Aldosterone-Signaling Defect Exacerbates Sodium Wasting in Very Preterm Neonates: The Premaldo Study

J Clin Endocrinol Metab. 2015 Nov;100(11):4074-81. doi: 10.1210/jc.2015-2272. Epub 2015 Sep 8.

Abstract

Context: The neonatal period, notably in preterm infants, is characterized by high sodium wasting, implying that aldosterone, the main hormone regulating sodium reabsorption, is unable to maintain sodium homeostasis.

Objective: This study sought to assess aldosterone secretion and action in neonates according to gestational age (GA).

Design and setting: This was a multicenter prospective study (NCT01176162) conducted between 2011 and 2014 at five neonatology departments in France. Infants were followed during their first 3 months.

Participants: The 155 newborns included were classified into three groups: Group 1 (n = 46 patients), <33 gestational weeks (GW); Group 2 (n = 67 patients), 33-36 GW; and Group 3 (n = 42 patients), ≥37 GW.

Main outcome measures: Plasma aldosterone was measured in umbilical cord blood. Urinary aldosterone (UAldo) was assessed at day 0, day 3, month 1, and month 3 postnatal. The correlation between UAldo and the urinary Na/K ratio was determined as an index of renal aldosterone sensitivity.

Results: UAldo significantly increased with GA: from 8.8 ± 7.5 μg/mmol of creatinine (Group 1) to 21.1 ± 21.0 (Group 3) in correlation with plasma aldosterone levels in all groups (P < .001), demonstrating its reliability. The aldosterone/renin ratio significantly increased with GA, suggesting an aldosterone secretion defect in preterm infants. UAldo and urinary Na/K were correlated in very preterm but not in term neonates, consistent with very preterm neonates being renal-aldosterone sensitive and term neonates being aldosterone resistant.

Conclusions: Very preterm infants have a previously unrecognized defective aldosterone secretion but conserved renal aldosterone sensitivity in the neonatal period, which modifies the current view of sodium balance in these infants and suggests alternative management approaches.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aging / metabolism
  • Aldosterone / blood
  • Aldosterone / physiology*
  • Aldosterone / urine
  • Birth Weight
  • Electrolytes / urine
  • Female
  • Fetal Blood / chemistry
  • Gestational Age
  • Homeostasis
  • Humans
  • Infant, Extremely Premature
  • Infant, Newborn
  • Infant, Premature / metabolism
  • Male
  • Middle Aged
  • Pregnancy
  • Prospective Studies
  • Renin / blood
  • Signal Transduction / physiology*
  • Sodium / metabolism*

Substances

  • Electrolytes
  • Aldosterone
  • Sodium
  • Renin

Associated data

  • ClinicalTrials.gov/NCT01176162