학술논문
Atopic and non-atopic effects of fish oil supplementation during pregnancy.
Document Type
Academic Journal
Author
Bisgaard H; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Mikkelsen M; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Rasmussen MA; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.; Sevelsted A; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Schoos AM; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Department of Pediatrics, Slagelse Sygehus, Slagelse, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Brustad N; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Eliasen AU; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Thorsen J; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Chawes B; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Gürdeniz G; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Morin A; Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.; Stark K; Department of Kinesiology and Human Health, University of Waterloo, Waterloo, Ontario, Canada.; Stokholm J; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Department of Pediatrics, Slagelse Sygehus, Slagelse, Denmark.; Ober C; Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.; Pedersen CET; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark.; Bønnelykke K; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark kb@copsac.com.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Source
Publisher: British Medical Assn Country of Publication: England NLM ID: 0417353 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-3296 (Electronic) Linking ISSN: 00406376 NLM ISO Abbreviation: Thorax Subsets: MEDLINE
Subject
Language
English
Abstract
Background: 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.
Methods: 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.
Results: 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<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).
Conclusions: 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.
Trial Registration Number: NCT00798226.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Methods: 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.
Results: 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<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).
Conclusions: 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.
Trial Registration Number: NCT00798226.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)