Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children: Tracing the complexity of human postnatal steroidogenesis. Issue 154 (November 2015)

• Record Type: Journal Article
• Authors: Dhayat, Nasser A.; Frey, Andrea C.; Frey, Brigitte M.; d'Uscio, Claudia H.; Vogt, Bruno; Rousson, Valentin; Dick, Bernhard; Flück, Christa E.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 154(2015)
• Page Start: 226
• Page End: 236
• Publication Date: 2015-11
• Subjects: Newborn infants -- Gas chromatography-mass spectrometry -- Urinary steroid profile -- Reference values; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2015.07.024
• Languages: English
• ISSNs: 0960-0760

Abstract

Graphical abstract: Highlights: The steroid metabolome during fetal-neonatal transition varies with sex and postnatal age. For 67 urinary steroid compounds normative values have been quantified by GC–MS for the first year of life. Highest concentrations are found for progesterone metabolites and glucocorticoids. In both sexes, most compounds peak at week 3 and decrease to 20% by week 25. Normative data for the urine steroid metabolome provide a powerful diagnostic tool. Abstract: Context: Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by (a) the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal androgens until its involution 3–6 months postnatally, and (c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. Objective: The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. Methods: We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC–MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. Results: 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. Conclusion: The urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.