title: Metabolic signatures of birthweight in 18 288 adolescents and adults.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland peter.wurtz@computationalmedicine.fi.
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Niironen
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tuulia
authors.initials: T
authors.lastname: Tynkkynen
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Tiainen
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise, and Eating Disorders, University of Sydney, Sydney, NSW, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Skilton
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: Kauko
authors.initials: K
authors.lastname: Heikkilä
authors.affiliation: Center for Life Course Health Research and Biocenter Oulu, University of Oulu, Oulu, Finland.|Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.affiliation: Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rose
authors.affiliation: Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland.|Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.|Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology, and Medical Research Unit Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Kajantie
authors.affiliation: Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.|Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland.|Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.|Unit of General Practice, Helsinki University Hospital, Helsinki, Finland.|Folkhälsan Research Center, Helsinki, Finland.|Vasa Central Hospital, Vasa, Finland.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Center for Life Course Health Research and Biocenter Oulu, University of Oulu, Oulu, Finland.|Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Auro
mesh_terms: D050154:Adiposity; D000293:Adolescent; D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D004198:Disease Susceptibility / Q000097:blood* / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005387:Finland; D005865:Gestational Age; D057166:High-Throughput Screening Assays; D006801:Humans; D007230:Infant, Low Birth Weight / Q000097:blood* / Q000378:metabolism; D007231:Infant, Newborn; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D012307:Risk Factors; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D005227:Fatty Acids; D008074:Lipoproteins
keywords: Fetal programming; adiposity; amino acids; fatty acids; metabolic signatures; metabolomics