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

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 amulticenter 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, month1, 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 mu g/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.