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Molecular Biology

Impact of infant protein supply and other early life factors on plasma metabolome at 5.5 and 8 years of age: a randomized trial

International Journal of Obesity volume 44, pages 69–81 (2020)Cite this article

Subjects

Abstract

Objectives

A high dairy protein intake in infancy, maternal pre-pregnancy BMI, and delivery mode are documented early programming factors that modulate the later risk of obesity and other health outcomes, but the mechanisms of action are not understood.

Methods

The Childhood Obesity Project is a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants. Participating infants were either breastfed (BF) or randomized to receive higher (HP) or lower protein (LP) content formula in the first year of life. At the ages 5.5 years (n = 276) and 8 years (n = 232), we determined plasma metabolites by liquid chromatography tandem-mass-spectrometry of which 226 and 185 passed quality control at 5.5 years and 8 years, respectively. We assessed the effects of infant feeding, maternal pre-pregnancy BMI, smoking in pregnancy, delivery mode, parity, birth weight and length, and weight gain (0–24 months) on the metabolome at 5.5 and 8 years.

Results

At 5.5 years, plasma alpha-ketoglutarate and the acylcarnitine/BCAA ratios tended to be higher in the HP than in the LP group, but no metabolite reached statistical significance (Pbonferroni>0.09). There were no group differences at 8 years. Quantification of the impact of early programming factors revealed that the intervention group explained 0.6% of metabolome variance at both time points. Except for country of residence that explained 16% and 12% at 5.5 years and 8 years, respectively, none of the other factors explained considerably more variance than expected by chance.

Conclusions

Plasma metabolome was largely unaffected by feeding choice and other early programming factors and we could not prove the existence of a long term programming effect of the plasma metabolome.

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Acknowledgements

We gratefully thank Stephanie Winterstetter and Alexander Haag (Division of Metabolic and Nutritional Medicine, Dr von Hauner Children’s Hospital, University of Munich, Munich, Germany), who analyzed the blood plasma samples.

Funding

The authors’ work is financially supported in part by the Commission of the European Communities, Projects Early Nutrition (FP7-289346), DYNAHEALTH (H2020-633595) and LIFECYCLE (H2020-SC1-2016-RTD), and the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG 322605). No funding bodies had any role in the study design, data collection and analysis, decision to publish, or preparation of the paper.

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Authors and Affiliations

  1. Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Lindwurmstr. 4, 80337, Munich, Germany

    Franca Fabiana Kirchberg, Christian Hellmuth, Martina Totzauer, Olaf Uhl & Berthold Koletzko

  2. Pediatric, Nutrition and Human Development Research Unit, Universitat Rovira i Virgili, IISPV; C/ Dr. Mallafrè Guasch, 4, 43005, Tarragona Reus, Spain

    Ricardo Closa-Monasterolo & Joaquin Escribano

  3. Neonatal Department, Children’s Memorial Health Institute, aleja Dzieci Polskich 20; 04-730 Warszawa, Polen, Warszawa, Poland

    Dariusz Gruszfeld & Kinga Gradowska

  4. Department of Paediatrics, San Paolo Hospital, University of Milan, Via Antonio di Rudinì, 8, 20142, Milano, MI, Italy

    Elvira Verduci & Benedetta Mariani

  5. CHC Sant Vincent, Rue François-Lefèbvre 207, 4000, Liège, Belgium

    Melissa Moretti & Déborah Rousseaux

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  1. Franca Fabiana Kirchberg
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Correspondence to Berthold Koletzko.

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Clinical Trial Registry number and website: ClinicalTrials.gov; identifier: NCT00338689; https://clinicaltrials.gov/ct2/show/NCT00338689.

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Kirchberg, F.F., Hellmuth, C., Totzauer, M. et al. Impact of infant protein supply and other early life factors on plasma metabolome at 5.5 and 8 years of age: a randomized trial. Int J Obes 44, 69–81 (2020). https://doi.org/10.1038/s41366-019-0398-9

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