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Repeated exposure to anesthesia and surgery before the age of 2 years was a significant independent risk factor for the later development of learning disabilities in a matched cohort study involving children in one school district, adjustment for comorbidity, and multiple outcome measures.
No association was seen after a single episode of anesthesia and surgery, according to Dr. Randall P. Flick and his colleagues at the Mayo Clinic in Rochester, Minn.
In the past decade, animal studies have firmly established a relationship between the use of general anesthetics during periods of rapid brain growth and widespread apoptotic neurodegeneration, with adverse effects of learning and behavior, according to the researchers.
Some clinical studies have provided insight, but with mixed findings and without controlling for comorbidity and without examining multiple types of outcomes, they wrote.
Even with the new study, which identified multiple anesthesia exposures as a significant risk factor for the development of learning disabilities (hazard ratio of 2.16), the clinical relevance remains uncertain. But "at this point, we cannot exclude the possibility that multiple exposures to anesthesia/surgery may adversely affect neurodevelopment," said Dr. Flick of the department of anesthesiology, and his associates (Pediatrics 2011 [doi:10.1542/peds.2011-0351]).
The investigators followed a cohort of children born between 1976 and 1982 to mothers who resided in the same community, attended the same schools, and received virtually all their health care at the Mayo Clinic or at Olmstead Medical Center in Rochester, Minn.
Children who were exposed to anesthesia before age 2 years (350 of the 5,357 children in the cohort) were matched with two unexposed children (700 of the children in the cohort) on the basis on factors known to influence the incidence of learning disabilities, including gender, mother’s education, birth weight, and gestational age.
Two methods were used to quantify health status at age 5 years, and school records were used to track when children developed learning disabilities.
In addition to learning disabilities (overall as well as the subtypes of reading, written language, and mathematics), the study’s outcomes included receipt of an individualized education program (IEP) and results of group-administered tests of cognition and achievement.
By age 19, the cumulative incidence of learning disabilities (with adjustments made for comorbidities and health status) was 21.3% for unexposed controls, 23.6% for those with a single exposure, and 36.6% for those with multiple exposures.
A similar pattern was observed for each subtype of learning disability and in group-administered tests of achievement and cognition. Multiple exposures were associated with lower scores in most of the standardized tests.
Multiple exposures to anesthesia also appeared to affect the rate of children receiving an IEP for difficulties with speech and language, but had no effect on the need for an IEP relating to emotional/behavioral disorders, the investigators reported.
Of the 350 children exposed to general anesthesia early on, 286 were exposed once and 64 were exposed more than once. The most frequent anesthesia was a combination of halothane (87.5%) and nitrous oxide (88.1%).
The findings suggest that any neurodevelopmental effects of multiple exposure may be limited to impairment of speech and language rather than to developmental disorders more generally, the researchers wrote. "However, this can only be a provisional conclusion," they wrote, because the IEP for emotional/behavioral disorders captures only more severely disruptive behaviors.
Overall, they cautioned, the study cannot distinguish between the effects of anesthesia per se, and surgery or the need for surgery. In addition, the measures used to control for health status may not have captured all potential confounders.
Children who were severely mentally retarded were excluded from the study; of these 19 children, all but 1 were known to have profound neurodevelopmental deficits before exposure to anesthesia and surgery.
The study was supported by a grant from the U.S. National Institute of Aging. Dr. Flick and his colleagues reported no relevant financial relationships.
The clinical significance of anesthesia neurotoxicity is controversial and remains uncertain, but with publication of the study by researchers at the Mayo Clinic, pediatricians can expect questions from parents and should "verse themselves on the subject," said Dr. Robert K. Williams.
"From this point forward, pediatricians must be an intimate part of the discussion," he said. "As the primary drivers of most surgical and diagnostic procedures, pediatricians will have to assess whether the benefits [of procedures] justify the purported but completely unquantifiable risk of the anesthetic or sedative."
Anesthesia neurotoxicity is a difficult issue to investigate, he noted, as it is "extraordinarily difficult" to isolate the effects of general anesthesia per se. The Mayo group’s study is important, however, because it took advantage of a unique database, and because the findings suggest an association between 2 or more episodes of anesthesia and surgery, and the subsequent development of learning disabilities.
"Although the authors controlled for burden of illness as best as was practical, it is not possible to completely isolate the need for surgery and any potential effects of the surgical procedure from the effects of the anesthetic per se. The clinical significance of these limitations remains subject to vigorous debate," he said.
Pediatricians and parents should be reassured by the study’s "failure to reveal any discernible clinical effects after a single exposure," and the fact that "regional anesthesia seems to be free of risk from neurotoxicity," Dr. Williams said.
Several other prospective human trials are underway, he noted, but these studies will only examine the effect of a single exposure to surgery and anesthesia. A well-designed comprehensive study on the effects of multiple episodes seems "many years away at best and, perhaps ultimately, impractical."
In the meantime, pediatricians should be aware of the concerns about potential neurotoxicity of general anesthetics, but should "also understand the current limitations of the evidence," he said.
Dr. Williams is a pediatric anesthesiologist at the University of Vermont in Burlington. His comments were adapted from an accompanying editorial (Pediatrics 2011[doi:10.1542/peds.2011-2489]). Dr. Williams reported that he has no relevant financial relationships.
The clinical significance of anesthesia neurotoxicity is controversial and remains uncertain, but with publication of the study by researchers at the Mayo Clinic, pediatricians can expect questions from parents and should "verse themselves on the subject," said Dr. Robert K. Williams.
"From this point forward, pediatricians must be an intimate part of the discussion," he said. "As the primary drivers of most surgical and diagnostic procedures, pediatricians will have to assess whether the benefits [of procedures] justify the purported but completely unquantifiable risk of the anesthetic or sedative."
Anesthesia neurotoxicity is a difficult issue to investigate, he noted, as it is "extraordinarily difficult" to isolate the effects of general anesthesia per se. The Mayo group’s study is important, however, because it took advantage of a unique database, and because the findings suggest an association between 2 or more episodes of anesthesia and surgery, and the subsequent development of learning disabilities.
"Although the authors controlled for burden of illness as best as was practical, it is not possible to completely isolate the need for surgery and any potential effects of the surgical procedure from the effects of the anesthetic per se. The clinical significance of these limitations remains subject to vigorous debate," he said.
Pediatricians and parents should be reassured by the study’s "failure to reveal any discernible clinical effects after a single exposure," and the fact that "regional anesthesia seems to be free of risk from neurotoxicity," Dr. Williams said.
Several other prospective human trials are underway, he noted, but these studies will only examine the effect of a single exposure to surgery and anesthesia. A well-designed comprehensive study on the effects of multiple episodes seems "many years away at best and, perhaps ultimately, impractical."
In the meantime, pediatricians should be aware of the concerns about potential neurotoxicity of general anesthetics, but should "also understand the current limitations of the evidence," he said.
Dr. Williams is a pediatric anesthesiologist at the University of Vermont in Burlington. His comments were adapted from an accompanying editorial (Pediatrics 2011[doi:10.1542/peds.2011-2489]). Dr. Williams reported that he has no relevant financial relationships.
The clinical significance of anesthesia neurotoxicity is controversial and remains uncertain, but with publication of the study by researchers at the Mayo Clinic, pediatricians can expect questions from parents and should "verse themselves on the subject," said Dr. Robert K. Williams.
"From this point forward, pediatricians must be an intimate part of the discussion," he said. "As the primary drivers of most surgical and diagnostic procedures, pediatricians will have to assess whether the benefits [of procedures] justify the purported but completely unquantifiable risk of the anesthetic or sedative."
Anesthesia neurotoxicity is a difficult issue to investigate, he noted, as it is "extraordinarily difficult" to isolate the effects of general anesthesia per se. The Mayo group’s study is important, however, because it took advantage of a unique database, and because the findings suggest an association between 2 or more episodes of anesthesia and surgery, and the subsequent development of learning disabilities.
"Although the authors controlled for burden of illness as best as was practical, it is not possible to completely isolate the need for surgery and any potential effects of the surgical procedure from the effects of the anesthetic per se. The clinical significance of these limitations remains subject to vigorous debate," he said.
Pediatricians and parents should be reassured by the study’s "failure to reveal any discernible clinical effects after a single exposure," and the fact that "regional anesthesia seems to be free of risk from neurotoxicity," Dr. Williams said.
Several other prospective human trials are underway, he noted, but these studies will only examine the effect of a single exposure to surgery and anesthesia. A well-designed comprehensive study on the effects of multiple episodes seems "many years away at best and, perhaps ultimately, impractical."
In the meantime, pediatricians should be aware of the concerns about potential neurotoxicity of general anesthetics, but should "also understand the current limitations of the evidence," he said.
Dr. Williams is a pediatric anesthesiologist at the University of Vermont in Burlington. His comments were adapted from an accompanying editorial (Pediatrics 2011[doi:10.1542/peds.2011-2489]). Dr. Williams reported that he has no relevant financial relationships.
Repeated exposure to anesthesia and surgery before the age of 2 years was a significant independent risk factor for the later development of learning disabilities in a matched cohort study involving children in one school district, adjustment for comorbidity, and multiple outcome measures.
No association was seen after a single episode of anesthesia and surgery, according to Dr. Randall P. Flick and his colleagues at the Mayo Clinic in Rochester, Minn.
In the past decade, animal studies have firmly established a relationship between the use of general anesthetics during periods of rapid brain growth and widespread apoptotic neurodegeneration, with adverse effects of learning and behavior, according to the researchers.
Some clinical studies have provided insight, but with mixed findings and without controlling for comorbidity and without examining multiple types of outcomes, they wrote.
Even with the new study, which identified multiple anesthesia exposures as a significant risk factor for the development of learning disabilities (hazard ratio of 2.16), the clinical relevance remains uncertain. But "at this point, we cannot exclude the possibility that multiple exposures to anesthesia/surgery may adversely affect neurodevelopment," said Dr. Flick of the department of anesthesiology, and his associates (Pediatrics 2011 [doi:10.1542/peds.2011-0351]).
The investigators followed a cohort of children born between 1976 and 1982 to mothers who resided in the same community, attended the same schools, and received virtually all their health care at the Mayo Clinic or at Olmstead Medical Center in Rochester, Minn.
Children who were exposed to anesthesia before age 2 years (350 of the 5,357 children in the cohort) were matched with two unexposed children (700 of the children in the cohort) on the basis on factors known to influence the incidence of learning disabilities, including gender, mother’s education, birth weight, and gestational age.
Two methods were used to quantify health status at age 5 years, and school records were used to track when children developed learning disabilities.
In addition to learning disabilities (overall as well as the subtypes of reading, written language, and mathematics), the study’s outcomes included receipt of an individualized education program (IEP) and results of group-administered tests of cognition and achievement.
By age 19, the cumulative incidence of learning disabilities (with adjustments made for comorbidities and health status) was 21.3% for unexposed controls, 23.6% for those with a single exposure, and 36.6% for those with multiple exposures.
A similar pattern was observed for each subtype of learning disability and in group-administered tests of achievement and cognition. Multiple exposures were associated with lower scores in most of the standardized tests.
Multiple exposures to anesthesia also appeared to affect the rate of children receiving an IEP for difficulties with speech and language, but had no effect on the need for an IEP relating to emotional/behavioral disorders, the investigators reported.
Of the 350 children exposed to general anesthesia early on, 286 were exposed once and 64 were exposed more than once. The most frequent anesthesia was a combination of halothane (87.5%) and nitrous oxide (88.1%).
The findings suggest that any neurodevelopmental effects of multiple exposure may be limited to impairment of speech and language rather than to developmental disorders more generally, the researchers wrote. "However, this can only be a provisional conclusion," they wrote, because the IEP for emotional/behavioral disorders captures only more severely disruptive behaviors.
Overall, they cautioned, the study cannot distinguish between the effects of anesthesia per se, and surgery or the need for surgery. In addition, the measures used to control for health status may not have captured all potential confounders.
Children who were severely mentally retarded were excluded from the study; of these 19 children, all but 1 were known to have profound neurodevelopmental deficits before exposure to anesthesia and surgery.
The study was supported by a grant from the U.S. National Institute of Aging. Dr. Flick and his colleagues reported no relevant financial relationships.
Repeated exposure to anesthesia and surgery before the age of 2 years was a significant independent risk factor for the later development of learning disabilities in a matched cohort study involving children in one school district, adjustment for comorbidity, and multiple outcome measures.
No association was seen after a single episode of anesthesia and surgery, according to Dr. Randall P. Flick and his colleagues at the Mayo Clinic in Rochester, Minn.
In the past decade, animal studies have firmly established a relationship between the use of general anesthetics during periods of rapid brain growth and widespread apoptotic neurodegeneration, with adverse effects of learning and behavior, according to the researchers.
Some clinical studies have provided insight, but with mixed findings and without controlling for comorbidity and without examining multiple types of outcomes, they wrote.
Even with the new study, which identified multiple anesthesia exposures as a significant risk factor for the development of learning disabilities (hazard ratio of 2.16), the clinical relevance remains uncertain. But "at this point, we cannot exclude the possibility that multiple exposures to anesthesia/surgery may adversely affect neurodevelopment," said Dr. Flick of the department of anesthesiology, and his associates (Pediatrics 2011 [doi:10.1542/peds.2011-0351]).
The investigators followed a cohort of children born between 1976 and 1982 to mothers who resided in the same community, attended the same schools, and received virtually all their health care at the Mayo Clinic or at Olmstead Medical Center in Rochester, Minn.
Children who were exposed to anesthesia before age 2 years (350 of the 5,357 children in the cohort) were matched with two unexposed children (700 of the children in the cohort) on the basis on factors known to influence the incidence of learning disabilities, including gender, mother’s education, birth weight, and gestational age.
Two methods were used to quantify health status at age 5 years, and school records were used to track when children developed learning disabilities.
In addition to learning disabilities (overall as well as the subtypes of reading, written language, and mathematics), the study’s outcomes included receipt of an individualized education program (IEP) and results of group-administered tests of cognition and achievement.
By age 19, the cumulative incidence of learning disabilities (with adjustments made for comorbidities and health status) was 21.3% for unexposed controls, 23.6% for those with a single exposure, and 36.6% for those with multiple exposures.
A similar pattern was observed for each subtype of learning disability and in group-administered tests of achievement and cognition. Multiple exposures were associated with lower scores in most of the standardized tests.
Multiple exposures to anesthesia also appeared to affect the rate of children receiving an IEP for difficulties with speech and language, but had no effect on the need for an IEP relating to emotional/behavioral disorders, the investigators reported.
Of the 350 children exposed to general anesthesia early on, 286 were exposed once and 64 were exposed more than once. The most frequent anesthesia was a combination of halothane (87.5%) and nitrous oxide (88.1%).
The findings suggest that any neurodevelopmental effects of multiple exposure may be limited to impairment of speech and language rather than to developmental disorders more generally, the researchers wrote. "However, this can only be a provisional conclusion," they wrote, because the IEP for emotional/behavioral disorders captures only more severely disruptive behaviors.
Overall, they cautioned, the study cannot distinguish between the effects of anesthesia per se, and surgery or the need for surgery. In addition, the measures used to control for health status may not have captured all potential confounders.
Children who were severely mentally retarded were excluded from the study; of these 19 children, all but 1 were known to have profound neurodevelopmental deficits before exposure to anesthesia and surgery.
The study was supported by a grant from the U.S. National Institute of Aging. Dr. Flick and his colleagues reported no relevant financial relationships.
FROM PEDIATRICS
Major Finding: Repeated exposure to anesthesia before age 2 was a significant, independent risk factor for later development of learning disabilities and receipt of individual education plans related to speech and language. The cumulative incidence of learning disabilities (with adjustments made for comorbidities and health status) was 21.3% for unexposed controls, 23.6% for those with a single exposure, and 36.6% for those with multiple exposures.
Data Source: Matched single-community cohort study in which 350 children who underwent procedures with general anesthesia before age 2 were each matched with two unexposed children and followed for numerous measures of learning and behavior.
Disclosures: Dr. Flick and his colleagues reported no relevant financial relationships.