Sibling analysis shows no difference in early cognitive outcomes after a single surgery
Authors: Dori F Zaleznik, MD, Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston, Reviewer; and Dorothy Caputo, MA, BSN, RN,
Written by Judy George, Contributing Writer, MedPage
Young children who had surgical procedures with general anesthesia prior to primary school entry did not have an increased risk of detectable adverse neurodevelopment outcomes compared with their siblings who did not have surgery, according to a Canadian analysis.
After adjusting for confounding factors, no significant differences were found between exposed and unexposed children in early developmental vulnerability or in each of the major domains of the Early Development Instrument (EDI), a teacher-assessed measure of primary school readiness, reported James O’Leary, MD, and co-authors of the Hospital for Sick Children in Toronto, writing in JAMA Pediatrics.
“These findings further support that exposure to anesthesia and surgery in early childhood is not associated with detectable adverse child development outcomes,” O’Leary told MedPage Today.
But “while the findings are generalizable to the majority of young children who have a single surgical procedure performed, it is still not known whether children with repeated or lengthy exposures to surgery and anesthesia are at increased risk of altered neurodevelopment,” he added.
This research is not the first to look at developmental outcomes of children and surgery with general anesthesia. “Based on currently available literature from the GAS trial, PANDA study, and MASK study, we know that single exposures of anesthesia in young healthy children are unlikely to be associated with any long-term adverse neurocognitive effects,” said Lena Sun, MD, of Columbia University in New York City, who was not involved with the study.
The study by O’Leary and colleagues provides additional support for that finding, Sun told MedPage Today: “Because the study employs a sibling cohort design, it minimizes the confounding of socioeconomic status and maternal education, factors that importantly contribute to neurodevelopment.”
Other studies have demonstrated mixed results, but do not account for biological or home environmental factors, O’Leary noted. Preclinical studies have shown that developing brains are susceptible to injury from general anesthetic drugs. And in 2017, the FDA issued a safety communication that exposure to general anesthetic drugs for “lengthy periods of time or over multiple surgeries or procedures may negatively affect brain development in children younger than 3 years.”
“Considering the substantial number of children who require general anesthesia every year — almost three million in the U.S. annually — even small differences in child development outcomes after surgical procedures that require general anesthesia may have significant public health implications,” O’Leary pointed out.
In the analysis, O’Leary and his team linked Ontario health administrative databases to EDI records from 2004 to 2012 and identified a total of 10,897 sibling pairs (average age 5.7 years), including 2,346 pairs with only one child exposed to surgery. Children in a sibling pair had the same birth mother and data from the EDI, a 103-item teacher-completed questionnaire used to assess child development before primary school entry, on file.
Most children who had surgery were age 2 or older at the time of first surgery (59.6%), had same-day surgery and discharge (78.9%), and had only one surgery performed before EDI completion (80.8%). The most common anatomical categories of surgical procedures performed were ear and mastoid (38.1%), oral cavity and pharynx (33.6%), male genital organs (15.0%), and musculoskeletal (13.9%).
After adjusting for confounding factors — age at EDI completion, sex, mother’s age at birth, and eldest sibling status — the researchers found no significant differences between exposed and unexposed children in early developmental vulnerability, defined as any major domain of the EDI in the lowest 10th percentile of the Ontario population (OR 1.03, 95% CI 0.98-1.14;P=0.58). They also did not find differences in the adjusted scores in any of the following five major EDI domains:
- Language and cognitive development: OR 0.96, 95% CI 0.80-1.14; P=0.61
- Physical health and well-being: OR 1.09, 95% CI 0.96-1.24; P=0.19
- Social knowledge and competence: OR 0.98, 95% CI 0.84-1.14; P=0.83
- Emotional health and maturity: OR 0.98, 95% CI 0.84-1.14; P=0.81
- Communication skills and general knowledge: OR 0.90, 95% CI 0.77-1.05; P=0.17
There also were no significant differences in these measures between biological siblings in the 2,346 discordant sibling pairs, after adjusting for confounding factors.
“Based on this study as well as other studies in children, parents whose children are healthy should not delay needed procedures that may require anesthesia,” Sun observed. “However, research is still needed to identify subgroups of children who may have developmental vulnerability to anesthesia exposure.”
“We should keep in mind that this study is in children having anesthesia for surgical procedures,” she added. “Considerations of what could cause or be associated with injury should include the inflammatory responses to surgery and the direct effects of anesthetic agents, as well as the effects of the entire experience of surgery, anesthesia, and hospital encounter.”
O’Leary and colleagues reported several limitations to their study. Its observational nature means that causality cannot be determined, and unmeasured sources of confounding may affect results. The analysis relied on administrative databases, so clinical factors that might be relevant — such as the type and duration of anesthetic — were not included. In addition, whether sibling pairs had the same biological father could not be determined, and while the EDI is a validated tool to assess developmental health before primary school entry, it was not designed to identify specific neurodevelopmental deficits in individual children, the researchers noted.