TY - JOUR
T1 - Atopic and non-atopic effects of fish oil supplementation during pregnancy
AU - Bisgaard, Hans
AU - Mikkelsen, Marianne
AU - Rasmussen, Morten Arendt
AU - Sevelsted, Astrid
AU - Schoos, Ann-Marie Malby
AU - Brustad, Nicklas
AU - Eliasen, Anders U
AU - Thorsen, Jonathan
AU - Chawes, Bo
AU - Gürdeniz, Gözde
AU - Morin, Andreanne
AU - Stark, Ken
AU - Stokholm, Jakob
AU - Ober, Carole
AU - Pedersen, Casper Emil Tingskov
AU - Bønnelykke, Klaus
N1 - © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Child
KW - Female
KW - Humans
KW - Pregnancy
KW - Fish Oils/therapeutic use
KW - Dietary Supplements
KW - Fatty Acids, Omega-3
KW - Asthma/prevention & control
KW - Fatty Acids
UR - http://www.scopus.com/inward/record.url?scp=85172396767&partnerID=8YFLogxK
U2 - 10.1136/thorax-2022-219725
DO - 10.1136/thorax-2022-219725
M3 - Journal article
C2 - 37696621
SN - 0040-6376
VL - 78
SP - 1168
EP - 1174
JO - Thorax
JF - Thorax
IS - 12
ER -