Strategies for caffeine administration in preterm infants: route, dosing, monitoring, and adjunctive interventions - a systematic review
In brief
Two small trials leave the best caffeine route and schedule unclear
A review found only two trials, involving 78 preterm infants, that compared intravenous with oral caffeine or once-daily with twice-daily dosing. The evidence was too uncertain to show which approach improves outcomes, and no studies tested dose changes or giving caffeine with surfactant. Caffeine benefits preterm infants, but better trials are needed to guide how it is given.
- Journal
- Italian journal of pediatrics (Q1)
- Published
- 21 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Alaa A M Osman, Chiara Russo, Maria Rojas-Reyes, Franciszek Borys, Michelle Fiander, Roger Soll, et al.
- PMID
- 42778959
- DOI
- 10.1186/s13052-026-02344-0
Why clinicians should know about it
- Picked for Pharmacology (medical) (paper of the day, 26 September 2026): Very uncertain effects of IV vs oral caffeine
Abstract
INTRODUCTION: Caffeine is widely used in preterm infants, yet the optimal administration strategy remains unclear. This systematic review aims to evaluate different caffeine administration approaches, including route, frequency, dose modifications, and co-administration with surfactant in preterm infants. METHODS: We searched three databases and two trial registries up to October 2024. Data collection and analysis followed Cochrane methodology; certainty of evidence was assessed using GRADE; and reporting followed PRISMA. RESULTS: Three RCTs were identified, two provided data for analyses: one study (38 infants) on route of administration (intravenous versus oral caffeine) and one study (40 infants) on frequency of administration (once versus twice daily). The evidence is very uncertain about the effects of intravenous versus oral administration on: mortality (RR 0.14, 95% CI 0.01-2.59); mechanical ventilation duration (MD 1.00, 95% CI -8.05 to 10.05); hospital stay (MD 8.00, 95%CI -5.35-21.35); severe intraventricular hemorrhage (RR 1.00, 95%CI 0.29-3.43); and chronic lung disease (RR 5.00, 95%CI 0.26-97.70). The evidence is very uncertain about the effects of twice-daily versus once-daily caffeine on: mortality (RR 1.00, 95%CI 0.29-3.45); ventilation duration (MD 0.81, 95%CI -7.56-9.18); and hospital stay (MD -2.70, 95%CI -8.12-2.72). We found no studies on caffeine dose modifications and co-administration with surfactant. Two trials on adjusting caffeine dose and route of administration are ongoing. CONCLUSION: Although caffeine clearly benefits preterm infants, evidence guiding optimal administration strategies, such as route, frequency, and dose modifications, is limited. High-quality studies are urgently needed to inform clinical practice and guidelines.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.