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Association of pre-pregnancy body mass index with future offspring metabolic profile: findings from three independent European birth cohorts

Diana L. Santos Ferreira, Dylan M. Williams, Antti J. Kangas, Pasi Soininen, Mika Ala-Korpela, George Davey Smith, Marjo-Riitta Jarvelin, Debbie A. Lawlor
doi: https://doi.org/10.1101/114413
Diana L. Santos Ferreira
1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
2School of Social and Community Medicine, University of Bristol, UK
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Dylan M. Williams
3Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK
4Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm
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Antti J. Kangas
5Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
6Biocenter Oulu, University of Oulu, Aapistie 5A, P.O. Box 5000, 90014 Oulu, Finland
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Pasi Soininen
5Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
6Biocenter Oulu, University of Oulu, Aapistie 5A, P.O. Box 5000, 90014 Oulu, Finland
7NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
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Mika Ala-Korpela
1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
2School of Social and Community Medicine, University of Bristol, UK
5Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
6Biocenter Oulu, University of Oulu, Aapistie 5A, P.O. Box 5000, 90014 Oulu, Finland
7NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
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George Davey Smith
1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
2School of Social and Community Medicine, University of Bristol, UK
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Marjo-Riitta Jarvelin
3Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK
6Biocenter Oulu, University of Oulu, Aapistie 5A, P.O. Box 5000, 90014 Oulu, Finland
8Center for Life-Course Health Research and Northern Finland Cohort Center, Faculty of Medicine, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland
9Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, 90029 OYS, P.O. Box 20, 90220 Oulu, Finland
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Debbie A. Lawlor
1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
2School of Social and Community Medicine, University of Bristol, UK
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  • Abstract
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Abstract

Background A high proportion of women start pregnancy overweight/obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives, and, thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) with offspring systemic metabolite profile are causal via intrauterine mechanisms or familial factors.

Methods and Findings We used one and two-stage individual participant data (IPD) metaanalysis, and a negative-control (paternal BMI) to examine the association between maternal prepregnancy BMI and offspring serum metabolome from three European birth cohorts (offspring age at metabolite assessment 16, 17 and 31 years). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from one-stage IPD meta-analysis (N=5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with VLDL-lipoproteins, VLDL-C, VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with HDL-lipoprotein, HDL-diameter, HDL-C, HDL2-C and HDL3-C (all P<0.003). Stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations, however there was no strong statistical evidence for heterogeneity between them (all bootstrap P >0.003, equivalent to 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the two-stage analysis. Offspring BMI showed similar patterns of crosssectional association with metabolic profiles as for parental pre-pregnancy BMI associations, but with greater magnitudes. Adjustment of the parent BMI-offspring metabolite associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI measures with offspring BMI.

Conclusion Our findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding, rather than intrauterine programming mechanisms. They do not support the introduction of measures to reduce maternal BMI in order to prevent adverse offspring cardio-metabolic health.

Footnotes

  • * E-mail: d.a.lawlor{at}bristol.ac.uk (DAL)

  • Abbreviations

    ALSPAC
    Avon Longitudinal Study of Parents and Children;
    BMI
    body mass index;
    C
    cholesterol;
    FA
    fatty acids;
    HDL
    high-density lipoprotein;
    IDL
    intermediate-density lipoprotein;
    IPD
    individual participant data;
    LA
    linoleic acid;
    LDL
    low-density lipoprotein;
    MUFA
    mono-unsaturated fatty acids;
    NFBC66
    Northern Finland Birth Cohort of 1966;
    NFBC86
    Northern Finland Birth Cohort of 1986;
    NMR
    nuclear magnetic resonance;
    PCA
    principal component analysis;
    PUFA
    polyunsaturated fatty acids;
    SD
    standard deviation;
    VLDL
    very-low-density lipoprotein.
  • Copyright 
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    Posted March 07, 2017.
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    Association of pre-pregnancy body mass index with future offspring metabolic profile: findings from three independent European birth cohorts
    Diana L. Santos Ferreira, Dylan M. Williams, Antti J. Kangas, Pasi Soininen, Mika Ala-Korpela, George Davey Smith, Marjo-Riitta Jarvelin, Debbie A. Lawlor
    bioRxiv 114413; doi: https://doi.org/10.1101/114413
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    Association of pre-pregnancy body mass index with future offspring metabolic profile: findings from three independent European birth cohorts
    Diana L. Santos Ferreira, Dylan M. Williams, Antti J. Kangas, Pasi Soininen, Mika Ala-Korpela, George Davey Smith, Marjo-Riitta Jarvelin, Debbie A. Lawlor
    bioRxiv 114413; doi: https://doi.org/10.1101/114413

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