considering food folate, fortified foods, and supplementation with folic acid. We conclude that fortifying foods with folic acid at the current levels reduces the inadequacy of folate intake in the diet, but not enough to assure safe levels and to meet the nutritional requirements of pregnant women in Brazil.

A deficiência de folato pode acarretar prejuízos irreversíveis como os defeitos do tubo neural. O objetivo deste artigo é determinar o padrão de consumo de folato por gestantes no Vale do Jequitinhonha, Minas Gerais, Brasil, uma das regiões mais pobres do mundo. A pesquisa descritiva do tipo transversal foi realizada com 492 gestantes atendidas em Unidades Básicas de Saúde do SUS em 15 municípios do Vale do Jequitinhonha no ano de 2013. Para a coleta de dados foi utilizado um questionário padronizado, que inclui um questionário socioeconômico e inquérito de frequência alimentar. Os dados foram analisados e comparados estatisticamente através de razão de prevalências e intervalo de confiança de 95%. A prevalência de consumo insuficiente de folato mostrou-se associada com alguns fatores socioeconômicos: foi maior em gestantes com baixa renda, de baixa escolaridade e em gestantes mais jovens e que realizavam menos refeições por dia. Observou-se que a prevalência de consumo insuficiente de folato na dieta foi de 94,7% desconsiderando a inclusão de alimentos fortificados, 49,2% considerando a dieta com alimentos fortificados e 17,1% considerando a dieta, a fortificação e a suplementação medicamentosa com ácido fólico. Conclui-se que a fortificação de alimentos com ácido fólico nos níveis atuais reduz a inadequação do consumo na dieta, mas não é suficiente para suprir as necessidade e garantir os níveis seguros da oferta deste nutriente entre gestantes brasileiras.