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Caffeine to prevent intermittent hypoxaemia in late preterm infants: randomised controlled dosage trial
Elizabeth Anne Oliphant1,2, Christopher Jd McKinlay1,3, David McNamara2
1Department of Paediatrics: Child and Youth Health, The University of Auckland, Auckland, New Zealand.
Insights
Caffeine citrate effectively prevents intermittent hypoxaemia (IH) in late preterm infants. The 20 mg/kg/day dose demonstrated the greatest efficacy, improving oxygen saturation without significant adverse effects.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Pediatric Critical Care
Background:
- Intermittent hypoxaemia (IH) is a significant concern in late preterm infants.
- Optimizing treatment requires establishing the most effective caffeine citrate dosage.
- Previous research has not definitively determined the optimal dose for IH prevention in this population.
Purpose of the Study:
- To determine the optimal dose of caffeine citrate for preventing intermittent hypoxaemia (IH) in late preterm infants.
- To evaluate the safety and efficacy of different caffeine citrate doses.
- To identify the best-tolerated and most effective dose for IH management.
Main Methods:
- A Phase IIB, double-blind, randomized controlled trial was conducted in two tertiary maternity hospitals.
- Late preterm infants (34-36 weeks gestation) received varying enteral doses of caffeine citrate (loading dose followed by daily maintenance) or placebo.
- Intermittent hypoxaemia (IH) was assessed as the primary outcome, defined by oxygen saturation drops of ≥10% below baseline for ≤2 minutes, measured per hour.
Main Results:
- Caffeine citrate significantly reduced the rate of IH at two weeks post-randomization compared to placebo.
- The 20 mg/kg/day dose of caffeine citrate was most effective, showing statistically significant reductions in IH events.
- The 20 mg/kg/day dose also improved mean pulse oximetry oxygen saturation and reduced the percentage of time with SpO2 <90% without adverse effects on growth or sleep.
Conclusions:
- Caffeine citrate is effective in reducing intermittent hypoxaemia in late preterm infants.
- The optimal and most effective dose of caffeine citrate for IH prevention in this population is 20 mg/kg/day.
- This dose is well-tolerated and does not appear to cause significant adverse effects on infant growth or sleep patterns.
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+0-36+6 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 (SpO2) (97.2 (1.0) vs placebo 96.0 (0.8); p<0.001), and reduced median (IQR) percentage of time SpO2 <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.
