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The factors that increase risk for opioid use in the adult, as well as those that perpetuate risk for the caregiver and child, oftentimes replicate across generations and may be more likely to affect child neurodevelopment than the opioid exposure itself. In this article, we review the prenatal opioid exposure literature with the perspective that this is not a singular event but an intergenerational cascade of events. We highlight several mechanisms of transmission across generations: biological factors, including genetics and epigenetics and the gut\u2013brain axis; parent\u2013child mechanisms, such as prepregnancy experience of child maltreatment, quality of parenting, infant behaviors, neonatal opioid withdrawal diagnosis, and broader environmental contributors including poverty, violence exposure, stigma, and Child Protective Services involvement. We conclude by describing ways in which intergenerational transmission can be disrupted by early intervention.<\/jats:p>","DOI":"10.1111\/jcpp.13761","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T02:25:08Z","timestamp":1675823108000},"page":"566-578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Annual Research Review: Prenatal opioid exposure \u2013 a two\u2010generation approach to conceptualizing neurodevelopmental outcomes"],"prefix":"10.1111","volume":"64","author":[{"given":"Elisabeth","family":"Conradt","sequence":"first","affiliation":[{"name":"Department of Psychiatry Duke University  Durham NC USA"},{"name":"Department of Pediatrics Duke University  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Camerota","sequence":"additional","affiliation":[{"name":"Brown Center for the Study of Children at Risk, Department of 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