MedicalResearch: What are the main findings of the study?
Dr. Morriss: Our aim was to assess the association between surgery performed during the initial hospitalization of very low- birth-weight infants and subsequent death or neurodevelopmental impairment at 18-22 months’ corrected age. We conducted a retrospective cohort analysis of patients who were prospectively enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998 to 2009. Surgery was classified by the expected anesthesia type as either major surgery that likely would have been performed under general anesthesia; or minor surgery, that is, procedures that could have been performed under non-general anesthesia and in general were shorter in duration. There were 2,186 major surgery patients and 784 minor surgery patients and more than 9,000 patients who did not undergo surgery.
We found that any surgical procedure increased the adjusted risk of death or neurodevelopmental impairment in low birth weight infants by about 30%. Not all surgical procedures were associated with increased risk, however. Compared with those who did not undergo surgery, patients who were classified as having major surgery had a risk-adjusted odds ratio of death or neurodevelopmental impairment of 1.52 (95% confidence interval 1.24-1.87). However, those who were classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who did not undergo surgery the risk-adjusted odds ratio for neurodevelopmental impairment was 1.56 (95% confidence interval 1.26-1.93), and the risk-adjusted mean Bayley II Mental Developmental Index and mean Psychomotor Developmental Index values were significantly lower.
MedicalResearch: Were any of the findings unexpected?
Dr. Morriss: We were happily surprised that those patients whom we classified as minor surgery had no increased adjusted risk of death or neurodevelopmental impairment. In addition, a sensitivity analysis in which we changed the classification of certain abdominal surgical procedures (repair of inguinal hernia, gastroschisis or omphalocele) from minor to major surgery resulted in no increased risk for the major surgery patients, suggesting a relatively low adverse risk for this group of procedures.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Morriss: Our study supports the concern that surgery usually requiring general anesthesia during a vulnerable period of infancy has an adverse effect on neurodevelopmental outcome and extends that concern to very low birth weight neonates. Yet, we failed to demonstrate an increased risk of neurodevelopmental impairment after some surgical procedures that may have been performed under anesthesia other than general anesthesia or for shorter surgical duration.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Morriss: This was a retrospective cohort study in which we were able to adjust for a large number of potentially confounding variables that were in the database, but important factors that are associated with the outcomes, such as analgesia and possibly other drugs, hypoxemia, hypotension and other physiological disturbances, were not available. It will be important in future research to exclude these potentially confounding factors as responsible for adverse outcomes observed. The actual type of anesthesia, the duration of anesthesia and the class of agent used for general anesthesia for each procedure were not available to us, so the classification into major and minor surgery groups may be associated with factors other than anesthesia type, pharmacologic class of agent or duration of exposure that are, in fact, responsible for the observed results. Future studies should consider these factors as contributors to the adverse outcomes.
We don’t know the postconceptual developmental window of vulnerability for increased risk of adverse outcomes after major surgery in infants; going forward we need to learn this interval so that we can postpone some procedures until after the window closes, if possible. We don’t know if we can effectively administer a neuroprotective agent to neonates who must have major surgery to reduce the risk. There are several ongoing studies, including randomized clinical trials, that may provide these answers.