Metabolic phenotyping identifies early interindividual variation in infant energy expenditure with implications for...

Pediatric obesity is a major public health crisis. Early identification of metabolic traits that increase individual risk are emerging. As such, identification of variability in early energy expenditure would reveal the need for precision nutritional approaches from birth.

To evaluate the interindividual variability in components of energy expenditure for the purpose of understanding early nutritional considerations in very young infants.

Infant participants (<3 months of age) underwent extensive energy expenditure phenotyping using a combination of doubly labeled water for total daily energy expenditure and a novel infant metabolic chamber for sleeping energy expenditure. Descriptive statistics, intraclass correlation coefficients, and univariable and multivariable linear regression analyses were used to assess reliability and characterize variability, predictors, and phenotypes of energy expenditure. We identified interindividual variability in total, mass-adjusted, and fat-free mass adjusted energy expenditures. Energy phenotypes (thrifty and spendthrift) were assigned based on the residuals between measured and predicted energy expenditure from metabolic mass. Discrepancies between measured energy expenditure and predicted by national dietary recommendations for infants (2023 DRI) were evaluated.

Total daily and sleeping energy expenditures were 368±60 kcal/d and 250±60 kcal/d, respectively. Energy expenditure related to activity accounted for 21±9% of total measured. Age (r=.59), weight (r=.83), length (r=.75), and fat-free mass (r=.82) were positively associated with sleeping energy expenditure. We identified 40% of measured infants with a thrifty energy phenotype, classified as having sleeping energy expenditure under that predicted by cohort age, sex, and fat and fat-free mass. Mean prediction error of the 2023 DRI from our cohort was 10±7% and was positively associated with the amount of energy expenditure attributed to activity.

These findings warrant further comprehensive metabolic phenotyping studies in young infants to understand how early energy expenditure tracks through the life course and influences obesity risk as well as the thorough evaluation and refinement of infant nutritional recommendations.