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We aimed to investigate the causal relationship between maternal smoking during pregnancy and offspring autism using conventional analysis and causal inference methods. In the Avon Longitudinal Study of Parents and Children we investigated the association of maternal smoking during pregnancy (exposure) with offspring autism spectrum disorder (ASD) or possible ASD diagnosis (<jats:italic>n<\/jats:italic>\u2009=\u200911,946) and high scores on four autism-related traits (outcomes) (<jats:italic>n<\/jats:italic>\u2009=\u20097402\u20139152). Maternal smoking was self-reported and also measured using an epigenetic score (<jats:italic>n<\/jats:italic>\u2009=\u2009866\u2013964). Partner\u2019s smoking was used as a negative control for intrauterine exposure (<jats:italic>n<\/jats:italic>\u2009=\u20096616\u201310,995). Mendelian randomisation (<jats:italic>n<\/jats:italic>\u2009=\u20091002\u20132037) was carried out using a genetic variant at the <jats:italic>CHRNA3<\/jats:italic> locus in maternal DNA as a proxy for heaviness of smoking. In observational analysis, we observed an association between smoking during pregnancy and impairments in social communication [OR\u2009=\u20091.56, 95% CI\u2009=\u20091.29, 1.87] and repetitive behaviours, but multivariable adjustment suggested evidence for confounding. There was weaker evidence of such association for the other traits or a diagnosis of autism. The magnitude of association for partner\u2019s smoking with impairments in social communication was similar [OR\u2009=\u20091.56, 95% CI\u2009=\u20091.30, 1.87] suggesting potential for shared confounding. There was weak evidence for an association of the epigenetic score or genetic variation at <jats:italic>CHRNA3<\/jats:italic> with ASD or any of the autism-related traits. In conclusion, using several analytic methods, we did not find enough evidence to support a causal association between maternal smoking during pregnancy and offspring autism or related traits.<\/jats:p>","DOI":"10.1038\/s41398-018-0313-5","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T13:35:59Z","timestamp":1543498559000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Maternal smoking during pregnancy and autism: using causal inference methods in a birth cohort study"],"prefix":"10.1038","volume":"8","author":[{"given":"Doretta","family":"Caramaschi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C.","family":"Richmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-0423","authenticated-orcid":false,"given":"Karoline Alexandra","family":"Havdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Golding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline L.","family":"Relton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-993X","authenticated-orcid":false,"given":"Marcus R.","family":"Munaf\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-8314","authenticated-orcid":false,"given":"George","family":"Davey Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dheeraj","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,29]]},"reference":[{"key":"313_CR1","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1093\/ije\/dyt282","volume":"43","author":"K Lyall","year":"2014","unstructured":"Lyall, K., Schmidt, R. 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