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Original Investigation |

Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood

Lena S. Sun, MD1; Guohua Li, MD, DrPH2; Tonya L. K. Miller, MD3; Cynthia Salorio, PhD4; Mary W. Byrne, PhD, MPH5; David C. Bellinger, PhD, MSc3; Caleb Ing, MD, MS1; Raymond Park, MD3; Jerilynn Radcliffe, PhD6; Stephen R. Hays, MD, MS7; Charles J. DiMaggio, PhD8; Timothy J. Cooper, PsyD7; Virginia Rauh, ScD9; Lynne G. Maxwell, MD6; Ahrim Youn, PhD9; Francis X. McGowan, MD6
[+] Author Affiliations
1Morgan Stanley Children’s Hospital–New York Presbyterian, Columbia University Medical Center, New York, New York
2Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York
3Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
4Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
5School of Nursing and College of Physicians and Surgeons, Columbia University, New York, New York
6Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
7Monroe Carell Jr Children’s Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, Tennessee
8New York University School of Medicine, New York, New York
9Mailman School of Public Health, Columbia University, New York, New York
JAMA. 2016;315(21):2312-2320. doi:10.1001/jama.2016.6967.
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Importance  Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand.

Objective  To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood.

Design, Setting, and Participants  Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data.

Exposures  A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months.

Main Outcomes and Measures  The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior.

Results  Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = −0.2 (95% CI, −2.6 to 2.9); performance = 0.5 (95% CI, −2.7 to 3.7); and verbal = −0.5 (95% CI, −3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior.

Conclusions and Relevance  Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.

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Participant Flow in the Pediatric Anesthesia Neurodevelopment Assessment Study

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