A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial (2025)

Kouwenhoven, S. M. P., Antl, N., Finken, M. J. J., Twisk, J. W. R., van der Beek, E. M., Abrahamse-Berkeveld, M., van de Heijning, B. J. M., Schierbeek, H., Holdt, L. M., van Goudoever, J. B., & Koletzko, B. V. (2020). A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial. American Journal of Clinical Nutrition, 111(5), 962-974. https://doi.org/10.1093/ajcn/nqz308

Kouwenhoven, Stefanie M P ; Antl, Nadja ; Finken, Martijn J J et al. / A modified low-protein infant formula supports adequate growth in healthy, term infants : a randomized, double-blind, equivalence trial. In: American Journal of Clinical Nutrition. 2020 ; Vol. 111, No. 5. pp. 962-974.

@article{3e302ff631e64be38be4142b07f200bc,

title = "A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial",

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. ",

keywords = "infants, infant nutrition, growth, body composition, safety, protein quality, protein quantity, protein intake, amino acids, 1ST MONTH, CLINICAL-VARIABLES, CHILDHOOD-OBESITY, WEIGHT-GAIN, HUMAN-MILK, FOLLOW-UP, FAT MASS, LIFE, AGE, REQUIREMENT",

author = "Kouwenhoven, {Stefanie M P} and Nadja Antl and Finken, {Martijn J J} and Twisk, {Jos W R} and {van der Beek}, {Eline M} and Marieke Abrahamse-Berkeveld and {van de Heijning}, {Bert J M} and Henk Schierbeek and Holdt, {Lesca M} and {van Goudoever}, {Johannes B} and Koletzko, {Berthold V}",

note = "Copyright {\textcopyright} The Author(s) 2019.",

year = "2020",

month = may,

doi = "10.1093/ajcn/nqz308",

language = "English",

volume = "111",

pages = "962--974",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "Oxford University Press",

number = "5",

}

Kouwenhoven, SMP, Antl, N, Finken, MJJ, Twisk, JWR, van der Beek, EM, Abrahamse-Berkeveld, M, van de Heijning, BJM, Schierbeek, H, Holdt, LM, van Goudoever, JB & Koletzko, BV 2020, 'A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial', American Journal of Clinical Nutrition, vol. 111, no. 5, pp. 962-974. https://doi.org/10.1093/ajcn/nqz308

A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial. / Kouwenhoven, Stefanie M P; Antl, Nadja; Finken, Martijn J J et al.
In: American Journal of Clinical Nutrition, Vol. 111, No. 5, 05.2020, p. 962-974.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - A modified low-protein infant formula supports adequate growth in healthy, term infants

T2 - a randomized, double-blind, equivalence trial

AU - Kouwenhoven, Stefanie M P

AU - Antl, Nadja

AU - Finken, Martijn J J

AU - Twisk, Jos W R

AU - van der Beek, Eline M

AU - Abrahamse-Berkeveld, Marieke

AU - van de Heijning, Bert J M

AU - Schierbeek, Henk

AU - Holdt, Lesca M

AU - van Goudoever, Johannes B

AU - Koletzko, Berthold V

N1 - Copyright © The Author(s) 2019.

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

KW - infants

KW - infant nutrition

KW - growth

KW - body composition

KW - safety

KW - protein quality

KW - protein quantity

KW - protein intake

KW - amino acids

KW - 1ST MONTH

KW - CLINICAL-VARIABLES

KW - CHILDHOOD-OBESITY

KW - WEIGHT-GAIN

KW - HUMAN-MILK

KW - FOLLOW-UP

KW - FAT MASS

KW - LIFE

KW - AGE

KW - REQUIREMENT

U2 - 10.1093/ajcn/nqz308

DO - 10.1093/ajcn/nqz308

M3 - Article

C2 - 31868201

SN - 0002-9165

VL - 111

SP - 962

EP - 974

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 5

ER -

Kouwenhoven SMP, Antl N, Finken MJJ, Twisk JWR, van der Beek EM, Abrahamse-Berkeveld M et al. A modified low-protein infant formula supports adequate growth in healthy, term infants: a randomized, double-blind, equivalence trial. American Journal of Clinical Nutrition. 2020 May;111(5):962-974. Epub 2019 Dec 23. doi: 10.1093/ajcn/nqz308