Iranian Journal of Neonatology

Iranian Journal of Neonatology

Comparison of Caffeine and Aminophylline in Treating Apnea of Prematurity with Historical Data: A Single Center, Observational Study in Taiwan

Document Type : Original Article

Authors
Fong-Cheng Ho 1
Tsai-Hui Duh 2
Hao-Wei Chung 1
Shu-Ting Yang 1
Hsiu-Lin Chen 1
1 Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
2 Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
10.22038/ijn.2024.75703.2458
Abstract
Background: For treatment of apnea of prematurity (AOP), aminophylline is the first line medication in Taiwan. There are limited trials in Taiwan regarding the therapeutic benefits and adverse effects of caffeine for the treatment of AOP.
Methods: This observational study conducted between January 2018 and December 2018 investigated the clinical effectiveness and safety of caffeine for AOP in the neonatal intensive care unit (NICU) at a hospital in Taiwan. Very preterm neonates with very low birth weight and apnea were treated with a loading dose of caffeine citrate at 20 mg/kg, followed by a 5–10 mg/kg maintenance dose every 24 h. Preterm infants admitted to the NICU between January 2017 and December 2018 and treated with aminophylline/theophylline were included for comparison.
Results: Seventeen infants receiving caffeine therapy and 43 receiving aminophylline/theophylline therapy were enrolled in this study. Although fewer apneic spells were observed from the second week of commencing caffeine treatment (P=0.028), the mean duration of apnea and episodes of apneic spells during the first four weeks of treatment were similar between the two groups. There were no significant differences in short-term side effects, duration of intubation, noninvasive respiratory support, hospitalization, and medical expenses between the two groups.
Conclusion: Caffeine treatment can reduce the frequency of apnea after one week of administration; however, both caffeine and aminophylline/theophylline showed similar effects in treating AOP.
 
Keywords
Apnea of prematurity
Caffeine
Methylxanthine
Preterm
  1. Williamson JR, Bliss DW, Paydarfar D. Forecasting respiratory collapse: theory and practice for averting life-threatening infant apneas. Respir Physiol Neurobiol 2013;189:223-2
  2. Zhao J, Gonzalez F, Mu D. Apnea of prematurity: from cause to treatment. Eur J Pediatr Eur J Pediatr. 2011;170(9):1097-1105.
  3. Janvier A, Khairy M, Kokkotis A, Cormier C, Messmer D, Barrington KJ. Apnea is associated with neurodevelopmental impairment in very low birth weight infants. J Perinatol 2004;24(12):763-76
  4. Taylor HG, Klein N, Schatschneider C, Hack M. Predictors of early school age outcomes in very low birth weight children. J Dev Behav Pediatr 1998;19(4):235-2
  5. Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database Syst Rev. 2010;(12):CD000140.
  6. Lodha A, Seshia M, McMillan DD, Barrington K, Yang J, Lee SK, et al; Canadian Neonatal Network. Association of early caffeine administration and neonatal outcomes in very preterm neonates. JAMA Pediatr. 2015;169(1):33-38.
  7. Morton SU, Smith VC. Treatment options for apnoea of prematurity. Arch Dis Child Fetal Neonatal Ed. 2016;101(4):F352-356.
  8. Jeong K, Kim HS, Song ES, Choi YY. Comparison between caffeine and theophylline therapy for apnea of prematurity. Neonatal Med 2015;22(1):
    14-20.
  9. Mishra G, Chandrashekhar SR. Management of diabetes insipidus in children. Indian J Endocrinol Metab. 2011;15(Suppl3):S180-18
  10. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7):1723-1729.
  11. Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr. 1987;17(4):213-288.
  12. Kim KR, Jung SW, Kim DW. Risk factors associated with germinal matrix-intraventricular hemorrhage in preterm neonates. J Korean Neurosurg Soc. 2014;56(4):334-337.
  13. Chen HL, Tseng HI, Yang SN, Yang RC. Bone status and associated factors measured by quantitative ultrasound in preterm and full-term newborn infants. Early Hum Dev. 2012;88(8):617-622.
  14. Patwardhan G, Soni A, Rachwani N, Kadam S, Patole S, Pandit A. Factors associated with time to full feeds in preterm very low birth weight infants. J Trop Pediatr. 2018;64(6):495-500.
  15. Shrestha B, Jawa G. Caffeine citrate - Is it a silver bullet in neonatology? Pediatr Neonatol. 2017;58(5):391-397.
  16. Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin Jr DK, Smith PB. Medication use in the neonatal intensive care unit. American journal of perinatology. 2014;31(09):811-822.
  17. Henderson-Smart DJ, Steer PA. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev. 2010;2010(1):CD000273.
  18. Skouroliakou M, Bacopoulou F, Markantonis SL. Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial. J Paediatr Child Health. 2009;45(10):587-592.
  19. Shivakumar M, Jayashree P, Najih M, Lewis LES, Bhat Y R, Kamath A, et al. Comparative Efficacy and safety of caffeine and aminophylline for apnea of prematurity in preterm (≤34 weeks) neonates: A randomized controlled trial. Indian Pediatr. 2017;54(4):279-283.
  20. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al; Caffeine for apnea of prematurity trial group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112-2121.
  21. 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(1):9.
  22. Gouyon JB, Guignard JP. Renal effects of theophylline and caffeine in newborn rabbits. Pediatr Res. 1987;21(6):615-618.
  23. Gillot I, Gouyon JB, Guignard JP. Renal effects of caffeine in preterm infants. Biol Neonate. 1990;58(3):133-136.
  24. Zanardo V, Dani C, Trevisanuto D, Meneghetti S, Guglielmi A, Zacchello G, et al. Methylxanthines increase renal calcium excretion in preterm infants. Biol Neonate. 1995;68(3):169-174.
  25. Foldes AJ, Rimon A, Keinan DD, Popovtzer MM. Quantitative ultrasound of the tibia: a novel approach for assessment of bone status. Bone. 1995;17(4):363-367.
  26. Guglielmi G, Adams J, Link TM. Quantitative ultrasound in the assessment of skeletal status. Eur Radiol. 2009;19(8):1837-1848.
  27. Zhang H, Jia Q, Piao M, Chang Y, Zhang J, Tong X, et al. Screening of serum alkaline phosphatase and phosphate helps early detection of metabolic bone disease in extremely low birth weight infants. Front Pediatr. 2021;9:642158.
  28. Humayun J, Löfqvist C, Ley D, Hellström A, Gyllensten H. Systematic review of the healthcare cost of bronchopulmonary dysplasia. BMJ Open. 2021;11(8):e045729.
  29. Beam AL, Fried I, Palmer N, Agniel D, Brat G, Fox K, et al. Estimates of healthcare spending for preterm and low-birthweight infants in a commercially insured population: 2008-2016. J Perinatol. 2020;40(7):1091-1099.
  30. Mowitz ME, Ayyagari R, Gao W, Zhao J, Mangili A, Sarda SP. Health care burden of bronchopulmonary dysplasia among extremely preterm infants. Front Pediatr 2019;7:510.
  31. Lai KC, Lorch SA. Healthcare costs of major morbidities associated with prematurity in US children's hospitals. J Pediatr. 2023 May 1;256:53-62.

 

Iranian Journal of Neonatology
Volume 16, Issue 1
Winter 2025
Pages 40-47