When to start and stop caffeine and why respiratory status matters.

Caffeine as tested in the CAP trial is safe and effective for preterm infants with birthweights less than 1250 g. Evidence for its use beyond the indications and timing used in this trial is of low quality and conflicting. Some studies suggest that earlier use of caffeine increases the risk of mortality while others suggest it has important benefits. It appears that infants with apnea of prematurity and those receiving assisted ventilation are the most likely to benefit from caffeine. Based on currently available evidence, routine early prescription of caffeine does not appear to be indicated. Infants continue to have potentially damaging episodes of hypoxia secondary to apnea beyond 34 weeks' postmenstrual age. It is unclear whether prolonged use of caffeine improves outcomes in these infants. Randomized trials to resolve these uncertainties are required. They need to be large, at least the size of the CAP trial, and include neurodevelopmental outcomes.