Aldosterone Resistance in Preterm Infants (PREMALDO)

PREMALDO : Aldosterone Resistance in Preterm Infants : Assessment by a Non Invasive Measurement of Urinary Aldosterone

In the neonatal period, the human kidney is characterized by a functional immaturity responsible for an impaired ability to regulate water and sodium homeostasis, which is exacerbated by prematurity. This altered sodium handling could be related to a partial renal aldosterone resistance. Renal sodium reabsorption and potassium excretion are mainly controlled by aldosterone, after binding to the mineralocorticoid receptor (MR). The investigators have analyzed MR expression throughout human and mouse renal development, and the investigators found a weak MR expression at birth. The investigators have conducted a pilot study in full-term newborns, which confirmed a partial neonatal aldosterone resistance. This study also highlighted that urinary aldosterone is the best index to accurately assess aldosterone sensitivity at birth.

Study Overview

• Status: Completed
• Conditions: Newborn

Detailed Description

Principal objective:

To assess aldosterone resistance at birth by a non invasive measurement of urinary aldosterone, in order to evaluate its intensity as a function of gestational age. Determination of normal values of urinary aldosterone concentration in each group.

Secondary objectives:

Comparison of plasma and urinary electrolytes concentrations with hormonal measurements and clinical parameters. Evolution of these biological parameters throughout the first year of life, depending on gestational age at birth.

Methodology : multicentric study, open study Two hundred-forty newborns will be included in order to constitute 4 groups of 60 children, classified according to their gestational age: < 28 GW, 28 - < 33 GW, 33- < 37 GW, > 37 GW.

Inclusion criteria: every newborn will be included, after written parental consent was obtained.

Study :

Urinary samples will be collected onto a gauze compress, during the first 24 hours of life, at day three, and at 1, 3, 6 and 12 months. A blood sample will be obtained from systematic umbilical cord blood collection at birth and during the Guthrie test at day three. Aldosterone and renin concentrations will be measured in BICETRE Hospital laboratory. Plasma and urinary electrolyte concentrations will be measured in the Biochemistry department. DNA samples will also be gathered from umbilical cord blood for future genetic investigations (functional polymorphisms of the MR gene).

Perspectives This study will permit to assess the intensity of aldosterone resistance in full-term and preterm newborns, by a non invasive method. It should bring new insights into the mechanisms of hormonal regulation of sodium balance in preterm newborns and during the first year of life. Urinary aldosterone assessments may open new perspectives for therapeutic management of water and sodium waste in premature infants.

• Study Type: Observational
• Enrollment (Actual): 170

Contacts and Locations

Study Locations

• France
  • Ile de France
    • Clamart, Ile de France, France, 92140
      • Assistance Publique- Hôpitaux de Paris: Antoine Beclere Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 9 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Every newborn without congenital malformation will be included, after written parental consent was obtained

Description

Inclusion criteria :

• Maternal

  • Maternal age ≥ 18 and ≤ 45 years,
  • Written parental consent
  • Normal obstetrical ultrasounds
• Neonatal - Birth by vaginal delivery or cesarean section

Exclusion criteria :

• Maternal

  • Type 1 or type 2 diabetes,
  • Adrenal or hypophyseal deficiency
  • Treatment for arterial hypertension

• Neonatal

  • Perinatal anoxia (defined by an Apgar score < 5 at 5 min and pH < 7,10 and lactacidemia > 9 mmol/l at blood cord).
  • Congenital malformation
  • Chromosomic abnormalities

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Group "< 28"; • Gestational Age < 28 weeks
Group "28 - < 33"; • Gestational Age : 28 - < 33 weeks
Group "33- < 37"; Gestational Age : 33- < 37 weeks
Group "> 37"; Gestational Age > 37 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
urinary aldosterone	Determination of normal values of urinary aldosterone concentration in each group (24 first hours, day three, and at 1 and 3 months)	during the first year of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma electrolytes concentrations	Comparison of plasma and urinary electrolytes concentrations with hormonal measurements and clinical parameters. Evolution of these biological parameters throughout the first year of life, depending on gestational age at birth.	first year of life
urinary electrolytes concentrations	Comparison of plasma and urinary electrolytes concentrations with hormonal measurements and clinical parameters. Evolution of these biological parameters throughout the first year of life, depending on gestational age at birth.	first year of life
hormonal measurements	Comparison of plasma and urinary electrolytes concentrations with hormonal measurements and clinical parameters. Evolution of these biological parameters throughout the first year of life, depending on gestational age at birth.	first year of life
clinical parameters	Comparison of plasma and urinary electrolytes concentrations with hormonal measurements and clinical parameters. Evolution of these biological parameters throughout the first year of life, depending on gestational age at birth.	first year of life

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Pascal BOILEAU, MD PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Martinerie L, Viengchareun S, Delezoide AL, Jaubert F, Sinico M, Prevot S, Boileau P, Meduri G, Lombes M. Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates. Endocrinology. 2009 Sep;150(9):4414-24. doi: 10.1210/en.2008-1498. Epub 2009 May 28.
• Martinerie L, Pussard E, Yousef N, Cosson C, Lema I, Husseini K, Mur S, Lombes M, Boileau P. 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: August 4, 2010
• First Posted (Estimate): August 5, 2010

Study Record Updates

• Last Update Posted (Estimate): April 30, 2014
• Last Update Submitted That Met QC Criteria: April 28, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Preterm infants; Non Invasive measurement; Aldosterone resistance
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: P081211; B91017-20 (Other Grant/Funding Number: Proper Authorithies : AFSSaPS)