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Administration time of caffeine in preterm infants: systematic review and meta-analysis
Gabriela S Trindade1,2, Renato S Procianoy3,4, Victoria Baptista Dos Santos5
1Postgraduate Masters Degree in Program of Health of Child and Adolescent, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Insights
Administering caffeine to premature infants within the first 24 hours of life reduces major morbidities. However, this early caffeine administration may be associated with increased mortality, potentially due to survival bias.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Clinical Research
Background:
- Caffeine is widely used in neonatal intensive care units for preterm infants.
- The optimal timing for initiating caffeine therapy remains a critical question for improving outcomes.
Purpose of the Study:
- To determine the ideal time for caffeine administration in preterm infants.
- To evaluate the effects and safety of early versus late caffeine initiation.
Main Methods:
- A meta-analysis of 18 studies involving 76,998 preterm infants (<32 weeks GA or BW <1500g).
- Comparison of caffeine administration timing: <24 vs. ≥24 hours, <48 vs. ≥48 hours, <72 vs. ≥72 hours.
Main Results:
- Early caffeine (<24 hours) was associated with reduced rates of patent ductus arteriosus, retinopathy of prematurity, severe brain injury, and bronchopulmonary dysplasia (BPD).
- A composite outcome of BPD or death was also reduced with early caffeine administration.
- An increased mortality risk was observed with early caffeine, though this finding had very low evidence and may be influenced by survival bias.
Conclusions:
- Initiating caffeine therapy within the first 24 hours of life demonstrates significant benefits in reducing key morbidities in preterm infants.
- The observed increase in mortality warrants further investigation, considering potential confounding factors like survival bias.
Abstract:
To assess the ideal time for caffeine administration in preterms, identifying its effects and safety. Study Design: Meta-analysis conducted including preterms <32 weeks GA or BW < 1500 g, comparing caffeine administration time: <24 x ≥24HOL, <48 x ≥48HOL, <72 x ≥72HOL. 18 studies included 76.998 patients. The median age of starting caffeine was the first 24 HOL. In the overall comparisons, there was reduction in patent ductus arteriosus (OR 0.71 [0.55, 0. 92]; low evidence), retinopathy of prematurity (OR 0.71 [0.54, 0.93]; moderate evidence), severe brain injury (OR 0.79 [0.70, 0.91]; moderate evidence), bronchopulmonary dysplasia (BPD) (OR 0.69 [0.59, 0.81]; moderate evidence), composite outcome of BPD or death (OR 0.76 [0.66, 0.88]; moderate evidence). Mortality increase was found (OR 1.20 [1.12, 1.29], very low evidence).Caffeine in the first 24 HOL has benefits in reducing morbidities associated with prematurity. Mortality finding is potentially due to survival bias.
