Related Experiment Video
Updated: Aug 6, 2026
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Association of Postnatal Opioid Exposure and 2-Year Neurodevelopmental Outcomes in Infants Undergoing Cardiac Surgery
Michael L O'Byrne1, Keith Baxelbaum2, Vicky Tam2
1Division of Cardiology, The Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Leonard Davis Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Clinical Futures, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Cardiovascular Outcomes, Quality, and Evaluative Research Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Insights
Greater opioid exposure in infants undergoing heart surgery is linked to poorer neurodevelopmental outcomes. This highlights the need for strategies to minimize opioid use while maintaining critical cardiac care.
Area of Science:
- Pediatric Cardiology
- Neonatal Neurodevelopment
- Pharmacology
Background:
- Opioids are frequently used for pain management in infants undergoing congenital heart surgery.
- The long-term impact of neonatal and infant opioid exposure on neurodevelopment remains unclear.
Purpose of the Study:
- To investigate the association between cumulative opioid exposure in the first year of life and neurodevelopmental outcomes at two years of age.
- To assess cognitive, language, and motor scores using the Bayley Scales of Infant and Toddler Development-Third/Fourth Edition (Bayley-III/IV).
Main Methods:
- A retrospective cohort study involving 526 infants who underwent congenital heart surgery.
- Multivariable linear regression was employed to adjust for potential confounding factors.
- Cumulative opioid exposure was quantified as morphine milligram equivalents.
Main Results:
- Higher cumulative opioid exposure was significantly associated with lower Bayley-III/IV cognitive, language, and motor scores.
- Adjusted analyses revealed negative associations between opioid exposure and all neurodevelopmental domains (P < 0.05).
- Factors like hospital length of stay, prematurity, genetic syndromes, and socioeconomic status also correlated with poorer outcomes.
Conclusions:
- Increased postnatal opioid exposure in infants with congenital heart disease is independently associated with adverse neurodevelopmental outcomes.
- These findings underscore the importance of research into opioid-sparing strategies in neonatal cardiac intensive care.
- Further investigation is warranted to balance effective pain management with neurodevelopmental protection.
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.
