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A single exposure to general anesthesia poses no cognitive risk to healthy children under age three, a critical time in brain development, according to a multicenter study led by researchers at Columbia University Medical Center and NewYork-Presbyterian/Morgan Stanley Children’s Hospital. Findings from the study, the largest and most comprehensive of its kind, were published today in the Journal of the American Medical Association.

“A number of animal studies have suggested that exposure to commonly used anesthetic agents in early development could lead to deficits in learning, memory, attention, and other cognitive functions,” said lead author Lena S. Sun, MD, the Emanuel M. Papper Professor of Pediatric Anesthesiology and professor of pediatrics at Columbia, and chief of pediatric anesthesiology at NewYork-Presbyterian/Morgan Stanley Children’s Hospital. “However, few clinical studies have adequately addressed whether this is also true in humans. Based on our findings, we can reassure parents that one exposure to anesthesia is safe for healthy young children.”

“The potential neurotoxicity of anesthetic agents commonly used in general anesthesia has been one of the most pressing concerns in pediatric surgery in the past decade. The PANDA project is among the most rigorously designed studies aimed at addressing this concern. Our findings should be reassuring to millions of parents whose young children need to undergo surgical procedures under general anesthesia across the world each year,” said Guohua Li, DrPH, MD, professor of epidemiology at Columbia University’s Mailman School of Public Health and College of Physicians and Surgeons and a co-author of the paper. 

An estimated two million children in the U.S. undergo anesthesia each year, roughly two-thirds for surgical procedures such as hernia repair, circumcision, and tonsillectomy. Anesthesia is also often used in diagnostic procedures, including imaging studies and endoscopies.

The Pediatric Anesthesia Neurodevelopment Assessment (PANDA) study examined whether exposure to a single anesthetic of short duration (median of 80 minutes) in children under age three had an effect on global cognitive function (IQ) later in life.

The study included 105 healthy children who underwent surgical repair of inguinal hernia — one of the most common operations of early childhood — at one of four sites.

IQ scores and secondary neurodevelopmental outcomes, including memory, learning, processing speed, visuospatial function, attention, executive function, language, and behavior, were assessed when the children were between the ages of 8 and 15, allowing enough time after exposure to anesthesia for any impairments to emerge. Outcomes for each child were compared to those of a healthy, biologically related sibling of a similar age who was not exposed to anesthesia.

“There was no significant difference in IQ scores between the children who were exposed to anesthesia and siblings who were not,” says Dr. Sun. “We also saw no difference in most of the secondary outcomes, although more children in the group exposed to anesthesia exhibited internalizing behavior that required further clinical evaluation. That’s an area that needs to be further explored.”

Internalizing behaviors are behaviors that are directed inward. Examples of negative or problematic internalizing behaviors include anxiety, social withdrawal, and feelings of loneliness and guilt.

“Overall, this is good news for parents whose children need anesthesia for elective surgery or a diagnostic procedure,” said Dr. Sun.

“But the PANDA study leaves some important questions unanswered,” she added. “We need to take a closer look at the effect of anesthesia on cognitive function in girls, since most of the subjects in the group exposed to anesthesia were boys. Also, we need to look at the effects of repeated and prolonged exposure to anesthesia, as well as the effects of anesthesia on more vulnerable subgroups, such as children with serious medical conditions.”

The study is titled, “Association Between A Single General Anesthetic Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood.” The other contributors are: Tonya L.K. Miller (Harvard Medical School, Boston, MA), Cynthia Salorio (Johns Hopkins University School of Medicine, Baltimore, MD), Mary W. Byrne (CUMC), David C. Bellinger (Harvard), Caleb H. Ing (NYP/MSCH), Raymond Park (Harvard), Jerilynn Radcliffe (University of Pennsylvania, Philadelphia, PA), Stephen R. Hays (Vanderbilt University School of Medicine Nashville, TN), Charles J. DiMaggio (New York University School of Medicine New York, NY), Timothy J. Cooper (Vanderbilt), Virginia Rauh (Mailman School of Public Health, Columbia), Lynne G. Maxwell (University of Pennsylvania), Ahrim Youn (Mailman School of Public Health, Columbia), and Francis X. McGowan (University of Pennsylvania).

The study was supported by grants from the National Institutes of Health (R34 HD060741 and UL1 TR000040), the Food and Drug Administration (HHSF223200810036C), SmartTots, Columbia University, Vanderbilt University, Boston Children’s Hospital, Children’s Hospital of Philadelphia, and the National Center for Advancing Translational Sciences.

Dr. Sun receives consultant fees from Merck Research Laboratories to attend a Pediatric Anesthesia Scientific Investigators Engagement meeting. Dr. Li serves as director of the Columbia University CDC-funded Injury Control Research Center (1 R49 CE002096). He also receives research funding from the AAA Foundation for Traffic Safety. Dr. Bellinger serves as a co-investigator on the General Anesthesia Study (GAS) Trial. He is the PI (with ME McCann) of a grant from the National Institute of Child Health and Human Development, National Institutes of Health (HD084566) that funds the U.S. sites of the GAS trial. Dr. Radcliffe reports receiving NIH funding for research, as well as consultant fees from the City of Philadelphia and Columbia University unrelated to the PANDA project. Dr. Maxwell has served on the data safety monitoring board for a clinical trial funded by The Medicines Company (Parsippany, NJ), for which she received a consulting fee. She also reports serving as site PI for two clinical trials funded by Grunenthal (Aachen, Germany). Dr. McGowan reports receiving consulting fees from Merck Research Laboratories (Kenilworth, NJ). Dr. Hays reports being a site primary investigator for industry-sponsored licensing studies from Endo Pharmaceuticals Inc. (Dublin, Ireland), Cadence Pharmaceuticals, Inc. (San Diego, CA, USA), Mallinckrodt Pharmaceuticals (Dublin, Ireland), and the Grunenthal Group (Aachen, Germany), outside the submitted work. No other authors reported disclosures.  

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

NewYork-Presbyterian/Morgan Stanley Children’s Hospital

NewYork-Presbyterian/Morgan Stanley Children’s Hospital, located in New York City, offers the best available care in every area of pediatrics — including the most complex neonatal and critical care, and all areas of pediatric subspecialties — in a family-friendly and technologically advanced setting. Building a reputation for more than a century as one of the nation’s premier children’s hospitals, Morgan Stanley Children’s Hospital is affiliated with the Department of Pediatrics at Columbia University College of Physicians and Surgeons, and is Manhattan’s only hospital dedicated solely to the care of children and one of the largest providers of children’s health services in the tri-state area with a long-standing commitment to its community. It is also a major international referral center, meeting the special needs of children from infancy through adolescence worldwide. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Westchester Division, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian/Lower Manhattan Hospital. The hospital is also closely affiliated with NewYork-Presbyterian/Hudson Valley Hospital, NewYork-Presbyterian/Lawrence Hospital and NewYork-Presbyterian/Queens. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area, according to U.S. News & World Report, and consistently named to the magazine’s Honor Roll of best hospitals in the nation. For more information, visit www.nyp.org.