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Higher maternal oxidative stress (OS) during pregnancy (<jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub>) is linked to offspring mental disorders. Environmental factors contribute to <jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub>. However, the role of <jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub> in childhood EBP is unclear. We investigated the associations between (i) <jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub> and offspring EBP; (ii) social and prenatal environmental factors and <jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub>; and (iii) social and prenatal factors and childhood EBP and evaluated whether <jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub> mediated these associations. Maternal urinary OS biomarkers, 8-hydroxyguanosine (8-OHGua; an oxidative RNA damage marker) and 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG; an oxidative DNA damage marker), at 36 weeks of pregnancy were quantified by liquid chromatography-mass spectrometry in a population-derived birth cohort, Barwon Infant Study (<jats:italic>n<\/jats:italic>\u2009=\u20091074 mother-infant pairs). Social and prenatal environmental factors were collected by mother-reported questionnaires. Offspring total EBP was measured by Child Behavior Checklist Total Problems T-scores at age two (<jats:italic>n<\/jats:italic>\u2009=\u2009675) and Strengths and Difficulties Questionnaire Total Difficulties score at age four (<jats:italic>n<\/jats:italic>\u2009=\u2009791). Prospective associations were examined by multivariable regression analyses adjusted for covariates. Mediation effects were evaluated using counterfactual-based mediation analysis. Higher maternal urinary 8-OHGua at 36 weeks (<jats:sub>mat<\/jats:sub>8-OHGua<jats:sub>36w<\/jats:sub>) was associated with greater offspring total EBP at age four (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.38, 95% CI (0.07, 0.69), <jats:italic>P<\/jats:italic>\u2009=\u20090.02) and age two (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.62, 95% CI (\u22120.06, 1.30), <jats:italic>P<\/jats:italic>\u2009=\u20090.07). Weaker evidence of association was detected for 8-OHdG. Five early-life factors were associated with both <jats:sub>mat<\/jats:sub>8-OHGua<jats:sub>36w<\/jats:sub> and childhood EBP (<jats:italic>P-<\/jats:italic>range\u2009&lt;\u20090.001\u20130.05), including lower maternal education, socioeconomic disadvantage and prenatal tobacco smoking. These risk factor-childhood EBP associations were partly mediated by higher <jats:sub>mat<\/jats:sub>8-OHGua<jats:sub>36w<\/jats:sub> (<jats:italic>P-<\/jats:italic>range\u2009=\u20090.01\u20130.05). Higher <jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub>, particularly oxidant RNA damage, is associated with later offspring EBP. Effects of some social and prenatal lifestyle factors on childhood EBP were partly mediated by <jats:sub>mat<\/jats:sub>OS<jats:sub>preg<\/jats:sub>. Future studies are warranted to further elucidate the role of early-life oxidant damage in childhood EBP.<\/jats:p>","DOI":"10.1038\/s41380-023-02284-9","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T04:01:25Z","timestamp":1697428885000},"page":"3760-3768","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Maternal oxidative stress during pregnancy associated with emotional and behavioural problems in early childhood: implications for foetal programming"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0271-9230","authenticated-orcid":false,"given":"Cindy","family":"Pham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5120-3997","authenticated-orcid":false,"given":"Sarah","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Tong","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vuillermin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-1207","authenticated-orcid":false,"given":"Martin","family":"O\u2019Hely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8304-4302","authenticated-orcid":false,"given":"David","family":"Burgner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Tanner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-4181","authenticated-orcid":false,"given":"Richard","family":"Saffery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-6331","authenticated-orcid":false,"given":"Toby","family":"Mansell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sze","family":"Bong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0556-8389","authenticated-orcid":false,"given":"Elaine","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6305-2201","authenticated-orcid":false,"given":"Peter D.","family":"Sly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0094-5245","authenticated-orcid":false,"given":"Nicola","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-3657","authenticated-orcid":false,"given":"Anne-Louise","family":"Ponsonby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Barwon Infant Study Investigator Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Carlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Collier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Loughman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarath","family":"Ranganathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,16]]},"reference":[{"key":"2284_CR1","unstructured":"Scott JG, Mihalopoulos C, Erskine HE, Roberts J, Rahman A. 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