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Alterations of adrenal steroidomic profiles in preterm infants at birth
  1. Simon Travers1,2,3,
  2. Laetitia Martinerie1,4,5,6,
  3. Pascal Boileau5,7,8,
  4. Marc Lombès1,2,5,9,10,
  5. Eric Pussard1,2,3,10
  1. 1Inserm, U1185, Le Kremlin-Bicêtre, France
  2. 2Fac Med Paris-Sud, Univ, Paris-Sud, Universitè Paris Saclay, Le Kremlin-Bicêtre, France
  3. 3Service de Gènètique Molèculaire, Pharmacogènètique et Hormonologie, Hôpital de Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique'Hôpitaux de Paris, Le Kremlin Bicêtre, France
  4. 4Service d'Endocrinologie Pèdiatrique, Hôpital Robert Debrè, Assistance Publique Hôpitaux de Paris, Paris, France
  5. 5PremUp Foundation, Paris, France
  6. 6Universitè Paris Diderot, Sorbonne Paris Citè, Paris, France
  7. 7Service de Rèanimation Nèonatale, CH Poissy St'Germain en'Laye, Poissy, France
  8. 8EA 7285, UFR des Sciences de la Santè, Simone Veil, Universitè Versailles St-Quentin en Yvelines, Montigny le Bretonneux, France
  9. 9Service d'Endocrinologie et Maladies de la Reproduction, Hôpital de Bicêtre, Hôpitaux Universitaires Paris Sud, Assistance Publique'Hêpitaux de Paris, Le Kremlin Bicêtre, France
  10. 10Institut Biomèdical de Bicêtre, Le Kremlin-Bicêtre, France
  1. Correspondence to Dr Eric Pussard, Gènètique Molèculaire, Pharmacogènètique et Hormonologie, Hôpital de Bicêtre, 75 rue du Gènèral Leclerc, 94275, Le Kremlin Bicêtre Cedex France; eric.pussard{at}aphp.fr

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)): ≥37 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.

  • prematurity
  • steroid profiling
  • mineralocorticoids
  • glucocorticoids
  • adrenal cortex

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Footnotes

  • Contributors All authors contributed to the design of the study. ST and EP performed the analyses. All authors analysed and interpreted the data. ST, ML and EP wrote a first draft of the manuscript, and all coauthors critically evaluated and suggested revisions to the manuscript and approved the final submission.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval CCP Comitè de protection des personnes, Ile de France.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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