Stefanie M P Kouwenhoven1, Nadja Antl2, Martijn J J Finken3, Jos W R Twisk4, Eline M van der Beek5,6, Marieke Abrahamse-Berkeveld5, Bert J M van de Heijning5, Henk Schierbeek7, Lesca M Holdt8, Johannes B van Goudoever1, Berthold V Koletzko2. 1. Emma Children's Hospital, Amsterdam UMC, Vije Universiteit Amsterdam, University of Amsterdam, Amsterdam, Netherlands. 2. Division of Metabolic and Nutritional Medicine, LMU - Ludwig-Maximilians-Universität Munich, University of Munich Medical Centre, Dr. von Hauner Children's Hospital, Munich, Germany. 3. Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 4. Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 5. Danone Nutricia Research, Utrecht, Netherlands. 6. Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. 7. Stable Isotope Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 8. Institute of Laboratory Medicine, LMU - Ludwig-Maximilians-Universität Munich, University of Munich Medical Centre, Munich, Germany.
Abstract
BACKGROUND: A high protein intake in early life is associated with a risk of obesity later in life. The essential amino acid requirements of formula-fed infants have been reassessed recently, enabling a reduction in total protein content and thus in protein intake. OBJECTIVES: We aimed to assess the safety of an infant formula with a modified amino acid profile and a modified low-protein (mLP) content in healthy term-born infants. Outcomes were compared with a specifically designed control (CTRL) infant formula. METHODS: In this double-blind, randomized controlled equivalence trial, infants received either mLP (1.7 g protein/100 kcal; n = 90) or CTRL formula (2.1 g protein/100 kcal; n = 88) from enrollment (age ≤ 45 d) to 6 mo of age. A breastfed group served as a reference (n = 67). Anthropometry and body composition were determined at baseline, 17 wk (including safety blood parameters), and 6 mo of age. The primary outcome was daily weight gain from enrollment up until the age of 17 wk (at an equivalence margin of ±3.0 g/d). RESULTS:Weight gain from baseline (mean ± SD age: 31 ± 9 d) up to the age of 17 wk was equivalent between the mLP and CTRL formula groups (27.9 and 28.8 g/d, respectively; difference: -0.86 g/d; 90% CI: -2.36, 0.63 g/d). No differences in other growth parameters, body composition, or in adverse events were observed. Urea was significantly lower in the mLP formula group than in the CTRL formula group (-0.74 mmol/L; 95% CI: -0.97, -0.51 mmol/L; P < 0.001). Growth rates, fat mass, fat-free mass, and several essential amino acids were significantly higher in both formula groups than in the breastfed reference group. CONCLUSIONS: Feeding an infant formula with a modified amino acid profile and a lower protein content from an average age of 1 mo until the age of 6 mo is safe and supports an adequate growth, similar to that of infants consuming CTRL formula. This trial was registered at www.trialregister.nl as Trial NL4677.
RCT Entities:
BACKGROUND: A high protein intake in early life is associated with a risk of obesity later in life. The essential amino acid requirements of formula-fed infants have been reassessed recently, enabling a reduction in total protein content and thus in protein intake. OBJECTIVES: We aimed to assess the safety of an infant formula with a modified amino acid profile and a modified low-protein (mLP) content in healthy term-born infants. Outcomes were compared with a specifically designed control (CTRL) infant formula. METHODS: In this double-blind, randomized controlled equivalence trial, infants received either mLP (1.7 g protein/100 kcal; n = 90) or CTRL formula (2.1 g protein/100 kcal; n = 88) from enrollment (age ≤ 45 d) to 6 mo of age. A breastfed group served as a reference (n = 67). Anthropometry and body composition were determined at baseline, 17 wk (including safety blood parameters), and 6 mo of age. The primary outcome was daily weight gain from enrollment up until the age of 17 wk (at an equivalence margin of ±3.0 g/d). RESULTS: Weight gain from baseline (mean ± SD age: 31 ± 9 d) up to the age of 17 wk was equivalent between the mLP and CTRL formula groups (27.9 and 28.8 g/d, respectively; difference: -0.86 g/d; 90% CI: -2.36, 0.63 g/d). No differences in other growth parameters, body composition, or in adverse events were observed. Urea was significantly lower in the mLP formula group than in the CTRL formula group (-0.74 mmol/L; 95% CI: -0.97, -0.51 mmol/L; P < 0.001). Growth rates, fat mass, fat-free mass, and several essential amino acids were significantly higher in both formula groups than in the breastfed reference group. CONCLUSIONS: Feeding an infant formula with a modified amino acid profile and a lower protein content from an average age of 1 mo until the age of 6 mo is safe and supports an adequate growth, similar to that of infants consuming CTRL formula. This trial was registered at www.trialregister.nl as Trial NL4677.
Authors: Stefanie M P Kouwenhoven; Manja Fleddermann; Martijn J J Finken; Jos W R Twisk; Eline M van der Beek; Marieke Abrahamse-Berkeveld; Bert J M van de Heijning; Dewi van Harskamp; Johannes B van Goudoever; Berthold V Koletzko Journal: Nutrients Date: 2021-04-01 Impact factor: 5.717
Authors: James Hedrick; Michael Yeiser; Cheryl L Harris; Jennifer L Wampler; Hila Elisha London; Ashley C Patterson; Steven S Wu Journal: Nutrients Date: 2021-12-18 Impact factor: 5.717
Authors: Stefanie M P Kouwenhoven; Jacqueline Muts; Martijn J J Finken; Johannes B van Goudoever Journal: Nutrients Date: 2022-06-30 Impact factor: 6.706
Authors: Kathryn G Dewey; Darcy Güngör; Sharon M Donovan; Emily M Madan; Sudha Venkatramanan; Teresa A Davis; Ronald E Kleinman; Elsie M Taveras; Regan L Bailey; Rachel Novotny; Nancy Terry; Gisela Butera; Julie Obbagy; Janet de Jesus; Eve Stoody Journal: Am J Clin Nutr Date: 2021-11-08 Impact factor: 8.472