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

Abstract

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 in morphine mg equivalent) over the first year of life and 2-year neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-Third/Fourth Edition [Bayley-III/IV] cognitive, language, and motor scores).

Methods: A 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-European Association for Cardio-Thoracic Surgery category 4 or 5 operations. In unadjusted analyses, higher total exposure to opioids was associated with worse scores across all 3 Bayley-III/IV domain scores (all P < 0.05). After adjustment for measured confounders, greater opioid exposure was associated with lower Bayley-III/IV scores (cognitive: β = -1.0 per log-transformed morphine mg equivalents, P = 0.04; language: β = -1.2, P = 0.04; and motor: β = -1.1, P = 0.02). 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 worse Bayley-III/IV scores across all domains (all P < 0.05).

Conclusions: Greater postnatal exposure to opioids was associated with worse neurodevelopmental outcomes across cognitive, language, and motor domains, independent of other less modifiable factors. This finding should motivate research and efforts to explore reduction in opioid exposure while preserving quality cardiac intensive care.

Keywords: congenital heart disease; critical care; health services research; neurodevelopment; outcomes research; pediatrics; surgery.