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Metabolic bone disease of prematurity – review article


Authors: T. Matějek 1;  M. Navratilova 1;  Z. Kokštein 1;  V. Palička 2
Authors‘ workplace: Dětská klinika FN a LF UK, Hradec Králové přednosta prof. MUDr. M. Bayer, CSc. 1;  Ústav klinické biochemie a diagnostiky FN a LF UK, Hradec Králové přednostka MUDr. L. Pavlíková 2
Published in: Čes-slov Pediat 2015; 70 (5): 303-312.
Category: Review

Overview

Premature infants, particularly those born before the 28th week of gestation, are at a significant risk for reduced bone mineral content because a major part of fetal bone mineralization occurs during the third trimester of gestation with maximum close to the term labor. After birth, another important reduction of bone mineral density occurs due to early start of bone remodeling, relatively fast bone growth, and low mineral intake (compared with intake during intrauterine development). These postnatal changes are responsible for a disease known as metabolic bone disease of prematurity (MBD).

Incidence of MBD (30–55%) remains unchanged despite improvements of neonatal intensive care during the last 20 years. Although occurrence of pathological fractures due to MBD appears to have decreased, the risk of this early complication is still over 10%. Changes seen in the bones of ex-preterm newborns in childhood and in young adults (reduction of final height and, eventually, of bone mineral density) suggest that it could be a significant risk factor for the development of early osteoporosis in adulthood. The risk factors contributing to the development of MBD of prematurity have been well described. Diagnosis of metabolic bone disease is done by biochemical analysis. Low serum levels of phosphorus and high levels of alkaline phosphatase are suggested as a gold standard, despite the strong evidence of limited use of these parameters. The key of successful treatment is consistent prevention, which is based on early and optimal delivery of calcium, phosphorus and vitamin D through parenteral and enteral nutrition. This article reviews the pathophysiology, incidence, diagnostics, therapy and consequnces of MBD of prematurity.

Key words:
metabolic bone disease of prematurity, osteopenia, vitamin D, parathyroid hormone, alkaline phosphatase, newborn


Sources

1. Rauch F, Schoenau E. Skeletal development in premature infants: a review of bone physiology beyond nutritional aspects. Arch Dis Child Fetal Neonatal Ed 2002; 86 (2): 82–85.

2. Hay W, Thureen P. Neonatal Nutrition and Metabolism. 2nd ed. Cambridge: Cambridge University Press, 2006: 185–259.

3. Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (3): 443–456.

4. Pieltan C, de Halleux V, Senterre Th, Rigo J. Prematurity and bone health. World Rev Nutr Diet 2013; 130: 181–188.

5. Harrison CM. Osteopenia in preterm infants. Arch Dis Child Fetal Neonatal Ed 2013; 98: 272–275.

6. Viswanathan S, Khasawneh W, McNelis K, et al. Metabolic bone disease: a continued challenge in extremely low birth weight infants. J Parenter Enteral Nutr 2014; 38 (8): 982–990.

7. Mitchell SM, Rogers SP, Hicks PD, et al. High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support. BMC Pediatr 2009; 9: 47.

8. Tinnion RJ, Embleton ND. How to use... alkaline phosphatase in neonatology. Arch Dis Child Educ Pract Ed 2012; 97 (4): 157–163.

9. Bishop N, Sprigg A, Dalton A. Unexplained fractures in infancy: looking for fragile bones. Arch Dis Child 2007; 92 (3): 251–256.

10. Gerding H, Busse H. Myopia of prematurity (MOP) is definitely not a consequence of skull deformation. Eur J Pediatr 1995; 154 (3): 245–247.

11. Ichiba H, Shintaku H, Fujimaru M, et al. Bone mineral density of the lumbar spine in very-low-birth-weight infants: a longitudinal study. Eur J Pediatr 2000; 159 (3): 215–218.

12. Yeste D, Almar J, Clemente M, et al. Areal bone mineral density of the lumbar spine in 80 premature newborns: a prospective and longitudinal study. J Pediatr Endocrinol Metab 2004; 17 (7): 959–966.

13. Quintal VS, Diniz EM, de Caparbo VF, Pereira RM. Bone densitometry by dual-energy X-ray absorptiometry (DXA) in preterm newborns compared with full-term peers in the first six months of life. J Pediatr (Rio J) 2014; 90 (6): 556–562.

14. Bowden LS, Jones CJ, Ryan SW. Bone mineralisation in ex-preterm infants aged 8 years. Eur J Pediatr 1999; 158 (8): 658–661.

15. Smith CM, Coombs RC, Gibson AT, Eastell R. Adaptation of the Carter method to adjust lumbar spine bone mineral content for age and body size: application to children who were born preterm. J Clin Densitom 2006; 9 (1): 114–119.

16. Chan GM, Armstrong C, Moyer-Mileur L, Hoff C. Growth and bone mineralization in children born prematurely. J Perinatol 2008; 28 (9): 619–623.

17. Fewtrell MS, Williams JE, Singhal A, et al. Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm. Bone 2009; 45 (1): 142–149.

18. Frost HM, Schönau E. The „muscle-bone unit“ in children and adolescents: a 2000 overview. J Pediatr Endocrinol Metab 2000; 13 (6): 571–590.

19. Rauch F, Schoenau E. The developing bone: slave or master of its cells and molecules? Pediatr Res 2001 Sep; 50 (3): 309–314.

20. Harrison CM, Johnson K, McKechnie E. Osteopenia of prematurity: a national survey and review of practice. Acta Paediatr 2008; 97 (4): 407–413.

21. Bayer M., Kutílek Š, a kol. Metabolická onemocnění skeletu u dětí. 1. vyd. Praha: Grada Publishing, 2002: 185–193.

22. Rigo J, Nyamugabo K, Picaud JC, et al. Reference values of body composition obtained by dual energy X-ray absorptiometry in preterm and term neonates. J Pediatr Gastroenterol Nutr. 1998;27(2):184-90.

23. Backström MC, Kouri T, Kuusela AL, et al. Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity. Acta Paediatr 2000; 89 (7): 867–873.

24. Bayer M. Reference values of osteocalcin and procollagen type I N-propeptide plasma levels in a healthy Central European population aged 0-18 years. Osteoporos Int 2014; 25 (2): 729–736.

25. Hung YL, Chen PC, Jeng SF, et al. Serial measurements of serum alkaline phosphatase for early prediction of osteopaenia in preterm infants. J Paediatr Child Health 2011; 47 (3): 134–139.

26. Faerk J, Peitersen B, Petersen S, Michaelsen KF. Bone mineralisation in premature infants cannot be predicted from serum alkaline phosphatase or serum phosphate. Arch Dis Child Fetal Neonatal Ed 2002; 87 (2): 133–136.

27. De Curtis M, Rigo J. Nutrition and kidney in preterm infant. J Matern Fetal Neonatal Med 2012; 25: 55–59.

28. Quarles LD. Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 2008; 118 (12): 3820–3828.

29. Hellstern G, Pöschl J, Linderkamp O. Renal phosphate handling of premature infants of 23-25 weeks gestational age. Pediatr Nephrol 2003; 18 (8): 756–758.

30. Janota J, Straňák Z. Neonatologie. 1. vyd. Praha: Mladá fronta, 2013: 294–297.

31. Boehm G, Wiener M, Schmidt C, et al. Usefulness of short-term urine collection in the nutritional monitoring of low birthweight infants. Acta Paediatr 1998; 87 (3): 339–343.

32. Pohlandt F. Prevention of postnatal bone demineralization in very low-birth-weight infants by individually monitored supplementation with calcium and phosphorus. Pediatr Res 1994; 35 (1): 125–129.

33. Aladangady N, Coen PG, White MP, et al. Urinary excretion of calcium and phosphate in preterm infants. Pediatr Nephrol 2004; 19 (11): 1225–1231.

34. Catache M, Leone CR. Role of plasma and urinary calcium and phosphorus measurements in early detection of phosphorus deficiency in very low birthweight infants. Acta Paediatr 2003; 92 (1): 76–80.

35. Kovacs CS. Bone development in the fetus and neonate: role of the calciotropic hormones. Curr Osteoporos Rep 2011 Dec; 9 (4): 274–283.

36. Kovacs CS. Bone metabolism in the fetus and neonate. Pediatr Nephrol 2014; 29 (5): 793–803.

37. Rodriguez A, García-Esteban R, Basterretxea M, et al. Associations of maternal circulating 25-hydroxyvitamin D3 concentration with pregnancy and birth outcomes. BJOG 2014; doi: 10.1111/1471-0528.13074.

38. Salle BL, Delvin EE, Lapillonne A, et al. Perinatal metabolism of vitamin D. Am J Clin Nutr 2000; 71 (5): 1317–1324.

39. Hsu SC, Levine MA. Perinatal calcium metabolism: physiology and pathophysiology. Semin Neonatol 2004; 9 (1): 23–36.

40. Agostoni C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr 2010; 50 (1): 85–91.

41. Ferenczová J, Podracká Ľ. Vitamín D – nový pohľad na starý vitamín. Čes-slov Pediat 2009; 64 (7–8): 344–351.

42. Abrams SA. Committee on Nutrition. Calcium and vitamin d requirements of enterally fed preterm infants. Pediatrics 2013; 131 (5): e1676–1683.

43. Við Streym S, Kristine Moller U, Rejnmark L et al. Maternal and infant vitamin D status during the first 9 months of infant life-a cohort study. Eur J Clin Nutr 2013; 67 (10): 1022–1028.

44. Monangi N, Slaughter JL, Dawodu A, et al. Vitamin D status of early preterm infants and the effects of vitamin D intake during hospital stay. Arch Dis Child Fetal Neonatal Ed 2014; 99 (2): F166–168.

45. Dawodu A, Nath R. High prevalence of moderately severe vitamin D deficiency in preterm infants. Pediatr Int 2011; 53 (2): 207–210.

46. Javaid MK, Crozier SR, Harvey NC, et al. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet 2006; 367 (9504): 36–43.

47. Natarajan CK, Sankar MJ, Agarwal R, et al. Trial of daily vitamin D supplementation in preterm infants. Pediatrics 2014; 133 (3): e628–634.

48. Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child 2008; 93 (6): 512–517.

49. Reinholz M, Ruzicka T, Schauber J. Vitamin D and its role in allergic disease. Clin Exp Allergy 2012; 42 (6): 817–826.

50. Whitehouse AJ, Holt BJ, Serralha M, et al. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics 2012; 129 (3): 485–493.

51. Walker VP, Zhang X, Rastegar I, et al. Cord blood vitamin D status impacts innate immune responses. J Clin Endocrinol Metab 2011; 96 (6): 1835–1843.

52. Dinlen N, Zenciroglu A, Beken S, et al. Association of vitamin D deficiency with acute lower respiratory tract infections in newborns. J Matern Fetal Neonatal Med 2015; 19: 1–5.

53. Camargo CA Jr, Ingham T, Wickens K, et al. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics 2011; 127 (1): 180–187.

54. Cetinkaya M, Cekmez F, Buyukkale G, et al. Lower vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants. J Perinatol 2015; 35 (1): 39–45.

55. Onwuneme C, Martin F, McCarthy R, et al. The Association of vitamin D status with acute respiratory morbidity in preterm infants. J Pediatr 2015; 166 (5): 1175–1180.

56. Misra M, Pacaud D, Petryk A, et al. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics 2008; 122 (2): 398–417.

57. Ross AC, Taylor CL, Yaktine AL, et al. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US), 2011.

58. Harrison CM, Johnson K, McKechnie E. Osteopenia of prematurity: a national survey and review of practice. Acta Paediatr 2008; 97 (4): 407–413.

59. Backström MC, Mäki R, Kuusela AL, et al. Randomised controlled trial of vitamin D supplementation on bone density and biochemical indices in preterm infants. Arch Dis Child Fetal Neonatal Ed 1999; 80 (3): 161–166.

60. Lothe A, Sinn J, Stone M. Metabolic bone disease of prematurity and secondary hyperparathyroidism. J Paediatr Child Health 2011; 47 (8): 550–553.

61. Moreira A, February M, Geary C.. Parathyroid hormone levels in neonates with suspected osteopenia. J Paediatr Child Health 2013; 49: E12–E16.

62. Yeşiltepe Mutlu G, Kırmızıbekmez H, Ozsu E, et al. Metabolic bone disease of prematurity: report of four cases. J Clin Res Pediatr Endocrinol 2014; 6 (2): 111–115.

63. Moreira A, Swischuk L, Malloy M, Mudd D. Parathyroid hormone as a marker of metabolic bone disease of prematurity. J Perinatol 2014; 34 (10): 787–791.

64. Pereira-da-Silva L, Costa A, Pereira L, et al. Early high calcium and phosphorus intake by parenteral nutrition prevents short-term bone strength decline in preterm infants. J Pediatr Gastroenterol Nutr 2011; 52 (2): 203–209.

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