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Arch Dis Child Fetal Neonatal Ed. 2018 Mar;103(2):F143-F151. doi: 10.1136/archdischild-2016-312457. Epub 2017 Jul 26.

Alterations of adrenal steroidomic profiles in preterm infants at birth.

Travers S1,2,3, Martinerie L1,4,5,6, Boileau P5,7,8, Lombès M#1,2,5,9,10, Pussard E#1,2,3,10.

Author information

1
Inserm, U1185, Le Kremlin-Bicêtre, France.
2
Fac Med Paris-Sud, Univ, Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, France.
3
Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Hôpital de Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique'Hôpitaux de Paris, Le Kremlin Bicêtre, France.
4
Service d'Endocrinologie Pédiatrique, Hôpital Robert Debré, Assistance Publique Hôpitaux de Paris, Paris, France.
5
PremUp Foundation, Paris, France.
6
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
7
Service de Réanimation Néonatale, CH Poissy St'Germain en'Laye, Poissy, France.
8
EA 7285, UFR des Sciences de la Santé, Simone Veil, Université Versailles St-Quentin en Yvelines, Montigny le Bretonneux, France.
9
Service d'Endocrinologie et Maladies de la Reproduction, Hôpital de Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique'Hêpitaux de Paris, Le Kremlin Bicêtre, France.
10
Institut Biomédical de Bicêtre, Le Kremlin-Bicêtre, France.
#
Contributed equally

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.

KEYWORDS:

adrenal cortex; glucocorticoids; mineralocorticoids; prematurity; steroid profiling

[Indexed for MEDLINE]

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