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Academic Performance, Motor Function, and Behavior 11 Years After Neonatal Caffeine Citrate Therapy for Apnea of
Barbara Schmidt1, Robin S Roberts2, Peter J Anderson3
1Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada2Division of Neonatology, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia.
Insights
Neonatal caffeine citrate therapy for apnea of prematurity did not reduce combined academic, motor, or behavioral impairments at 11 years. However, it was associated with a reduced risk of motor impairment in very low birth weight children.
Area of Science:
- Neonatal care
- Developmental pediatrics
- Pharmacology
Background:
- Apnea of prematurity (AOP) is common in very low birth weight (VLBW) infants.
- Caffeine citrate therapy is a standard treatment for AOP.
- Previous studies indicated benefits of caffeine for AOP at earlier ages.
Purpose of the Study:
- To evaluate long-term functional outcomes at 11 years of age in children treated with caffeine citrate for AOP.
- To assess the association between neonatal caffeine therapy and academic, motor, and behavioral impairments at school age.
Main Methods:
- A follow-up study of children from the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial.
- Participants were VLBW infants treated with caffeine citrate or placebo for AOP.
- Functional impairment was assessed at a median age of 11.4 years using standardized tests for academic, motor, and behavioral outcomes.
Main Results:
- The combined rate of functional impairment (academic, motor, behavioral) was not significantly different between caffeine and placebo groups (31.7% vs 37.6%).
- Rates of poor academic performance and behavior problems were similar between groups.
- Caffeine therapy was associated with a significantly reduced risk of motor impairment (19.7% vs 27.5%; P=.009).
Conclusions:
- Neonatal caffeine citrate therapy for AOP did not significantly reduce the combined rate of academic, motor, and behavioral impairments at 11 years.
- However, caffeine therapy was linked to a lower risk of motor impairment in VLBW children.
- Neonatal caffeine therapy appears safe and effective into middle school age at the doses used.
Importance:
Caffeine citrate therapy for apnea of prematurity reduces the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability at 18 months and may improve motor function at 5 years.
Objective:
To evaluate whether neonatal caffeine therapy is associated with improved functional outcomes 11 years later.
Design, Setting, And Participants:
A follow-up study was conducted at 14 academic hospitals in Canada, Australia, and the United Kingdom from May 7, 2011, to May 27, 2016, of English- or French-speaking children who had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between October 11, 1999, and October 22, 2004. A total of 1202 children with birth weights of 500 to 1250 g were eligible for this study; 920 (76.5%) had adequate data for the main outcome.
Interventions:
Caffeine citrate or placebo until drug therapy for apnea of prematurity was no longer needed.
Main Outcomes And Measures:
Functional impairment was a composite of poor academic performance (defined as at least 1 standard score greater than 2 SD below the mean on the Wide Range Achievement Test-4), motor impairment (defined as a percentile rank of ≤5 on the Movement Assessment Battery for Children-Second Edition), and behavior problems (defined as a Total Problem T score ≥2 SD above the mean on the Child Behavior Checklist).
Results:
Among the 920 children (444 females and 476 males; median age, 11.4 years [interquartile range, 11.1-11.8 years]), the combined rates of functional impairment were not significantly different between the 457 children assigned to receive caffeine compared with the 463 children assigned to receive placebo (145 [31.7%] vs 174 [37.6%]; adjusted odds ratio, 0.78; 95% CI, 0.59-1.02; P = .07). With all available data, including those from up to 24 Swedish trial participants, the rates of poor academic performance on 1 or more of 4 subtests (66 of 458 [14.4%] vs 61 of 462 [13.2%]; adjusted odds ratio, 1.11; 95% CI, 0.77-1.61; P = .58) and behavior problems (52 of 476 [10.9%] vs 40 of 481 [8.3%]; adjusted odds ratio, 1.32; 95% CI, 0.85-2.07; P = .22) were broadly similar between the group that received caffeine and the group that received placebo. However, caffeine therapy was associated with a reduced risk of motor impairment compared with placebo (90 of 457 [19.7%] vs 130 of 473 [27.5%]; adjusted odds ratio, 0.66; 95% CI, 0.48-0.90; P = .009).
Conclusions And Relevance:
Caffeine therapy for apnea of prematurity did not significantly reduce the combined rate of academic, motor, and behavioral impairments but was associated with a reduced risk of motor impairment in 11-year-old children with very low birth weight. At the doses used in this trial, neonatal caffeine therapy is effective and safe into middle school age.
Trial Registration:
clinicaltrials.gov Identifier: NCT00182312; isrctn.org Identifier: ISRCTN44364365.
