{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:51:07Z","timestamp":1787791867986,"version":"build-2784847793"},"reference-count":31,"publisher":"BMJ","issue":"12","funder":[{"name":"National Institute of Health","award":["129735"],"award-info":[{"award-number":["129735"]}]},{"DOI":"10.13039\/100007398","name":"Danish Council for Strategic Research","doi-asserted-by":"crossref","award":["0603-00280B"],"award-info":[{"award-number":["0603-00280B"]}],"id":[{"id":"10.13039\/100007398","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Lundbeck Foundation","award":["R16-A1694"],"award-info":[{"award-number":["R16-A1694"]}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["946228"],"award-info":[{"award-number":["946228"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Ministry of Health","award":["903516"],"award-info":[{"award-number":["903516"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2023,8,15]]},"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>We recently conducted a double-blinded randomised controlled trial showing that fish-oil supplementation during pregnancy reduced the risk of persistent wheeze or asthma in the child by 30%. Here, we explore the mechanisms of the intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>736 pregnant women were given either placebo or n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the third trimester in a randomised controlled trial. Deep clinical follow-up of the 695 children in the trial was done at 12 visits until age 6 years, including assessment of genotype at the fatty acid desaturase (FADS) locus, plasma fatty acids, airway DNA methylation, gene expression, microbiome and metabolomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Supplementation with n-3 LCPUFA reduced the overall risk of non-atopic asthma by 73% at age 6 (relative risk (RR) 0.27 (95% CI 0.06 to 0.85), p=0.042). In contrast, there was no overall effect on asthma with atopic traits (RR 1.42 (95% CI 0.63 to 3.38), p=0.40), but this was significantly modified by maternal FADS genotype and LCPUFA blood levels (interaction p&lt;0.05), and supplementation did reduce the risk of atopic asthma in the subgroup of mothers with FADS risk variants and\/or low blood levels of n-3 LCPUFA before the intervention (RR 0.31 (95% CI 0.11 to 0.75), p=0.016). Furthermore, n-3 LCPUFA significantly reduced the number of infections (croup, gastroenteritis, tonsillitis, otitis media and pneumonia) by 16% (incidence rate ratio 0.84 (95% CI 0.74 to 0.96), p=0.009).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>n-3 LCPUFA supplementation in pregnancy showed protective effects on non-atopic asthma and infections. Protective effects on atopic asthma depended on maternal FADS genotype and n-3 LCPUFA levels. This indicates that the fatty acid pathway is involved in multiple mechanisms affecting the risk of asthma subtypes and infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT00798226\">NCT00798226<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/thorax-2022-219725","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T17:21:11Z","timestamp":1694452871000},"page":"1168-1174","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Atopic and non-atopic effects of fish oil supplementation during pregnancy"],"prefix":"10.1136","volume":"78","clinical-trial-number":[{"clinical-trial-number":"nct00798226","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00856947","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01012557","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00798226","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Hans","family":"Bisgaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-1549","authenticated-orcid":false,"given":"Marianne","family":"Mikkelsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten 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