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Asthma
Original research
Atopic and non-atopic effects of fish oil supplementation during pregnancy
  1. Hans Bisgaard1,
  2. Marianne Mikkelsen1,
  3. Morten Arendt Rasmussen1,2,
  4. Astrid Sevelsted1,
  5. Ann-Marie Malby Schoos1,3,4,
  6. Nicklas Brustad1,
  7. Anders U Eliasen1,
  8. Jonathan Thorsen1,
  9. Bo Chawes1,4,
  10. Gözde Gürdeniz1,
  11. Andreanne Morin5,
  12. Ken Stark6,
  13. Jakob Stokholm1,3,
  14. Carole Ober5,
  15. Casper Emil Tingskov Pedersen1,
  16. Klaus Bønnelykke1,4
  1. 1 COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark
  2. 2 Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
  3. 3 Department of Pediatrics, Slagelse Sygehus, Slagelse, Denmark
  4. 4 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  5. 5 Department of Human Genetics, University of Chicago, Chicago, Illinois, USA
  6. 6 Department of Kinesiology and Human Health, University of Waterloo, Waterloo, Ontario, Canada
  1. Correspondence to Dr Klaus Bønnelykke, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital - Herlev and Gentofte, Gentofte, Denmark; kb{at}copsac.com

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.

  • asthma
  • respiratory infection

Data availability statement

All data that supports the findings in this study, including clinical data, are available from the corresponding author upon reasonable request: participant-level personally identifiable data are protected under the Danish Data Protection Act and European Regulation 2016/679 of the European Parliament and of the Council (GDPR) that prohibit distribution even in pseudo-anonymised form, but can be made available under a data transfer agreement as a collaboration effort.

https://doi.org/10.1136/thorax-2022-219725

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    Data availability statement

    All data that supports the findings in this study, including clinical data, are available from the corresponding author upon reasonable request: participant-level personally identifiable data are protected under the Danish Data Protection Act and European Regulation 2016/679 of the European Parliament and of the Council (GDPR) that prohibit distribution even in pseudo-anonymised form, but can be made available under a data transfer agreement as a collaboration effort.

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    Footnotes

    • Deceased HB died on 8 September 2022

    • Contributors KB and HB were responsible for conception and design of the study and drafted the manuscript. All coauthors (MM, MAR, AS, A-MMS, NB, AUE, JT, BLKC, GG, AM, KS, JS, CO, CETP and KB) have provided important intellectual input and contributed considerably to the analyses and interpretation of the data, and have approved the final version of the manuscript. The corresponding author (KB) is the guarantor of the study and had full access to the data, guarantee the accuracy and integrity of the work, and had final responsibility for the decision to submit for publication.

    • Funding All funding received by COPSAC is listed on www.copsac.com. The Lundbeck Foundation (Grant no R16-A1694); The Ministry of Health (Grant no 903516); Danish Council for Strategic Research (grant no 0603-00280B) and The Capital Region Research Foundation have provided core support to the COPSAC research centre. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 946228) to BLKC and NB and from NIH grant R01 HL129735 to O, KB and HB.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.