Background: Several experimental studies have suggested that early exposure to anesthetic agents, i.e., before completion of synaptogenesis, can result in widespread apoptotic neuronal degeneration and late cognitive impairment, but human data are lacking. The authors performed a retrospective pilot study to test the feasibility and calculate sample sizes for a larger epidemiologic study of disturbed neurobehavioral development as a function of age at the time of first anesthetic exposure. Pediatric urological procedures were selected because the timing of surgery depends mainly on the age at which a diagnosis is made.
Methods: Neurobehavioral development was assessed using the validated 120-item parental Child Behavior CheckList/4-18 in 314 children who were operated for pediatric urological procedures between the ages of 0 and 6 yr.
Results: Of 243 questionnaires returned, the total problem score was clinically deviant in 41 (23%) of children aged less than 24 months at the time of first surgery and 13 (20%) aged greater than 24 months. Crude and adjusted odds ratios for a clinically deviant Child Behavior CheckList/4-18 score increased with younger age at the time of surgery, but the confidence intervals were very wide. Adjusted odds ratio was 1.38 (0.59-3.22) when operated at age less than 6 months, 1.19 (0.45-3.18) when operated between 6 and 12 months of age, and 1.20 (0.45-3.20) when operated between 12 and 24 months (using operated at greater than 24 months of age as reference category). A properly powered cohort study would require at least 2,268 children.
Conclusions: Children undergoing urologic surgery at age less than 24 months showed more behavioral disturbances than children in whom surgery was performed after age 2 yr, although the results were not statistically significant. To confirm or refute an effect of anesthesia on cognitive development, at least 2,268 children need to be studied. With retrospective study designs, residual confounding remains an issue that can only be solved in prospective randomized studies.