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evident
Original paper
2006NEJMPediatrics

Caffeine for Apnea of Prematurity

Caffeine therapy for apnea of prematurity

RCTNeonatology

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Overview

In very-low-birth-weight infants, caffeine reduced oxygen use at 36 weeks postmenstrual age versus placebo, with temporarily lower weight gain.

Clinical takeaway

Caffeine started in the first 10 days of life reduced supplemental oxygen at 36 weeks postmenstrual age among infants still alive at that age, and allowed positive airway pressure to stop a week earlier. Weight gain was temporarily lower. Death, brain-injury ultrasound findings, and necrotizing enterocolitis did not differ.

Key result

Among infants alive at 36 weeks postmenstrual age, supplemental oxygen was used in 350 of 963 (36%) assigned to caffeine vs 447 of 954 (47%) assigned to placebo (adjusted OR 0.63, 95% CI 0.52-0.76; P<0.001).

Practice impact

Use caffeine for apnea of prematurity in very-low-birth-weight infants to reduce bronchopulmonary dysplasia; expect a short-term dip in weight gain.

Evidence

Study design

Randomized trial of caffeine versus placebo until drug therapy for apnea of prematurity was no longer needed, with short-term outcomes evaluated before the first discharge home.

Enrollment

2,006

Follow-up

Short-term outcomes before the first discharge home, including supplemental oxygen at 36 weeks postmenstrual age.

Geography

Not listed

Clinical question

Does caffeine therapy for apnea of prematurity reduce bronchopulmonary dysplasia and other short-term adverse outcomes in very-low-birth-weight infants?

Population

  • 2006 infants with birth weights of 500 to 1250 g, randomized during the first 10 days of life.

Intervention

Caffeine until drug therapy for apnea of prematurity was no longer needed.

Comparator

Placebo until drug therapy for apnea of prematurity was no longer needed.

Primary outcome

Short-term outcomes before first discharge home; the result featured in the conclusions is bronchopulmonary dysplasia, reported as supplemental oxygen at 36 weeks postmenstrual age among infants still alive.

Of infants assigned to caffeine who remained alive at 36 weeks postmenstrual age, 350 of 963 (36%) received supplemental oxygen vs 447 of 954 (47%) assigned to placebo (adjusted OR 0.63, 95% CI 0.52-0.76; P<0.001).

Adjusted odds ratio / 0.63 / 95% CI 0.52-0.76 / p<0.001

Key results

  • Among infants who remained alive at 36 weeks postmenstrual age, supplemental oxygen was used in 350 of 963 (36%) assigned to caffeine vs 447 of 954 (47%) assigned to placebo (adjusted OR 0.63, 95% CI 0.52-0.76; P<0.001).
  • Positive airway pressure was discontinued one week earlier with caffeine (median postmenstrual age 31.0 weeks, IQR 29.4-33.0) than with placebo (32.0 weeks, IQR 30.3-34.0; P<0.001).
  • Caffeine reduced weight gain temporarily. The mean difference versus placebo was greatest after two weeks (mean difference -23 g, 95% CI -32 to -13; P<0.001).
  • Rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between groups.

Harms

  • Caffeine reduced weight gain temporarily; the mean difference versus placebo was greatest after two weeks (-23 g, 95% CI -32 to -13; P<0.001).
  • Death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly.

Clinical Use

Practice impact

  • Start caffeine in the first 10 days of life for very-low-birth-weight infants treated for apnea of prematurity to reduce oxygen use at 36 weeks postmenstrual age.

Applicability

  • Most applicable to infants with birth weights of 500 to 1250 g who can start caffeine or placebo in the first 10 days of life and who remain in hospital through 36 weeks postmenstrual age.

Limitations

  • 2006 infants were randomized; the oxygen comparison used those still alive at 36 weeks postmenstrual age (963 caffeine, 954 placebo).
  • This paper reports short-term outcomes before first discharge home, not later neurodevelopment.
  • The abstract does not state the caffeine dose.

Common misinterpretations

  • The oxygen result is among infants alive at 36 weeks postmenstrual age, not among all 2006 randomized infants.
  • Do not infer a reduction in death, brain injury, or necrotizing enterocolitis; those rates did not differ significantly.

Related evidence

SUPPORT - Later Trial

Citation

Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112-2121. doi:10.1056/NEJMoa054065

Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight.