Association of Postnatal Opioid Exposure and 2-Year Neuro developmental Outcomes in Infants Undergoing Cardiac Surgery

BACKGROUND Opioids are commonly used to provide analgesia during and after congenital heart surgery. The effects of exposure to opioids on neurodevelopment in neonates and infants are not well understood. OBJECTIVES This study sought to evaluate the associations between cumulative opioid exposure (measured inmorphine mg equivalent) over thefirst year of life and 2-year neurodevelopmental outcomes (Bayley Scales of Infant andToddler Development-Third/Fourth Edition [Bayley-III/IV] cognitive, language, and motor scores).METHODSA single-center retrospective cohort study of infants undergoing congenital heart surgery was performed.Adjustment for measurable confounders was performed through multivariable linear regression. RESULTS A total of 526 subjects were studied, of whom 32% underwent Society for Thoracic Surgeons-EuropeanAssociation for Cardio-Thoracic Surgery category 4 or 5 operations. In unadjusted analyses, higher total exposure toopioids was associated with worse scores across all 3 Bayley-III/IV domain scores (allP<0.05). After adjustment formeasured confounders, greater opioid exposure was associated with lower Bayley-III/IV scores (cognitive:b<1/4>1.0 perlog-transformed morphine mg equivalents,P 1/40.04; language:b 1/41.2,P 1/40.04; and motor:b 1/41.1,P 1/40.02).Total hospital length of stay, prematurity, genetic syndromes, and worse neighborhood socioeconomic status(represented either by Social Vulnerability Index or Childhood Opportunity Index) were all associated with worseBayley-III/IV scores across all domains (allP<0.05). CONCLUSIONS Greater postnatal exposure to opioids was associated with worse neurodevelopmental outcomesacross cognitive, language, and motor domains, independent of other less modifiable factors. Thisfinding shouldmotivate research and efforts to explore reduction in opioid exposure while preserving quality cardiac intensive care.(JACC. 2024;84:1010-1021) (c) 2024 by the American College of Cardiology Foundation.