Handakas, EvangelosKeski-Rahkonen, PekkaChatzi, LedaAlfano, RossellaRoumeliotaki, TheanoPlusquin, MichelleMaitre, LéaRichiardi, LorenzoBrescianini, SoniaScalbert, AugustinRobinot, NivonirinaNawrot, Tim S.Sassi, FrancoVrijheid, MartineVineis, PaoloRobinson, Oliver2022-05-242022-05-242021Handakas E, Keski-Rahkonen P, Chatzi L, Alfano R, Roumeliotaki T, Plusquin M, Maitre L, Richiardi L, Brescianini S, Scalbert A, Robinot N, Nawrot T, Sassi F, Vrijheid M, Vineis P, Robinson O. Cord blood metabolic signatures predictive of childhood overweight and rapid growth. Int J Obes (Lond). 2021 Oct;45(10):2252-60. DOI: 10.1038/s41366-021-00888-10307-0565http://hdl.handle.net/10230/53216Introduction: Metabolomics may identify biological pathways predisposing children to the risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts. Methods: Untargeted liquid chromatography-mass spectrometry metabolomic profiles were measured in cord blood from 399 newborns from four European cohorts (ENVIRONAGE, Rhea, INMA and Piccolipiu). Rapid growth in the first year of life and overweight in childhood was defined with reference to WHO growth charts. Metabolome-wide association scans for rapid growth and overweight on over 4500 metabolic features were performed using multiple adjusted logistic mixed-effect models and controlling the false discovery rate (FDR) at 5%. In addition, we performed a look-up analysis of 43 pre-annotated metabolites, previously associated with birthweight or rapid growth. Results: In the Metabolome-Wide Association Study analysis, we identified three and eight metabolites associated with rapid growth and overweight, respectively, after FDR correction. Higher levels of cholestenone, a cholesterol derivative produced by microbial catabolism, were predictive of rapid growth (p = 1.6 × 10-3). Lower levels of the branched-chain amino acid (BCAA) valine (p = 8.6 × 10-6) were predictive of overweight in childhood. The area under the receiver operator curve for multivariate prediction models including these metabolites and traditional risk factors was 0.77 for rapid growth and 0.82 for overweight, compared with 0.69 and 0.69, respectively, for models using traditional risk factors alone. Among the 43 pre-annotated metabolites, seven and five metabolites were nominally associated (P < 0.05) with rapid growth and overweight, respectively. The BCAA leucine, remained associated (1.6 × 10-3) with overweight after FDR correction. Conclusion: The metabolites identified here may assist in the identification of children at risk of developing obesity and improve understanding of mechanisms involved in postnatal growth. Cholestenone and BCAAs are suggestive of a role of the gut microbiome and nutrient signalling respectively in child growth trajectories.application/pdfeng© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41366-021-00888-1BiochemistryChemical biologyEpidemiologyObesityRisk factorsinfo:eu-repo/semantics/openAccess