Low Protein Formula: Consequences of Quantitative Effects of Pre-analytical Factors on Amino Acid Concentrations in Plasma of Healthy Infants

Abstract

Objective: Quantifying pre-analytical effects of postprandial sampling delay and daily protein intake on plasma amino acid concentrations in healthy infants fed formula with low protein content (1.8–1.9 g/100 kcal). Intake of formula with higher protein content bears a risk for later obesity (Kirchberg, J Clin Endocrinol Metab 100(1):149–158, 2015). Formulas containing less than 1.8 g protein might be adequate but not safe (Fomon, J Pediatr Gastroenterol Nutr 28:495–501, 1999). With on-demand feeding reproducible controls of indispensible amino acid concentration cannot be made at trough level.

Methods: Data of 102 healthy infants aged 1 month and 79 aged 4 months fed formula with low protein content were obtained from a previous study (Haschke-Becher, J Inherit Metab Dis 39(1):25–37, 2016). They were analysed by multiple regression. Independent variables were the postprandial sampling delay from 2.25 to 4.5 h and the daily protein intake. Dependant variables were the amino acid concentrations. The combined effect was calculated with the natural logarithm of the amino acid concentration.

Results: Most amino acids fitted a significant exponential decrease due to the sampling delay, except of aspartate, citrulline, glutamine, glutamate, histidine, tryptophan and tyrosine at 1 month; and at 4 months except of citrulline, glutamine, glutamate, glycine and ornithine. Significant effects of protein intake were found for lysine and serine at 1 month and for glutamate at 4 months of age. Lowest limits of significant amino acid concentrations were calculated by extrapolation of sampling delay to 5 h and using the 10th percentile after back-transformation to μmol/L. A procedure to avoid the pitfall of overestimating amino acid concentration is presented.

Appendices

Take-Home Message

For the interpretation of plasma amino acid concentrations data of the postprandial delay of sampling must be obtained and taken into account.

Compliance with Ethics Guidelines

Conflict of Interest

Alexander Kainz was funded by the research fund of the central clinical chemistry laboratory (CHUV, Lausanne) for his statistical work.

All authors declare no conflict of interest.

The authors confirm independence from Nestec Inc. The content of the article has not been influenced by any company or institution.

Informed Consent

All procedures were in accordance with the ethical standards of the responsible committees on human experimentation (national and international) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the parents of all infants included in the original studies from which the data of this study were extracted.

Contribution of the Authors

C. Bachmann contributed by the conception, the planning, multiple regression statistics and analysis of the laboratory results, their interpretation as well as drafting and revising of the manuscript. He is the guarantor of the final manuscript.

A. Kainz contributed by the statistics including quantile regression, drafting and revising the manuscript.

E. Haschke-Becher contributed by the conception, the drafting and revision of the manuscript.