The first thousand days of life are the basis of metabolic programming. How to help with artifi cial feeding?

   Background. The first year of a baby's life is a unique period. Growth rates at this age are very high. There is also intensive formation of the entire body, including the gastrointestinal tract; under these conditions, the process of formation of microbiota also occurs, which has a decisive influence on the digestibility of nutrients, the state of the immune system, nervous and other systems. This period of time provides the greatest opportunity to provide optimal nutrition for the normal development of the child, being, in fact, an open ″window of opportunity.″ The most important epigenetic factors that determine the expression of certain genes and, accordingly, human health are nutrition, stress, physical activity and the environment. Epigenetics is the science of the inherited properties of an organism that are not associated with changes in the actual nucleotide sequence of DNA and can be encoded not directly, but indirectly in the genome. Within the framework of the concept of nutritional programming, normalization of the body weight of the expectant mother and nutritious nutrition with sufficient amounts of macro- and micronutrients are extremely important factors determining the health of the child. Breastfeeding provides the best nutrition for the infant in terms of proper development and epigenetic effects. Breast milk has an optimal composition and maximum bioavailability of all its constituent substances. Unfortunately, there are a number of objective reasons that limit or make breastfeeding impossible. In such cases, the child is fed with adapted milk formulas based on cow's or goat's milk. For artificial feeding, it is necessary to choose modern, high-quality formulas that are as close as possible in composition to breast milk and selected individually, taking into account the child’s condition.

   Results. According to many studies, goat's milk has some features that make it more similar to human milk, unlike cow's milk, and make the use of mixtures based on it attractive. Goat's milk, like human milk, contains exclusively A2 β-casein. The existing difference in the protein components of cow's and goat's milk contributes to easier digestion of mixtures based on goat's milk, facilitating the absorption of epigenetically significant nutrients. The milk formulas of the mixture based on goat's milk are enriched with a unique fat complex containing 42 % β-palmitate, which makes the digestibility of the mixtures even closer to breast milk. The process of metabolic programming is influenced by the state of the infant's intestinal microbiota. High levels of β-palmitate have a beneficial effect on the development of microbiota in formulafed infants and promote healthy metabolic programming. The most important prebiotic, substrate and carbon source for the growth of normal microflora in the infant’s intestines are breast milk oligosaccharides. The content of oligosaccharides in goat's milk is significantly lower than in women's milk (about 0.25-0.3 g/l), but higher than in cow's milk (0.03-0.04 g/l). Goat milk contains at least 14 oligosaccharides, some with molecular similarities, and 5 of them are completely identical to the oligosaccharides of breast milk and have similar beneficial effects. Thus, goat milk is an attractive natural source of oligosaccharides for the production of quality infant formulas.

1. The first thousand days of child development and nutritional programming: is it real? Genetics in the hands of pediatricians. Meditsinskiy sovet. 2020; (1): 15-22. doi: 10.21518/2079-701X-2020-1-15-22. (In Russ.)

2. Volobuyev A. N., Romanchuk N. P., Bulgakova S. V. Neurogenetics of the brain: sleep and human longevity. Byulleten' nauki i praktiki. 2021; 3 (7). doi: 10.33619/2414-2948/64. (In Russ.)

3. Sarah Cusick, Georgieff M. K. The first 1,000 days of life: The brain’s window of opportunity. https://www.unicef-irc.org/article/958-the-first-1000-days-of-life-the-brains-window-of-opportunity.html.

4. Kamalova A. A. Modern approaches to the prevention of obesity in children. Ros. vestnik perinatol. i pediatr. 2016; 61 (6): 43-48. DOI: 10.21508/1027-4065-2016-61-6-43-48. (In Russ.)

5. Maksimenko L. V. Epigenetics as an evidence base for the influence of lifestyle on health and disease. Profilakticheskaya meditsina. 2019; 22 (2): 115 120. doi: 10.17116/profmed201922021115. (In Russ.)

6. Lukoyanova O. L., Borovik T. E. Nutritional epigenetics and epigenetic effects of breast milk. Vopr. pitaniya. 2015; 5: 4-15. (In Russ.)

7. Romantsova T. I. Obesity epidemic: obvious and probable causes. Ozhireniye i metabolizm. 2011; 51: 5-19. (In Russ.)

8. Healthy maternal nutrition: a better start in life. Vsemirnaya organizatsiya zdravookhraneniya, 2016. (In Russ.)]

9. Robinson S., Crozier S., Harvey N., et al. Modifiable early-ife risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention. Am J Clin Nutr. 2015; 101: 368-375.

10. Klimov L. Ya. et al. The role of maternal endocrine pathology in the pathogenesis of disorders of intrauterine and postnatal development of children: a modern view within the framework of the concept of nutritional programming (literature review). doi: 10.21518/2079-701X-2018-17-38-46. (In Russ.)

11. Bel'mer S. V. Particular issues of food programming: fetal programming. Voprosy detskoy diyetologii. 2016; 14 (1): 26-31. (In Russ.)

12. Program for optimizing feeding of children in the first year of life in the Russian Federation. Metodicheskiye rekomendatsii. M., 2019 g. (In Russ.)

13. Gromova O. A., Torshin I. Yu., Sonina N. P., Kerimkulova N. V. How much omega-3 PUFA should be prescribed to a pregnant woman? About preventive, therapeutic and excess dose. On the dosage of omega-3 PUFAs for somatic and obstetric pathologies. Issues of effectiveness and safety. Zemskiy Vrach. 2013; 3 (20). (In Russ.)

14. Donnet-Hughes A., et al. Bioactive molecules in milk and their role in health and disease: the role of transforming growth factor-beta. Immunol. Cell Biol. 2000; 78: 74-79.

15. Karatas Z., Durmus Aydogdu S., Dinleyici E. C., et al. Breastmilk ghrelin, leptin, and fat levels changing foremilk to hindmilk: is that important for self-control of feeding? Eur J Pediatr. 2011; 170 (10): 1273-1280. doi: 10.1007/s00431-011-1438-1.

16. Ukraintsev S. Ye., Samal' T. N. Breast milk as we did not know it: chronobiology of breast milk. Voprosy sovremennoy pediatrii. 2018; 17 (2): 148-151. DOI: 10.15690/vsp.v17i2.1881. (In Russ.)

17. Lukoyanova O. L. Scientific substantiation and development of new technologies for organizing and supporting breastfeeding : dissertation ... d. m. n.: 14.01.08, 2017. P. 259. (In Russ.)

18. Kazyukova T. V., Il'yenko L. I., Kotlukov V. K. Goat’s milk in the nutrition of infants and young children. Pediatriya. 2017; 96 (1): 75-82. (In Russ.)

19. Geppe N. A., Meleshkina A. V., Yablokova Ye. A., Chebysheva S. N. Advantages of adapted formulas based on goat milk for functional disorders of the gastrointestinal tract in bottle-fed infants. The Lechaschi Vrach Journal. 2020; 3: 43-49. DOI: 10.26295/OS.2020.72.94.007. (In Russ.)

20. Koletzko B., Chourdakis M., Grote V., et al. Regulation of early human growth: impact on long-term health. Ann Nutr Metab. 2014; 65: 99-107.

21. Zakharova I. N., Dmitriyeva Yu. A., Gordeyeva Ye. A. Improving infant formula – on the way to approaching human milk. Meditsinskiy sovet. 2016; 1. (In Russ.)

22. Ryumina I. I. Mixtures based on goat’s milk when choosing artificial feeding of a newborn and a child of the first year of life. Meditsinskiy sovet. 2021; 1: 30-36. (In Russ.)

23. Komarova O. N. Possible benefits of whole goat milk in infant formula for a healthy child. The Lechaschi Vrach Journal. 2021; 9 (24): 9-14. DOI: 10.51793/OS.2021.24.9.002. (In Russ.)

24. Khavkin A. I., Vasina M. N., Novikova V. P. Biological role of casomorphins (part 1). Eksperimental'naya i klinicheskaya gastroenterologiya. 2021; 196 (12): 102-109. DOI: 10.31146/1682-8658-ecg-196-12-102-109. (In Russ.)

25. Jung T. H., Hwang H. J., Yun S. S., Lee W. J., Kim J. W., Ahn J. Y., Jeon W. M., Han K. S. Hypoallergenic and Physicochemical Properties of the A2 β-Casein Fractionof Goat Milk. Korean J Food SciAnimResour. 2017; 37 (6): 940-947. DOI: 10.5851/kosfa.2017.37.6.940.

26. Annet Maathuis, Robert Havenaar, Tao He, Susann Bellmann. Protein Digestionand Quality of Goat and Cow Milk Infant Formula and Human Milk Under Simulated Infant Conditions. Journal of Pediatric Gastroenterology and Nutrition. 2017; 6 (65).

27. Federal clinical guidelines for the provision of medical care to children with allergies to cow's milk proteins, 2015. (In Russ.)

28. EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy. Allergy. 2014; 69: 590-601.

29. Geppe N. A., Velikoretskaya M. D., Shatalina S. I., Aksenova M. B., Venerin A. A., Polyanskaya A. V., Chebysheva S. N. Alternative introduction of infant formula based on goat milk: discoveries and prospects. The Lechaschi Vrach Journal. 2022; 5-6 (25): 46-53. DOI: 10.51793/OS.2022.25.6.008. (In Russ.)

30. Merenkova S. P. Physiological significance of the nutrient composition of adapted milk formulas. Vestnik YUUrGU. 2013; 1 (1): 56-62 (In Russ.)

31. Suganuma Tamaki, Workman J. L. Nucleotide Metabolism Behind Epigenetics. Frontiers in endocrinology. 2021; 12: 731648. DOI: 10.3389/fendo.2021.731648.

32. Meleshkina A. V., Geppe N. A., Chebysheva S. N., Velikoretskaya M. D., Dagbayeva D. V. Immunity, breast milk and infant formula: searching for the optimal balance. Pediatriya. Consilium Medicum. 2021; 2: 177-184. (In Russ.)

33. Komarova O. N. The influence of the fat component of mixtures on the development of a child. The Lechaschi Vrach Journal. 2013; 7: 76. (In Russ.)

34. Borovik T. E., Semenova N. N., Lukoyanova O. L., Zvonkova N. G., Skvortsova V. A., Zakharova I. N., Stepanova T. N. On the issue of the possibility of using goat milk and adapted mixtures based on it in baby food. Issues of modern pediatrics. Voprosy sovremennoy pediatrii. 2013; 12 (1): 8-16. doi: 10.15690/vsp.v12i1.553. (In Russ.)

35. Bar-Yoseph F., Lifshitz Y., Cohen T., Malard P., Li Z., et al. SN2-Palmitate Im-proves Crying and Sleep in Infants Fed Formula with Prebiotics: A Double-Blind Randomized Clinical Trial. Clinics Mother Child Health. 2017; 14: 263. DOI: 10.1097/MPG.0000000000000971.

36. Gladyshev M. I. Essential polyunsaturated fatty acids and their food sources for humans. Journal of Siberian Federal University. Biology 4. 2012; 5: 352-386. (In Russ.)

37. Price P. T., Nelson C. M., Clarke S. D. Omega-3 polyunsaturated fatty acid regulation of gene expression. Curr Opin Lipidol. 2000; 11 (1): 3-7. DOI: 10.1097/00041433-200002000-00002.

38. Kulikov V. A., Grebennikov I. N. Resolvins, protectins and maresins are new mediators of inflammation. Vestnik VGMU. 2012; 1 (11). (In Russ.)

39. Hoffman D. R., Boettcher J. A., Diersen-Schade D. A. Toward optimizing vision and cogni-tion in term infants by dietary docosahexaenoic and arachidonic acid supplementation: A review of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2009; 81: 151-158.

40. Prentice P. M., Schoemaker M. H., Vervoort J., Hettinga K., Lambers T. T., van Tol E. A. F. Acerini C. L., Olga L., Petry C. J., Hughes I. A., et al. Human milk shortchain fatty acid composition is associated with adiposity in infants. J. Nutr. 2019; 149: 716-722.

41. Kozhevnikov A. A., Raskina K. V., Martynova Ye. Yu. et al. Intestinal microbiota: modern ideas about species composition, functions and research methods. RMJ. 2017; 17: 1244-1247. (In Russ.)

42. Abdullayeva G. D., Aminova A. I., Prodeus A. P. i dr. On the role of intestinal microbiota in the development of food allergies from the perspective of modern intestinal microbiology. Voprosy detskoy diyetologii. 2019; 17 (5): 62-69. (In Russ.)

43. Bliss E. S., Whiteside E. The Gut-Brain Axis, the Human Gut Microbiota and Their Inte-gration in the Development of Obesity. FrontPhysiol. 2018; 9: 900. DOI: 10.3389/fphys.2018.00900. PMID: 30050464; PMCID: PMC6052131.

44. Khavkin A. I., Bogdanova N. M., Novikova V. P. The biological role of zonulin and the effectiveness of its use as a biomarker of leaky intestinal syndrome. Ros. vestn. perinatol. i pediatr 2021; 66 (1): 31-38. DOI: 10.21508/1027-4065-2021-66-1-31-38. (In Russ.)

45. Nikolayeva I. V., Tsaregorodtsev A. D., Shaykhiyeva G. S. Formation of a child’s intestinal microbiota and factors influencing this process. Ros. vestn. perinatol. i pediatr. 2018; 63 (3): 13-18. DOI: 10.21508/1027-4065-2018-63-3-13-18. (In Russ.)

46. Alessandra Consales идр.The hidden universe of human milk microbiome: origin, composition, determinants, role, and future perspectives European Journal of Pediatrics. 2022; 181: 1811-1820. doi: 10.1007/s00431-022-04383-1.

47. Wang L., Bravo-Ruiseco G., Happe R., He T., van Dijl J. M., Harmsen H. J. M. The effect of calcium palmitate on bacteria associated with infant gut microbiota. Microbiologyopen. 2021; 10 (3): e1187. DOI: 10.1002/mbo3.1187.

48. Menni C., Zierer J., Pallister T., Jackson M. A., Tao Long, Mohney R. P., Steves C. J., Spector T. D., Valdes A. M. Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women Scientific Reports 7, Article number: 11079, 2017.

49. Donovan S. M., Comstock S. S. Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity. Ann Nutr Metab. 2016; 69 Suppl. 2 (Suppl. 2): 42-51. DOI: 10.1159/000452818.

50. Daddaoua A., Puerta V., Requena P., et al. Goat milk oligosaccharides are anti-inflammatory in rats with hapten-induced colitis. J Nutr. 2006; 136 (3): 672-676. DOI: 10.1093/jn/136.3.672.

51. Steenhout P., Sperisen P., Martin F.-P., et al. Term infant formula supplemented with human milk oligosaccharides (2' fucosyllactose and lacto-N-neotetraose) shifts stool mi-crobiota and metabolic signatures closer to that of breastfed infants. FASEB J. 2016; 30 (Suppl. 1): 275-277.

52. Andreyeva I. V., Stetsyuk O. U. Efficacy and safety of the combination of Lactobacillus acidophilus LA5 and Bifidobacterium lactis BB-12. Klin. mikrobiol. antimikrob. khimioter. 201; 2 (18). (In Russ.)

53. Chen Y. L., Liao F. H., Lin S. H., Chien Y. W. A Prebiotic Formula Improves the Gastrointes-tinal Bacterial Flora in Toddlers. Gastroenterol Res Pract. 2016; 2016: 3504282.

54. He T., Woudstra F., Panzer F., Haandrikman A., Verkade H. J. , van Lee L. Goat Milk Based Infant Formula in Newborns: A Double-Blind Randomized Controlled Trial on Growth and Safety. J Pediatr Gastroenterol Nutr. 2022; 75 (2): 215-220. DOI: 10.1097/MPG.0000000000003493.

55. Diet of a nursing mother: what a pediatrician should and can recommend. Overview of an educational online seminar. Review of the speech by I. N. Zakharova, A. E. Kuchina. Pediatriya. Consilium Medicum. 2020; 3: 20-27. URL: https://cyberleninka.ru/article/n/dieta-kormyaschey-mamy-chto-dolzhen-i-mozhet-rekomendovat-pediatr-obzor-obrazovatelnogo-onlayn-seminara?ysclid=lq276w1y6c808130653. (In Russ.)

56. Fidler Mis N., Braegger C., Bronsky Ji. at all. Sugar in Infants, Children and Adolescents: A Position Paper of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. Journal of Pediatric Gastroenterology and Nutrition. 2017; 6 (65): 681-696. DOI: 10.1097/MPG.0000000000001733.