Does a single anesthesia exposure in infancy have a long-term cognitive effect?

Andrew Davidson, MD

Anesthesia can be scary at any age, but even moreso for infants with rapidly developing neurologic systems. Several new studies, however, may help to calm these fears.

In a new report published in The Lancet, researchers determined that an hour of general anesthesia in early infancy did not result in any neurodevelopmental problems by age 5.¹ The infants in the study had who received a median of 54 minutes of general anesthesia scored the same in intelligence quotient (IQ) scores as children who had regional anesthesia, according to the report.

Roughly half the general anesthetics administered to infants last for less than an hour, according to Andrew Davidson, MD, head of Anaesthesia Research at the Murdoch Children’s Research Institute and professor in the Department of Paediatrics, University of Melbourne, Australia, a co-author of the report, who says the findings should offer some reassurance to both parents and providers.

“Anesthesia exposure for under an hour in infancy does not have an impact on cognition as tested at the age of 5 and thus is most unlikely to result in an increased risk of worse neurodevelopmental outcome,” Davidson says.

The study was the first to investigate the effects of general anesthesia to developing brains by age 5 years in a randomized controlled trial, following a previously published study led by Davidson on the neurodevelopmental effects of general anesthesia in children up to age 2 years.

In that study, roughly 300 infants who received general anesthesia for an hour or less were tested against a cohort that had received regional anesthesia, with no significant difference in cognitive testing outcomes by age 2 years.²

In this new study, more than 700 infants who had been placed under general anesthesia with sevoflurane at about age 70 days were tested against a cohort that had received regional anesthesia only. Again, researchers found no significant difference in cognitive scores or neurodevelopment between the 2 cohorts.

In an editorial published alongside the most recent study, experts suggest this demonstrates the strongest evidence to date that single, brief exposures to general anesthesia in infancy will not cause lasting neurodevelopmental harm later in childhood.³

Study limitations

The studies did have some limitations, in that they investigated the use of sevoflurane only, and not other anesthetics that may be used in pediatric surgery. The studies also did not investigate the effects of multiple occurrences of anesthesia or procedures requiring longer periods of anesthesia-2 situations that prompted a warning in 2017 from the US Food and Drug Administration (FDA) based on outcomes observed in animal studies in which long-term behavior and learning problems resulted from general anesthesia lasting more than 3 hours. The studies of infants at age 2 years and age 5 years did not evaluate the effects of multiple or lengthy (more than 1 hour) encounters with general anesthesia.

Previous animal models and human cohort investigations have previously revealed neurodevelopmental changes or, at the very least, mixed results about the effects of anesthesia during infancy. However, using this data could place a number of children at unnecessary risk. According to the study authors, roughly 10% of children in developing countries-millions of children each year-require general anesthesia for medical procedures. Although even small effects on brain development from general anesthesia in these children could have huge implications, the study authors also consider the effects of the missed opportunity of required surgeries in these children should anesthesia be avoided out of concern for neurologic impairment related to anesthesia.

Davidson says the studies demonstrate that randomized trials provided much better data than previous cohort studies. He says he hopes the results will result in fewer children having surgery delayed over concerns about neurodevelopmental problems.

References:

1. McCann ME, de Graaff JC, Dorris L, et al; GAS Consortium. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet. 2019;393(10172):664-677.

2. Davidson AJ, Disma N, de Graaff JC, et al; GAS Consortium. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387(10015):239-250.

3. O’Leary JD, Orser BA. Neurodevelopment after general anaesthesia in infants. Lancet. 2019;383(10172):614-615.