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.
Methotrexate is given weekly as an intramuscular injection of 15 to 25 mg. Side effects are rare and include leukopenia and hypersensitivity interstitial pneumonitis. Hepatic fibrosis is the most severe potential sequela of long-term therapy. Patients with concomitant alcohol abuse and/or morbid obesity are more likely to develop hepatic fibrosis and therefore should not be treated with methotrexate. It is prudent to obtain a baseline chest radiograph and to monitor complete blood count, liver function and renal function every two weeks until the patient is receiving oral therapy, and every one to three months thereafter. Before methotrexate therapy is initiated, the risks of treatment and the possible need for a liver biopsy should be discussed with the patient.