Caffeine to prevent intermittent hypoxaemia in late preterm infants: randomised controlled dosage trial.

OBJECTIVE

To establish the most effective and best tolerated dose of caffeine citrate for the prevention of intermittent hypoxaemia (IH) in late preterm infants.

DESIGN

Phase IIB, double-blind, five-arm, parallel, randomised controlled trial.

SETTING

Neonatal units and postnatal wards of two tertiary maternity hospitals in New Zealand.

PARTICIPANTS

Late preterm infants born at 34-36 weeks' gestation, recruited within 72 hours of birth.

INTERVENTION

Infants were randomly assigned to receive a loading dose (10, 20, 30 or 40 mg/kg) followed by 5, 10, 15 or 20 mg/kg/day equivolume enteral caffeine citrate or placebo daily until term corrected age.

PRIMARY OUTCOME

IH (events/hour with oxygen saturation concentration ≥10% below baseline for ≤2 min), 2 weeks postrandomisation.

RESULTS

132 infants with mean (SD) birth weight 2561 (481) g and gestational age 35.7 (0.8) weeks were randomised (24-28 per group). Caffeine reduced the rate of IH at 2 weeks postrandomisation (geometric mean (GM): 4.6, 4.6, 2.0, 3.8 and 1.7 events/hour for placebo, 5, 10, 15 and 20 mg/kg/day, respectively), with differences statistically significant for 10 mg/kg/day (GM ratio (95% CI] 0.39 (0.20 to 0.76]; p=0.006) and 20 mg/kg/day (GM ratio (95% CI] 0.33 (0.17 to 0.68]; p=0.003) compared with placebo. The 20 mg/kg/day dose increased mean (SD) pulse oximetry oxygen saturation (SpO) (97.2 (1.0) vs placebo 96.0 (0.8); p<0.001), and reduced median (IQR) percentage of time SpO <90% (0.5 (0.2-0.8) vs 1.1 (0.6-2.4); p<0.001) at 2 weeks, without significant adverse effects on growth velocity or sleeping.

CONCLUSION

Caffeine reduces IH in late preterm infants at 2 weeks of age, with 20 mg/kg/day being the most effective dose.

TRIAL REGISTRATION NUMBER

ACTRN12618001745235.