Abstract and Introduction
Abstract
Objective: To determine if early caffeine (EC) therapy is associated with decreased bronchopulmonary dysplasia (BPD) or death, decreased treatment of patent ductus arteriosus (PDA), or shortened duration of ventilation.
Study Design: In a retrospective cohort of 140 neonates ≤1250 g at birth, infants receiving EC (initiation <3 days of life) were compared with those receiving late caffeine (LC, initiation ≥3 days of life) using logistic regression.
Result: Of infants receiving EC, 25% (21/83) died or developed BPD compared with 53% (30/57) of infants receiving LC (adjusted odds ratio (aOR) 0.26, 95% confidence interval (CI) 0.09 to 0.70; P<0.01). PDA required treatment in 10% of EC infants versus 36% of LC infants (aOR 0.28, 95%CI 0.10 to 0.73; P=0.01). Duration of mechanical ventilation was shorter in infants receiving EC (EC, 6 days; LC, 22 days; P<0.01).
Conclusion: Infants receiving EC therapy had improved neonatal outcomes. Further studies are needed to determine if caffeine prophylaxis should be recommended for preterm infants.
Introduction
Despite improvements in survival for very low birth weight infants over the past two decades, bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) remain common morbidities affecting this vulnerable population. Over 40% of very low birth weight infants develop BPD based on recent estimates and BPD remains the most common chronic lung disease of infancy. Neonates with BPD are at high risk of long-term lung disease, adverse neurodevelopmental outcomes and readmission to the hospital in the first year of life. Despite the significant morbidities associated with BPD, few safe and effective therapies are available to prevent the disease. In addition to BPD, a persistent PDA is a common problem affecting approximately half of neonates <29 weeks gestation with over two-thirds receiving drug therapy for closure and approximately one-fourth requiring surgical closure. The presence of a persistent PDA is associated with increased neonatal morbidity such as prolonged ventilation and, although controversial, may also increase the risk of developing BPD.
Given the adverse outcomes associated with BPD and PDA, therapies targeted at reducing or preventing these morbidities are of significant value. In the Caffeine for Apnea of Prematurity (CAP) trial, caffeine therapy or placebo was initiated during the first 10 days of life (DOL) in infants weighing 500 to 1250 g at birth. Infants treated with caffeine had a decreased incidence of both BPD and PDA when compared with placebo. In addition, caffeine therapy reduced the duration of mechanical ventilation by approximately 1 week. Importantly, caffeine therapy also resulted in improved long-term neurodevelopmental outcomes. A post-hoc analysis of the CAP trial suggested that the efficacy of caffeine may be dependent on the timing of initiation of study drug. However, the trial only included infants who met inclusion criteria by DOL 10, potentially excluding a significant group of infants who did not meet clinical criteria for treatment.
Early caffeine (EC) therapy may carry additional benefit during a critical period of susceptibility to both lung and brain injury in the first few days of a premature infant's life. We compared infants ≤1250 g at birth who received caffeine early in their hospital course with those who were treated later to determine if the timing of caffeine therapy would impact common morbidities of prematurity. Our primary hypothesis was that extremely preterm infants who receive EC therapy (initiation before DOL 3) would have a decreased incidence of BPD or death, when compared with infants who were treated with caffeine later in their hospital course (initiation at or after DOL 3). As secondary outcomes, we evaluated if EC initiation would be associated with a reduction in the treatment of PDA and a decreased duration of endotracheal ventilation.