Impact of the Administration of Fludrocortisone in Very Premature Infants
Status:
Completed
Trial end date:
2020-09-08
Target enrollment:
Participant gender:
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.