A major international study provides new reassurance around the question of whether young children who have anesthesia are more likely to develop learning disabilities
The issue has troubled pediatric anesthesiologists and parents for well over a decade, after research on animals suggested that there was a connection.
Do the drugs that make it possible to perform vital surgical procedures without pain cause lasting damage to the developing human brain? Several large studies have found ways to tease out the effects of actual surgeries and anesthetic exposures on children.
The new study, in the British journal The Lancet, is a randomized controlled trial involving more than 700 infants who needed hernia repairs. The babies, at 28 hospitals in seven countries, were randomly assigned to receive either general anesthesia or regional (spinal) anesthesia for these short operations — the mean duration of general anesthesia was 54 minutes. The study, called the GAS study — for general anesthesia compared to spinal — compared neurodevelopmental outcomes at 5 years of age, and found no significant difference in the children’s performance in the two groups.
Dr. Andrew Davidson, a professor in the department of anesthesia at the Royal Children’s Hospital of Melbourne and one of the two lead investigators on the trial, said that this prospective, randomized design allows researchers to avoid many confounding factors that have complicated previous studies, and answer a very specific question.
Preliminary data from testing the children at age 2 had shown no significant differences between the groups, and the children were then evaluated at the age of school entry. “If you have an hour of anesthesia as a child, then you are at no greater risk of deficits of cognition at the age of 5,” Dr. Davidson said. “It doesn’t increase the risk of poor neurodevelopmental outcome.”
As a pediatrician, I can tell you that pediatric anesthesiologists tend to have excellent people skills. They’re the ones talking to you and to your child right before surgery, reassuring parents, answering questions, and are highly skilled at explaining scary stuff like surgery, anesthesia and pain. They can talk to children at their different developmental levels, and to parents at their different pitches of anxiety. And they acknowledged and took on this globally scary question of whether a little anesthesia leaves a little patient with a changed brain.
General anesthesia is one of the great blessings of medical science, making surgery possible without the agonies suffered in the past. The drugs that temporarily erase awareness have always seemed both miraculous and frightening, not least because with all the research of modern medicine, we still don’t understand exactly how and why they do what they do to our brains.
Dr. Lena S. Sun, the chief of the division of pediatric anesthesiology at Columbia University, pointed to an animal study published in 2003 as raising this concern. There was evidence from animal research that exposure to large doses of general anesthesia, like exposure to alcohol, could have lasting effects on the developing brain, with cellular changes, neuron death and subsequent changes in the animals’ behavior and cognition.
“All the animal studies have been very consistent, very robust,” Dr. Sun said. The association observed in animal studies between the prolonged drug exposure and the effects made it imperative to find ways to look at children.
In 2017, after reviewing existing evidence, the Food and Drug Administration warned that long anesthetic exposures or multiple exposures might affect brain development in young children, so parents and pregnant women should discuss the potential risks with their doctors.
Some retrospective studies suggested associations between multiple surgeries with anesthesia and later learning disabilities. But children who required two or three major operations and developed learning disabilities later in life can’t be easily compared with children who had no operations without taking into account the medical problems that were the reason for the anesthesia exposures and all the other possible effects of those medical problems and their treatments.
Dr. Sun, one of the first people to sound the alarm about a possible long-term impact of general anesthesia, was the lead investigator on the Pediatric Anesthesia Neurodevelopment Assessment study, known as the Panda study (acronyms are very important in medical trials, maybe especially when children are involved). It used pairs of siblings to look at the association between a single exposure to general anesthesia before a child was 3, and later cognitive function. The results, published in 2016, showed that there was no statistically significant difference between the siblings who were exposed and those who were not, in I.Q. and other tests of neurocognitive function and behavior.
And now the new study, which represents a huge international collaborative effort, shows that single, relatively brief exposures to anesthesia did not lead to learning problems.
“They’re very important studies since most exposures are single brief exposures,” said Dr. Randall Flick, professor of anesthesiology and pediatrics at the Mayo Clinic Children’s Center. The average duration of anesthesia in children is about an hour.
The pattern that emerged from early studies, Dr. Flick said, is that “a single exposure prior to age 3 or 4 seemed to have no impact on the frequency of diagnosis of a specific learning disability in children, but once you had two or more anesthetic exposures you saw a near-doubling of the frequency.”
In a study of a population of children in Minnesota, approximately one in seven children under 3 received anesthesia, and a quarter of those had either multiple operations, or else a single prolonged exposure.
Dr. Flick was a co-principal investigator in the Mayo Anesthesia Safety in Kids (MASK) study, which made use of the health and education data on the children of Olmsted County, Minn., comparing children with no early life anesthesia exposures, a single exposure and multiple exposures. The children underwent a comprehensive neurodevelopmental battery of tests.
“There was no impact on full-scale I.Q. in single or multiple exposures,” Dr. Flick said. But when there were two or more anesthesia exposures, researchers found an association with problems in fine motor skills and processing speed. Also, parents in the multiple exposure group rated their children as having more difficulty with behavior, particularly around attention.
There needs to be more research looking at longer exposures, Dr. Davidson said, and at whether some specific drugs are safer than others, as well as at the stress of having surgery itself.
“One thing that has come out of all this is that there is now considerably more interest in what is actually the optimal anesthetic form for neonates,” he said.
But these studies should be reassuring to parents with a healthy child who needs a single surgical procedure, Dr. Sun said. “There is probably no increased risk in terms of long-term neurodevelopmental problems, in terms of data we have right now,” she said.
For all children, medical necessity is still the most important context, she said. “We don’t want any children not to have the surgery they need.”
This is part of a series of columns on children’s pain. Other topics include pain after surgery, pain from needles, chronic pain and the use of opioids.
