Fish-oil supplementation in pregnancy, child metabolomics and asthma risk
Rago D, Rasmussen MA, Lee-Sarwar KA, Weiss ST, Lasky-Su J, Stokholm J, Bønnelykke K, Chawes BL, Bisgaard H
EBioMedicine · 56 citations
How it was studied
- Design
- Randomized controlled trial (classified by our AI screen)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- Strategiske Forskningsråd
- Nonprofit
- Lundbeckfonden
- Government
- Ministry of Health, British Columbia
- Government
- Ministeriet Sundhed Forebyggelse
- Government
- National Institutes of Health
- Government
- National Heart, Lung, and Blood Institute
- Government
- NHLBI NIH HHS
- Grants
- Ministry of Health, British Columbia (903516); Strategiske Forskningsråd (0603–00280B); Lundbeckfonden (R16‐A1694); Ministeriet Sundhed Forebyggelse (903516); National Heart, Lung, and Blood Institute (R01 HL123915); National Heart, Lung, and Blood Institute (R01 HL141826); National Institutes of Health (R01 HL141826)
Based on 7 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2019-08-01 · EBioMedicine · vol. 46 · pp. 399–410
- Publisher
- Elsevier BV
- Cited
- 72 citations · more than 96% of similar papers · 4.8× the field average
- Impact
- Top 10% most cited in its field
- References
- 34 works
- Access
- Open access (journal) · CC-BY-NC-ND
- Research areas
- Fatty Acid Research and Health · Asthma and respiratory diseases · Neonatal Respiratory Health Research
- Keywords
- Pregnancy, Asthma, Metabolomics, Fish <Actinopterygii>, Fish oil, Medicine, Bioinformatics, Biology, Internal medicine, Fishery, Genetics
- MeSH
- humans, asthma, prenatal exposure delayed effects, fish oils, chromatography, liquid, risk assessment, risk factors, follow-up studies, maternal exposure, pregnancy, dietary supplements, child, preschool, infant, female, mass spectrometry, metabolomics, metabolome, kaplan-meier estimate, biomarkers
9 authors
From DK, US
- Daniela RagoUniversity of Copenhagen; Gentofte Hospital; Copenhagen Prospective Studies on Asthma in Childhood
- Morten Arendt RasmussenUniversity of Copenhagen; Gentofte Hospital; Copenhagen Prospective Studies on Asthma in Childhood
- Kathleen A. Lee‐SarwarBrigham and Women's Hospital; Harvard University
- Scott T. WeissBrigham and Women's Hospital; Harvard University
- Jessica Ann Lasky-SuBrigham and Women's Hospital; Harvard University
- Jakob StokholmUniversity of Copenhagen; Gentofte Hospital; Slagelse Hospital; Copenhagen Prospective Studies on Asthma in Childhood
Abstract
Background
We recently demonstrated that maternal dietary supplementation with fish oil-derived n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy reduces the risk of asthma in the offspring but the mechanisms involved are unknown.
Methods
Here we investigated potential metabolic mechanisms using untargeted liquid chromatography-mass spectrometry-based metabolomics on 577 plasma samples collected at age 6 months in the offspring of mothers participating in the n-3 LCPUFA randomized controlled trial. First, associations between the n-3 LCPUFA supplementation groups and child metabolite levels were investigated using univariate regression models and data-driven partial least square discriminant analyses (PLS-DA). Second, we analyzed the association between the n-3 LCPUFA metabolomic profile and asthma development using Cox-regression. Third, we conducted mediation analyses to investigate whether the protective effect of n-3 LCPUFA on asthma was mediated via the metabolome.
Findings
The univariate analyses and the PLS-DA showed that maternal fish oil supplementation affected the child's metabolome, especially with lower levels of the n-6 LCPUFA pathway-related metabolites and saturated and monounsaturated long-chain fatty acids-containing compounds, lower levels of metabolites of the tryptophan pathway, and higher levels of metabolites in the tyrosine and glutamic acid pathway. This fish oil-related metabolic profile at age 6 months was significantly associated with a reduced risk of asthma by age 5 and the metabolic profile explained 24% of the observed asthma-protective effect in the mediation analysis.
Interpretation
Several of the observed pathways may be involved in the asthma-protective effect of maternal n-3 LCPUFA supplementation and act as mediators between the intervention and disease development.
Funding
COPSAC is funded by private and public research funds all listed on www.copsac.com.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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