Prediction of bone metabolism disorders in premature babies

Introduction. Premature newborns suffer from osteopenia, which scientists attribute to vitamin D deficiency. Its deficiency leads to impaired development, the success of which depends on the first years of life. Given the increase in the number of premature babies born after in vitro fertilization, the question arises regarding the risk of them developing vitamin D deficiency.

Aim to establish risk factors and develop prognostic tables for vitamin D deficiency in premature infants of the first three years of life born by in vitro fertilization and naturally.

Materials and methods. We studied premature newborns (n = 189), which we divided into two groups, born by in vitro fertilization and naturally (comparison group). In each group, two subgroups of infants were identified. In the main in vitro fertilization group, the 1st subgroup included newborns weighing 1,000–1,500 g (n = 52), and the 2nd – weighing less than 1,000 g (n = 49). The comparison group included infants born naturally with a body weight of 1,000–1,500 g (n = 46) and those with a body weight of less than 1,000 g (n = 42).

Results. Vitamin D deficiency was established in 67.7 ± 4.8% premature babies during the first year of life. In the second year of life, with intake of vitamin D 1000 IU/day, the level of calcidiol stabilized to normal value. The most sensitive group concerning vitamin D insufficiency is the group of babies with breast-milk substitutes. Factors associated with in vitro fertilization had not shown statistically significant influence on the vitamin D insufficiency in premature babies.

Conclusion. We have proposed beneficial predictive tables for an individual risk evaluation of possible bone metabolic conditions in premature babies.

1. Hartl C., Obermeier V., Gerdes L.A., Brugel M., von Kries R., Kumpfel T. Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients. J Neurol Sci. 2017;(375):160–164. https://doi.org/10.1016/j.jns.2017.01.059.

2. Di Spigna G., Del Puente A., Covelli B., Abete E., Varriale E., Salzano S., Postiglione L. Vitamin D receptor polymorphisms as tool for early screening of severe bone loss in women patients with rheumatoid arthritis. Eur Rev Med Pharmacol Sci. 2016;20(22):4664–4669. Available at: https://pubmed.ncbi.nlm.nih.gov/27906437/.

3. Sahin O.A., Goksen D., Ozpinar A., Serdar M., Onay H. Association of vitamin D receptor polymorphisms and type 1 diabetes susceptibility in children: A meta-analysis. Endocr Connect. 2017;6(3):159–171. https://doi.org/10.1530/EC-16-0110.

4. Zhao D.D., Yu D.D., Ren Q.Q., Dong B., Zhao F., Sun Y.H. Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: A meta-analysis. Pediatr Pulmonol. 2017;52(4):423–429. https://doi.org/10.1002/ppul.23548.

5. Gubatan J., Mitsuhashi S., Zenlea T., Rosenberg L., Robson S., Moss A.C. Low serum vitamin D during remission increases risk of clinical relapse in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2017;15(2):240–246. https://doi.org/10.1016/j.cgh.2016.05.035.

6. Elidrissy A.T. The return of congenital rickets: are we missing occult cases? Calcif Tissue Int. 2016;99(3):227–236. https://doi.org/10.1007/s00223-016-0146-2.

7. Karpen H.E. Mineral homeostasis and effects on bone mineralization in the preterm neonate. Clin Perinatol. 2018;45(1):129–141. https://doi.org/10.1016/j.clp.2017.11.005.

8. Proceedings of the Global Neonatal Consensus Symposium: Feeding The Preterm Infant, 2010, Chicago, Illinois. Guest Ed. R. Uauy. J Pediatr. 2013;162(3):S1–116. Available at: https://pubmed.ncbi.nlm.nih.gov/23620879/.

9. Eichenwald E.C., Hansen A.R., Stark A.R., Martin C.R. Cloherty and Stark’s manual of neonatal care. 8th ed. Wolters Kluwer; 2016. 1124 p. Available at: http://infinity.wecabrio.com/1496343611-cloherty-and-stark-s-manual-of-neonatal-care-8%C2%AA-e.pdf.

10. Onwuneme C., Martin F., McCarthy R., Carroll A., Segurado R. et al. The association of vitamin D status with acute respiratory morbidity in preterm infants. J Pediatr. 2015;166(5):1175–1180. https://doi.org/10.1016/j.jpeds.2015.01.055.

11. Lai S.H., Liao S.L., Tsai M.H., Hua M.C., Chiu C.Y., Yeh K.W. et al. Low cord-serum 25-hydroxyvitamin D levels are associated with poor lung function performance and increased respiratory infection in infancy. PLoS ONE. 2017;12(3):e0173268. https://doi.org/10.1371/journal.pone.0173268.

12. Abrams S.A. Calcium and vitamin D requirements of enterally fed preterm infants. Pediatrics. 2013;131(5):e1676–1683. https://doi.org/10.1542/peds.

13. Faienza M.F., D’Amato E., Natale M.P., Grano M., Chiarito M., Brunetti G., D’Amato G. Metabolic bone disease of prematurity: diagnosis and treatment. Front Pediatr. 2019;(7):143. https://doi.org/10.3389/fped.2019.00143.

14. Klimov L.Y., Zakharova I.N., Kuryaninova V.A., Dolbnya S.V., Arutyunyan T.M., Kasyanova A.N. et al. Vitamin D status in children in the south of Rusia in the autumn-winter period. Meditsinskiy Sovet. 2015;(14):14–19. (In Russ.) https://doi.org/10.21518/2079-701X-2015-14-14-19.

15. Uauy R., Koletzko B. Defining the nutritional needs of preterm infants. World Rev Nutr Diet. 2014;(110):4–10. https://doi.org/10.1159/000358453.

16. Munns C.F., Shaw N., Kiely M., Specker B.L., Thacher T.D., Ozono K. et al. Global consensus recommendations on prevention and management of nutritional rickets. Horm Res Paediatr. 2016;85(2):83–106. https://doi.org/10.1159/000443136.

17. Pfotenhauer K.M., Shubrook J.H. Vitamin D deficiency, its role in health and disease, and current supplementation recommendations. J Am Osteopath Assoc. 2017;117(5):301–305. https://doi.org/10.7556/jaoa.2017.055.

18. Greer F.R. Controversies in neonatal nutrition: macronutrients and micronutrients. Gastroenterology and Nutrition: Neonatology Question and Controversies. 2nd ed. Ed. J. Neu. Philadelphia: Elsevier, Saunders, 2012, рр. 129–155. Available at: https://cpncampus.com/biblioteca/files/original/ed135abeea5b0420d489cdff72fbf7a7.pdf.

19. Adamkin D.H., Radmacher P.G. Current trends and future challenges in neonatal parenteral nutrition. J Neonatal Perinatal Med. 2014;7(3)157–164. https://doi.org/10.3233/NPM-14814008.

20. Mimouni F.B. Vitamin D in the newborn, part I: Assessment of status and deficiency risk factors. NeoReviews. 2014;15(5):e187–e192. https://doi.org/10.1542/neo.15-5-e187.

21. Gadzhimuradova N.D., Pykhtina L.A., Filkina O.M., Shanina T.G., Nazarov S.B., Pisareva S.E. Features of the state of health of children of the first year of life born after in vitro fertilization from a singleton pregnancy. Modern Problems of Science and Education. 2016;(2). (In Russ.) Available at: https://science-education.ru/ru/article/view?id=24320.

22. Druzhinina N.A., Merzlyakova D.R. Peculiarities of health and bone metabolism of children born through IVF. Meditsinskiy Sovet. 2019;(2):231–239. (In Russ.) https://doi.org/10.21518/2079-701X-2019-2-231-239.

23. Ivashikina T.M., Kotova T.N., Omarova P.Sh., Khlekhlina Yu. V., Berestovskaya V.S., Ponkratova T.S. Age-related changes in the level of serum bone markers in healthy children. Klinichescheskaya Laboratornaya Diagnostika. 2010;(11):7–10. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=15514857.

24. Kishkun A.A. Rukovodstvo po laboratornyim metodam diagnostiki. Moscow: GEOTAR-Media; 2014. 760 p. (In Russ.) Available at: https://www.rosmedlib.ru/book/ISBN9785970431023.html.

25. Forst T., Kunt T., Pohlmann K., Engelbach M., Beyer J., Pfutzner A. Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus. J Clin Invest. 1998;101(10):2036–2041. https://doi.org/10.1172/JCI2147.

26. Lee J., Park H.K., Kim J.H., Choi Y.Y., Lee H.J. Bone mineral density according to dual energy X-ray absorptiometry is associated with serial serum alkaline phosphatase level in extremely low birth weight infants at discharge. Pediatr Neonatol. 2017;58(3):251–257. https://doi.org/10.1016/j.pedneo.2016.05.005.

27. Chang S.W., Lee H.C. Vitamin D and health-The missing vitamin in humans. Pediatr Neonatol. 2019;60(3):237–244. https://doi.org/10.1016/j.pedneo.2019.04.007.

28. Yılmaz B., Aygün C., Çetinoğlu E. Vitamin D levels in newborns and association with neonatal hypocalcemia. J Matern Fetal Neonatal Med. 2018;31(14):1889–1893. https://doi.org/10.1080/14767058.2017.1331430.

29. Elsori D.H., Hammoud M.S. Vitamin D deficiency in mothers, neonates and children. J Steroid Biochem Mol Biol. 2018;(175):195–199. https://doi.org/10.1016/j.jsbmb.2017.01.023.

30. Avila-Alvarez A., Urisarri A., Fuentes-Carballal J., Mandiá N., Sucasas-Alonso A., Couce M.L. Metabolic Bone Disease of Prematurity: Risk Factors and Associated Short-Term Outcomes. Nutrients. 2020;12(12):3786. https://doi.org/10.3390/nu12123786.

31. Liu X., Zhang W., Xu Y., Chu Y., Wang X., Li Q. et al. Effect of vitamin D status on normal fertilization rate following in vitro fertilization. Reprod Biol Endocrinol. 2019;17(1):59. https://doi.org/10.1186/s12958-019-0500-0.

32. Chinoy A., Mughal M.Z., Padidela R. Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences. Arch Dis Child Fetal Neonatal Ed. 2019;104(5):F560-6. https://doi.org/10.1136/archdischild-2018-316330.

33. Khadilkar A., Khadilkar V., Chinnappa J., Rathi N., Khadgawat R., Balasubramanian S. et al. Prevention and treatment of vitamin D and calcium deficiency in children and adolescents: Indian Academy of Pediatrics (IAP) Guidelines. Indian Pediatr. 2017;54(7):567–573. https://doi.org/10.1007/s13312-017-1070-x.

34. Gubler E.V. Computational methods for the analysis and recognition of pathological processes. Leningrad: Meditsina. Leningr. otdelenie; 1978. 294 p. (In Russ.) Available at: https://search.rsl.ru/ru/record/01007621409.