A Food and Drug Administration (FDA) “drug safety communication” warning about the effect of anesthesia on the neurodevelopment of children under the age of three has elicited concerns among some pediatric neurologists and other clinicians that the advisory could cause unnecessary delays in needed surgical and diagnostic procedures and research in young patients.
The FDA communication, issued in December 2016, noted that animal studies and some studies in children had shown that the use of general anesthesia and sedative drugs for more than three hours caused widespread loss of nerve cells in the brain and neurodevelopment delays.
The FDA also cited epidemiologic studies investigating the association between childhood anesthesia exposure and adverse neurodevelopmental outcomes published between 2009 and 2014.
For example, a 2011 study in Anesthesia & Analgesia reviewed data on 10,450 siblings born between 1999 and enrolled in the New York State Medicaid program. The exposed group included 304 children without a history of developmental or behavioral disorders who underwent surgery when they were younger than 3 years, compared with 10,146 children who did not receive any surgical procedures. The researchers found that the incidence of developmental and behavioral disorders was 128.2 diagnoses per 1,000 person-years for the exposed cohort and 56.3 diagnoses per 1,000 person-years for the unexposed cohort.
The FDA safety alert advised health care professionals to “balance the benefits of appropriate anesthesia in young children and pregnant women against the potential risks,” especially for procedures that may last longer than three hours or if multiple procedures are required in children under 3 years.
But in an editorial in the February 8 online edition of The New England Journal of Medicine (NEJM) and interviews with Neurology Today, clinicians said that some of the observational human studies cited by the FDA were compromised by methodological problems, especially confounding factors that may have accounted for adverse neurological development in children who receive anesthesia.
More recent clinical research, for example, the General Anesthesia vs. Spinal Anesthesia (GAS) study and the Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study, revealed that a brief, single exposure to general anesthesia was not associated with poorer neurodevelopmental outcomes, wrote Dean B. Andropoulous, MD, professor of anesthesiology at Baylor College of Medicine and Michael F. Greene, MD, chief of obstetrics at Massachusetts General Hospital in Boston, in the NEJM editorial.
The study, a sibling-matched observational cohort study, examined whether a single anesthesia exposure in healthy children younger than 3 years is associated with an increased risk of impaired global cognitive function (IQ) as the primary outcome, and abnormal domain-specific neurocognitive functions and behavior as secondary outcomes at ages 8 to 15 years.
Exposed children (n=105) had a single episode of general anesthesia before 3 years for elective inguinal hernia surgery and were 36 weeks’ gestational age or older at birth. The unexposed cohort (n=105) were biologically related siblings closest in age (within 3 years) to the exposed child, also 36 weeks’ gestational age or older at birth but with no anesthesia exposure before 3 years. The study found that mean IQ scores were not significantly different between the exposed and unexposed siblings, with both groups scoring somewhat higher than average.