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Neurodevelopmental Outcomes After Initial Childhood Anesthetic Exposure Between Ages 3 and 10 Years

Ing, Caleb H. MD, MS*; DiMaggio, Charles J. PhD, MPH, PA-C; Whitehouse, Andrew J.O. PhD; Hegarty, Mary K. MBBS, FANZCA§; Sun, Ming MS; von Ungern-Sternberg, Britta S. MD, PhD§¶; Davidson, Andrew J. MD#; Wall, Melanie M. PhD**; Li, Guohua MD, DrPH; Sun, Lena S. MD††

Journal of Neurosurgical Anesthesiology: October 2014 - Volume 26 - Issue 4 - p 377–386
doi: 10.1097/ANA.0000000000000121
Departments: Supplement: Fourth Pediatric Anesthesia and Neuro-Development Assessment (PANDA) Symposium

Introduction: Epidemiologic studies examining the association between anesthetic exposure and neurodevelopmental outcomes have primarily focused on exposures occurring under 3 years of age. In this study, we assess outcomes associated with initial anesthetic exposure occurring between 3 and 10 years of age.

Methods: We used data from the Western Australian Pregnancy Cohort (Raine) Study to examine the risk of cognitive deficit at age 10 in children with initial anesthetic exposure between 3 and 5 years and between 5 and 10 years of age compared with children unexposed at those ages. The cohort included 2868 children born from 1989 to 1992 evaluated using a range of neuropsychological tests. A modified multivariable Poisson regression model was used to determine the adjusted association of initial anesthetic exposure in each age group with outcomes.

Results: Exposed and unexposed children were found to have similar neuropsychological test results except for the McCarron Assessment of Neuromuscular Development (MAND) motor function scores. Even after adjusting for demographic and comorbidity differences, children exposed to anesthesia had a higher risk of motor deficit after initial exposure between ages 3 and 5 years (adjusted risk ratio, 2.32; 95% confidence interval, 1.42-3.79) and between 5 and 10 years (adjusted risk ratio, 2.33; 95% confidence interval, 1.21-4.48) compared with unexposed children.

Conclusions: Initial exposure to anesthesia after age 3 had no measurable effects on language or cognitive function. Decreased motor function was found in children initially exposed after age 3 even after accounting for comorbid illness and injury history. These results suggest that there may be distinct windows of vulnerability for different neurodevelopmental domains in children.

Departments of *Anesthesiology

††Anesthesiology and Pediatrics, Columbia University College of Physicians and Surgeons

Departments of Anesthesiology and Epidemiology

Anesthesiology and Biostatistics

**Psychiatry and Biostatistics, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY

Telethon Kids Institute

School of Medicine and Pharmacology, The University of Western Australia

§Department of Anaesthesia and Pain Management, Princess Margaret Hospital for Children, Perth, WA

#Department of Anaesthesia, Murdoch Childrens Research Institute & Royal Children’s Hospital, Melbourne, Vic., Australia

Supported in part by a grant from SmartTots (San Francisco, CA). The Western Australian Pregnancy Cohort (Raine) Study is funded by project and program grants from the National Health and Medical Research Council of Australia (Canberra, Australia). Core management funding is provided by the Raine Medical Research Foundation, the Telethon Kids Institute, the University of Western Australia (UWA), the UWA Faculty of Medicine, Dentistry and Health Sciences, the Women and Infants Research Foundation, and Curtin University. All institutions providing core management funding reside in Perth, Australia. B.S.v.U.-S. is partly funded by the Princess Margaret Hospital Foundation and Woolworths Australia (Perth, Australia). Supported in part by Grant 1 R49 CE002096 from the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention to the Center for Injury Epidemiology and Prevention at Columbia University.

The authors have no conflicts of interest to disclose.

Reprints: Caleb H. Ing, MD, MS, Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. BHN 4-440, New York, NY 10032 (e-mail:

Received July 22, 2014

Accepted July 2, 2014

© 2014 by Lippincott Williams & Wilkins