{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:06:11Z","timestamp":1779465971523,"version":"3.53.1"},"reference-count":68,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Antenatal opioid exposure is associated with adverse neurodevelopmental outcomes and smaller brain volumes, but the effects of opioids on newborn cortical folding maturation have not been defined. The Advancing Clinical Trials in Neonatal Opioid Withdrawal Outcomes of Babies With Opioid Exposure (OBOE) Study is a multisite prospective longitudinal cohort study examining the association of antenatal opioid exposure with brain maturation and outcomes in newborns.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare cerebral cortical folding in newborns exposed to opioids vs nonexposed controls.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n In this cohort study, full-term newborns from the OBOE study with antenatal opioid exposure and nonexposed controls were recruited at 4 US sites, including obstetric clinics, maternal substance use treatment programs, and birth hospitals, from August 5, 2020, to December 28, 2023. Data analysis was performed from August 19, 2020, to March 25, 2026.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Newborn opioid exposure, including opioid-only and polysubstance exposure as well as exposure to specific opioids.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Nonsedated T2-weighted magnetic resonance imaging (MRI) data were acquired via harmonized protocols, and 3D brain images were segmented and parcellated using the Developing Brain Region Annotation With Expectation\u2013Maximization pipeline. The inner cortical gray matter surface was used to measure cortical folding across the frontal, parietal, temporal, and occipital lobes. Group differences between opioid-exposed and nonexposed newborns were compared via analysis of covariance, adjusting for postmenstrual age at MRI, sex, birth weight, maternal age, smoking status, and education level.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 259 newborns (mean [SD] gestational age at birth, 39.1 [1.0] weeks; 145 [56.0%] male) were included in the analysis, of whom 164 had antenatal exposure to opioids and 95 were nonexposed controls (mean [SD] postmenstrual age at MRI, 42.8\u2009[2.2] and 42.9 [2.0] weeks, respectively). Compared with nonexposed controls, newborns who had been exposed to opioids had significantly decreased sulcal depth in the frontal (difference, \u22120.11 mm [95% CI, \u22120.20 to \u22120.02 mm]), parietal (difference, \u22120.19 mm [95% CI, \u22120.31 to \u22120.07 mm]), and global (difference, \u22120.09 mm [95% CI, \u22120.18 to \u22120.01 mm]) regions, as well as decreased surface area in the frontal (difference, \u22121048 mm\n 2<\/jats:sup>\n [95% CI, \u22121497 to \u2212598 mm\n 2<\/jats:sup>\n ]), parietal (difference, \u2212501 mm\n 2<\/jats:sup>\n [95% CI, \u2212834 to \u2212168 mm\n 2<\/jats:sup>\n ]), temporal (difference, \u2212422 mm\n 2<\/jats:sup>\n [95% CI, \u2212682 to \u2212162 mm\n 2<\/jats:sup>\n ]), occipital (difference, \u2212232 mm\n 2<\/jats:sup>\n [95% CI, \u2212439 to \u221226 mm\n 2<\/jats:sup>\n ]), and global (difference, \u22122185 mm\n 2<\/jats:sup>\n [95% CI, \u22123327 to \u22121043 mm\n 2<\/jats:sup>\n ]) surfaces. Compared with controls, newborns exposed to methadone showed larger reductions in frontal, parietal, and global surface areas than those exposed to buprenorphine, with parietal surface area significantly reduced only in the methadone-exposed group (difference, \u2212656 mm\n 2<\/jats:sup>\n [95% CI, \u22121111 to \u2212202 mm\n 2<\/jats:sup>\n ]). Newborns with polysubstance exposure had significantly reduced sulcal depth in the frontal, parietal, and global surfaces, as well as reduced surface area across all lobes compared with controls, whereas opioid-only exposed newborns showed fewer significant differences from controls, with reduced parietal sulcal depth and decreased frontal and global surface areas.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study, newborns with antenatal exposure to opioids had reduced cerebral cortical sulcal depth and surface area compared with nonexposed controls, with greater reductions among newborns exposed to methadone compared with those exposed to buprenorphine, and in newborns with polysubstance exposure compared with those with opioid exposure only. Ongoing serial MRI and long-term follow-up are under way to assess the impact of these early cortical maturational differences on later neurodevelopment and behavior.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.14115","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T15:30:16Z","timestamp":1779463816000},"page":"e2614115","source":"Crossref","is-referenced-by-count":0,"title":["Antenatal Opioid Exposure and Cerebral Cortical Maturation in Newborns"],"prefix":"10.1001","volume":"9","author":[{"given":"Yao","family":"Wu","sequence":"first","affiliation":[{"name":"Developing Brain Institute, Children\u2019s National Hospital, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Merhar","sequence":"additional","affiliation":[{"name":"Perinatal Institute, Division of Neonatology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"},{"name":"Department of Pediatrics, 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