Caffeine and other methylxanthines' impact on bronchiolitis-related apnea in under 12-months-old children-a systematic review with meta-analyses.

The aim of this study was to assess the impact of caffeine and other methylxanthines on bronchiolitis-related apnea (BRA) in infants under 12 months of age, through a systematic review and meta-analysis. The review was conducted in accordance with the PRISMA guidelines. Inclusion criteria were studies published from January 1990 to August 2023, in English or French, and involving children from 35 weeks' gestational age to 1 year with BRA. Relevant articles were selected and data extracted by 2 members of the blinded investigative team. Four hundred sixty-nine articles were retrieved. Eleven studies conducted in Europe and North America were considered in the systematic review. Six studies were used in the meta-analysis. The meta-analysis showed no positive impact of caffeine on the length of non-invasive ventilation (mean difference =  - 0.26 days, 95% CI [- 1.71; 1.20], p = 0.53), invasive ventilation requirement (mean difference =  - 0.05 [- 0.24; 0.13], p = 0.44), or length of pediatric intensive care unit and hospital stay (mean difference =  - 0.62 days, 95% CI [- 9.31; 8.07], p = 0.79; mean difference = 1.60 days, 95% CI [- 3.65; 6.85], p = 0.32, respectively). However, caffeine was associated with a trend towards a decrease in the total length of respiratory support (mean difference =  - 2.63 days, 95% CI [- 5.61; 0.34], p = 0.06).

conclusionThis study highlights the ongoing debate surrounding the role of caffeine and other methylxanthines in BRA. The general paucity of literature, its low level of quality, the heterogeneity of results, different caffeine regimens, and population definition greatly impaired the quality of the conclusions. However, by identifying gaps in the literature, this study helps build a framework for future trials. WHAT IS KNOWN: • Apnea is a recognized complication of bronchiolitis in infants, particularly in those born preterm or at a young corrected age, and may necessitate intensive respiratory support. • While caffeine is a cornerstone therapy for apnea of prematurity, evidence supporting its use in bronchiolitis-related apnea (BRA) remains limited and inconclusive. WHAT IS NEW: • This is the first systematic review with meta-analysis evaluating caffeine in BRA, showing no significant improvement in major clinical outcomes, but suggesting a possible reduction in overall respiratory support duration. • The study identifies critical methodological limitations in the existing literature, including heterogeneous apnea definitions and non-standardized caffeine dosing, and proposes a framework for future controlled studies.