Impact of antenatal dexamethasone administration on respiratory distress syndrome in surfactant-treated infants.

Neonatal lung disease is primarily responsible for the perinatal morbidity and mortality associated with preterm birth. Recently exogenous surfactant replacement therapy has been used to prevent or treat respiratory distress syndrome. As part of a multicenter, preventive trial between February 1986 and December 1988 using calf-lung surfactant extract, we treated 147 infants with single dose calf-lung surfactant extract. We analyzed this experience to evaluate the possibility that antenatal steroids may be additive (with calf-lung surfactant extract) in reducing both the incidence and severity of respiratory distress syndrome. Although a reduction in the incidence of respiratory distress syndrome was observed among the 33 neonates exposed to antenatal dexamethasone when compared with the 114 infants given calf-lung surfactant extract alone, the difference was not significant (37.7% vs. 24.2% p = 0.15). However, comparison of neonatal subsets previously shown to benefit most from steroid use revealed an additive effect between calf-lung surfactant extract and dexamethasone in reducing both the incidence and severity of respiratory distress syndrome. Of the 99 singleton pregnancies, only 2 of 16 infants treated with calf-lung surfactant extract and dexamethasone developed respiratory distress syndrome, compared with the 33 of 83 calf-lung surfactant extract cases (p less than 0.05). A similar reduction was observed in infants between 28 and 32 weeks' gestation (calf-lung surfactant extract, 21 of 79 vs. calf-lung surfactant extract and dexamethasone, 0 of 24; p less than 0.05). A reduction in disease severity was observed in male offspring (moderate or severe respiratory distress syndrome only; 22 of 63 vs. 2 of 22; p less than 0.05). Potential confounding variables (e.g., gestational age at birth, birth weight, exposure to tocolytics before delivery, fetal pH at birth) were similar in all comparisons. We conclude that an additive effect between dexamethasone and calf-lung surfactant extract is observed in selected cases. It may therefore be appropriate to maximize antenatal steroid use in centers where exogenous surfactant is available.