The incidence of apnoea of prematurity (AOP) is inversely proportional to gestational age and birth weight. Almost all infants born earlier than 28 weeks’ gestation are affected by this condition. Caffeine has largely replaced other methylxanthines for the treatment of AOP due to its wider therapeutic index and longer half-life.

Caffeine is used to stimulate the respiratory centre of the medulla and increase skeletal muscle tone, contractility of the diaphragm, and sensitivity to carbon dioxide. It may also have anti-inflammatory effects in the immature lung. A large placebo-controlled trial studying infants up to their first discharge home demonstrated a significant reduction in the incidence of bronchopulmonary dysplasia in the caffeine-treated group. As this condition is an important risk factor for neurosensory impairment, it was hypothesised that the benefits of caffeine might extend into childhood and beyond.

An eleven-year follow-up of these patients has recently been published. This study provides the most comprehensive evidence on the long-term safety and efficacy of caffeine for AOP to date. While the rate of academic and behavioural impairment was not significantly different, the incidence of motor impairment was reduced in the caffeine-treated group. Motor impairment, defined as a percentile rank of five or less on the Movement Assessment Battery for Children – Second Edition, occurred in 19.7% of the caffeine group compared to 27.5% of the placebo group. Long-term harmful effects were not identified. Earlier trials identified reduced weight gain in the first four to six weeks of therapy as a significant short-term risk.


  1. Eichenwald EC. Apnea of prematurity. Pediatr. 2016; 137(1): e 20153757.Schmidt B, Roberts RS, Anderson PJ, Asztalos EV, Costantini L, Davis PG, et al. Academic performance, motor function, and behavior 11 years after neonatal caffeine citrate therapy for apnea of prematurity: an 11-year follow-up of the cap randomized clinical trial. JAMA Pediatr. 2017; 17(16): 564-72.
  2. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006; 354: 2112-21.

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