Хронические болезни взрослых запрограммированы в детском возрасте?

Условия развития человека на этапах раннего онтогенеза имеют большое значение для его здоровья на протяжении всей дальнейшей жизни. Период внутриутробного развития и детство представляют собой уязвимые стадии формирования организма, когда метаболические процессы имеют наибольшую пластичность и могут быть подвержены деформации. Воздействие ряда внешних факторов в этот период времени способно оказать существенное влияние на функциональную активность генов, контролирующих нейротрансмиссию, иммунный ответ, эндокринные функции и тем самым запрограммировать спектр метаболических нарушений, которые могут привести впоследствии к формированию хронических заболеваний: ожирения, сахарного диабета второго типа, атеросклероза и болезней сердечно-сосудистой системы. Отрицательное программирующее влияние на метаболический профиль и сердечно-сосудистый риск оказывают такие факторы, как материнское ожирение, осложненное течение беременности и родов, недоношенность, ранняя разлука с матерью, нарушение вскармливания ребенка на 1-м году жизни. Риск раннего развития сердечно-сосудистых заболеваний, метаболического синдрома, ожирения и сахарного диабета значительно возрастает у лиц, перенесших в детском возрасте травмирующие стрессовые воздействия, связанные с экономическим неблагополучием семьи, разводом родителей, безнадзорностью, жестоким обращением, родительским неглектом, сексуальным насилием, смертью родителей, членов семьи, близких друзей, буллингом в детском коллективе. Глубокое изучение данной проблемы, наряду с разработкой и организацией мероприятий по мониторингу и профилактике, в перспективе может снизить бремя хронических неинфекционных заболеваний, улучшить качество жизни, уменьшить потери трудоспособности, инвалидизацию и смертность во взрослой популяции. 

1. Montazeri P., Vrijheid M., Martinez D., Basterrechea M., FernandezSomoano A., Guxens M. et al. Maternal metabolic health parameters during pregnancy in relation to early childhood BMI trajectories. Obesity (Silver Spring). 2018;26(3):588–596. https://doi.org/10.1002/oby.22095.

2. Chang R., Mei H., Zhang Y., Xu K., Yang S., Zhang J. Early childhood body mass index trajectory and overweight/obesity risk differed by maternal weight status. Eur J Clin Nutr. 2021. https://doi.org/10.1038/s41430-021-00975-6.

3. Kaseva N., Vääräsmäki, M., Matinolli, H.-M., Sipola-Leppänen M., Tikanmäki M., Heinonen K. et al. Pre-pregnancy overweight or obesity and gestational diabetes as predictors of body composition in offspring twenty years later: evidence from two birth cohort studies. Int J Obes (Lond). 2018;42(4):872–879. https://doi.org/10.1038/ijo.2017.277.

4. Gaillard R., Welten M., Oddy W.H., Beilin L.J., Mori T.A., Jaddoe V.W.V., Huang R.-C. Associations of maternal prepregnancy body mass index and gestational weight gain with cardio‐metabolic risk factors in adolescent offspring: a prospective cohort study. BJOG. 2016;123(2):207–216. https://doi.org/10.1111/1471-0528.13700.

5. Johns E.C., Denison F.C., Reynolds R.M. The impact of maternal obesity in pregnancy on placental glucocorticoid and macronutrient transport and metabolism. Biochim Biophys Acta Molecular Basis Dis. 2020;1866(2):165374. https://doi.org/10.1016/j.bbadis.2018.12.025.

6. Shrestha A., Prowak M., Berlandi-Short V.-M., Garay J., Ramalingam L. Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring. Front Cardiovasc Med. 2021;8:696812. https://doi.org/10.3389/fcvm.2021.696812.

7. Pullar J., Wickramasinghe K., Demaio A.R., Roberts N., Perez-Blanco K.-M., Noonan K., Townsend N. The impact of maternal nutrition on offspring’s risk of non-communicable diseases in adulthood: a systematic review. J Glob Health. 2019;9(2):020405. https://doi.org/10.7189/jogh.09.020405.

8. Lumey L.H., Stein A.D., Kahn H.S., van der Pal-de Bruin K.M., Blauw G.J., Zybert P.A., Susser E.S. Cohort profile: the Dutch Hunger Winter families study. Int J Epidemiol. 2007;36(6):1196–1204. https://doi.org/10.1093/ije/dym126.

9. Lumey L.H., van Poppel F.W.A. The Dutch famine of 1944–1945 as a human laboratory: Changes in the early life environment and adult health. In: Early life nutrition and adult health and development. New-York: Nova Science Publishers; 2013. 59–76 p. Available at: https://research.rug.nl/en/publications/the-dutch-famine-of1944-45-as-a-human-laboratory-changes-in-the-.

10. Lumey L.H., Ekamper P., Bijwaard G., Conti G., van Poppel F. Overweight and obesity at age 19 after pre-natal famine exposure. Int J Obes (Lond). 2021;45(8):1668–1676. https://doi.org/10.1038/s41366-021-00824-3.

11. Li C., Lumey L.H. Exposure to the Chinese famine of 1959–1961 in early life and long-term health conditions: a systematic review and meta-analysis. Int J Epidemiol. 2017;46(4):1157–1170. https://doi.org/10.1093/ije/dyx013.

12. Lumey L.H., Khalangot M.D., Vaiserman A.M. Association between type 2 diabetes and prenatal exposure to the Ukraine famine of 1932– 1933: a retrospective cohort study. Lancet Diabetes Endocrinol. 2015;3(10):787–794. https://doi.org/10.1016/S2213-8587(15)00279-X.

13. Stanner S.A., Do Bulmer K., Andrès C., Lantseva O.E., Borodina V., Poteen V.V., Yudkin J.S. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. BMJ. 1997;315(7119):1342–1348. https://doi.org/10.1136/bmj.315.7119.1342.

14. Могучая Е.В., Ротарь О.П., Конради А.О. Внутриутробное голодание и риск артериальной гипертензии и сердечно-сосудистых осложнений. Артериальная гипертензия. 2013;19(4):299–304. https://doi.org/10.18705/1607-419X-2013-19-4-203-213.

15. Квиткова Л.В., Смакотина С.А., Сотникова Ю.М. Истоки ожирения у взрослых: роль антенатального и раннего постнатального периодов. Эндокринология: новости, мнения, обучение. 2019;8(2):67–73. https://doi.org/10.24411/2304-9529-2019-12008.

16. Alsnes I.V., Vatten L.J., Fraser A., Bjørngaard J.H., Rich-Edwards J., Romundstad P.R., Åsvold B.O. Hypertension in pregnancy and offspring cardiovascular risk in young adulthood: prospective and sibling studies in the HUNT study (Nord-Trøndelag Health Study) in Norway. Hypertension. 2017;69(4):591–598. https://doi.org/10.1161/HYPERTENSIONAHA.116.08414.

17. Crispi F., Miranda J., Gratacós E. Long-term cardiovascular consequences of fetal growth restriction: biology, clinical implications, and opportunities for prevention of adult disease. Am J Obstet Gynecol. 2018;218(2S): S869–S879. https://doi.org/10.1016/j.ajog.2017.12.012.

18. Rogers J.M. Smoking and pregnancy: Epigenetics and developmental origins of the metabolic syndrome. Birth Defects Res. 2019;111(17): 1259–1269. https://doi.org/10.1002/bdr2.1550.

19. Lamichhane N., Olsen N.J., Mortensen E.L., Obel C., Heitmann B.L., Hände M.N. Associations between maternal stress during pregnancy and offspring obesity risk later in life – A systematic literature review. Obes Rev. 2020;21(2):e12951. https://doi.org/10.1111/obr.12951.

20. Markopoulou P., Papanikolaou E., Analytis A., Zoumakis E., Siahanidou T. Preterm birth as a risk factor for metabolic syndrome and cardiovascular disease in adult life: a systematic review and meta-analysis. J Pediatr. 2019;210:69–80.e5. https://doi.org/10.1016/j.jpeds.2019.02.041.

21. Wang J., Perona J.S., Schmidt-RioValle J., Chen Y., Jing J., GonzálezJiménez E. Metabolic syndrome and its associated early-life factors among Chinese and Spanish adolescents: A pilot study. Nutrients. 2019;11(7);1568. https://doi.org/10.3390/nu11071568.

22. Wisnieski L., Kerver J., Holzman C., Todem D., Margerison-Zilko C. Breastfeeding and risk of metabolic syndrome in children and adolescents: a systematic review. J Hum Lact. 2018;34(3):515–525. https://doi.org/10.1177/0890334417737038.

23. Karatekin C., Hill M. Expanding the original definition of adverse childhood experiences (ACEs). J Child Adolesc Trauma. 2018;12(3):289–306. https://doi.org/10.1007/s40653-018-0237-5.

24. Noll J.G., Shalev I. (eds.) The biology of early life stress: understanding child maltreatment and trauma. Springer; 2018. 162 p. https://doi.org/10.1007/978-3-319-72589-5.

25. Felitti V.J., Anda R.F., Nordenberg D., Williamson D.F., Spitz A.M., Edwards V. et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245–258. https://doi.org/10.1016/S0749-3797(98)00017-8.

26. Bush N.R., Savitz J., Coccia M., Jones-Mason K., Adler N., Boyce W.T. et al. Maternal stress during pregnancy predicts infant infectious and noninfectious illness. J Pediatr. 2021;228:117–125.e2. https://doi.org/10.1016/j.jpeds.2020.08.041.

27. Gonzalez A., Catherine N., Boyle M., Jack S.M., Atkinson L., Kobor M. et al. Healthy Foundations Study: a randomised controlled trial to evaluate biological embedding of early-life experiences. BMJ Open. 2018;8(1):e018915. https://doi.org/10.1136/bmjopen-2017-018915.

28. Leeb R.T., Paulozzi L., Melanson C., Simon T., Arias I. Child maltreatment surveillance: Uniform definitions for public health and recommended data elements. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2008. 148 p. Available at: https://www.cdc.gov/violenceprevention/pdf/cm_surveillance-a.pdf.

29. Jakubowski K.P., Cundiff J.M., Matthews K.A. Cumulative childhood adversity and adult cardiometabolic disease: A meta-analysis. Health Psychol. 2018;37(8):701–715. https://doi.org/10.1037/hea0000637.

30. Price J., Kassam-Adams N., Alderfer M.A., Christofferson J., Kazak A.E. Systematic review: A reevaluation and update of the integrative (trajectory) model of pediatric medical traumatic stress. J Pediatr Psychol.2016;41(1):86–97. https://doi.org/10.1093/jpepsy/jsv074.

31. Liossi C., Howard R.F. Pediatric chronic pain: biopsychosocial assessment and formulation. Pediatrics.2016;138(5):e20160331. https://doi.org/10.1542/peds.2016-0331.

32. McCrae J.S., Bender K., Brown S.M., Phillips J.D., Rienks S. Adverse childhood experiences and complex health concerns among child welfare-involved children. Children’s Health Care. 2019;48(1):38–58. https://doi.org/10.1080/02739615.2018.1446140.

33. Afifi T.O., MacMillan H.L., Boyle M., Cheung K., Taillieu T., Turner S., Sareen J. Child abuse and physical health in adulthood. 2016;27(3):10–18. Available at: https://pubmed.ncbi.nlm.nih.gov/26983007/.

34. Suglia S.F., Koenen K.C., Boynton-Jarrett R., Chan P.S., Clark C.J., Danese A. et al. Childhood and adolescent adversity and cardiometabolic outcomes: A scientific statement from the American Heart Association. Circulation.2018;137(5):e15–e28. https://doi.org/10.1161/CIR.0000000000000536.

35. Halonen J.I., Stenholm S., Pentti J., Kawachi I., Subramanian S.V., Kivimäki M., Vahtera J. Childhood psychosocial adversity and adult neighborhood disadvantage as predictors of cardiovascular disease: a cohort study. Circulation. 2015;132(5):371–379. https://doi.org/10.1161/CIRCULATIONAHA.115.015392.

36. Pretty C., O’Leary D.D., Cairney J., Wade T.J. Adverse childhood experiences and the cardiovascular health of children: a cross-sectional study. BMC Pediatr. 2013;13:208. https://doi.org/10.1186/1471-2431-13-208.

37. Hughes K., Bellis M.A., Hardcastle K.A., Sethi D., Butchart A., Mikton C. et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health. 2017;2(8):e356–e366. https://doi.org/10.1016/S2468-2667(17)30118-4.

38. Lin L., Wang H.H., Lu C., Chen W., Guo V.Y. Adverse childhood experiences and subsequent chronic diseases among middle-aged or older adults in china and associations with demographic and socioeconomic characteristics. JAMA Netw Open. 2021;4(10):e2130143. https://doi.org/10.1001/jamanetworkopen.2021.30143.

39. Klassen S.A., Chirico D., O’Leary D.D., Cairney J., Wade T.J. Linking systemic arterial stiffness among adolescents to adverse childhood experiences. Child Abuse Negl. 2016;56:1–10. https://doi.org/10.1016/j.chiabu.2016.04.002.

40. Hakulinen C., Pulkki-Råback L., Elovainio M., Kubzansky L.D., Jokela M., Hintsanen M. et al. Childhood psychosocial cumulative risks and carotid intima-media thickness in adulthood: The Cardiovascular Risk in Young Finns Study. Psychosom Med. 2016;78(2):171–181. https://doi.org/10.1097/PSY.0000000000000246.

41. Renna M.E., Peng J., Shrout M.R., Madison A.A., Andridge R., Alfano C.M. et al. Childhood abuse histories predict steeper inflammatory trajectories across time. Brain Behav Immun. 2021;91:541–545. https://doi.org/10.1016/j.bbi.2020.11.012.

42. Bull M.J., Plummer N.T. Part 1: The human gut microbiome in health and disease. Integr Med (Encinitas). 2014;13(6):17–22. Available at: https://pubmed.ncbi.nlm.nih.gov/26770121/

43. Agorastos A., Pervanidou P., Chrousos G.P., Baker D.G. Developmental trajectories of early life stress and trauma: a narrative review on neurobiological aspects beyond stress system dysregulation. Front Psychiatry. 2019;10:118. https://doi.org/10.3389/fpsyt.2019.00118.

44. Mariani N., Borsini A., Cecil C.A.M., Felix J.F., Sebert S., Cattaneo A. et al. Identifying causative mechanisms linking early-life stress to psycho-cardiometabolic multi-morbidity: The Early Cause project. PloS One. 2021;16(1):e0245475. https://doi.org/10.1371/journal.pone.0245475.

45. van Bodegom M., Homberg J.R., Henckens M.J.A.G. Modulation of the hypothalamic-pituitary-adrenal axis by early life stress exposure. Front Cell Neurosci. 2017;11:87. https://doi.org/10.3389/fncel.2017.00087.

46. Maniam J., Antoniadis C., Morris M.J. Early-life stress, HPA axis adaptation, and mechanisms contributing to later health outcomes. Front Endocrinol (Lausanne). 2014;5:73. https://doi.org/10.3389/fendo.2014.00073.

47. Baumeister D., Akhtar R., Ciufolini S., Pariante C.M., Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. 2016;21(5):642–649. https://doi.org/10.1038/mp.2015.67.

48. Hostinar C.E., Lachman M.E., Mroczek D.K., Seeman T.E., Miller G.E. Additive contributions of childhood adversity and recent stressors to inflammation at midlife: Findings from the MIDUS study. Dev Psychol. 2015;51(11): 1630–1644. https://doi.org/10.1037/dev0000049.

49. Sharp G.C., Salas L.A., Monnereau C., Allard C., Yousefi P., Everson T.M. et al. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium. Hum Mol Gen. 2017;26(20):4067–2085. https://doi.org/10.1093/hmg/ddx290.

50. Alexander N., Kirschbaum C., Wankerl M., Stauch B.J., Stalder T., SteudteSchmiedgen S. et al. Glucocorticoid receptor gene methylation moderates the association of childhood trauma and cortisol stress reactivity. Psychoneuroendocrinology. 2018;90:68–75. https://doi.org/10.1016/j.psyneuen.2018.01.020.

51. Parmar P., Lowry E., Cugliari G., Suderman M., Wilson R., Karhunen V. et al. Association of maternal prenatal smoking GFI1 -locus and cardio-metabolic phenotypes in 18,212 adults. EBioMedicine. 2018;38:206–216. https://doi.org/10.1016/j.ebiom.2018.10.066.

52. Kundakovic M., Gudsnuk K., Herbstman J.B., Tang D., Perera F.P., Champagne F.A. DNA methylation of BDNF as a biomarker of early-life adversity. Proc Natl Acad Sci U S A. 2015;112(22):6807–6813. https://doi.org/10.1073/pnas.1408355111.

53. Eberle C., Fasig T., Brüseke F., Stichling S. Impact of maternal prenatal stress by glucocorticoids on metabolic and cardiovascular outcomes in their offspring: A systematic scoping review. PloS One. 2021;16(1):e0245386. https://doi.org/10.1371/journal.pone.0245386.

54. Ridout K.K., Khan M., Ridout S.J. Adverse childhood experiences run deep: toxic early life stress, telomeres, and mitochondrial DNA copy number, the biological markers of cumulative stress. Bioessays. 2018;40(9):e1800077. https://doi.org/10.1002/bies.201800126.

55. Ashar F.N., Zhang Y., Longchamps R.J., Lane J., Moes A., Grove M.L. et al. Association of mitochondrial DNA copy number with cardiovascular disease. JAMA Cardiol. 2017;2(11):1247–1255. https://doi.org/10.1001/jamacardio.2017.3683.

56. Cowan C.S.M., Stylianakis A.A., Richardson R. Early-life stress, microbiota, and brain development: probiotics reverse the effects of maternal separation on neural circuits underpinning fear expression and extinction in infant rats. Dev Cogn Neurosci. 2019;37:100627. https://doi.org/10.1016/j.dcn.2019.100627.

57. Pusceddu M.M., Aidy S.E., Crispie F., O’Sullivan O., Cotter P., Stanton C. et al. N-3 polyunsaturated fatty acids (PUFAs) reverse the impact of early-life stress on the gut microbiota. PloS One. 2015;10(10):e0139721. https://doi.org/10.1371/journal.pone.0139721.