title: Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence.
abstract: BACKGROUND
  Pregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood.
  
  
  METHODS
  Detailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24-49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status.
  
  
  RESULTS
  Compared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters.
  
  
  CONCLUSIONS
  Pregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.
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: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.|Department of Obstetrics and Gynecology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Auro
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|Heart Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.|School of Biological Sciences, University of Adelaide, Adelaide, Australia.
authors.forename: Ville-Petteri
authors.initials: VP
authors.lastname: Mäkinen
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: 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: 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: Center for Life Course Health Research and Biocenter Oulu, University of Oulu, Oulu, Finland.|Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Jokelainen
authors.affiliation: Department of Medical Microbiology and Immunology, and MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Santalahti
authors.affiliation: Department of Medical Microbiology and Immunology, and MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg, Lübeck, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg, Lübeck, Kiel, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Department of Medicine, University of Turku, Turku, Finland.|Division of Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
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, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.|Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: Department of Medical Microbiology and Immunology, and MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Center for Life Course Health Research and Biocenter Oulu, University of Oulu, Oulu, Finland.|Unit of Primary Care, Oulu University Hospital, Oulu, Finland.|Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
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: 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.|National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: Medical Research Council Integrative Epidemiology Unit at the 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: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland. mika.ala-korpela@computationalmedicine.fi.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland. mika.ala-korpela@computationalmedicine.fi.|Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. mika.ala-korpela@computationalmedicine.fi.|School of Social and Community Medicine, University of Bristol, Bristol, UK. mika.ala-korpela@computationalmedicine.fi.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D005387:Finland; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D011247:Pregnancy / Q000378:metabolism*; D055815:Young Adult
keywords: Amino acids; Cytokines; Fatty acids; Hormones; Inflammation; Lipoprotein lipids; Metabolic networks; Metabolomics; Postpartum; Pregnancy; Trimesters