Prophylactic versus therapeutic caffeine for apnea of prematurity: a randomized controlled trial

Abstract

Background: Therapeutic initiation of methyxanthines for treatment of apnea in preterm infants was the standard policy. Caffeine therapy is beneficial for various outcomes of preterm infants.

Aim: To evaluate the efficacy of early prophylactic compared to routine therapeutic caffeine therapy on duration of oxygen support and other outcomes of preterm infants.

Methods: In a randomized controlled trial including preterm infants < 32 weeks' gestation, prophylactic (in the first 72 h of life) versus therapeutic (only if apnea exists or infant requires mechanical ventilation) decision of caffeine was compared. The primary outcome was the duration of oxygen therapy. Secondary outcomes included duration of respiratory support modalities; bronchoplumonary dysplasia (BPD); necrotizing enterocolitis; intra-ventricular hemorrhage; retinopathy of prematurity; length of hospital stay (LOS); neonatal mortality; and caffeine side effects.

Results: We enrolled 90 infants in the prophylactic and 91 infants in therapeutic groups respectively. Prophylactic caffeine decreased the duration of oxygen therapy [median and IQR of 28 (18-36) days versus 34 (23-51) days, p = .005 respectively]. Prophylactic caffeine significantly decreased the durations of respiratory support modalities, LOS, and incidences of mild to moderate BPD without reported effects on the incidence of severe BPD or other clinical outcomes compared to therapeutic caffeine. A significantly higher proportion of infants in the prophylactic caffeine group did not require mechanical ventilation during their NICU admission and a significant lower proportion required late mechanical ventilation compared to the prophylactic caffeine group.

Conclusion: Prophylactic caffeine decreased the duration of oxygen therapy, invasive and noninvasive ventilation, incidences of mild to moderate BPD, and LOS in preterm infants.

Keywords: Preterm infant; apnea; caffeine; mechanical ventilation; neonatal respiratory distress syndrome; xanthines.