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We conducted a systematic review to determine: (1) if the literature supports a causal role of maternal prenatal substance use on offspring externalizing disorders diagnosis and (2) whether these associations differ across externalizing disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched Web of Science, Embase, PsycINFO and Medline databases. Risk of bias assessment was conducted using the Newcastle\u2013Ottawa Scale (NOS), and where possible meta\u2010analysis was conducted for studies classed as low risk of bias. We included studies of any design that examined prenatal smoking, alcohol or caffeine use. Studies in non\u2010English language, fetal alcohol syndrome and comorbid autism spectrum disorders were excluded. Participants in the included studies were mothers and their offspring. Measurements included prenatal smoking, alcohol or caffeine use as an exposure, and diagnosis of attention\u2010deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) in offspring as an outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 63 studies, 46 of which investigated smoking and ADHD. All studies were narratively synthesized, and seven studies on smoking and ADHD were meta\u2010analysed. The largest meta\u2010analysis based on genetically sensitive design included 1\u2009011\u2009546 participants and did not find evidence for an association [odds ratio (OR)\n                      <jats:sub>1\u20139\u2009cigarettes<\/jats:sub>\n                      \u2009=\u20090.90, 95% confidence interval (CI)\u2009=\u20090.83\u20131.11; OR\u00a0\n                      <jats:sub>&gt;\u200910\u2009cigarettes<\/jats:sub>\n                      \u2009=\u20091.04, 95% CI\u2009=\u20090.79\u20131.36). Studies on alcohol exposure in all the outcomes reported inconsistent findings and no strong conclusions on causality can be made. Studies on caffeine exposure were mainly limited to ADHD and these studies do not support a causal effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There appears to be no clear evidence to support a causal relationship between maternal prenatal smoking and offspring attention\u2010deficit hyperactivity disorder. Findings with alcohol and caffeine exposures and conduct disorder and oppositional\u2013defiant disorder need more research, using more genetically sensitive designs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.15858","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T19:09:40Z","timestamp":1649272180000},"page":"2602-2613","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Prenatal smoking, alcohol and caffeine exposure and offspring externalizing disorders: a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8872-1248","authenticated-orcid":false,"given":"Elis","family":"Haan","sequence":"first","affiliation":[{"name":"School of Psychological Science University of Bristol  Bristol UK"},{"name":"MRC Integrative Epidemiology Unit University of Bristol  Bristol 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