Metabolic signatures of birthweight 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 LawlorGeorge Davey Smith, Marjo-Riitta Järvelin, Mika Ala-Korpela, Kirsi Auro

Research output: Contribution to journalArticle (Academic Journal)peer-review

20 Citations (Scopus)
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Abstract

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 (R(2) = 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.

Original languageEnglish
Pages (from-to)1539-1550
Number of pages12
JournalInternational Journal of Epidemiology
Volume45
Issue number5
Early online date7 Nov 2016
DOIs
Publication statusPublished - 2016

Keywords

  • Fetal programming
  • metabolic signatures
  • metabolomics
  • adiposity
  • fatty acids
  • amino acids

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