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Regression-based reference limits for urinary amino acids in a pediatric population
Rafael Venta1, Belén Prieto, Francisco V Alvarez
1Servicio de Análisis Clínicos, Hospital San Agustin, Avilés, Asturias, Spain. rventa@hsag.insalud.es
Insights
Continuous reference limits for urinary amino acid excretion in children aged 0-12 years were developed using regression models. These novel limits offer a more practical approach for monitoring amino acid metabolism disorders.
Area of Science:
- Biochemistry
- Pediatric Medicine
- Clinical Chemistry
Background:
- Urinary amino acid excretion exhibits significant age-related variations.
- Conventional reference intervals are less practical during rapid developmental changes in infancy and childhood.
- Continuous reference limits offer a more adaptable approach for pediatric age groups.
Purpose of the Study:
- To establish regression-based continuous reference limits for urinary amino acid excretion in healthy children aged 0-12 years.
- To compare regression-based limits with conventional reference intervals.
- To provide a more practical tool for monitoring amino acid metabolism.
Main Methods:
- Analyzed urinary excretion of 23 amino acids in 148 healthy individuals (0-12 years).
- Modeled urinary excretion and age-specific standard deviation using polynomial and piece-wise linear regression.
- Employed residual analysis to select best-fitting models and calculate 95% reference limits and confidence intervals.
Main Results:
- Urinary excretion of 19 amino acids decreased rapidly in the first year, followed by a slow decline, fitting a piece-wise model.
- Four amino acids showed a steady decrease, fitting linear or quadratic models.
- Regression-based limits differed from conventional limits, providing narrower confidence intervals and smoothly changing values.
Conclusions:
- Regression-based continuous reference limits provide a more accurate and practical method for assessing urinary amino acid excretion in children.
- These novel limits facilitate the follow-up of patients with inborn errors of amino acid metabolism.
- Smoothly changing limits avoid partitioning issues inherent in conventional methods.
Abstract:
Age-related variation of the urinary excretion of amino acids has been widely reported. Instead of the conventional reference intervals, continuous reference limits might be a more practical approach during periods of rapid changes such as infancy or childhood. Regression-based reference limits have been produced for the urinary excretion of 23 amino acids analyzed in 148 healthy individuals from 0 to 12 years of age. Urinary excretion was modeled as a function of age by two parametric procedures: the polynomial and the piece-wise linear regression methods. Likewise, age-specific standard deviation was estimated by the regression of the absolute values of the residuals on age. Residual analysis was employed to select the best-fitting model and the 95% reference limits, and their 95% confidence intervals were calculated and plotted against the raw data. The urinary excretion of 19 amino acids decreased rapidly during the first year of life with a further slow decline thereafter. These amino acids fit better the piecewise model. The other four amino acids displayed a steady decrease in the urinary excretion from birth to puberty, and the excretion patterns fit better the quadratic or linear model. Fifteen amino acids showed a significant change in standard deviation with age. Regression-based reference limits differed consistently from conventional limits (<3 years) and narrower confidence intervals were obtained throughout the entire period studied. Avoiding partitioning gave rise to smoothly changing limits. Therefore, such alternative way of presenting amino acid reference limits may facilitate the follow-up of patients with inborn errors of amino acid metabolism.