{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:30:17Z","timestamp":1793493017122,"version":"4.5.0"},"reference-count":75,"publisher":"American Academy of Pediatrics (AAP)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A retrospective cohort of high-risk infants younger than 1 year admitted to a tertiary children\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Overall, 330 high-risk infants were identified, and 70.6% demonstrated neurodevelopmental impairment. Cumulative MME negatively correlated with cognitive (P\u2009&amp;lt;\u2009.001), motor (P\u2009&amp;lt;\u2009.001), and language (P\u2009=\u2009.004) scores. On multivariable linear regression, increasing MME was significantly associated with decreasing cognitive (P\u2009&amp;lt;\u2009.001) scores but not motor or language scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1542\/hpeds.2025-008965","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:02:46Z","timestamp":1786924966000},"page":"938-951","source":"Crossref","is-referenced-by-count":0,"title":["Cumulative Opioid Exposures in the First Year of Life and Cognitive Neurodevelopment in High-Risk Infants"],"prefix":"10.1542","volume":"16","author":[{"given":"Olivia A.","family":"Keane","sequence":"first","affiliation":[{"name":"1Division of Pediatric Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, California"},{"name":"2Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadassa","family":"Ourshalimian","sequence":"additional","affiliation":[{"name":"1Division of Pediatric Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, California"},{"name":"2Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwini","family":"Lakshmanan","sequence":"additional","affiliation":[{"name":"3Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ross","sequence":"additional","affiliation":[{"name":"4Division of Critical Care Medicine, Department of Anesthesiology and Pediatrics, Children\u2019s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Kim","sequence":"additional","affiliation":[{"name":"5Division of Pain Medicine, Children\u2019s Hospital Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry C.","family":"Lee","sequence":"additional","affiliation":[{"name":"6Division of Neonatology, University of California San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Hintz","sequence":"additional","affiliation":[{"name":"7Department of Pediatrics, Division of Neonatology, Stanford University School of Medicine, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam","family":"Nguyen","sequence":"additional","affiliation":[{"name":"1Division of Pediatric Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, California"},{"name":"2Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Ing","sequence":"additional","affiliation":[{"name":"1Division of Pediatric Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, California"},{"name":"2Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Kaplan","sequence":"additional","affiliation":[{"name":"8USC Gehr Family Center for Health Systems Science and Innovation, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine B.","family":"Mirzaian","sequence":"additional","affiliation":[{"name":"9Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California"},{"name":"10Division of General Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Vanderbilt","sequence":"additional","affiliation":[{"name":"9Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California"},{"name":"10Division of General Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwaljeet S.","family":"Anand","sequence":"additional","affiliation":[{"name":"11Department of Pediatrics and of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine I.","family":"Kelley-Quon","sequence":"additional","affiliation":[{"name":"1Division of Pediatric Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, California"},{"name":"2Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California"},{"name":"12Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"issue":"3","key":"2026103120013548700_r1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/pan.13056","article-title":"The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic 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