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Combined effect of folate and adiposity on homocysteine in children at three years of age

  • Cho, Su Jin (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Lee, Hye Ah (Department of Preventive Medicine, Ewha Womans University School of Medicine) ;
  • Park, Bo Hyun (Department of Preventive Medicine, Ewha Womans University School of Medicine) ;
  • Ha, Eun Hee (Department of Preventive Medicine, Ewha Womans University School of Medicine) ;
  • Kim, Young Ju (Department of Obstetrics, Ewha Womans University School of Medicine) ;
  • Park, Eun Ae (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Park, Hyesook (Department of Preventive Medicine, Ewha Womans University School of Medicine)
  • Received : 2015.04.22
  • Accepted : 2015.11.25
  • Published : 2016.02.01

Abstract

BACKGROUND/OBJECTIVES: Cardiovascular diseases is a major cause of death and is responsible for 23.8% of deaths in Korea. Clinical symptoms manifest in adulthood, but susceptibility begins in utero. Elevated homocysteine levels and adiposity might be linked to a greater risk in children as well as adults. We hypothesized that those who have simultaneous risk for folate and adiposity would be affected with elevated homocysteine levels at 3 years of age. SUBJECTS/METHODS: From the ongoing birth cohort at Ewha Womans University Mok-Dong Hospital, we compared adiposity parameters, serum homocysteine, and folate levels in 238 children (118 boys and 120 girls) at three years of age. The relationship between birth outcome, current weight and body mass index (BMI), postnatal growth, and homocysteine level were assessed using correlation and general linear model. Additionally, we assessed the combined effect between blood folate status and adiposity on current homocysteine levels. RESULTS: Birth characteristics were not correlated with homocysteine. Current weight, BMI, upper-arm circumference, skinfold thickness, waist circumference, and hip circumference were positively correlated with homocysteine at three years of age (P < 0.05). Folate level was negatively correlated with homocysteine at three years of age (P < 0.0001). A relative high anthropometric measure which is compatible with adiposity and low folate level was associated with high homocysteine levels. CONCLUSION: We found a combined effect of adiposity and folate levels with homocysteine levels at three years of age. This implicates the beneficial role of folate supplementation in the high-risk population at an early age.

Keywords

References

  1. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801-9. https://doi.org/10.1038/362801a0
  2. Burke V. Obesity in childhood and cardiovascular risk. Clin Exp Pharmacol Physiol 2006;33:831-7. https://doi.org/10.1111/j.1440-1681.2006.04449.x
  3. Berenson GS, Wattigney WA, Tracy RE, Newman WP 3rd, Srinivasan SR, Webber LS, Dalferes ER Jr, Strong JP. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study). Am J Cardiol 1992;70:851-8. https://doi.org/10.1016/0002-9149(92)90726-F
  4. Barker DJ, Osmond C, Forsen TJ, Kajantie E, Eriksson JG. Trajectories of growth among children who have coronary events as adults. N Engl J Med 2005;353:1802-9. https://doi.org/10.1056/NEJMoa044160
  5. Huxley RR, Shiell AW, Law CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 2000;18:815-31. https://doi.org/10.1097/00004872-200018070-00002
  6. American Academy of Pediatrics. Cardiovascular risk reduction in high-risk pediatric populations. Pediatrics 2007;119:618-21. https://doi.org/10.1542/peds.2006-3557
  7. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990;1:228-37. https://doi.org/10.1016/0955-2863(90)90070-2
  8. Groner JA, Joshi M, Bauer JA. Pediatric precursors of adult cardiovascular disease: noninvasive assessment of early vascular changes in children and adolescents. Pediatrics 2006;118:1683-91. https://doi.org/10.1542/peds.2005-2992
  9. Jakubowski H. Pathophysiological consequences of homocysteine excess. J Nutr 2006;136:1741S-1749S. https://doi.org/10.1093/jn/136.6.1741S
  10. Haim M, Tanne D, Goldbourt U, Doolman R, Boyko V, Brunner D, Sela BA, Behar S. Serum homocysteine and long-term risk of myocardial infarction and sudden death in patients with coronary heart disease. Cardiology 2007;107:52-6. https://doi.org/10.1159/000093697
  11. Tonstad S, Refsum H, Sivertsen M, Christophersen B, Ose L, Ueland PM. Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives. Pediatr Res 1996;40:47-52. https://doi.org/10.1203/00006450-199607000-00009
  12. Vilaseca MA, Moyano D, Ferrer I, Artuch R. Total homocysteine in pediatric patients. Clin Chem 1997;43:690-2.
  13. Shen MH, Chu NF, Wu DM, Chang JB. Plasma homocyst(e)ine, folate and vitamin B(12) levels among school children in Taiwan: The Taipei Children Heart Study. Clin Biochem 2002;35:495-8. https://doi.org/10.1016/S0009-9120(02)00344-2
  14. Leal AA, Palmeira AC, Castro GM, Simoes MO, Ramos AT, Medeiros CC. Homocysteine: cardiovascular risk factor in children and adolescents? Rev Assoc Med Bras 2013;59:622-8. https://doi.org/10.1016/j.ramb.2013.05.004
  15. Min JW, Kong KA, Park BH, Hong JH, Park EA, Cho SJ, Ha EH, Park H. Effect of postnatal catch-up growth on blood pressure in children at 3 years of age. J Hum Hypertens 2007;21:868-74. https://doi.org/10.1038/sj.jhh.1002215
  16. Korea Center for Disease Control and Prevention; Korean Pediatric Society. 2007 Korean Children and Adolescents Growth Standard; 2008 [cited 2013 July 10]. Available from: http://www.cdc.go.kr/CDC/notice/CdcKrInfo0301.jsp?menuIds=HOME001-MNU0004-MNU0036-MNU0037&cid=12103.
  17. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Biomed Sci Appl 1987;422: 43-52. https://doi.org/10.1016/0378-4347(87)80438-3
  18. World Health Organization (CH). Serum and Red Blood Cell Folate Concentrations for Assessing Folate Status in Populations. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization; 2012.
  19. Fukagawa NK, Martin JM, Wurthmann A, Prue AH, Ebenstein D, O'Rourke B. Sex-related differences in methionine metabolism and plasma homocysteine concentrations. Am J Clin Nutr 2000;72:22-9. https://doi.org/10.1093/ajcn/72.1.22
  20. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG, Group MS; MTHFR Studies Collaboration Group. MTHFR 677C-->T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288:2023-31. https://doi.org/10.1001/jama.288.16.2023
  21. Humphrey LL, Fu R, Rogers K, Freeman M, Helfand M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc 2008;83:1203-12. https://doi.org/10.4065/83.11.1203
  22. Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993;341:938-41. https://doi.org/10.1016/0140-6736(93)91224-A
  23. Leeson CP, Whincup PH, Cook DG, Donald AE, Papacosta O, Lucas A, Deanfield JE. Flow-mediated dilation in 9- to 11-year-old children: the influence of intrauterine and childhood factors. Circulation 1997;96:2233-8. https://doi.org/10.1161/01.CIR.96.7.2233
  24. Bergen NE, Jaddoe VW, Timmermans S, Hofman A, Lindemans J, Russcher H, Raat H, Steegers-Theunissen RP, Steegers EA. Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study. BJOG 2012;119:739-51. https://doi.org/10.1111/j.1471-0528.2012.03321.x
  25. Ouyang F, Parker M, Cerda S, Pearson C, Fu L, Gillman MW, Zuckerman B, Wang X. Placental weight mediates the effects of prenatal factors on fetal growth: the extent differs by preterm status. Obesity (Silver Spring) 2013;21:609-20. https://doi.org/10.1002/oby.20254
  26. Thornburg KL, O'Tierney PF, Louey S. Review: the placenta is a programming agent for cardiovascular disease. Placenta 2010;31 Suppl:S54-9. https://doi.org/10.1016/j.placenta.2010.01.002
  27. Papandreou D, Mavromichalis I, Makedou A, Rousso I, Arvanitidou M. Total serum homocysteine, folate and vitamin B12 in a Greek school age population. Clin Nutr 2006;25:797-802. https://doi.org/10.1016/j.clnu.2006.02.006
  28. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325:1202-6. https://doi.org/10.1136/bmj.325.7374.1202
  29. Osganian SK, Stampfer MJ, Spiegelman D, Rimm E, Cutler JA, Feldman HA, Montgomery DH, Webber LS, Lytle LA, Bausserman L, Nader PR. Distribution of and factors associated with serum homocysteine levels in children: Child and Adolescent Trial for Cardiovascular Health. JAMA 1999;281:1189-96. https://doi.org/10.1001/jama.281.13.1189
  30. Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 2006;333:1114-7. https://doi.org/10.1136/bmj.39000.486701.68
  31. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-77. https://doi.org/10.1056/NEJMoa060900
  32. Berdanier CD, Feldman EB, Dwyer J. Ch10. Potential benefits for the use of vitamin and mineral supplements. In: Cotter R, Moreines J, Ellenbogen L, editors. Handbook of Nutrition and Food, Second Edition. Boca Raton (FL): CRC Press; 2007. p.200.
  33. Delvin EE, Rozen R, Merouani A, Genest J Jr, Lambert M. Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children. Am J Clin Nutr 2000;72:1469-73. https://doi.org/10.1093/ajcn/72.6.1469
  34. Hong J, Lee HA, Park EA, Kim YJ, Lee H, Park BH, Ha EH, Kong KA, Chang N, Park H. Association of mid-pregnancy antioxidative vitamin and oxidative stress levels with infant growth during the first 3 years of life. Food Nutr Res 2014;58:20207. https://doi.org/10.3402/fnr.v58.20207

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