Pia Glatz1, Rolf H Sandin1, Nancy L Pedersen2, Anna-Karin Bonamy3, Lars I Eriksson4, Fredrik Granath3. 1. Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden2Department of Anesthesiology and Intensive Care Medicine, Kalmar County Hospital, Kalmar, Sweden. 2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 3. Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 4. Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden5Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Abstract
IMPORTANCE: The results of preclinical studies suggest that anesthetic drugs administered to neonatal animals cause widespread neuronal apoptosis and later neurocognitive impairment. Adequately powered studies in the pediatric surgical population are scarce, and it is unclear whether such preclinical findings are relevant for the pediatric setting. OBJECTIVE: To examine the association of anesthesia and surgery before age 4 years with long-term academic and cognitive performance indexed by school grades at age 16 years and IQ test scores at military conscription. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a cohort study among all children born in Sweden between January 1973 and December 1993. The dates of analysis were April 2013 to October 2015. Among all 2 174 073 Swedish children born between 1973 and 1993, we identified a primary study cohort of 33 514 children with 1 anesthesia and surgery exposure before age 4 years and no subsequent hospitalization and 159 619 matched unexposed control children. In addition, 3640 children with multiple surgical procedures before age 4 years were studied. EXPOSURE: Having at least 1 surgical procedure in the Swedish Patient Register before age 4 years. MAIN OUTCOMES AND MEASURES: The mean school grades at age 16 years and IQ test scores at military conscription at age 18 years. The mean difference between the exposed cohort and unexposed cohort was estimated in a model that included sex, month of birth during the same year, gestational age at delivery, Apgar score at 5 minutes, maternal and paternal educational levels, annual taxable household income, cohabiting parents, and number of siblings. RESULTS: Among 33 514 exposed children (22 484 male and 11 030 female) and 159 619 unexposed children (105 812 male and 53 807 female) in the primary study cohort, 1 exposure before age 4 years was associated with a mean difference of 0.41% (95% CI, 0.12%-0.70%) lower school grades and 0.97% (95% CI, 0.15%-1.78%) lower IQ test scores. The magnitude of the difference was the same after multiple exposures. There was no difference in school grades with 1 exposure before ages 6 months, 7 to 12 months, 13 to 24 months, or 25 to 36 months. The overall difference was markedly less than the differences associated with sex, maternal educational level, or month of birth during the same year. CONCLUSIONS AND RELEVANCE: Exposure to anesthesia and surgery before age 4 years has a small association with later academic performance or cognitive performance in adolescence on a population level. While more vulnerable subgroups of children may exist, the low overall difference in academic performance after childhood exposure to surgery is reassuring. These findings should be interpreted in light of potential adverse effects of postponing surgery.
IMPORTANCE: The results of preclinical studies suggest that anesthetic drugs administered to neonatal animals cause widespread neuronal apoptosis and later neurocognitive impairment. Adequately powered studies in the pediatric surgical population are scarce, and it is unclear whether such preclinical findings are relevant for the pediatric setting. OBJECTIVE: To examine the association of anesthesia and surgery before age 4 years with long-term academic and cognitive performance indexed by school grades at age 16 years and IQ test scores at military conscription. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a cohort study among all children born in Sweden between January 1973 and December 1993. The dates of analysis were April 2013 to October 2015. Among all 2 174 073 Swedish children born between 1973 and 1993, we identified a primary study cohort of 33 514 children with 1 anesthesia and surgery exposure before age 4 years and no subsequent hospitalization and 159 619 matched unexposed control children. In addition, 3640 children with multiple surgical procedures before age 4 years were studied. EXPOSURE: Having at least 1 surgical procedure in the Swedish Patient Register before age 4 years. MAIN OUTCOMES AND MEASURES: The mean school grades at age 16 years and IQ test scores at military conscription at age 18 years. The mean difference between the exposed cohort and unexposed cohort was estimated in a model that included sex, month of birth during the same year, gestational age at delivery, Apgar score at 5 minutes, maternal and paternal educational levels, annual taxable household income, cohabiting parents, and number of siblings. RESULTS: Among 33 514 exposed children (22 484 male and 11 030 female) and 159 619 unexposed children (105 812 male and 53 807 female) in the primary study cohort, 1 exposure before age 4 years was associated with a mean difference of 0.41% (95% CI, 0.12%-0.70%) lower school grades and 0.97% (95% CI, 0.15%-1.78%) lower IQ test scores. The magnitude of the difference was the same after multiple exposures. There was no difference in school grades with 1 exposure before ages 6 months, 7 to 12 months, 13 to 24 months, or 25 to 36 months. The overall difference was markedly less than the differences associated with sex, maternal educational level, or month of birth during the same year. CONCLUSIONS AND RELEVANCE: Exposure to anesthesia and surgery before age 4 years has a small association with later academic performance or cognitive performance in adolescence on a population level. While more vulnerable subgroups of children may exist, the low overall difference in academic performance after childhood exposure to surgery is reassuring. These findings should be interpreted in light of potential adverse effects of postponing surgery.
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