ProtEUs

The prevalence of childhood obesity is increasing rapidly, its prevention is becoming a public health priority. Several
observational studies have shown an association between early nutrition and the risk of developing obesity later in life.

Formula-fed infants are more likely to become overweight compared with breast-fed infants. An important reason for this
appears to be the higher protein content of formula. An infant formula with improved protein quality and a lower protein
quantity may be of benefit to infants.

Objective of the study:

To assess the effect of an infant formula with an optimized amino acid composition and a lower total protein content
during the first four months of life on infant growth.
Study design:

Multicenter, double blind, randomized controlled trial.

Study population:

Healthy term infants.

Intervention (if applicable):

The intervention group (group A) will receive an infant formula with an optimized amino acid composition and reduced
protein content (test product) and the control group (group B) will receive infant formula with a standard amino acid
composition until the 26th week of age (control product). The intervention will start before the 45th day of life. Data on theprimary and secondary endpoints will be collected until 26 weeks of age.
A reference group with breast-fed infants (group C) will undergo the same measurements at the same time points.

Primary study parameters/outcome of the study:
Infant weight gain from inclusion to the age of 17 weeks.

Secundary study parameters/outcome of the study (if applicable):

- Body composition

- Blood concentrations of total IGF-1, glucose, insulin, IGFBP1, IGFBP2, IGFBP3, leptin, amino acid profile, urea,
metabolomics.

- Anthropometric measurements: length, waist circumference, head circumference, mid-arm circumference.

- Composition of fecal microbiota.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if
applicable):

The infants will visit the hospital 3 times during the study: at baseline and at 4 and 6 months of age. Each visit will take
about an hour. A blood sample will be taken at the age of 4 months. The amount of blood that will be taken is minimal (3
ml). During the intervention period, nutritional intake will be measured by a food questionnaire. For the determination of
body composition, the infants will visit the hospital 3 times during the intervention period.

There are no reasons to expect any risks from consumption of a formula partially based on free amino acids. There are
various reasons to hypothesize that infant formula with an optimized amino acid profile and a lower protein level exhibits
beneficial effects on growth, body composition and metabolic diseases in later life. Therefore it is possible that infants
fed with this formula may benefit from participation in the study by lower risk of overweight later in life.



Countries of recruitment: The Netherlands and Germany

We hypothesize that an infant formula with an optimized amino acid composition and a lower protein content during the first 26 weeks of age is safe and results in comparable growth to standard formula fed infants at 17 weeks of age.

Furthermore we hypothesize that infant formula with an optimized amino acid profile and a lower protein level exhibits beneficial effects on weight gain, body composition and metabolic diseases in later life.

The infants will visit the hospital 3 times during the study: at baseline and at 4 and 6 months of age. During the whole intervention period, nutritional intake will be measured by a food questionnaire.

Formula-fed infants will be randomized into group A (test product) or group B (control product). Infants in group A will receive an infant formula with an optimized amino acid composition and infants in group B will receive an infant formula based on the standard amino acid composition. The study intervention ends at 26 weeks of age.