NEW YORK (Reuters Health) – While respiratory stimulation with caffeine in very preterm infants with apnea of prematurity reduces rates of impairment at 18 months, the benefits are no longer apparent at 5 years, trial investigators report in the Journal of the American Medical Association for January 18.

“Although the observed rates of the combined main outcome of death or disability continued to favor caffeine over placebo treatment, the difference between the groups was not statistically significant,” the authors conclude.

Dr. Barbara Schmidt, at the Hospital of the University of Pennsylvania, Philadelphia, and colleagues began the Caffeine for Apnea of Prematurity (CAP) trial in 1999.  Originally, 2000 preterm infants with birth weights between 500 and 1200 grams were randomly assigned to receive caffeine citrate or saline placebo to treat or prevent apnea.

The researchers found that caffeine improved the rate of survival without neurodevelopmental disability at a corrected age of 18 months.  In the current study, they report outcomes at 5 years in 1640 of the children for whom there were adequate data.

The primary outcome was death or survival with at least one impairment – that is, motor impairment, cognitive impairment, behavior problems, poor general health, severe hearing loss, or bilateral blindness.  The 5-year rate was not significantly different in the two groups, at 21.1% among the children who received caffeine therapy compared to 24.8% in those assigned to placebo (odds ratio 0.82; p=0.09), according to the report.

The investigators also found rates of the individual components of the composite endpoint did not differ significantly between the two arms.  However, a secondary analysis indicated that caffeine therapy was associated with better gross motor function, manual dexterity and visual perception.

The rates of cognitive impairment declined considerably between 18 months and 5 years, and at that point there was no significant difference between the caffeine and placebo arms (4.9% versus 5.1%, respectively), Dr. Schmidt and colleagues report.

This suggests “that cognitive delay during the second year of life may not be a lasting outcome after very preterm birth,” they conclude.

The authors of an accompanying editorial observe: “As the CAP trial demonstrates, long-term follow-up is essential for reaching accurate conclusions about the efficacy of new therapies in preterm infants.”

JAMA 2012;307:275-282,304-305.