Risk Factors and Clinical Characteristics of Metabolic Bone Disease of Prematurity

Abstract

Objective The study aimed to analyze the risk factors and clinical features of metabolic bone disease of prematurity (MBDP) in premature infants compared with infants of similar gestational age and birth weight without MBDP.

Study Design This retrospective case–control study was performed by comparing 81 cases of MBDP with 63 controls to identify potential risk factors. Premature infants with a gestational age ≤33 weeks and birth weight <1,500 g were included. Medical records were examined in terms of maternal conditions, potential risk factors, and clinical characteristics.

Results Bone fractures and invasive ventilator dependence were the most common clinical features of MBDP. Duration of invasive ventilation and total mechanical ventilation days, necrotizing enterocolitis, corticosteroid use, anticonvulsive drug use, duration of dexamethasone and caffeine use, total parenteral nutrition, and length of hospitalization were significantly higher in neonates with MBDP (p < 0.05). Breastfed neonates and those receiving human milk fortifier had a lower incidence of MBDP than those premature formula or mixed feeding (p < 0.05). Anticonvulsive drug use (odds ratio: 2.935; 95% confidence interval: 1.265–6.810) was identified as a risk factor for MBDP at multiple regression analysis.

Conclusion Our results show that anticonvulsive drug use is a significant risk factor for the development of MBDP. If long-term use is not required, anticonvulsive drugs should be stopped as soon as possible. Further studies involving patients with MBDP are required to determine the risk factors and clinical features.

Key Points

• MBDP is a multifactorial disorder.

• Anticonvulsive drug use is an important risk factor for the development of MBDP.

• Bone fractures and invasive ventilator dependence are the most common clinical features of MBDP.

Keywords

metabolic bone disease - prematurity - risk factor

Publikationsverlauf

Eingereicht: 19. Januar 2021

Angenommen: 16. März 2021

Artikel online veröffentlicht:
11. Mai 2021

• References

• 1 Rigo J, Mohamed WM, De Curtis M. Disorders of calcium, phosphorus, and magnesium metabolism. In: Martin RJ, Fanaroff AA, Walsh MC. eds. Fanaroff and Martin's Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed.. St. Louis: Elsevier Mosby; 2011: 1523-1556
• 2 Abrams SA. Committee on Nutrition. Calcium and vitamin d requirements of enterally fed preterm infants. Pediatrics 2013; 131 (05) e1676-e1683
• 3 Harrison CM, Gibson AT. Osteopenia in preterm infants. Arch Dis Child Fetal Neonatal Ed 2013; 98 (03) F272-F275
• 4 Rustico SE, Calabria AC, Garber SJ. Metabolic bone disease of prematurity. J Clin Transl Endocrinol 2014; 1 (03) 85-91
• 5 Dokos C, Tsakalidis C, Tragiannidis A, Rallis D. Inside the “fragile” infant: pathophysiology, molecular background, risk factors and investigation of neonatal osteopenia. Clin Cases Miner Bone Metab 2013; 10 (02) 86-90
• 6 Faienza MF, D'Amato E, Natale MP. et al. Metabolic bone disease of prematurity: diagnosis and management. Front Pediatr 2019; 7: 143
• 7 Ognean ML, Boanta O, Gradinariu G. Metabolic bone disease of prematurity. Neonatology 2010; 2 (04) 29-53
• 8 Chinoy A, Mughal MZ, Padidela R. Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences. Arch Dis Child Fetal Neonatal Ed 2019; 104 (05) F560-F566
• 9 Rao R. Osteopenia of prematurity. In: Gomella TL, Cunningham MD, Eyal FG. eds. Neonatology. 6th ed.. New York: McGraw-Hill; 2009: 613-617
• 10 Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013; 13: 59
• 11 Ali E, Rockman-Greenberg C, Moffatt M, Narvey M, Reed M, Jiang D. Caffeine is a risk factor for osteopenia of prematurity in preterm infants: a cohort study. BMC Pediatr 2018; 18 (01) 9
• 12 Scher SM. Seizures in neonates. In: Martin RJ, Fanaroff AA, Walsh MC. eds. Fanaroff and Martin's Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed.. St. Louis: Elsevier Mosby; 2011: 976-977
• 13 Fan HC, Lee HS, Chang KP. et al. The impact of anti-epileptic drugs on growth and bone metabolism. Int J Mol Sci 2016; 17 (08) 1242
• 14 Nissen-Meyer LS, Svalheim S, Taubøll E. et al. Levetiracetam, phenytoin, and valproate act differently on rat bone mass, structure, and metabolism. Epilepsia 2007; 48 (10) 1850-1860
• 15 Karesova I, Simko J, Fekete S. et al. The effect of levetiracetam on rat bone mineral density, bone structure and biochemical markers of bone metabolism. Eur J Pharmacol 2018; 824: 115-119
• 16 Cakir M, Mungan I, Karahan C, Can G, Okten A. Necrotizing enterocolitis increases the bone resorption in premature infants. Early Hum Dev 2006; 82 (06) 405-409
• 17 Wallis K, Walters JR, Forbes A. Review article: glucagon-like peptide 2--current applications and future directions. Aliment Pharmacol Ther 2007; 25 (04) 365-372
• 18 Ukarapong S, Venkatarayappa SKB, Navarrete C, Berkovitz G. Risk factors of metabolic bone disease of prematurity. Early Hum Dev 2017; 112: 29-34
• 19 Glasgow JF, Thomas PS. Rachitic respiratory distress in small preterm infants. Arch Dis Child 1977; 52 (04) 268-273
• 20 Ruiz-Gaspà S, Martinez-Ferrer A, Guañabens N. et al. Effects of bilirubin and sera from jaundiced patients on osteoblasts: contribution to the development of osteoporosis in liver diseases. Hepatology 2011; 54 (06) 2104-2113
• 21 You SK, Lee JE, Lee SM, Cho HH. Metabolic bone disease in preterm infants: relationship between radiologic grading in the wrist and serum biochemical markers. Diagn Interv Imaging 2017; 98 (11) 785-791