Alfano, RossellaPlusquin, MichelleRobinson, OliverBrescianini, SoniaChatzi, LedaKeski-Rahkonen, PekkaHandakas, EvangelosMaitre, LéaNawrot, Tim S.Robinot, NivonirinaRoumeliotaki, TheanoSassi, FrancoScalbert, AugustinVrijheid, MartineVineis, PaoloRichiardi, LorenzoZugna, Daniela2022-12-132022-12-132022Alfano R, Plusquin M, Robinson O, Brescianini S, Chatzi L, Keski-Rahkonen P, Handakas E, Maitre L, Nawrot T, Robinot N, Roumeliotaki T, Sassi F, Scalbert A, Vrijheid M, Vineis P, Richiardi L, Zugna D. Cord blood metabolites and rapid postnatal growth as multiple mediators in the prenatal propensity to childhood overweight. Int J Obes (Lond). 2022 Jul;46(7):1384-93. DOI: 10.1038/s41366-022-01108-00307-0565http://hdl.handle.net/10230/55104Background: The mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediator on childhood overweight, alone and sequentially to each metabolite. Methods: Within four European birth-cohorts (N = 375 mother-child dyads), information on seven prenatal exposures (maternal education, pre-pregnancy BMI, weight gain and tobacco smoke during pregnancy, age at delivery, parity, and child gestational age), selected as obesogenic according to a-priori knowledge, was collected. Cord blood levels of 31 metabolites, associated with rapid postnatal growth and/or childhood overweight in a previous study, were measured via liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry. Rapid growth at 12 months and childhood overweight (including obesity) between four and eight years were defined with reference to WHO growth charts. Single mediation analysis was performed using the imputation approach and multiple mediation analysis using the extended-imputation approach. Results: Single mediation suggested that the effect of maternal education, pregnancy weight gain, parity, and gestational age on rapid postnatal growth but not on childhood overweight was partly mediated by seven metabolites, including cholestenone, decenoylcarnitine(C10:1), phosphatidylcholine(C34:3), progesterone and three unidentified metabolites; and the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth. Multiple mediation suggested that the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth and that the mediating role of the metabolites was marginal. Conclusion: Our findings provide evidence of the involvement of in utero metabolism in the propensity to rapid postnatal growth and of rapid postnatal growth in the propensity to childhood overweight. We did not find evidence supporting a mediating role of the studied metabolites alone between the studied prenatal exposures and the propensity to childhood overweight.application/pdfeng© The Author(s) 2022. 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/s41366-022-01108-0EpidemiologyRisk factorsinfo:eu-repo/semantics/openAccess