Download PDF
CC BY 4.0 · Rev Bras Ginecol Obstet 2023; 45(04): 207-214
DOI: 10.1055/s-0043-1769001
Review Article

Impact of Maternal Folic Acid Supplementation on Descendants' Kidney in Adulthood

Impacto da suplementação materna com ácido fólico no rim dos descendentes na vida adulta
Thayane Ferreira da Costa Fernandes 
1   Universidade Federal do Rio de Janeiro, Macaé, RJ, Brazil
,
Poliana dos Santos Conde 
2   Universidade Federal Fluminense, Rio das Ostras, RJ, Brazi
,
Flavia de Bittencourt Brasil 
2   Universidade Federal Fluminense, Rio das Ostras, RJ, Brazi
,
Marcos Roberto de Oliveira 
3   Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Supplementation with folic acid (FA) during gestation has been recommended by medical society all over the world, but some studies have shown that intake of high folic acid diet may unleash damages to the descendants. Objectives: Describing the effects of maternal supplementation with FA during gestation on offspring's kidney at late life stages. Data Source: It is a systematic review by which were consulted the following databases: Medline, through Pubmed, Lilacs, and SciELO. The research was performed using the keywords “Folic acid”, “Gestation” and “Kidney”. Study Selection: Eight studies were regarded for this systematic review. Data Collection: Only studies that evaluated folic acid consumption during gestation and its effects exclusively on descendants' kidney at several phases of life were regarded. Results: Gestational FA intake did not change the renal volume, glomerular filtration rate and the expression of some essential genes in the kidney of puppies whose dams were supplemented with FA. Maternal consumption of double FA plus selenium diet was effective in preserving antioxidant enzymes activity in the kidney of descendants from mothers exposed to alcohol. FA supplementation decreased some gross anomalies in the puppies caused by teratogenic drug despite of had not been effective in preventing some renal architectural damages. Conclusion: FA supplementation did not cause renal toxicity; it exerted an antioxidant protective effect and mitigated some renal disorders caused by severe aggressions.

Resumo

A suplementação com ácido fólico (AF) durante a gestação tem sido recomendada pela sociedade médica em todo o mundo, mas alguns estudos têm mostrado que a ingestão de altas quantidades de ácido fólico na dieta pode desencadear danos aos descendentes. Objetivos: Descrever os efeitos da suplementação materna com AF durante a gestação no rim da prole em fases tardias da vida. Fonte de Dados: Trata-se de uma revisão sistemática realizada através da consulta das seguintes bases de dados: Medline, através da Plataforma Pubmed, Lilacs e Scielo. A pesquisa foi realizada utilizando-se as palavras-chave “Ácido Fólico”, “Gestação” e “Rim”. Seleção dos Estudos: Oito estudos foram considerados para esta revisão sistemática. Coleta de Dados: Foram incluídos estudos que abordaram o consumo de ácido fólico durante a gestação e seus efeitos exclusivamente no rim dos descendentes em diferentes fases da vida. Resultados: O consumo gestacional de AF não alterou o volume renal, a taxa de filtração glomerular e a expressão de alguns genes essenciais no rim dos filhotes de mães suplementadas com AF. A associação de AF e selênio na dieta materna foi eficaz na preservação da atividade de enzimas antioxidantes no rim da prole de mães expostas ao álcool. O consumo de AF diminuiu algumas anomalias importantes nos filhotes causadas por drogas teratogênicas, apesar de não ter sido eficiente na prevenção de alguns danos a arquitetura renal. Conclusão: A suplementação com AF não causou toxicicdade renal, exerceu efeito protetor antioxidante e mitigou algumas desordens renais causadas por agressões severas.

Keywords

Folic acid - Gestation - Kidney - Descendant - Adulthood

Palavras-chave

Ácido fólico - Gestação - Rim - Descendentes - Vida adulta


Publication History

Received: 25 July 2022

Accepted: 17 October 2022

Article published online:
24 May 2023

© 2023. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Vannucchi H, Jordão Júnior AA. Vitaminas hidrossolúveis. In: Dutra-de-Oliveira JE, Marchini JS. Ciências nutricionais. São Paulo: Sarvier; 1998: 191-207
    Search in Google Scholar
  • 2 Green T, Newton R, Bourn D. Estimated folic acid intakes from simulated fortification of the New Zealand food supply. N Z Med J 2003; 116 (1168): U294
    PubMedSearch in Google Scholar
  • 3 Merrell BJ, McMurry JP. Folic acid. In: StatPearls [Internet]. Treasure Island: StatPearls; 2020. [cited 2022 Mar 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554487/
    Search in Google Scholar
  • 4 Uehara SK, Rosa G. Associação da deficiência de ácido fólico com alterações patológicas e estratégias para sua prevenção: uma visão crítica. Rev Nutr 2010; 23 (05) 881-894
    CrossrefPubMedSearch in Google Scholar
  • 5 Fakouri A, Asghari A, Akbari G, Mortazavi P. Effects of folic acid administration on testicular ischemia/reperfusion injury in rats. Acta Cir Bras 2017; 32 (09) 755-766
    CrossrefPubMedSearch in Google Scholar
  • 6 Mahan LK, Escott-Stump S, Raymond JL. Krause alimentos, nutrição e dietoterapia. 9a ed. São Paulo: Roca; 1998
    Search in Google Scholar
  • 7 McGuire JJ, Coward JK. Pteroylpolyglutamates: biosynthesis, degradation, and function. In: Blakley RL, Benkovic SJ. editors. Folates and pterins, chemistry and biochemistry of folates. New York: Wiley-Interscience; 1984: 135-190
    Search in Google Scholar
  • 8 Baluz K, Carmo MG, Rosas G. O papel do ácido fólico na prevenção e na terapêutica oncológica: revisão. Rev Bras Cancerol 2002; 48 (04) 597-60
    CrossrefPubMedSearch in Google Scholar
  • 9 Lin Y, Dueker SR, Follett JR. et al. Quantitation of in vivo human folate metabolism. Am J Clin Nutr 2004; 80 (03) 680-691
    CrossrefPubMedSearch in Google Scholar
  • 10 Whitehead VM. Pharmacokinetics and physiological disposition of folate and its derivatives. In: Blakley RL, Whitehead VM. eds. Folates and pterins, chemistry and biochemistry of folates. New York: John Wiley & Sons; 1986: 177-205
    Search in Google Scholar
  • 11 Horne DW, Reed KA, Hoefs J, Said HM. 5-Methyltetrahydrofolate transport in basolateral membrane vesicles from human liver. Am J Clin Nutr 1993; 58 (01) 80-84
    CrossrefPubMedSearch in Google Scholar
  • 12 Suh JR, Herbig AK, Stover PJ. New perspectives on folate catabolism. Annu Rev Nutr 2001; 21: 255-282
    CrossrefPubMedSearch in Google Scholar
  • 13 Williams WM, Huang KC. Renal tubular transport of folic acid and methotrexate in the monkey. Am J Physiol 1982; 242 (05) F484-F490
    CrossrefPubMedSearch in Google Scholar
  • 14 Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Atenção Básica. Atenção ao pré-natal de baixo risco [Internet]. Brasília, DF: Editora do Ministério da Saúde; 2012. [cited 2022 Mar 20]. (Caderno de Atenção Básica; no. 32). Available from: http://bvsms.saude.gov.br/bvs/publicacoes/cadernos_atencao_basica_32_prenatal.pdf
    Search in Google Scholar
  • 15 Moran VH. A systematic review of dietary assessments of pregnant adolescents in industrialised countries. Br J Nutr 2007; 97 (03) 411-425
    CrossrefPubMedSearch in Google Scholar
  • 16 Hediger ML, Scholl TO, Khoo CS, Fischer RL. Diet, weight gain, and circulating micro-nutrients: evidence for nutritional depletion following adolescent pregnancy. J Adolesc Health 1992; 13 (01) 46
    CrossrefPubMedSearch in Google Scholar
  • 17 McDonald SD, Ferguson S, Tam L, Lougheed J, Walker MC. The prevention of congenital anomalies with periconceptional folic acid supplementation. J Obstet Gynaecol Can 2003; 25 (02) 115-121
    CrossrefPubMedSearch in Google Scholar
  • 18 Rangel-Rivera DA, Osma-Zambrano SE. Consumo de ácido fólico en el embarazo y reducción del riesgo de trastornos del espectro autista. Med UIS. 2015; 28 (03) 327-336
    CrossrefPubMedSearch in Google Scholar
  • 19 Wald NJ, Morris JK, Blakemore C. Public health failure in the prevention of neural tube defects: time to abandon the tolerable upper intake level of folate. Public Health Rev 2018; 39: 2
    CrossrefPubMedSearch in Google Scholar
  • 20 Santos LM, Pereira MZ. The effect of folic acid fortification on the reduction of neural tube defects. Cad Saude Publica 2007; 23 (01) 17-24
    CrossrefPubMedSearch in Google Scholar
  • 21 Valentin M, Coste Mazeau P, Zerah M, Ceccaldi PF, Benachi A, Luton D. Acid folic and pregnancy: A mandatory supplementation. Ann Endocrinol (Paris) 2018; 79 (02) 91-94
    CrossrefPubMedSearch in Google Scholar
  • 22 Liu J, Jin L, Li Z. et al. Prevalence and trend of isolated and complicated congenital hydrocephalus and preventive effect of folic acid in northern China, 2005-2015. Metab Brain Dis 2018; 33 (03) 837-842
    CrossrefPubMedSearch in Google Scholar
  • 23 Kancherla V, Ibne Hasan MOS, Hamid R. et al. Prenatal folic acid use associated with decreased risk of myelomeningocele: A case-control study offers further support for folic acid fortification in Bangladesh. PLoS One 2017; 12 (11) e0188726
    CrossrefPubMedSearch in Google Scholar
  • 24 Brasil FB, Amarante LH, Oliveira MR. Maternal folic acid consumption during gestation and its long-term effects on offspring's liver: a systematic review. Rev Bras Saúde Mater Infant 2017; 17 (01) 17-25
    CrossrefPubMedSearch in Google Scholar
  • 25 Wiens D, DeSoto MC. Is high folic acid intake a risk factor for autism? - A review. Brain Sci 2017; 7 (11) 149
    CrossrefPubMedSearch in Google Scholar
  • 26 Morakinyo AO, Samuel TA, Awobajo FO, Oludare GO, Mofolorunso A. High-dose perinatal folic-acid supplementation alters insulin sensitivity in sprague-dawley rats and diminishes the expression of adiponectin. J Diet Suppl 2019; 16 (01) 14-26
    CrossrefPubMedSearch in Google Scholar
  • 27 Barua S, Kuizon S, Brown WT, Junaid MA. DNA methylation profiling at single-base resolution reveals gestational folic acid supplementation influences the epigenome of mouse offspring cerebellum. Front Neurosci 2016; 10: 168
    CrossrefPubMedSearch in Google Scholar
  • 28 Leeming RJ, Lucock M. Autism: Is there a folate connection?. J Inherit Metab Dis 2009; 32 (03) 400-402
    CrossrefPubMedSearch in Google Scholar
  • 29 Raghavan R, Fallin MD, Wang X. Maternal plasma folate, vitamin B12 levels and multivitamin supplementation during pregnancy and risk of autism spectrum disorder in the Boston Birth Cohort. FASEB J 2016; 30 (S1): 151.6
    CrossrefPubMedSearch in Google Scholar
  • 30 Valera-Gran D, Navarrete-Muñoz EM, Garcia de la Hera M. et al; INMA Project. Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. Am J Clin Nutr 2017; 106 (03) 878-887
    CrossrefPubMedSearch in Google Scholar
  • 31 Costa MC, Bezerra Filho JG, Andrade Bezerra MG, Veríssimo de Oliveira MI, Carvalho de Oliveira RM, De Vasconcelos Silva AR. Gestação de risco: percepção e sentimentos das gestantes com amniorrexe prematura. Enferm Glob 2010; 9 (03) 1-11
    CrossrefPubMedSearch in Google Scholar
  • 32 Waterland RA, Garza C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr 1999; 69 (02) 179-197
    CrossrefPubMedSearch in Google Scholar
  • 33 Wu G, Bazer FW, Cudd TA, Meininger CJ, Spencer TE. Maternal nutrition and fetal development. J Nutr 2004; 134 (09) 2169-2172
    CrossrefPubMedSearch in Google Scholar
  • 34 Woods LL, Ingelfinger JR, Nyengaard JR, Rasch R. Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res 2001; 49 (04) 460-467
    CrossrefPubMedSearch in Google Scholar
  • 35 Langley-Evans SC, Welham SJ, Jackson AA. Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci 1999; 64 (11) 965-974
    CrossrefPubMedSearch in Google Scholar
  • 36 Franke K, Gaser C, Roseboom TJ, Schwab M, de Rooij SR. Premature brain aging in humans exposed to maternal nutrient restriction during early gestation. Neuroimage 2018; 173: 460-471
    CrossrefPubMedSearch in Google Scholar
  • 37 Batista TH, Giusti-Paiva A, Vilela FC. Maternal protein malnutrition induces autism-like symptoms in rat offspring. Nutr Neurosci 2019; 22 (09) 655-663
    CrossrefPubMedSearch in Google Scholar
  • 38 Lelièvre-Pégorier M, Vilar J, Ferrier ML. et al. Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int 1998; 54 (05) 1455-1462
    CrossrefPubMedSearch in Google Scholar
  • 39 Lisle SJ, Lewis RM, Petry CJ, Ozanne SE, Hales CN, Forhead AJ. Effect of maternal iron restriction during pregnancy on renal morphology in the adult rat offspring. Br J Nutr 2003; 90 (01) 33-39
    CrossrefPubMedSearch in Google Scholar
  • 40 Bunduki V, Martinelli S, Cabar FR. et al. Maternal and fetal serum and red blood cell folate levels in pregnancies complicated by neural tube defects. Rev Bras Ginecol Obstet 1998; 20 (06) 335-341 Portuguese.
    CrossrefPubMedSearch in Google Scholar
  • 41 Meher A, Joshi A, Joshi S. Differential regulation of hepatic transcription factors in the Wistar rat offspring born to dams fed folic acid, vitamin B12 deficient diets and supplemented with omega-3 fatty acids. PLoS One 2014; 9 (02) e90209
    CrossrefPubMedSearch in Google Scholar
  • 42 Maloney CA, Hay SM, Reid MD. et al. A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic proteome in the adult offspring. Genes Nutr 2013; 8 (02) 181-190
    CrossrefPubMedSearch in Google Scholar
  • 43 Lee YQ, Collins CE, Gordon A, Rae KM, Pringle KG. The relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans: a systematic review. Nutrients 2018; 10 (02) E241
    CrossrefPubMedSearch in Google Scholar
  • 44 Stewart CP, Christian P, Schulze KJ, Leclerq SC, West Jr KP, Khatry SK. Antenatal micronutrient supplementation reduces metabolic syndrome in 6- to 8-year-old children in rural Nepal. J Nutr 2009; 139 (08) 1575-1581
    CrossrefPubMedSearch in Google Scholar
  • 45 Miliku K, Mesu A, Franco OH, Hofman A, Steegers EAP, Jaddoe VWV. Maternal and fetal folate, vitamin B12, and homocysteine concentrations and childhood kidney outcomes. Am J Kidney Dis 2017; 69 (04) 521-530
    CrossrefPubMedSearch in Google Scholar
  • 46 Ly A, Ishiguro L, Kim D. et al. Maternal folic acid supplementation modulates DNA methylation and gene expression in the rat offspring in a gestation period-dependent and organ-specific manner. J Nutr Biochem 2016; 33: 103-110
    CrossrefPubMedSearch in Google Scholar
  • 47 Ojeda ML, Nogales F, Murillo ML, Carreras O. Selenium or selenium plus folic acid-supplemented diets ameliorate renal oxidation in ethanol-exposed pups. Alcohol Clin Exp Res 2012; 36 (11) 1863-1872
    CrossrefPubMedSearch in Google Scholar
  • 48 Ojeda ML, Jotty K, Nogales F, Murillo ML, Carreras O. Selenium or selenium plus folic acid intake improves the detrimental effects of ethanol on pups' selenium balance. Food Chem Toxicol 2010; 48 (12) 3486-3491
    CrossrefPubMedSearch in Google Scholar
  • 49 Król E, Krejpcio Z, Chmurzynska A. Folic acid and protein content in maternal diet and postnatal high-fat feeding affect the tissue levels of iron, zinc, and copper in the rat. Biol Trace Elem Res 2011; 144 (1-3): 885-893
    CrossrefPubMedSearch in Google Scholar
  • 50 El-Ashmawy IM, Bayad AE. Folic acid and grape seed extract prevent azathioprine-induced fetal malformations and renal toxicity in rats. Phytother Res 2016; 30 (12) 2027-2035
    CrossrefPubMedSearch in Google Scholar
  • 51 Kim YI. Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 1999; 10 (02) 66-88
    CrossrefPubMedSearch in Google Scholar
  • 52 Bergman D, Halje M, Nordin M, Engström W. Insulin-like growth factor 2 in development and disease: a mini-review. Gerontology 2013; 59 (03) 240-249
    CrossrefPubMedSearch in Google Scholar
  • 53 Bondesson M, Hao R, Lin CY, Williams C, Gustafsson JA. Estrogen receptor signaling during vertebrate development. Biochim Biophys Acta 2015; 1849 (02) 142-151
    CrossrefPubMedSearch in Google Scholar
  • 54 Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications–a review. Nutr J 2014; 13: 17
    CrossrefPubMedSearch in Google Scholar
  • 55 Michalik L, Auwerx J, Berger JP. et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 2006; 58 (04) 726-741
    CrossrefPubMedSearch in Google Scholar
  • 56 Feng S, Jacobsen SE, Reik W. Epigenetic reprogramming in plant and animal development. Science 2010; 330 (6004): 622-627
    CrossrefPubMedSearch in Google Scholar
  • 57 Kulis M, Esteller M. DNA methylation and cancer. Adv Genet 2010; 70: 27-56
    CrossrefPubMedSearch in Google Scholar
  • 58 Ojeda ML, Nogales F, Jotty K, Barrero MJ, Murillo ML, Carreras O. Dietary selenium plus folic acid as an antioxidant therapy for ethanol-exposed pups. Birth Defects Res B Dev Reprod Toxicol 2009; 86 (06) 490-495
    CrossrefPubMedSearch in Google Scholar
  • 59 Lee S, Murthy N. Targeted delivery of catalase and superoxide dismutase to macrophages using folate. Biochem Biophys Res Commun 2007; 360 (01) 275-279
    CrossrefPubMedSearch in Google Scholar
  • 60 Iborra A, Palacio JR, Martínez P. Oxidative stress and autoimmune response in the infertile woman. Chem Immunol Allergy 2005; 88: 150-162
    CrossrefPubMedSearch in Google Scholar
  • 61 Rodrigo R, Rivera G. Renal damage mediated by oxidative stress: a hypothesis of protective effects of red wine. Free Radic Biol Med 2002; 33 (03) 409-422
    CrossrefPubMedSearch in Google Scholar
  • 62 Dennery PA. Oxidative stress in development: nature or nurture?. Free Radic Biol Med 2010; 49 (07) 1147-1151
    CrossrefPubMedSearch in Google Scholar
  • 63 Araujo Guedes RC, de Alburquerque Paiva AM, Amâncio-dos-Santos A, Vieira-Filho LD, Oliveira da Paixão AD. On some physiological aspects of ethanol repercussion on neural and cardiorenal functions. Cent Nerv Syst Agents Med Chem 2009; 9 (04) 277-288
    CrossrefPubMedSearch in Google Scholar
  • 64 Hawkesworth S, Wagatsuma Y, Kahn AI. et al. Combined food and micronutrient supplements during pregnancy have limited impact on child blood pressure and kidney function in rural Bangladesh. J Nutr 2013; 143 (05) 728-734
    CrossrefPubMedSearch in Google Scholar