Alterations of adrenal steroidomic profiles in preterm infants at birth.

Abstract

OBJECTIVE:

Preterm infants have relative adrenal and kidney immaturity. Recently, we linked their urine sodium loss to a hypoaldosteronism at variance with an appropriate stimulation of the renin-angiotensin system. To investigate this defective aldosterone secretion, we analyse the biosynthesis pathways of adrenal steroids in neonates according to gestational age (GA).

DESIGN:

Multicentre study (Premaldo) including 152 neonates classified into three groups: group 1 (very preterm (VPT)): <33  gestational weeks (GW); group 2 (preterm (PT)): 33-36 GW and group 3 (term (T)): ≥GW.

METHOD:

Steroidomic profiles of mineralocorticoids, glucocorticoids and adrenal androgens were established from umbilical cord at birth (n=152) and peripheral blood at day 3 (n=70) using a recently developed liquid chromatography mass spectrometry method (LC-MS/MS). The enzymatic activity of each biosynthesis step was estimated by the product-to-substrate ratio.

RESULTS:

At birth, VPT infants exhibit a global defect in adrenal steroid synthesis pathways leading to lower levels of aldosterone, cortisol and androstenedione than in term infants. This defect was strongly related to GA. On day 3, steroid precursors (progesterone, 11-deoxycorticosterone (DOC), 17-hydroxyprogesterone(17-OH-P) and 11-deoxycortisol (S)) were higher in VPT and negatively correlated with GA. Despite of precursors' accumulation, aldosterone and cortisol were similar in the three groups. At birth and day 3, a low cortisol/11-deoxycortisol ratio was found in preterm infants, suggesting an 11-beta-hydroxylase activity (CYP11B1) deficiency.

CONCLUSIONS:

At birth, VPT infants exhibit a global deficit in mineralocorticoids, glucocorticoids and adrenal androgens that attenuates on day 3 of life. Steroid profiling using LC-MS/MS provides evidence for a partial defect in 11-hydroxylase along with prematurity.

• Authors: Simon Travers, Laetitia Martinerie, Pascal Boileau, Marc Lombès, Eric Pussard
• Journal: Archives of disease in childhood. Fetal and neonatal edition (Arch Dis Child Fetal Neonatal Ed) Vol. 103 Issue 2 Pg. F143-F151 (Mar 2018) ISSN: 1468-2052 [Electronic] England
• PMID: 28747362 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chemical References

• Adrenal Cortex Hormones
• Androgens
• Glucocorticoids
• Mineralocorticoids
• Cytochrome P-450 Enzyme System

Topics

• Adrenal Cortex Hormones (blood, metabolism)
• Androgens (metabolism)
• Chromatography, Liquid
• Cytochrome P-450 Enzyme System (metabolism)
• Fetal Blood (chemistry)
• Gestational Age
• Glucocorticoids (metabolism)
• Humans
• Hypoaldosteronism (metabolism)
• Infant, Extremely Premature
• Infant, Newborn
• Infant, Premature
• Mineralocorticoids (metabolism)
• Tandem Mass Spectrometry