Neurobehavioral Outcomes 11 Years After Neonatal Caffeine Therapy for Apnea of Prematurity.

Ines M Mürner-Lavanchy, Lex W Doyle, Barbara Schmidt, Robin S Roberts, Elizabeth V Asztalos, Lorrie Costantini, Peter G Davis, Deborah Dewey, Judy D'Ilario, Ruth E Grunau, Diane Moddemann, Harvey Nelson, Arne Ohlsson, Alfonso Solimano, Win Tin, Peter J Anderson

Journal: Pediatrics 2019;141(5):e20174047

PMID: 29643070

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Abstract

BACKGROUND AND OBJECTIVES

Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate effects of neonatal caffeine therapy in very low birth weight (500-1250 g) infants on neurobehavioral outcomes in 11-year-old participants of the Caffeine for Apnea of Prematurity trial.

METHODS

Thirteen academic hospitals in Canada, Australia, Great Britain, and Sweden participated in this part of the 11-year follow-up of the double-blind, randomized, placebo-controlled trial. Measures of general intelligence, attention, executive function, visuomotor integration and perception, and behavior were obtained in up to 870 children. The effects of caffeine therapy were assessed by using regression models.

RESULTS

Neurobehavioral outcomes were generally similar for both the caffeine and placebo group. The caffeine group performed better than the placebo group in fine motor coordination (mean difference [MD] = 2.9; 95% confidence interval [CI]: 0.7 to 5.1; = .01), visuomotor integration (MD = 1.8; 95% CI: 0.0 to 3.7; < .05), visual perception (MD = 2.0; 95% CI: 0.3 to 3.8; = .02), and visuospatial organization (MD = 1.2; 95% CI: 0.4 to 2.0; = .003).

CONCLUSIONS

Neonatal caffeine therapy for apnea of prematurity improved visuomotor, visuoperceptual, and visuospatial abilities at age 11 years. General intelligence, attention, and behavior were not adversely affected by caffeine, which highlights the long-term safety of caffeine therapy for apnea of prematurity in very low birth weight neonates.

Address: Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, Australia.; Murdoch Children's Research Institute, Melbourne, Australia.; Departments of Paediatrics and.; Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.; The Royal Women's Hospital, Melbourne, Australia.; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.; Division of Neonatology, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania.; Department of Paediatrics, University of Toronto, Toronto, Canada.; Alberta Children's Hospital Research Institute for Child and Maternal Health and Departments of Pediatrics and Community Health Sciences, University of Calgary, Calgary, Canada.; British Columbia Children's Hospital Research Institute, Vancouver, Canada.; Department of Pediatrics, University of British Columbia, Vancouver, Canada.; Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada; and.; Department of Pediatrics, James Cook University Hospital, Middlesbrough, England.; Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, Australia; [email protected].

DOI: 10.1542/peds.2017-4047

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MeSH Terms: Apnea, Caffeine, Central Nervous System Stimulants, Child, Child Development, Double-Blind Method, Female, Follow-Up Studies, Humans, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Infant, Very Low Birth Weight, Male, Motor Skills, Psychomotor Performance, Spatial Processing, Visual Perception