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In a landmark paper, Liggins and Howie showed that a single course of antenatal corticosteroid therapy administered to women at risk for preterm delivery (PTD) reduced the incidence and severity of respiratory distress syndrome (RDS) and mortality in offspring [ 1 ]. Over two dozen randomized trials have confirmed these findings [ 2 ]. Subsequent trials have also shown that antenatal corticosteroid therapy improves circulatory stability in preterm neonates, resulting in lower rates of intraventricular hemorrhage (IVH) and necrotizing enterocolitis compared with unexposed preterm neonates.
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.