Koffein für Frühgeborene: Evidence and Experience

Koffein gehört zu den am häufigsten verwendeten und in Studien am besten untersuchten Wirkstoffe in der Behandlung von Apnoen bei Frühgeborenen. In diesem Beitrag wird auf Pharmakologie, Wirkung und Nebenwirkungen einer Koffeintherapie mit Empfehlungen zu Dosis und Behandlungsbeginn eingegangen und dabei insbesondere die klinische Erfahrung des Autors mit eingebracht.

Schlüsselwörter

Koffeintherapie - ELBW infnats - Prophylaxe - early and high dose experience

• Literatur

• 1 Schmidt B, Roberts RS, Davis P. et al. Caffeine Therapy for Apnea of Prematurity. N Engl J Med 2006; 354: 2112-2121
• 2 Schmidt B, Roberts RS, Davis P. et al. Long-Term Effects of Caffeine Therapy for Apnea of Prematurity. N Engl J Med 2007; 357: 1893-1902
• 3 Schmidt B, Anderson PJ, Doyle LW. et al. Survival Without Disability to Age 5 Years After Neonatal Caffeine Therapy for Apnea of Prematurity. JAMA 2012; 307: 275-282
• 4 Schmidt B, Roberts RS, Anderson PJ. et al. Academic Performance, Motor Function, and Behavior 11 Years After Neonatal Caffeine Citrate Therapy for Apnea of Prematurity: An 11-Year Follow-up of the CAP Randomized Clinical Trial. JAMA Pediatr 2017; 171: 564-572
• 5 Pearlman S. Advancement in neonatology through quality improvement. J Perinatol 2022; 42: 1277-1282
• 6 Parikka V, Beck J, Zhai Q. et al. The effect of caffeine citrate on neural breathing pattern in preterm infants. Early Hum Dev 2015; 91: 565-568
• 7 Back SA, Craig A, Luo NL. et al. Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury. Ann Neurol 2006; 60: 696-705
• 8 Kreutzer K, Bassler D. Caffeine for apnea of prematurity: a neonatal success story. Neonatology 2014; 105: 332-336
• 9 Soloveychik V, Bin-Nun A, Ionchev A. et al. Acute hemodynamic effects of caffeine administration in premature infants. J Perinatol 2009; 29: 205-208
• 10 Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database Syst Rev 2010; 12: CD000140
• 11 Dani C, Cecchi A, Ciarciá M al. Enteral and Parenteral Treatment with Caffeine for Preterm Infants in the Delivery Room: A Randomised Trial. Pediatric Drugs 2023; 25: 79-86
• 12 Long J-Y, Guo HL, He X. et al. Caffeine for the Pharmacological Treatment of Apnea of Prematurity in the NICU: Dose Selection Conundrum, Therapeutic Drug Monitoring and Genetic Factors. Front Pharmacol 2021; 12: 681842
• 13 Abdel-Hady H, Nasef N, Shabaan AE. et al. Caffeine therapy in preterm infants. World J Clin Pediatr 2015; 4: 81-89
• 14 Ahmed S, Rehman AU, Bibi Z. et al. Predictors for poor daily weight gain in preterm neonates exposed to different dose regimens of caffeine in ICU- a retrospective cohort study. BMC Pediatrics 2024; 24: 401
• 15 Hayata M, Ichikawa T, Nishida T. et al. Early caffeine therapy on the prevention of severe hyperkalemia in preterm infants. Pediatr Int 2023; 65: e15526
• 16 Steer PA, Flenady V, Shearman A. et al. High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2004; 89: F499-F503
• 17 Miao Y, Zhou Y, Zhao S. 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: e0274882
• 18 Anderson BJ, Gunn TR, Holford NHG. et al. Caffeine Overdose in a Premature Infant: Clinical Course and Pharmacokinetics. Anaesth Intensive Care 1999; 27: 307-311
• 19 Perrin C, Debruyne D, Lacotte J. et al. Treatment of Caffeine Intoxication by Exchange Transfusion in a Newborn. Acta Paediatr 1987; 76: 679-681
• 20 Davis PG, Schmidt B, Roberts RS. et al. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr 2010; 156: 382-387
• 21 Schmidt B. Caffeine for Apnea of Prematurity: Too Much or Too little of a Good Thing. J Pediatr 2023; 259: 1-5
• 22 Anup K, Ines F, Banerji A. et al. Caffeine and Less Invasive Surfactant Administration for Respiratory Distress Syndrome of the Newborn. NEJM Evid 2023; 2: 1-9
• 23 Katheria AC. A pilot randomized controlled trial of early versus routine caffeine in extremely premature infants. Am J Perinatol 2015; 32: 879-886
• 24 Moschino L, Zivanovic S, Hartley C. et al. Caffeine in preterm infants: where are we in 2020?. ERJ Open Res 2020; 6: 00330-2019
• 25 Gray HP, Flenady VJ, Charles BG. et al. Caffeine citrate for very preterm infants: Effects on development, temperament and behaviour. J Paediatr Child Health 2011; 47: 167-172
• 26 Lamba V, Winners O, Fort P. Early High-Dose Caffeine Improves Respiratory Outcomes in Preterm Infants. Children 2021; 8: 501
• 27 McPherson C, Neil JJ, Tjoeng TH. et al. A pilot randomized trial of high-dose caffeine therapy in preterm infants. Pediatr Res 2015; 78: 198-204
• 28 McPherson C, Lean RE, Cyr PEP. et al. Five-year outcomes of premature infants randomized to high or standard loading dose caffeine. J Perinatol 2022; 42: 631-635
• 29 Fireman B, Molnar A, Gray PH. Early high-dose caffeine citrate for extremely preterm infants: Neonatal and neurodevelopmental outcomes. J Paediatr Child Health 2019; 55: 1451-1457
• 30 Liu TS, Zhang X, Liu Y. et al. Early application of caffeine improves white matter development in very preterm infants. Respir Physiol Neurobiol 2020; 281: 103495
• 31 Vesoulis Z, Herco M, El Ters NM. et al. Cerebellar Hemorrhage: A 10-year Evaluation of Risk Factors. J Matern Fetal Neonatal Med 2020; 33: 3680-3688
• 32 Villamor-Martinez E, Fumagalli M, Alomar YI. et al. Cerebellar Hemorrhage in Preterm Infants: A Meta-Analysis on Risk Factors and Neurodevelopmental Outcome. Front Physiol 2019; 10: 800
• 33 Steer PA, Flenady VJ, Shearman A. et al. Periextubation caffeine in preterm neonates: A randomized dose response trial. J Paediatr Child Health 2003; 39: 511-515
• 34 Ines F, Hutson S, Coughlin K. et al. Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol. BMJ Open 2021; 11: e038343
• 35 Brattström P, Russo C, Ley D. et al. High-versus low-dose caffeine in preterm infants: a systematic review and meta-analysis. Acta Paediatrica 2019; 3: 401-410
• 36 Miao Y, Liu W, Zhao S. et al. Effect of prophylactic caffeine in the treatment of apnea in very low birth weight infants: a meta-analysis. J Maternal-Fetal Neonatal Med 2023; 36: 1-2214659
• 37 Bruschettini M, Brattström P, Russo C. et al. Caffeine dosing regimens in preterm infants with or at risk for apnea of prematurity. Cochrane Database Syst Rev 2023; 4: CD013873
• 38 Aranda JV, Turmen T. Methylxanthines in apnea of prematurity. Clin Perinatol 1979; 6: 87-108
• 39 Eichenwald EC. AAP Committee on fetus and newborn. Apnea of Prematurity. Pediatrics 2016; 137: e20153757
• 40 AWMF-Leitlinie „Therapie idiopathischer Apnoen, Bradykardien und Hypoxämien bei Früh- und Reifgeborenen“, Registernummer 024/013 (2020) und Entwicklungsstufe 2k+IDA. 2025
• 41 NICE Guideline. Specialist neonatal respiratory care for babies born preterm. 2019 Accessed May 12, 2025 at: www.nice.org.uk/guidance/ng124
• 42 Urru SA, Geist M, Carlinger R. et al. Strategies for cessation of caffeine administration in preterm infants. Cochrane Database Syst Rev 2024; 7: CD015802
• 43 Bonadies L, Cavicchiolo ME, Priante E. et al. Prematurity and BPD: what general pediatricians should know. Eur J Pediatr 2023; 182: 1505-1516