International Anesthesia Research Society, March 23, 2015.
P. Glatz1, R. H. Sandin1, N. L. Pedersen2, A. Edstedt Bonamy3, L. I. Eriksson1, F. N. Granath4
AFFILIATION: 1Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden, 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, 3Department of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, 4Department of Clinical Epidemiology, Karolinska Insitutet, Stockholm, Sweden.
INTRODUCTION: While preclinical studies strongly suggest that exposure to general anesthetics during infancy leads to increased neuronal apoptosis and later neurocognitive impairment1, there is contradictory information from human studies aiming to translate preclinical findings into outcome studies of children exposed to anesthesia and surgery before age 4 yrs2.
METHODS: After IRB approval we investigated a cohort of all, approximately 2 million children, born 1973-93. Data were collected from national health care and population registers to explore the association between pediatric exposure to anesthesia and surgery and ninth grade school results.
Among the 107,460 children with at least one surgical procedure before age 4 yrs, the primary analysis was restricted to those 34,480 children with only one exposure at age 0- 4 years, followed by no hospitalization or further surgery. Five unexposed controls matched on sex, parity, year and month of birth were selected for each exposed child.
Neuro- and cardiac surgery as well as cancer and diagnoses of malformations were excluded in the analyses. Primary outcome was average school marks at age 16 yrs.
RESULTS: Children having one exposure at 0-4 yrs had 0.47% lower average marks at age 16 yrs (CI -0.75%, -0.18%, p<0.001). More importantly, there was no detectable difference in school results at age 16 with one exposure at any of the younger age intervals 0-6 months, 7-12 or 13 – 24 months. Children exposed two or =3 times had 1.68%, and 1.69% lower average marks, respectively (Fig 1).
To put the minimal difference in the 0-4 age group into context, we compared our findings to other variables known to affect school results such as gender, month of birth and parents’ educational level. Males have 9.87% lower school marks, and children born in December have 5.31% lower school marks compared to those born in January (Fig 2). Children whose mothers lack university education have 9.92% lower school marks (Fig 2).
DISCUSSION: In this large, nation-wide outcome study we demonstrate a minimal risk of lower school marks at age 16 in children after one exposure to anesthesia and surgery at age 0-4 yrs compared to unexposed children, and no indication of increased vulnerability at younger ages. Among 4,552 children having 2 or more surgical procedures we found a minimal worsening of school achievements by approximately 1.5 %. Importantly, we cannot distinguish between the potential effects of anesthesia per se, and the effects of surgery or other factors such as stress response to surgery and comorbidities driving the need for surgery. Even if a very small effect in exposed children indeed was identified, this was several orders of magnitude less than that from socioeconomics, gender, and month of birth.
Based on these findings, early exposure to anesthesia and surgery does not constitute a public health problem and there is no reason to postpone imperative surgery during early childhood due to fear for potentially negative impact on later school achievements.
REFERENCES: 1. J Neurosci 2003 Feb 1;23(3):876-82 2. Curr Anesthesiol Rep (2013) 3:175-183