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. 2018 Mar 22;13(3):e0194316.
doi: 10.1371/journal.pone.0194316. eCollection 2018.

Metabolomic signatures of low birthweight: Pathways to insulin resistance and oxidative stress

Sarah Jane Metrustry  1 , Ville Karhunen  2   3 , Mark H Edwards  4 , Cristina Menni  1 , Thomas Geisendorfer  5 , Anja Huber  5 , Christian Reichel  5 , Elaine M Dennison  4   6 , Cyrus Cooper  4   7   8 , Tim Spector  1 , Marjo-Riitta Jarvelin  2   3   9   10 , Ana M Valdes  1   11
Affiliations

Metabolomic signatures of low birthweight: Pathways to insulin resistance and oxidative stress

Sarah Jane Metrustry et al. PLoS One. .

Abstract

Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins, aged 18-80, with weight at birth information available from the TwinsUK cohort and performed independent replication in two additional cohorts. Out of 422 compounds tested, 25 metabolites associated with birthweight in these twins, replicated in 1951 men and women from the Hertfordshire Cohort Study (HCS, aged 66) and in 2391 men and women from the North Finland Birth 1986 cohort (NFBC, aged 16). We found distinct heterogeneity between sexes and, after adjusting for multiple tests and heterogeneity, two metabolites were reproducible overall (propionylcarnitine and 3-4-hydroxyphenyllactate). Testing women only, we found other metabolites associated with lower birthweight from the meta-analysis of the three cohorts (2-hydroxy-butyric acid and γ-glutamylleucine). Higher levels of all these metabolites can be linked to insulin resistance, oxidative stress or a dysfunction of energy metabolism, suggesting that low birthweight in both twins and singletons are having an impact on these pathways in adulthood.

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Conflict of interest statement

Competing Interests: Professor Cyrus Cooper has received consultancy and honoraria from commercial companies: Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

References

    1. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008;359(1):61–73. Epub 2008/07/04. doi: 10.1056/NEJMra0708473 ; PubMed Central PMCID: PMC3923653. - DOI - PMC - PubMed
    1. Tsai PC, Van Dongen J, Tan Q, Willemsen G, Christiansen L, Boomsma DI, et al. DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins. Twin Res Hum Genet. 2015;18(6):635–46. Epub 2015/11/14. doi: 10.1017/thg.2015.76 . - DOI - PubMed
    1. McCormick M. The Contribution of Low Birth Weight to Infant Mortality and Childhood Morbidity. New England Journal of Medicine. 1985;312:82–90. doi: 10.1056/NEJM198501103120204 - DOI - PubMed
    1. Wu YW, Xing G, Fuentes-Afflick E, Danielson B, Smith LH, Gilbert WM. Racial, ethnic, and socioeconomic disparities in the prevalence of cerebral palsy. Pediatrics. 2011;127(3):e674–81. Epub 2011/02/23. doi: 10.1542/peds.2010-1656 ; PubMed Central PMCID: PMC3387914. - DOI - PMC - PubMed
    1. Brooks AM, Byrd RS, Weitzman M, Auinger P, McBride JT. Impact of low birth weight on early childhood asthma in the United States. Arch Pediatr Adolesc Med. 2001;155(3):401–6. Epub 2001/03/20. . - PubMed

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