Фетальное программирование как тренд современной медицины: в фокусе дефицит магния

В последние годы были проведены многочисленные исследования по выявлению роли микроэлементов в патологии и клинической практике. Особое внимание уделяется роли запасов магния у матери во время беременности как ключевого фактора внутриутробного развития плода и в постнатальной жизни, а также последствиям дефицита магния у матери во время беременности на состояние здоровья ребенка при рождении, в детстве и взрослом возрасте. К настоящему времени исследования показали связь между недостаточностью магния и некоторыми состояниями во время беременности, связанными с высокой смертностью и заболеваемостью, такими как гестационный диабет, преждевременные роды, преэклампсия, а также рождение младенцев малых для гестационного возраста или с задержкой внутриутробного развития. Низкие запасы магния у матери во время беременности следует включать в число многочисленных факторов, лежащих в основе фетального программирования заболеваний у взрослых.

1. Hirst J., Villar J., Kennedy S., Bhutta Z. Being born stunted and/or wasted need not be inevitable. International Pediatric Association Newsletter Year 2015. Vol. 10; Issue 1: 9–14.

2. Barker DJP. Mothers, Babies and Health in Later Life. Edinburgh: Churchill Livingstone; 1998. ISBN: 0443061653 (pbk.)

3. Barker DJP. Developmental origins of adult health and disease. Journal of Epidemiology and Community Health. 2004; 58: 114–115.

4. Lawlor DA, Davey Smith G, Ebrahim S. Birth weight is inversely associated with coronary heart disease in post-menopausal women: findings from the British women’s heart and health study. Journal of Epidemiology & Community Health. 2004; 58: 120–125.

5. Evsyukova I. I. Mechanisms of programming diseases of offspring in obstetric pathology. Journal of Obstetrics and Women’s Diseases. 2011; 3: 197–202.

6. Aleksandrova A.A., Gutnikova L.V., Derevyanchuk E.G. Genomic and postgenomic markers of placental and fetal development. Rostov n/d.: Southern Federal University, 2011. Pp. 48–70.

7. Rao Krishna R., Vishnu Bhat B. Molecular mechanisms of intrauterine growth restriction. J. Matern. Fetal Neonatal Med. 2018; 31 (19): 2634–2640.

8. Baker-Anderson D. et al. Dynamic DNA methylation: A prime candidate for genomic metaplasticity and behavioral adaptation. Trends Neurosci. 3–13 (2013).

9. Pilsner R. et al. (2017). Preconception urinary phthalate concentrations and sperm DNA methylation profiles among men undergoing IVF treatment: a cross-sectional study. Human Reproduction. https://doi.org/10.1093/humrep/dex283

10. Dupont C., Kappeler L., Saget S., Grandjean V., Lévy R. Role of miRNA in the Transmission of Metabolic Diseases Associated With Paternal Diet-Induced Obesity. Front. Genet. 2019; 10: 337. DOI: 10.3389/fgene.2019.00337

11. Lan KC, Chiang HJ, Huang TL, Chiou YJ, Hsu TY, Ou YC, Yang YH. Association between paternal age and risk of schizophrenia: a nationwide population-based study. J. Assist Reprod. Genet. 2021 Jan; 38 (1): 85–93. DOI: 10.1007/s10815-020- 01936-x. Epub 2020 Aug 30. PMID: 32862335; PMCID: PMC7822987

12. Day J., Savani S., Krempley B.D., Nguyen M., Kitlinska J.B. Influence of paternal preconception exposures on their offspring: Through epigenetics to phenotype. Am. J. Stem Cells. 2016; 5: 11–18.

13. Dimofski P, Meyre D, Dreumont N, Leininger-Muller B. Consequences of Paternal Nutrition on Offspring Health and Disease. Nutrients. 2021 Aug 17; 13 (8): 2818. DOI: 10.3390/nu13082818. PMID: 34444978; PMCID: PMC8400857

14. Bleker LS, de Rooij SR, Painter RC, Ravelli AC, Roseboom TJ. Cohort profile: the Dutch famine birth cohort (DFBC) – a prospective birth cohort study in the Netherlands. BMJ Open. 2021 Mar 4; 11 (3): e042078. DOI: 10.1136/bmjopen 2020-042078. PMID: 33664071; PMCID: PMC7934722

15. Lussana F, Painter RC, Ocke MC et al. Prenatal exposure to the Dutch famine is associated with a preference for fatty foods and a more atherogenic lipid profile. Am. J. Clin. Nutr. 2008; 88: 1648–52. 10.3945/ajcn.2008.26140PubMed

16. Roseboom TJ, Van Der Meulen JHP, Ravelli ACJ, et al. Perceived health of adults after prenatal exposure to the Dutch famine. Paediatr Perinat Epidemiol 2003; 17: 391–7. DOI: 10.1046/j.1365-3016.2003.00516.x

17. Roseboom TJ, Painter RC, van Abeelen AF, Veenendaal MV, de Rooij SR. 2011 Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas 70; 141–145. doi:10.1016/j.maturitas.2011.06.017

18. Lumey LH, Ravelli AC, Wiessing LG, et al. The Dutch famine birth cohort study: design, validation of exposure, and selected characteristics of subjects after 43 years follow-up. Paediatr Perinat Epidemiol 1993; 7: 354–67. DOI: 10.1111/j.1365- 3016.1993.tb00415.x

19. Орлова С. В., Никитина Е. А. Влияние микронутриентов на фетальное программирование. Медицинский алфавит № 26/2021. Современная гинекология (2). С 14–20.

20. Rueter K, Prescott SL, Palmer DJ. Nutritional approaches for the primary prevention of allergic disease: An update. J Paediatr Child Health. 2015 Oct;51(10):962–9; quiz 968–9. DOI: 10.1111/jpc.12951. Epub 2015 Jul 2. PMID: 26135523.

21. Reynolds LP, Borowicz PP, Caton JS, Crouse MS, Dahlen CR, Ward AK. Developmental Programming of Fetal Growth and Development. Vet Clin North Am Food Anim Pract. 2019 Jul; 35 (2): 229–247. DOI: 10.1016/j.cvfa.2019.02.006. PMID: 31103178

22. Bell A.W., Ehrhardt R.A. Regulation of placental nutrient transport and implications for fetal growth. Nutr. Res. Rev. 2002; 15: 211–230.

23. Marsal K. (2002) Intrauterine growth restriction. Curr. Opin. Obstet. Gynecol.14:127–135

24. Michie C.A. Neural tube defects in 18th century. Lancet. 1991; 337 (8739): 504.

25. Duff E.M. et al. Neural tube defects in hurricane aftermath. Lancet. 1991; 337–20 (8739): 120–121.

26. Takamura N. et al. Abnormal folic acid-homocysteine metabolism as maternal risk factors for Down syndrome in Japan. Eur. J. Nutr. 2004; 43 (5): 285–287.

27. Pace TW et al. Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am. J. Psychiatry. 2006; 163: 1630–1633.

28. Essex MJ, Klein MH, Cho E, Kalin NH. Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior. Biol Psychiatry. 2002 Oct 15; 52 (8): 776–84. PubMed PMID: 12372649

29. Rodríguez-Cano AM, Calzada-Mendoza CC, Estrada-Gutierrez G, Mendoza-Ortega JA, Perichart-Perera O. Nutrients, Mitochondrial Function, and Perinatal Health. Nutrients. 2020 Jul 21; 12 (7): 2166. DOI: 10.3390/nu12072166. PMID: 32708345; PMCID: PMC7401276

30. Komiya Y, Su L-T, Chen H-C, Habas R, Runnels LW (2014). Magnesium and embryonic development. Magnes Res. 27: 1–8. https://doi.org/10.1684/mrh.2014.0356

31. Takaya J, Yamato F, Kaneko K (2006). Possible relationship between low birth weight and magnesium status: from the standpoint of “fetal origin” hypothesis. Magnes Res. 19: 63–69

32. Catling LA, Abubakar I, Lake IR, Swift L, Hunter PR. A systematic review of analytical observational studies investigating the association between cardiovascular disease and drinking water hardness. J. Water Health. 2008 Dec; 6 (4): 433–42. DOI: 10.2166/wh.2008.054. PMID: 18401109

33. Сидельникова В.М. Применение препарата Магне В6 в клинике невынашивания беременности. Акушерство и гинекология. 2002; 6: 47–48. Sidelnikova V.M. Use of Magne B6 in a miscarriage clinic. Obstetrics and gynecology. 2002; 6: 47–48.

34. Makatsaria A.D., Bitsadze V.O., Khizroeva D. Kh., Jobava E.M. Deficiency prevalence magnesium in pregnant women observed in outpatient practice.Question Hynek Akush Perin. 2012; 11 (4).

35. Kovacs C. S., & Ward, L. M. (2020). Disorders of Calcium, Phosphorus, and Bone Metabolism During Fetal and Neonatal Development. Maternal-Fetal and Neonatal Endocrinology, 755–782. doi:10.1016/b978–0–12–814823–5.00045–3

36. Pasternak K., Kocot J., Horecka A. Biochemistry of magnesium. Journal of Elementology. 15 (3/2010): 601–616.

37. Fanni D, Gerosa C, Nurchi VM, Manchia M, Saba L, Coghe F, Crisponi G, Gibo Y, Van Eyken P, Fanos V, Faa G. The Role of Magnesium in Pregnancy and in Fetal Programming of Adult Diseases. Biol Trace Elem Res. 2021 Oct; 199(10): 3647–3657.

38. Viering DHHM, de Baaij JHF, Walsh SB, Kleta R, Bockenhauer D (2017). Genetic causes of hypomagnesemia, a clinical overview. Pediatr Nephrol. 32: 1123–1135.

39. Takaya J. Small for Gestational Age and Magnesium: Intrauterine magnesium deficiency may induce metabolic syndrome in later life. AIMS Public Health. 2015 Dec 4; 2 (4): 793–803. DOI: 10.3934/publichealth.2015.4.793. PMID: 29546136; PMCID: PMC5690443

40. Józefczuk J, Kasprzycka W, Czarnecki R, Graczyk A, Józefczuk P, Magda K, Lampart U. Homocysteine as a Diagnostic and Etiopathogenic Factor in Children with Autism Spectrum Disorder. J. Med. Food. 2017 Aug; 20 (8): 744–749. DOI: 10.1089/ jmf.2016.0150. Epub 2017 Jun 9. PMID: 28598237

41. Serra MJ, Baird JD, Dale T et al. Effects of magnesiumions on the stabilization of RNA oligomers of defined structures. RNA. 2002; 8: 307–323. Hartwig A. Role of magnesium in genomic stability. Mutat Res, 2001 Apr 18; 475 (1–2): 113–21.

42. Durlach J, Pagès N, Bac P, Bara M, Guiet-Bara A (2004). New data on the importance of gestational Mg deficiency. Magnes Res. 17: 116–125.

43. Kwon, E. J., & Kim, Y. J. (2017). What is fetal programming? a lifetime health is under the control of in utero health. Obstetrics & Gynecology Science, 60(6), 506. doi:10.5468/ogs.2017.60.6.506.

44. Venu L, Kishore YD, Raghunath M (2005). Maternal and perinatal magnesium restriction predisposes rat pups to insulin resistance and glucose intolerance. J. Nutr. 135: 1353–1358. https://doi.org/10.1093/jn/135.6.1353

45. Schlegel RN, Spiers JG, Moritz KM, Cullen CL, Björkman ST, Paravicini TM (2017). Maternal hypomagnesemia alters hippocampal NMDAR subunit expression and programs anxiety-like behaviour in adult offspring. Behav Brain Res. 328: 39–47. https://doi.org/10.1016/j.bbr.2017.04.009

46. Тakaya J (2015). Small for Gestational Age and Magnesium: Intrauterine magnesium deficiency may induce metabolic syndrome in later life. AIMS Public. Health. 2: 793–803. https://doi.org/10.3934/publichealth.2015.4.793

47. Takaya J. and Kaneko K. Small for Gestational Age and Magnesium in Cord Blood Platelets: Intrauterine Magnesium Deficiency May Induce Metabolic Syndrome in Later Life. J. Pregnancy. 2011: 1–5. https://doi.org/10.1155/2011/270474

48. Takaya J., Yamato F., Higashino H., Kaneko K. “Intracellular magnesium and adipokines in umbilical cord plasma and infant birth size,” Pediatric Research. 2007; 62 (6): 700–703.

49. Takaya J, Kaneko K (2005) Fetus and magnesium. Clin Calcium 15:105–110 CliCa051118671872

50. Hovdenak N, Haram K (2012). Influence of mineral and vitamin supplements on pregnancy outcome. Eur. J. Obstet. Gynecol. Reprod. Biol. 164: 127–132. https://doi.org/10.1016/j.ejogrb.2012.06.020

51. Makrides M, Crosby DD, Shepherd E, Crowther CA (2014). Magnesium supplementation in pregnancy. Cochrane Database Syst Rev. https://doi. org/10.1002/14651858.CD000937.pub2

52. Schlegel RN, Moritz KM, Paravicini TM (2016). Maternal hypomagnesemia alters renal function but does not program changes in the cardiovascular physiology of adult offspring. J. Dev. Orig. Health. Dis. 7: 473–480. https://doi. org/10.1017/S2040174416000106

53. Lai JS, Cai S, Feng L, Shek LP, Yap F, Tan KH, Chong YS, Godfrey KM, Meaney MJ, Rifkin-Graboi A, Broekman BFP, Chong MFF (2019–07–22). Associations of maternal zinc and magnesium with offspring learning abilities and cognitive development at 4 years in GUSTO. Nutritional Neuroscience. ScholarBank@NUS Repository. https://doi.org/10.1080/1028415X.2019.1643624

54. Орлова С. В., Никитина Е. А., Балашова Н. В., Исаев А.Н., Ершов А. В., Пронина О. Е., Водолазкая А.Н., Прокопенко Е. В. Оценка скрытого дефицита магния у беременных. Медицинский совет. 2022; 16 (5): 104–110. https://doi. org/10.21518/2079-701X 2022-16-5-104-110.

55. Rosanoff A, Wolf FI. A guided tour of presentations at the XIV International Magnesium Symposium. Magnes. Res. 2016 Mar 1; 29 (3): 55–59. DOI: 10.1684/ mrh.2016.0405

56. Walker AF, Marakis G, Christie S, Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnes Res. 2003 Sep; 16 (3): 183–91.

57. Громова О.А. Магний и пиридоксин: основы знаний. ПротоТип, 2006. 234 с. Gromova O. A. Magnesium and pyridoxine: basic knowledge. ProtoTip, 2006. 234 p.

58. Knysheva I. G., Jobava E. M., Dobrokhotova Yu. E. The role of magnesium deficiency in the pathogenesis of gestosis. Russian Bulletin of ObstetricianGynecologist. 2013; 13 (2): 30–35.

59. Unanyan A. L., Sidorova I. S. et al. The role of magnesium in the genesis and prevention of miscarriage. Medical advice. 2017; 9: 76–78. Young GL, Jewell D. Interventions for leg cramps in pregnancy. Cochrane atabase of Systematic Reviews 2002, Issue 1. Art. No.: CD000121. DOI: 10.1002/14651858. CD000121

60. Dalton LM, Ní Fhloinn DM, Gaydadzhieva GT, Mazurkiewicz OM, Leeson H, Wright CP (2016). Magnesium in pregnancy. Nutr. Rev. 74: 549–557. https://doi. org/10.1093/nutrit/nuw018