Cumulative Opioid Exposures in the First Year of Life and Cognitive Neurodevelopment in High-Risk Infants

Abstract

BACKGROUND: High-risk infants with significant neonatal-perinatal morbidities often require opioids, but prolonged exposures can impair neurodevelopment. We evaluated the effect of cumulative opioid exposures in the first year of life, measured by morphine milligrams equivalents (MME), on neurodevelopment. METHODS: A retrospective cohort of high-risk infants younger than 1 year admitted to a tertiary children's hospital from 2010 to 2020 was identified. International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/ICD-10) codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and thoracoabdominal surgery identified high-risk infants. Cumulative MME received over all hospitalizations in the first year of life were calculated alongside benzodiazepine dosing and neurodevelopmental scores at 18 months or older. Neurodevelopmental impairment was defined as a score more than 1 SD from the standardized mean. Multivariable linear regressions adjusted for demographics and comorbidities. RESULTS: Overall, 330 high-risk infants were identified, and 70.6% demonstrated neurodevelopmental impairment. Cumulative MME negatively correlated with cognitive (P < .001), motor (P < .001), and language (P = .004) scores. On multivariable linear regression, increasing MME was significantly associated with decreasing cognitive (P < .001) scores but not motor or language scores. CONCLUSION: Higher cumulative opioid exposure in the first year of life was associated with reduced cognitive scores at 18 months or older, independent of comorbidities. Opioid stewardship initiatives extended to high-risk infants may further optimize long-term neurodevelopment.