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Metabolic signatures of birth weight in 18 288 adolescents and adults

View ORCID ProfilePeter 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
doi: https://doi.org/10.1101/049247
Peter Würtz
1Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
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Qin Wang
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
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Marjo Niironen
3National Institute for Health and Welfare, Helsinki, Finland
4Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
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Tuulia Tynkkynen
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
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Mika Tiainen
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
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Fotios Drenos
5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom
6School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
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Antti J Kangas
1Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
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Pasi Soininen
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
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Michael R Skilton
7Boden Institute of Obesity, Nutrition, Exercise, and Eating Disorders, University of Sydney, Sydney, Australia
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Kauko Heikkilä
8Department of Public Health, University of Helsinki, Helsinki, Finland
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Anneli Pouta
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
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Mika Kähönen
11Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland
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Terho Lehtimäki
12Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland
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Richard J Rose
13Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA
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Eero Kajantie
3National Institute for Health and Welfare, Helsinki, Finland
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
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Markus Perola
3National Institute for Health and Welfare, Helsinki, Finland
4Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
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Jaakko Kaprio
3National Institute for Health and Welfare, Helsinki, Finland
4Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
8Department of Public Health, University of Helsinki, Helsinki, Finland
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Johan G Eriksson
3National Institute for Health and Welfare, Helsinki, 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
19Vasa Central Hospital, Vasa, Finland
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Olli T Raitakari
20Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
21Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
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Debbie A Lawlor
5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom
6School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
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George Davey Smith
5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom
6School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
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Marjo-Riitta Järvelin
9Center for Life Course Health Research and Biocenter Oulu, University of Oulu, Oulu, Finland
22Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom
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Mika Ala-Korpela
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
5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom
6School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
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Kirsi Auro
3National Institute for Health and Welfare, Helsinki, Finland
4Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
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ABSTRACT

Background Lower birth weight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birth weight 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 United Kingdom comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birth weight were assessed by linear regression models adjusted for sex, gestational age, and age at blood sampling. The metabolic associations with birth weight were compared to the corresponding associations with adult body mass index (BMI).

Results Lower birth weight 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 birth weight resembled the metabolic signature of higher adult BMI (R2=0.77). The resemblance indicated that 1-kg lower birth weight is associated with similar metabolic aberrations as caused by 0.92-units higher BMI in adulthood.

Conclusion Lower birth weight is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birth weight and higher adult adiposity suggest potentially shared underlying molecular mechanisms. However, the magnitudes of metabolic associations with birth weight are modest in comparison to the effects of adiposity, implying that birth weight is only a weak indicator of metabolic risk in adulthood.

KEY POINTS

  • Lower birth weight is adversely associated with a wide range of established and emerging circulating cardiometabolic biomarkers in adulthood, including lipoprotein subclasses and their lipids, fatty acid balance, amino acids, and markers of inflammation and liver function.

  • The metabolic associations are consistent across a wide age span from adolescence to retirement age, and similar for men and women.

  • The magnitudes of metabolic aberrations are weak for the variation in birth weight observed in general population cohorts. Although the metabolic associations with birth weight are statistically significant, they are likely to be of minor public health relevance.

  • The overall metabolic association pattern with lower birth weight closely resembles the metabolic signature of higher adult adiposity, suggesting that shared underlying metabolic pathways may be involved.

  • 1-kg lower birth weight (≈2 SD) is associated with similar adverse metabolic effects as caused by 0.92 higher BMI (≈0.25 SD) in adulthood. These findings indicate that fetal growth, as assessed by birth weight, only has minor effects on the adult metabolic risk profile in general population settings.

Footnotes

  • ↵# Joint senior authors on this work.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Metabolic signatures of birth weight in 18 288 adolescents and adults
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
bioRxiv 049247; doi: https://doi.org/10.1101/049247
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Metabolic signatures of birth weight in 18 288 adolescents and adults
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
bioRxiv 049247; doi: https://doi.org/10.1101/049247

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