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Metabolic signatures of birthweight in 18 288 adolescents and adults.

Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland peter.wurtz@computationalmedicine.fi. 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. Department of Genomics and Biomarkers, National Institute for Health and Welfare, Helsinki, Finland. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK. School of Social and Community Medicine, University of Bristol, Bristol, UK. Boden Institute of Obesity, Nutrition, Exercise, and Eating Disorders, University of Sydney, Sydney, NSW, Australia. Department of Public Health, University of Helsinki, Helsinki, Finland. 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. Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland. Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland. Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA. 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. 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. 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. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.

International journal of epidemiology. 2016;(5):1539-1550
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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 (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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Publication Type : Meta-Analysis

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