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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sun reports receiving consulting fees from Merck Research Laboratories to attend a Pediatric Anesthesia Scientific Investigators Engagement meeting. Dr Li reports serving as director of the Columbia University Centers for Disease Control and Prevention–funded Injury Control Research Center (1 R49 CE002096). He also reports receiving research funding from the AAA Foundation for Traffic Safety. Dr Bellinger reports serving as a coinvestigator on the GAS Trial. He is co–principal investigator of a grant from the National Institute of Child Health and Human Development, National Institutes of Health (NIH) (HD084566) that funds the US sites of the GAS trial. Dr Radcliffe reports receiving NIH funding for research, as well as consultant fees from the City of Philadelphia and Columbia University unrelated to the PANDA project. Dr Hays reports serving as site primary investigator for industry-sponsored licensing studies from Endo Pharmaceuticals, Cadence Pharmaceuticals, Mallinckrodt Pharmaceuticals, and Grünenthal Group. Dr Maxwell reports having served on the data safety monitoring board for a clinical trial funded by The Medicines Company (Parsipanny, NJ) for which she received a consulting fee. She also reports serving as site principal investigator for 2 clinical trials funded by Grunenthal (Aachen, Germany). Dr McGowan reports receiving consulting fees from Merck Research Laboratories. No other disclosures were reported.

Figures

Figure. Participant Flow in the Pediatric Anesthesia Neurodevelopment Assessment Study

ASA indicates American Society of Anesthesiologists.