Franca Fabiana Kirchberg1, Christian Hellmuth1, Martina Totzauer1, Olaf Uhl1, Ricardo Closa-Monasterolo2, Joaquin Escribano2, Dariusz Gruszfeld3, Kinga Gradowska3, Elvira Verduci4, Benedetta Mariani4, Melissa Moretti5, Déborah Rousseaux5, Berthold Koletzko6. 1. Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstr. 4, 80337, Munich, Germany. 2. Pediatric, Nutrition and Human Development Research Unit, Universitat Rovira i Virgili, IISPV; C/ Dr. Mallafrè Guasch, 4, 43005, Tarragona Reus, Spain. 3. Neonatal Department, Children's Memorial Health Institute, aleja Dzieci Polskich 20; 04-730 Warszawa, Polen, Warszawa, Poland. 4. Department of Paediatrics, San Paolo Hospital, University of Milan, Via Antonio di Rudinì, 8, 20142, Milano, MI, Italy. 5. CHC Sant Vincent, Rue François-Lefèbvre 207, 4000, Liège, Belgium. 6. Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstr. 4, 80337, Munich, Germany. office.koletzko@med.lmu.de.
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 toreceive 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.
RCT Entities:
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.