In February 2019, the New York Times published an article entitled, “Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows”1. The article unveiled the results of a randomly controlled trial that compared neural development between infants that were exposed to anesthesia, and the control cohort of infants who had no such exposure. This study conclusively found that there were no significant neurodevelopment differences among the cohort. In producing such results, the New York Times contributed to a larger debate in the surgical and anesthesia services community on the use of pediatric anesthesia. Over the past decade, multiple conflicting reports have emerged regarding the effects of administering anesthesia to pediatric patients on neurological development. The topic is oft-debated in the academic literature. A brief summary of important research to-date is useful for evaluating this question and deciding treatment plans for the pediatric population.
The theory suggesting that pediatric anesthesia administration could potentially impart negative effects on patients was early introduced on by results from animal studies. In 2003, Dr. Jevtovic-Todorovic and her research team discovered that exposure to nitrous oxide, isoflurane, and midazolam led to significant neurodevelopmental effects in neonatal rats2. In this study, the exposure to anesthesia agents was designed to mimic that of percentages utilized in surgery. Furthermore, the length of exposure similarly matched an average surgery, approximately 6 hours, in order to include time as a relevant factor. The results revealed that the neonatal rats exposed to anesthesia suffered apoptotic neurodegeneration, impaired memory and learning, and a decrease in hippocampal function. These specific and impactful results served as a cause for concern, as animal models often preempt human subjects’ trials. The result of this animal study therefore spurred debate among the anesthesiology and surgical academic fields as to the relevance of the results, as well as the possible mechanisms by which these effects occur.
Of note, Block et al revealed in a 2012 study that early exposure to anesthesia, defined in this study as before one year of age, results in a significant decrease of white matter in the brain3. The longitudinal study followed two cohorts, the anesthesia exposure cohort and the control, recording intellectual capability as measured by academic achievement over a decade. The study subjects also underwent significant neuro-imaging, including MRI. In this study, subjects who had anesthesia as infants reported a 4% decrease in white matter content compared to the control. For reference, white matter is linked with neural communications, as well as learning and neuronal function4.
In the same wave that academic research commenced a focus on these topics, national healthcare policy similarly followed suit. The U.S. Food and Drug Administration (FDA) has released multiple bulletins detailing that the agency warned against administering anesthesia to patients less than three years of age5. If anesthesia is necessary, the FDA recommended that the procedure be less than three hours in totality. These guidelines were readily adopted in multiple healthcare institutions across the States, according to FDA data.
However, in recent years, human subject studies have provided results in contrast with earlier research on this topic, thus suggesting that previous results may have been based on confounding factors. The Mayo Anesthesia Safety in Kids study, results published in 2018, compared three cohorts of pediatric patients and followed the subjects for up to 20 years post-exposure6. The cohorts included control of unexposed patients, patients who were exposed to anesthesia once, and patients who were exposed to anesthesia multiple times. The results showed that exposure of anesthesia before 3 years of age was not associated with negative impacts with regards to IQ and neuropsychological assessment. These results were supported by a recent large-scale study, which examined the effect of anesthesia exposure for more than 10,000 study subjects over time and found that exposure to anesthesia was not associated with any neurocognitive deficits7. Therefore, current studies clearly suggest that the previous links to neurological defects are not indicative of causality and are likely due to confounding or external biological and environmental factors.
Researchers in the anesthesia and surgical space will continue to study pediatric anesthesia and its specific effects until the advent of a clinically accepted definition. However, the recent press attributed to this topic underscores the importance of focusing clinical care on pediatric and other vulnerable populations, for anesthesia providers, researchers, and policy-makers alike.
1 Klass, Perri. “Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows.” The New York Times, The New York Times, 18 Feb. 2019, www.nytimes.com/2019/02/18/well/family/one-exposure-to-anesthesia-in-children-does-not-cause-learning-disabilities-new-research-shows.html.
2 Jevtovic-Todorovic, V, et al. “Early Exposure to Common Anesthetic Agents Causes Widespread Neurodegeneration in the Developing Rat Brain and Persistent Learning Deficits.” Journal of Neurosurgical Anesthesiology, vol. 15, no. 3, 1 Feb. 2003, pp. 295–296., doi:10.1097/00008506-200307000-00029.
3 Block, Robert I., et al. “Are Anesthesia and Surgery During Infancy Associated With Altered Academic Performance During Childhood?” Survey of Anesthesiology, vol. 57, no. 2, 2013, p. 80., doi:10.1097/sa.0b013e318287d938.
4 U.S. National Library of Medicine. “White Matter of the Brain: MedlinePlus Medical Encyclopedia.” MedlinePlus, U.S. National Library of Medicine, medlineplus.gov/ency/article/002344.htm.
5 Center for Drug Evaluation and Research. “Drug Safety and Availability – FDA Drug Safety Communication: FDA Review Results in New Warnings about Using General Anesthetics and Sedation Drugs in Young Children and Pregnant Women.” U S Food and Drug Administration Home Page, Center for Drug Evaluation and Research, www.fda.gov/drugs/drugsafety/ucm532356.htm.
6 Warner, David O, et al. “Neuropsychological and Behavioral Outcomes after Exposure of Young Children to Procedures Requiring General Anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study.” Anesthesiology, U.S. National Library of Medicine, July 2018, www.ncbi.nlm.nih.gov/pubmed/29672337.
7 O’Leary, James D., et al. “Influence of Surgical Procedures and General Anesthesia on Child Development Before Primary School Entry Among Matched Sibling Pairs.” JAMA Pediatrics, vol. 173, no. 1, 2019, p. 29., doi:10.1001/jamapediatrics.2018.3662.