University of Oulu

Peter Würtz, Qin Wang, Marjo Niironen, Tuulia Tynkkynen, Mika Tiainen, Fotios Drenos, Antti J Kangas, Pasi Soininen, Michael R Skilton, Kauko Heikkilä, Anneli Pouta, Mika Kähönen, Terho Lehtimäki, Richard J Rose, Eero Kajantie, Markus Perola, Jaakko Kaprio, Johan G Eriksson, Olli T Raitakari, Debbie A Lawlor, George Davey Smith, Marjo-Riitta Järvelin, Mika Ala-Korpela, Kirsi Auro, Metabolic signatures of birthweight in 18 288 adolescents and adults, International Journal of Epidemiology, Volume 45, Issue 5, October 2016, Pages 1539–1550,

Metabolic signatures of birthweight in 18 288 adolescents and adults

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Author: Würtz, Peter1; Wang, Qin1,2; Niironen, Marjo3,4;
Organizations: 1Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
2NMR Metabolomics Laboratory School of Pharmacy, University of Eastern Finland, Kuopio, Finland
3Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland
4Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
5Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK
6School of Social and Community Medicine, University of Bristol, Bristol, UK
7Boden Institute of Obesity, Nutrition, Exercise, and Eating Disorders, University of Sydney, Sydney, NSW, Australia
8Department of Public Health, University of Helsinki, Helsinki, Finland
9Center for Life Course Health Research and Biocenter Oulu, University of Oulu, Oulu, Finland
10Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland
11Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland
12Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland
13Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
14Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
15Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology, and Medical Research Unit Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
16Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
17Unit of General Practice, Helsinki University Hospital, Helsinki, Finland
18Folkhälsan Research Center, Helsinki, Finland Vasa Central Hospital, Vasa, Finland
19Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
20Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
21Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK
Format: article
Version: published version
Access: open
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Language: English
Published: Oxford University Press, 2016
Publish Date: 2019-05-10


Background: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults.

Methods: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI).

Results: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R2 = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood.

Conclusions: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.

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Series: International journal of epidemiology
ISSN: 0300-5771
ISSN-E: 1464-3685
ISSN-L: 0300-5771
Volume: 45
Issue: 5
Pages: 1539 - 1550
DOI: 10.1093/ije/dyw255
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Funding: This study was supported by the Strategic Research Funding from the University of Oulu, Finland, the Sigrid Juselius Foundation, the Novo Nordisk Foundation, the Yrjö Jahnsson Foundation, the Finnish Diabetes Research Foundation, the Finnish Medical Foundation, the Paulo Foundation, Biocenter Oulu, Finland, and the UK Medical Research Council via the University of Bristol Integrative Epidemiology Unit (IEU; MC_UU_12013/1 and MC_UU_12013/5). The Cardiovascular Risk in Young Finns Study is supported by the Academy of Finland (grants 286284, 134309, 126925, 121584, 124282, 129378, 117787 and 41071), Finnish Foundation for Cardiovascular Research, Oulu, Helsinki, Kuopio, Tampere, and Turku University Central Hospital Medical Funds, the Paavo Nurmi Foundation, the Juho Vainio Foundation, the Finnish Cultural Foundation and the Finnish Funding Agency for Technology and Innovation. The Northern Finland Birth Cohorts of 1966 and 1986 have received financial support from Academy of Finland, University Hospital Oulu, Biocenter Oulu, University of Oulu, the European Commission (EURO-BLCS, Framework 5 Award QLG1-CT-2000-01643, ENGAGE project and grant agreement HEALTH-F4-2007-201413, EurHEALTHAgeing (277849), European Regional Developmental Fund), EU H2020-PHC-2014 (grant no. 633595), DynaHEALTH, NHLBI grant 5R01HL087679-02 through the STAMPEED programme (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), Stanley Foundation, the UK Medical Research Council and Wellcome Trust. The UK Medical Research Council and Wellcome Trust (grant: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The contribution of D.A.L to this study is supported by grants from the US National Institute of Health (R01 DK10324), European Research Council (ObesityDevelop: grant no. 669545) and UK National Institute for Health Research (NF-SI-0166-10196). F.D., D.A.L., G.D.S. and M.A.K. work in a Unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1 and MC_UU_12013/5). The FinnTwin-12 and FinnTwin-16 studies have received support from the National Institute on Alcohol Abuse and Alcoholism (R37-AA12502, R01-AA09203 and K05-AA00145). The views expressed in this paper are those of the authors and not necessarily any funding body.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(277849) EURHEALTHAGEING - European ResearcH on DevElopmentAL, BirtH and Genetic Determinants of Ageing
Copyright information: © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.