Serum steroid metabolome dynamics in infancy: a longitudinal cohort study of healthy infants.

Busch AS; Ljubicic ML; Upners EN; Fischer MB; Hagen CP; Flück CE; Johannsen TH; Frederiksen H; Juul A

Abstract

OBJECTIVE - DESIGN - METHODS - RESULTS - CONCLUSIONS; The circulating steroid metabolome exhibits significant changes in both girls and boys during infancy, reflecting structural and functional changes in the adrenal cortex as well as the transient activation of the hypothalamic-pituitary-gonadal axis during minipuberty. However, longitudinal data characterizing these changes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) remain limited. This study aimed to map the temporal dynamics of the serum steroid metabolome in healthy infants and establish sex- and age-specific reference curves.; Prospective, longitudinal birth cohort study (Copenhagen Minipuberty Study, 2016-2018; NCT02784184) including healthy, term, singleton newborns followed with repeated assessments during the first year of life.; Serum levels of 16 steroid hormones were measured by LC-MS/MS in 88 girls and 101 boys in a total of 446 longitudinal samples. Age-specific reference values were modelled using Generalized Additive Models for Location, Scale and Shape (GAMLSS).; The steroid metabolome exhibited distinct patterns during infancy, characterized by increasing concentrations of cortisol and 11-deoxycorticosterone, and decreasing levels e.g., progesterone, 11-deoxycortisol, 17-hydroxyprogesterone, and androstenedione. These trends were largely independent of sex. Estimated activities of key steroidogenic enzymes did not differ significantly between sexes, except for sex-steroid-related conversion; specifically, 17β-hydroxysteroid dehydrogenase activity was significantly higher in boys than girls (p < 0.001).; These findings offer a comprehensive characterization of the serum steroid metabolome in healthy infants throughout the first year of life. The resulting age-specific reference curves may serve as valuable tools to support the clinical diagnosis and therapeutic monitoring of rare disorders of steroidogenesis.