The Caffeine for Apnea of Prematurity (CAP) Trial: Preliminary Outcomes at 5 Years

Abstract

Background: The Caffeine for Apnea of Prematurity (CAP) trial enrolled 2006 infants with birth weights less than 1250 grams who were randomly assigned to receive caffeine therapy or placebo for apnea of prematurity (ClinicalTrials.gov NCT00182312). Caffeine-treated infants had a significantly decreased risk of bronchopulmonary dysplasia (N Engl J Med 2006;354:2112), as well as an improved rate of survival without neurodevel- opmental impairment at 18 to 21 months corrected age (N Engl J Med 2007;357:1893). Objective: To reassess the CAP trial participants at a corrected age of 5 years in order to estimate more accurately the long-term effects of neonatal caffeine therapy, with particular emphasis on cognitive, behavioural and motor development. Design/Methods: The main outcome at age 5 years is a composite of death or survival with disability in at least one of 6 domains: cognition, neuromotor function, behavior, vision, hearing, and general health. Standardized tests included a thorough history and physical exam, application of the Gross Motor Function Classification System, the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and the Child Behavior Checklist Parent Form. Results: All but 4 of the original study centers participated in this extended follow up. These 4 centers enrolled a total of 74 infants, leaving 1932 children eligible for inclusion in the present study. As of November 23, 2010, vital status has been ascertained for 1800 children or 93% of the eligible cohort and adequate data for the composite outcome of death or disability have been received at the data center for 1636 children (85%). The last two assessments are booked for early December 2010 and the database will be declared closed in early 2011. The final analyses will be completed by the end of April 2011. Conclusions: To date, the CAP trial has shown that the benefits of caffeine therapy for apnea of prematurity outweigh any potential risks up to a corrected age of 18 to 21 months. However, several important potential long-term consequences of caffeine therapy may not become apparent until the study cohort reaches pre-school age. The present analysis will confirm or refute the longer-term safety of caffeine therapy for apnea of prematurity