Prevention of Hyaline Membrane Disease

The high mortality of respiratory distress syndrome in premature infants and the relative ineffectiveness of treatment' make two recent reports of special interest. They are clinical studies2 3 which attempt to clarify the role of corticosteroids in prevention and treatment. New forms of treatment for this puzzling disorder have sometimes been introduced without adequate trials, so that it is heartening to find that these are reports of well-documented controlled studies, and that there is a rational basis for reconsidering the use of corticosteroids. The stimulus to the use of corticosteroids in prevention came mainly from animal work. G. G. Liggins, a co-author of one of the trials, found in 1969 that lambs given intrafetal infusion of cortisol, dexamethasone, or corticotrophin were viable when born 24-28 days before term and had lungs which remained expanded after they had been killed.4 Lambs born more than 22 days before term develop features comparable to respiratory distress syndrome unless so treated.5 R. A. Delemos and co-workers6 then compared the lungs of lambs treated with corticosteroids in utero with those of their untreated twins. They found that animals treated within 47 days of term showed accelerated appearance of surfactant. This is a lipoprotein formed in alveolar cells and having as its main action the reduction in surface tension in the lungs, facilitation of expansion during inspiration, and prevention of collapse during expiration. Deficiency of surfactant is considered to be a crucial factor in causing respiratory distress syndrome.7 Evidence that corticosteroids are relatively deficient in babies with respiratory distress syndrome came from a necropsy study of R. L. Naeye and colleagues,8 who found that in infants dying of respiratory distress syndrome within 72 hr of birth the mean adrenal weight was 19% less than in infants dying of other causes. It was not clear whether the reduction of adrenal weight was the cause or the result of the disease. In the first of the recent trials2 corticosteroids were given to 282 mothers in whom premature delivery threatened, or delivery was planned, before 37 weeks gestation. Patients were randomly allocated either to a treated group and given by intramuscular injection a mixture containing 6 mg each of betamethasone acetate and betamethasone phosphate, or to a control group and given 6 mg of cortisone acetate, the