On the other hand, hydrocortisone has almost equal glucocorticoid and mineralocorticoid action, and the half-life is only 8 hours. Sick premature infants have relative adrenal insufficiency during acute illness because of developmental immaturity of the hypothalamic-pituitary-adrenal axis suggesting that an early physiological replacement of cortisol may be needed [ 21 – 24 ]. However, large doses above physiologic levels to achieve the anti-inflammatory action may cause significant mineralocorticoid side effects. Early use of hydrocortisone (<48 hours) was shown to decrease the risk of PDA but increased survival only in infants exposed to maternal chorioamnionitis or who had low cortisol values [ 22 , 23 ].
There have been no randomized trials examining the effect of hydrocortisone given after the first week of life or used to treat infants with prolonged ventilator dependence. One retrospective cohort study compared infants who required assisted ventilation and oxygen after the first one to two weeks of age and received hydrocortisone with a group of healthier infants who did not receive hydrocortisone.  Infants treated with hydrocortisone experienced decreasing oxygen requirements and were successfully weaned from assisted ventilation. After seven days of treatment, there were no differences in oxygen requirements between the two groups. On follow-up, there were no differences in head circumference, neurological outcome, psychomotor development or school performance. Magnetic resonance imaging performed at eight years of age on a similar cohort of infants treated with hydrocortisone showed that although, overall, children born preterm had significantly reduced grey matter volumes compared to term children, there were no differences in the intracranial volumes, grey matter volumes or white matter volumes between children who did and did not receive hydrocortisone for treatment of CLD.  There were also no differences in neurocognitive outcomes, assessed using the Wechsler Intelligence Scales for Children.