Palavras-chave
Desenvolvimento humano
Embriogênese
Gestação
Malformação fetal
Saúde pública
Tubo neural
Métricas
Como Citar
Dados de financiamento
-
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Números do Financiamento 302997/2022-9 -
Fundação de Amparo à Pesquisa do Estado de São Paulo
Números do Financiamento 2023/00608-0; 2017/02739-4; 2023/12635-2; 2024/20267-6; 2025/28580-8
Resumo
A gestação apresenta intensas adaptações fisiológicas e metabólicas destinadas a sustentar os estágios iniciais da embriogênese e o desenvolvimento fetal. Nesse contexto, o folato (vitamina B9) desempenha papel central em processos bioquímicos essenciais, como a síntese de DNA e RNA, a divisão celular e a regulação epigenética. A deficiência desse micronutriente induz instabilidade genômica e afeta diretamente a embriogênese, particularmente a formação do sistema nervoso central. Esta revisão analisou o papel do ácido fólico na formação do tubo neural, bem como sua influência no desenvolvimento fetal e na prevenção de malformações congênitas, além dos seus efeitos sobre a infância e vida adulta. Para isso, foram consultadas as bases de dados Web of Science e PubMed, utilizando os descritores “folic acid”, “deficiency”, “pregnancy”, “embryogenesis”, e “public health”, em estudos publicados entre 1976 e 2025, incluindo modelos pré-clínicos. Os estudos analisados demonstram associação consistente entre a deficiência de ácido fólico no período periconcepcional e o aumento da incidência de defeitos do tubo neural, como anencefalia e espinha bífida, reforçando a importância da suplementação adequada nas fases iniciais da gestação. Além disso, evidências emergentes indicam que exposições excessivas ao folato podem induzir alterações epigenéticas capazes de modular o risco de doenças metabólicas, cardiovasculares e neoplásicas ao longo da vida. Conclui-se que o ácido fólico é indispensável para a embriogênese normal e para a prevenção de malformações congênitas, sendo a suplementação periconcepcional uma estratégia consolidada de saúde pública. No entanto, os potenciais efeitos adversos do excesso de folato ressaltam a necessidade de aprofundar investigações que permitam definir recomendações mais precisas e individualizadas de suplementação durante a gestação e ao longo da vida adulta.
Referências
ADIBI, J. J.; LAYDEN, A. J.; BIRRU, R. L.; MIRAGAIA, A.; XUN, X.; SMITH, M. C.; YIN, Q.; MILLENSON, M. E.; O’CONNOR, T. G.; BARRETT, E. S.; SNYDER, N. W.; PEDDADA, S.; MITCHELL, R. T. First trimester mechanisms of gestational sac placental and foetal teratogenicity: a framework for birth cohort studies. Human Reproduction Update, v. 27, n. 4, p. 747–770, 2021. DOI: 10.1093/humupd/dmaa063.
ALI, M. A.; HAFEZ, H. A.; KAMEL, M. A.; GHAMRY, H. I.; SHUKRY, M.; FARAG, M. A. Dietary Vitamin B Complex: Orchestration in Human Nutrition throughout Life with Sex Differences. Nutrients, v. 14, n. 19, p. 3940, 2022. DOI: 10.3390/nu14193940.
AMERICAN ACADEMY OF PEDIATRICS, COMMITTEE ON GENETICS. Folic acid for the prevention of neural tube defects. Pediatrics, v. 104, n. 2, p. 325–327, 1999. DOI: 10.1542/peds.104.2.325.
BAHOUS, R. H.; JADAVJI, N. M.; DENG, L.; COSÍN-TOMÁS, M.; LU, J.; MALYSHEVA, O.; LEUNG, K.-Y.; HO, M.-K.; PALLÀS, M.; KALIMAN, P.; GREENE, N. D. E.; BEDELL, B. J.; CAUDILL, M. A.; ROZEN, R. High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short-term memory impairment in offspring. Human Molecular Genetics, v. 26, n. 5, p. 888–900, 2017. DOI: 10.1093/hmg/ddx004.
BAILEY, S. W.; AYLING, J. E. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proceedings of the National Academy of Sciences (PNAS), v. 106, n. 36, p. 15424–15429, 2009. DOI: 10.1073/pnas.0902072106.
BERRY, R. J.; LI, Z.; ERICKSON, J. D.; LI, S.; MOORE, C. A.; WANG, H.; MULINARE, J.; ZHAO, P.; WONG, L. Y. C.; GINDLER, J.; HONG, S. X.; CORREA, A. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. New England Journal of Medicine, v. 341, p. 1485–1490, 1999. DOI: 10.1056/NEJM199911113412001.
BJELAKOVIC, G.; STOJANOVIC, I.; JEVTOVIC-STOIMENOV, T.; PAVLOVIC, D.; KOCIC, G.; BJELAKOVIC, L.; KAMENOV, B.; SOKOLOVIC, D.; BASIC, J.; BJELAKOVIC, G. B. Is folic acid supplementation to food benefit or risk for human health? Pteridines, v. 24, n. 3-4, p. 165–181, 2013. DOI: 10.1515/pterid-2013-0024.
BRADY, M. V.; VACCARINO, F. M. Role of SHH in patterning human pluripotent cells towards ventral forebrain fates. Cells, v. 10, n. 4, p. 914, 2021. DOI: 10.3390/cells10040914.
BRASIL. Ministério da Saúde. Secretaria de Atenção Primária à Saúde. Guia de AtençãoPré-Natal. Brasília: Ministério da Saúde, 2021.
BREIMER, L. H.; NILSSON, T. K. Has folate a role in the developing nervous system after birth and not just during embryogenesis and gestation? Scandinavian Journal of Clinical and Laboratory Investigation, v. 72, n. 3, p. 185–191, 2012. DOI: 10.3109/00365513.2012.657230.
CANEVER, L.; VARELA, R.; MASTELLA, G. A.; DAMÁZIO, L. S.; VALVASSORI, S. S.; QUEVEDO, J. L.; ZUGNO, A. I. Effects of maternal folic acid supplementation on nuclear methyltransferase activity of adult rats subjected to an animal model of schizophrenia. International Journal of Developmental Neuroscience, v. 81, n. 5, p. 461–467, 2021. DOI: 10.1002/jdn.10109.
CASTAÑO, E.; CAVIEDES, L.; HIRSCH, S.; LLANOS, M.; IÑIGUEZ, G.; RONCO, A. M. Folate transporters in placentas from preterm newborns and their relation to cord blood folate and vitamin B12 levels. PLOS ONE, v. 12, n. 1, p. e0170389, 2017. DOI: 10.1371/journal.pone.0170389.
CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC). Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recommendations and Reports, v. 41, n. RR-14, p. 1–7, 1992.
CETIN, I.; BERTI, C.; CALABRESE, S. Role of micronutrients in the periconceptional period. Human Reproduction Update, v. 16, n. 1, p. 80–95, 2010. DOI: 10.1093/humupd/dmp025.
CHOI, J. H.; YATES, Z.; VEYSEY, M.; HEO, Y. R.; LUCOCK, M. Contemporary issues surrounding folic acid fortification initiatives. Preventive Nutrition and Food Science, v. 19, n. 4, p. 247–260, 2014. DOI: 10.3746/pnf.2014.19.4.247.
CORTÉS, F.; MELLADO, C.; PARDO, R. A.; VILLARROEL, L. A.; HERTRAMPF, E. Wheat flour fortification with folic acid: changes in neural tube defects rates in Chile. American Journal of Medical Genetics Part A, v. 158A, n. 8, p. 1885–1890, 2012. DOI: 10.1002/ajmg.a.35441.
CRIDER, K. S.; BAILEY, L. B.; BERRY, R. J. Balancing the benefits and risks of folic acid fortification. Public Health Reviews, v. 33, n. 2, p. 1–28, 2011. DOI: 10.1007/BF03391642.
CZEIZEL, A. E.; DUDÁS, I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. New England Journal of Medicine, v. 327, n. 26, p. 1832–1835, 1992. DOI: 10.1056/NEJM19921224327260.
DE WALS, P.; TAIROU, F.; VAN ALLEN, M. I.; et al. Reduction in neural-tube defects after folic acid fortification in Canada. New England Journal of Medicine, v. 357, n. 2, p. 135–142, 2007. DOI: 10.1056/NEJMoa067103.
DJUKIC, A. Folate-responsive neurologic diseases. Pediatric Neurology, v. 37, n. 6, p. 387–397, 2007. DOI: 10.1016/j.pediatrneurol.2007.09.001.
ESNAFOGLU, E.; OZTURAN, D. D. The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents. Child and Adolescent Mental Health, v. 25, n. 4, p. 249–255, 2020. DOI: 10.1111/camh.12387.
GONG, Y.; CHEN, H.; ZHANG, S.; HU, X.; XU, W.; WANG, H. Neurodevelopmental effects of maternal folic acid supplementation: a systematic review and meta-analysis. Critical Reviews in Food Science and Nutrition, v. 63, n. 19, p. 1-17, 2021. DOI: 10.1080/10408398.2021.1993781.
GREENBERG, J. A.; BELL, S. J.; GUAN, Y.; YU, Y. H. Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Reviews in Obstetrics and Gynecology, v. 4, n. 2, p. 52–59, 2011. PMID: 22102928.
HONEIN, M. A.; PAULOZZI, L. J.; MATHEWS, T. J.; ERICKSON, J. D.; WONG, L. Y. C. Impact of folic acid fortification of the U.S. food supply on the occurrence of neural tube defects. JAMA, v. 285, n. 23, p. 2981–2986, 2001. DOI: 10.1001/jama.285.23.2981.
HUANG, Y.; HE, Y.; SUN, X.; HE, Y.; LI, Y.; SUN, C. Maternal high folic acid supplement promotes glucose intolerance and insulin resistance in male mouse offspring fed a high-fat diet. International Journal of Molecular Sciences, v. 15, n. 4, p. 6298–6313, 2014. DOI: 10.3390/ijms15046298.
HUTSON, J. R.; STADE, B.; LEHOTAY, D. C.; COLLIER, C. P.; KAPUR, B. M. Folic acid transport to the human fetus is decreased in pregnancies with chronic alcohol exposure. PLOS ONE, v. 7, n. 5, p. e38057, 2012. DOI: 10.1371/journal.pone.0038057.
IKEDA, S.; KOYAMA, H.; SUGIMOTO, M.; KUME, S. Roles of One-carbon Metabolism in Preimplantation Period. Journal of Reproduction and Development, v. 58, n. 1, p. 38-43, 2012. DOI: 10.1262/jrd.2011-002.
INSTITUTE OF MEDICINE (IOM). Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academies Press, 1998. DOI: 10.17226/6015.
JONES, P.; etc. Folate and inflammation – links between folate and features of inflammatory conditions. Journal of Nutrition & Intermediary Metabolism, v. 18, p. 100104, 2019. DOI: 10.1016/j.jnim.2019.100104.
JOUBERT, B. R.; DEN DEKKER, M.; FELIX, J.; BOHLIN, J.; LIGTHART, S.; BECKETT, E.; TIEMEIER, H.; VAN MEURS, J.; UITTERLINDEN, A.; HOFMAN, B.; HABERG, S. E.; REESE, S. E.; PETERS, M.; ANDREASSEN, B. K.; STEEGERS, E.; NILSEN, R. M.; VOLLSET, S. E.; MIDTTUN, O.; UELAND, P. M.; LONDON, S. J. Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns. Nature Communications, v. 7, n. 1, 2016. DOI: 10.1038/ncomms10577.
KEATS, E. C.; HAIDER, B. A.; TAM, E.; BHUTTA, Z. A. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database of Systematic Reviews, v. 3, CD004905, 2019. DOI: 10.1002/14651858.CD004905.pub6.
KEULS, R. A.; FINNELL, R. H.; PARCHEM, R. J. Maternal metabolism influences neural tube closure. Trends in Endocrinology & Metabolism, 2023. DOI: 10.1016/j.tem.2023.06.005.
KOK, D. E.; RICHMOND, R.; ADRIAENS, M.; EVELO, C.; FORD, D.; MATHERS, J.; ROBINSON, N.; MCKAY, J. Impact of In Utero Folate Exposure on DNA Methylation and Its Potential Relevance for Later-Life Health—Evidence from Mouse Models Translated to Human Cohorts. Molecular Nutrition & Food Research, v. 66, n. 3, p. 2100789, 2022. DOI: 10.1002/mnfr.202100789.
KRANENBURG, E.; KUBANT, R.; CHO, C. E.; YANG, Z.; DATARS, M.; DONG, J.; ANDERSON, G. H. Folic Acid Reduces Insulin Resistance in Mice With Diet‐Induced Obesity by Altering One-Carbon Metabolism and DNA Methylation Patterns of Hypothalamic and Hepatic Insulin Receptor Gene. Molecular Nutrition & Food Research, 2025. DOI: 10.1002/mnfr.70181.
LAI, J. S.; PANG, W. W.; CAI, S.; LEE, Y. S.; CHAN, J. K. Y.; SHEK, L. P. C.; YAP, F. K. P.; TAN, K. H.; GODFREY, K. M.; VAN DAM, R. M.; CHONG, Y. S.; CHONG, M. F. F. High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus. Clinical Nutrition, v. 37, n. 3, p. 940–947, 2018. DOI: 10.1016/j.clnu.2017.03.022.
LAURENCE, K. M.; JAMES, N.; MILLER, M. H.; TENNANT, G. B.; CAMPBELL, H. Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects. British Medical Journal (Clinical Research Edition), v. 282, p. 1509–1511, 1981. DOI: 10.1136/bmj.282.6275.1509.
LI, B.; LI, S.; DING, Y.; CUI, H. Low maternal dietary folate alters retrotransposons by methylation regulation in intrauterine growth retardation (IUGR) fetuses in a mouse model. Medical Science Monitor, v. 25, p. 3354–3365, 2019. DOI: 10.12659/msm.914292.
LIU, S.; WEST, R.; RANDELL, E.; et al. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy and Childbirth, v. 4, n. 1, p. 20, 2004. DOI: 10.1186/1471-2393-4-20.
LIU, X.-H.; CAO, Z.-J.; CHEN, L.-W.; ZHANG, D.-L.; QU, X.-X.; LI, Y.-H.; TANG, Y.-P.; BAO, Y.-R.; YING, H. The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population. Public Health Nutrition, v. 26, n. 5, 2023. DOI: 10.1017/S136898002200194X.
LUAN, Y.; COSÍN-TOMÁS, M.; LECLERC, D.; MALYSHEVA, O. V.; CAUDILL, M. A.; ROZEN, R. Moderate Folic Acid Supplementation in Pregnant Mice Results in Altered Sex-Specific Gene Expression in Brain of Young Mice and Embryos. Nutrients, v. 14, n. 5, p. 1051, 2022. DOI: 10.3390/nu14051051.
MCKAY, J. A.; WILLIAMS, E. A.; MATHERS, J. C. Folate and epigenetics. Biochemical Society Transactions, v. 32, n. 6, p. 1006-1007, 2004. DOI: 10.1042/BST0321006.
MJAASETH, U. N.; NORRIS, J. C.; AARDEMA, N. D. J.; BUNNELL, M. L.; WARD, R. E.; HINTZE, K. J.; CHO, C. E. Excess vitamins or imbalance of folic acid and choline in the gestational diet alter the gut microbiota and obesogenic effects in Wistar rat offspring. Nutrients, v. 13, n. 12, p. 4510, 2021. DOI: 10.3390/nu13124510.
MRC VITAMIN STUDY RESEARCH GROUP. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. The Lancet, v. 338, n. 8760, p. 131–137, 1991. DOI: 10.1016/0140-6736(91)90133-A.
NATIONAL INSTITUTES OF HEALTH (NIH). Office of Dietary Supplements. Folate: Fact Sheet for Health Professionals. Bethesda: NIH, 2023. Disponível em:https://ods.od.nih.gov/factsheets/Folate-HealthProfessional.
NEWSTEAD, S. Structural basis for recognition and transport of folic acid in mammalian cells. Current Opinion in Structural Biology, v. 74, 102353, 2022. DOI: 10.1016/j.sbi.2022.102353.
NORTHRUP, H.; VOLCIK, K. A. Spina bifida and folate. Molecular Genetics and Metabolism, v. 71, n. 1-2, p. 1-10, 2000. DOI: 10.1067/mpp.2000.
OBEID, R.; WARNKE, I.; KOLETZKO, B. Unmetabolized folic acid and relation to folate status in pregnancy. American Journal of Clinical Nutrition, v. 107, n. 3, p. 420–427, 2018. DOI: 10.1093/ajcn/nqx067.
O’LEARY, F.; SAMMAN, S. Vitamin B12 in health and disease. Nutrients, v. 2, n. 3, p. 299–316, 2010. DOI: 10.3390/nu2030299.
PACHECO, S. S.; BRAGA, M. C.; SOUZA, A. I.; FIGUEIROA, J. N. Efeito da fortificação das farinhas com ácido fólico sobre a prevalência de defeitos do tubo neural. Revista de SaúdePública, v. 50, n. 49, 2016. DOI: 10.1590/S1518-8787.2016050006209.
PIEDRAHITA, J. A.; OETAMA, B.; BENNETT, G. D.; VAN WAES, J.; KAMEN, B. A.; RICHARDSON, J.; FINNELL, R. H. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nature Genetics, v. 23, n. 2, p. 228–232, 1999. DOI: 10.1038/13861.
PLUMPTRE, L.; MASIH, S. P.; LY, A.; AUFREITER, S.; SOHN, K. J.; CROXFORD, R.; LAUSMAN, A. Y.; BERGER, H.; O’CONNOR, D. L.; KIM, Y. I. Unmetabolized folic acid is detected in nearly all serum samples from pregnant women in Canada. American Journal of Clinical Nutrition, v. 101, n. 5, p. 1020–1027, 2015. DOI: 10.3945/ajcn.114.103788.
POURIÉ, G.; MARTIN, N.; DAVAL, J. L. Folate and neuroprotection. International Journal of Molecular Sciences, v. 21, n. 21, p. 8008, 2020. DOI: 10.3390/ijms21218008.
REES, W. D. Folate and development. Proceedings of the Nutrition Society, v. 61, n. 1, p. 1-10, 2002. DOI: 10.1079/pns2001137.
RODRIGUES, V. B.; SILVA, E. N.; DOS SANTOS, A. M.; SANTOS, L. M. P. Prevented cases of neural tube defects and cost savings after folic acid fortification of flour in Brazil. PLoS ONE, v. 18, n. 2, e0281077, 2023. DOI: 10.1371/journal.pone.0281077.
SALIH, M. A.; MURSHID, W. R.; SEIDAHMED, M. Z. Epidemiology, prenatal management, and prevention of neural tube defects. Saudi Medical Journal, v. 35, Supl. 1, p. S15–S28, 2014. PMID: 25551106.
SANTANDER BALLESTÍN, S.; GIMÉNEZ CAMPOS, M. I.; BALLESTÍN BALLESTÍN, J.; LUESMA BARTOLOMÉ, M. J. Is Supplementation with Micronutrients Still Necessary during Pregnancy? A Review. Nutrients, v. 13, n. 9, p. 3134, 2021. DOI: 10.3390/nu13093134.
SHANE, B. Folate chemistry and metabolism. Journal of Nutrition, v. 141, n. 4, p. 535–539, 2011. DOI: 10.3945/jn.110.128819.
SHULPEKOVA, Y.; NECHAEV, V.; KARDASHEVA, S.; SEDOVA, A.; KURBATOVA, A.; BUEVEROVA, E.; KOPYLOV, A.; MALSAGOVA, K.; DLAMINI, J. C.; IVASHKIN, V. The concept of folic acid in health and disease. Molecules, v. 26, n. 12, p. 3731, 2021. DOI: 10.3390/molecules26123731.
SMITH, A. D.; KIM, Y.-I.; REFSUM, H. Is folic acid good for everyone? American Journal of Clinical Nutrition, v. 87, n. 3, p. 517–533, 2008. DOI: 10.1093/ajcn/87.3.517.
SMITH, A. D.; etc. Folate and clinical chemistry. Annals of Clinical Biochemistry, v. 61, n. 1, p. 1-10, 2024. DOI: 10.1177/00045632241280344.
SMITHELLS, R. W.; SHEPPARD, S.; SCHORAH, C. J. Vitamin deficiencies and neural tube defects. Archives of Disease in Childhood, v. 51, n. 12, p. 944–949, 1976. DOI: 10.1136/adc.51.12.944.
SOLANKY, N.; etc. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta, v. 31, n. 2, p. 134–143, 2010. DOI: 10.1016/j.placenta.2009.11.008.
STOVER, P. J. Folate biochemical pathways and the role of folate in one-carbon metabolism. The Journal of Nutrition, v. 141, n. 4, p. 619–625, 2011. DOI: 10.3945/jn.110.128504.
UNITED NATIONS. Transforming our world: the 2030 Agenda for Sustainable Development. New York: United Nations, 2015.
U.S. PREVENTIVE SERVICES TASK FORCE (USPSTF). Folic Acid Supplementation for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement. JAMA, v. 317, n. 2, p. 183–189, 2017. DOI: 10.1001/jama.2016.19438.
U.S. PREVENTIVE SERVICES TASK FORCE (USPSTF). Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA, v. 330, n. 5, p. 454–459, 2023. DOI: 10.1001/jama.2023.12876.
VALERA-GRAN, D.; GARCÍA DE LA HERA, M.; NAVARRETE-MUÑOZ, E. M.; FERNANDEZ-SOMOANO, A.; TARDÓN, A.; JULVEZ, J.; FORNS, J.; LERTXUNDI, N.; IBARLUZEA, J. M.; MURCIA, M.; REBAGLIATO, M.; VIOQUE, J. Folicacidsupplementsandchildpsychomotordevelopment. JAMA Pediatrics, v. 168, n. 11, p. 1-10, 2014. DOI: 10.1001/jamapediatrics.2014.2611.
VIRDI, S.; JADAVJI, N. M. Folateandmetabolism. Metabolites, v. 12, n. 9, p. 876, 2022. DOI: 10.3390/metabo12090876.
WANG, L.; CHANG, S.; WANG, Z.; WANG, S.; HUO, J.; DING, G.; LI, R.; LIU, C.; SHANGGUAN, S.; LU, X. Altered GNAS imprinting due to folic acid deficiency contributes to poor embryo development and may lead to neural tube defects. Oncotarget, v. 8, n. 67, p. 110797-110810, 2017. DOI: 10.18632/oncotarget.22731.
WANG, X.; YU, J.; WANG, J. Neural tube defects and folate deficiency: Is DNA Repair Defective? International Journal of Molecular Sciences, v. 24, n. 3, p. 2220, 2023. DOI: 10.3390/ijms24032220.
WORLD HEALTH ORGANIZATION (WHO).Daily iron and folic acid supplementation in pregnant women. Geneva: WHO, 2012.
YAJNIK, C. S.; DESHPANDE, S. S.; JACKSON, A. A.; REFSUM, H.; RAO, S.; FISHER, D. J.; BHAT, D. S.; NAIK, S. S.; COYAJI, K. J.; JOGLEKAR, C. V.; LUBREE, H. G.; DESHPANDE, V. U.; REGE, S. S.; FALL, C. H. D. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia, v. 51, n. 1, p. 29–38, 2008. DOI: 10.1007/s00125-007-0793-y.
ZHANG, G.; REN, Q.; LIN, Y.; ZHOU, D.; HUANG, L.; LI, W.; CHANG, H.; HUANG, G.; LI, Z.; YAN, J. Folate and nutritional biochemistry. Journal of Nutritional Biochemistry, v. 115, p. 109455, 2023. DOI: 10.1016/j.jnutbio.2023.109455.
ZHOU, X.; REN, Q.; ZHANG, G.; LIN, Y.; ZHOU, D.; HUANG, L.; LI, W.; CHANG, H.; HUANG, G.; LI, Z.; YAN, J. Folate and gene expression. International Journal of Molecular Sciences, v. 23, n. 13, p. 6948, 2022. DOI: 10.3390/ijms23136948.
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Copyright (c) 2026 BioEns@ios