Impact of the Administration of Fludrocortisone in Very Premature Infants

• Status: Completed
• Trial end date: 2020-09-08
• Target enrollment: 0
• Participant gender: All

Summary

Water and electrolytic homeostasis is remarkably controlled by the mineralocorticoid pathway (renin-angiotensin-aldosterone system acting on the renal tubule). However, the neonatal period in humans is characterized by a reduced ability of the kidney to ensure normal functions of urine concentration and maintenance of sodium and water balance. This renal functional immaturity, is associated in the very premature infants (VPT) (born <32 weeks of amenorrhea (SA)) to an immaturity of the adrenal responsible for a default of aldosterone biosynthesis . This relative aldosterone deficiency induces difficulties for VPT to adapt to extra-uterine life when maintaining a positive sodium balance is essential for postnatal growth. The improvement of perinatal care (antenatal corticosteroids maturation, ventilation techniques and use of surfactant) have increased the survival of these children . Nevertheless, extreme prematurity (less than 32 weeks), which concerns nearly 2% of live births in France, remains associated with neurodevelopmental sequelae in nearly 40% of children at 5 years .

Secondary hydroelectrolytic disorders with transient mineralocorticoid adrenal insufficiency is probably one of the factors responsible of these neurological deleterious outcomes as well as the occurrence of other complications (bronchopulmonary dysplasia, enterocolitis necrotizing) of extreme prematurity. Indeed, aside from the administration of antenatal steroids to induce maturation, the prevention of postnatal dehydration reduces the risk of intracranial hemorrhage in that population. However, high fluid intake are associated with an increased incidence of patent ductus arteriosus, of bronchopulmonary dysplasia and necrotizing enterocolitis. This necessitates the evaluation of preventive measures to avoid such fluid and electrolyte imbalances by a pharmacological approach based on mineralocorticoid administration in very premature infants, due to the relative aldosterone deficiency identified in this population.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Fludrocortisone

Criteria

Inclusion Criteria:

• Very premature newborns defined by a gestational age <32 and ≥ 26 gestational weeks

• Eutrophic: birth weight between the 10th and 90th percentile of the French reference curves

• Absence of malformations or chromosomal abnormality identified

• Lack of adrenal, pituitary or gonadal diseases diagnosed prior birth

• Lack of participation in another research protocol

• "Inborn": born and hospitalized in the four neonatology departments participating in the study

• Informed consent of the holders of parental authority

Exclusion criteria:

• Maternal treatment prior to pregnancy: systemic or inhaled corticosteroids, hormone therapy for adrenal or pituitary insufficiency, antihypertensive treatment (calcium channel blockers, beta blockers, angiotensin)

• Lack or incomplete treatment of antenatal glucocorticoids (betamethasone)