Safety and efficacy of use of aminophylline and caffeine in management of apnea of prematurity

Authors

  • Mohammad A. Haque Department of Pediatrics, Institute of Child & Mother Health (ICMH), Dhaka, Bangladesh
  • Mohammad M. Rahman Department of Pediatrics, Institute of Child & Mother Health (ICMH), Dhaka, Bangladesh
  • Mohammad A. Adnan Department of Pediatrics, Institute of Child & Mother Health (ICMH), Dhaka, Bangladesh
  • Afroza Y. Rumi Department of Pediatrics, Institute of Child & Mother Health (ICMH), Dhaka, Bangladesh
  • Mahbub Ahmed Department of Pediatrics, Institute of Child & Mother Health (ICMH), Dhaka, Bangladesh
  • Mohammad T. Islam Department of Pediatrics, Institute of Child & Mother Health (ICMH), Dhaka, Bangladesh

DOI:

https://doi.org/10.18203/2349-3291.ijcp20253480

Keywords:

Apnea, Aminophylline, Caffeine, Prematurity

Abstract

Background: Both aminophylline and caffeine have been used to manage apnea of prematurity in various NICUs. We aimed to investigate the efficacy and safety of these two drugs in the mentioned scenario.

Methods: This randomized controlled trial was carried out from July 2024 to June 2025 in the ICMH, Dhaka. All the preterm newborns with ≤ 34 completed weeks of GA were enrolled. Those having major congenital anomalies, respiratory depression from medications and patent ductus arteriosus (PDA) as a cause of apnea were excluded. Among 53 participants, 27 received caffeine and 26 received aminophylline.

Results: In the caffeine group average gestational age was 33.1 days and the birth weight was 1330 grams. On average, treatment was started at 2.5 days and was continued for 18 days. While in the aminophylline group average gestational age was 32.8 days and the birth weight was 1402 grams. On average, treatment was started at 4.1 days and was continued for 21 days. The aminophylline group observed relatively more apneic spells and other adverse effects. Except for treatment starting days, neither of the changes in these groups was statistically significant.     

Conclusions: Regarding effectiveness and safety, caffeine exerted as much performance as aminophylline without any superiority of one over the other.

Metrics

Metrics Loading ...

References

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;354:2112‑21. DOI: https://doi.org/10.1056/NEJMoa054065

Pillekamp F, Hermann C, Keller T, von Gontard A, Kribs A, Roth B. Factors influencing apnea and bradycardia of prematurity‑implications for neurodevelopment. Neonatology. 2007;91:155‑161. DOI: https://doi.org/10.1159/000097446

Ducrocq S, Biran‑Mucignat V, Boelle PY, Lebas F, Baudon JJ, Gold F. Apnea of prematurity: Risk factors and ambulatory treatment with caffeine citrate. Arch Pediatr. 2006;13:1299‑304. DOI: https://doi.org/10.1016/j.arcped.2006.06.016

Martin RJ, Abu‑Shaweesh JM, Baird TM. Apnoea of prematurity. Paediatr Respir. 2004;5(1):377‑82. DOI: https://doi.org/10.1016/S1526-0542(04)90067-X

Siu A, James A. Apnea of prematurity pharmacotherapy. US Pharm. 2010;35:2‑6.

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;24:763‑8. DOI: https://doi.org/10.1038/sj.jp.7211182

Zhao J, Gonzalez F, Mu D. Apnea of prematurity: From cause to treatment. Eur J Pediatr. 2011;170:1097‑105. DOI: https://doi.org/10.1007/s00431-011-1409-6

Henderson‑Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database Syst Rev. 2010;140:697. DOI: https://doi.org/10.1002/14651858.CD000140.pub2

Pantalitschka T, Sievers J, Urschitz MS, Herberts T, Reher C, Poets CF. Randomised crossover trial of four nasal respiratory support systems for apnoea of prematurity in very low birthweight infants. Arch Dis Child Fetal Neonatal. 2009;94:245‑8. DOI: https://doi.org/10.1136/adc.2008.148981

Lemyre B, Davis PG, de Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity. Cochrane Database Syst Rev. 2002;2:272. DOI: https://doi.org/10.1002/14651858.CD002272

Hendy H, Wandita S, Kardana IM. Efficacy of aminophylline vs caffeine for preventing apnea of prematurity. Paediatri Indonesia. 2014;54(6):365-8. DOI: https://doi.org/10.14238/pi54.6.2014.365-71

Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Long-term effects of caffeine therapy for apnea of prematurity. New England J Med. 2007;357(19):1893-902. DOI: https://doi.org/10.1056/NEJMoa073679

Miao Y, Zhou Y, Zhao S, Liu W, Wang A, Zhang Y, et al. Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity: A systematic review and meta-analysis. PloS One. 2022;17(9):274882. DOI: https://doi.org/10.1371/journal.pone.0274882

Lin YC, Tan YL, Yen TA, Chen CY, Tsao PN, Chou HC. Specific Premature Groups Have Better Benefits When Treating Apnea With Caffeine Than Aminophylline/Theophylline. Front Pediat. 2022;10:817624. DOI: https://doi.org/10.3389/fped.2022.817624

Ye C, Miao C, Yu L, Dong Z, Zhang J, Mao Y, et al. Factors affecting the efficacy and safety of aminophylline in treatment of apnea of prematurity in neonatal intensive care unit. Pediat Neonatol. 2019;60(1):43-9. DOI: https://doi.org/10.1016/j.pedneo.2018.03.008

Brouard C, Moriette G, Murat I, Flouvat B, Pajot N, Walti H, et al. Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants. American J Dis Child. 1985;139(7):698-700. DOI: https://doi.org/10.1001/archpedi.1985.02140090060028

Larsen PB, Brendstrup L, Skov L, Flachs H. Aminophylline versus caffeine citrate for apnea and bradycardia prophylaxis in premature neonates. Acta paediat. 1995;84(4):360-4. DOI: https://doi.org/10.1111/j.1651-2227.1995.tb13649.x

Nagasato A, Nakamura M, Kamimura H. Comparative study of the efficacy and safety of caffeine and aminophylline for the treatment of apnea in preterm infants. J Pharma Soc Japan. 2018;138(2):237-42. DOI: https://doi.org/10.1248/yakushi.17-00144

Shivakumar M, Jayashree P, Najih M, Lewis LE, Kamath A, Shashikala. Comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity in preterm (≤ 34 weeks) neonates: a randomized controlled trial. Indian Pediat. 2017;54(4):279-83. DOI: https://doi.org/10.1007/s13312-017-1088-0

Zhang CY, Liu DJ, Hua SD, Guo S, Li XY, Zhang B, et al. Caffeine versus aminophylline in combination with oxygen therapy for apnea of prematurity: A retrospective cohort study. Exp Therap Med. 2020;20(5):46. DOI: https://doi.org/10.3892/etm.2020.9175

Downloads

Published

2025-10-28

How to Cite

Haque, M. A., M. Rahman, M., Adnan, M. A., Rumi, A. Y., Ahmed, M., & Islam, M. T. (2025). Safety and efficacy of use of aminophylline and caffeine in management of apnea of prematurity. International Journal of Contemporary Pediatrics, 12(11), 1773–1777. https://doi.org/10.18203/2349-3291.ijcp20253480

Issue

Section

Original Research Articles