Shifting the Boundaries for Early Caffeine Initiation in Neonatal Practice: Results of a Prospective, Multicenter Study on Very Preterm Infants with Respiratory Distress Syndrome

Background: There is growing evidence that supports the benefits of early use of caffeine in preterm neonates with RDS; however, no formal recommendations specifying the exact timing of therapy initiation have been provided.

Objectives: We compared neonatal outcomes in infants receiving early (initial dose on the 1st day of life) and late (initial dose on day 2+ of life) caffeine therapy.

Methods: Using data from a prospective, cohort study, we identified 986 infants ≤32 weeks' gestation with RDS and assessed the timing of caffeine therapy initiation, need for ventilatory support, mortality and incidence of typical complications of prematurity. To adjust for baseline severity, the early and late caffeine groups were propensity score (PS) matched to 286 infants (1:1). Clinical outcomes were compared between the PS-matched groups.

Results: Early treatment with caffeine citrate was associated with a significantly reduced need for invasive ventilation (71.3% vs 83.2%; P = 0.0165) and total duration of mechanical ventilation (mean 5 ± 11.1 days vs 10.8 ± 14.6 days; P = 0.0000) and significantly lower odds of intraventricular hemorrhage (IVH) (OR 0.4827; 95% CI 0.2999-0.7787) and patent ductus arteriosus (PDA) (OR 0.5686; 95% CI 0.3395-0.9523). The incidence of bronchopulmonary dysplasia (BPD) (36.4% vs 45.8%) and rates of moderate and severe BPD were not significantly different between the two groups. The mortality rates were comparable between the two groups (8.6% vs 8.5%, P = ns).

Conclusion: Early caffeine initiation was associated with a decreased need for invasive ventilatory support and lower incidence of IVH and PDA.