We measured the physiological and biochemical responses of preterm lambs to intra-amniotic injection of interleukin-1α (IL-1α). Singleton lamb fetuses at 126 days of gestation were randomized to receive 125 μg IL-1α or vehicle control via ultrasound-guided intra-amniotic injection. Each lamb was delivered 48 h later by cesarian section and ventilated for 120 min. Relative to controls, IL-1α-treated lambs had higher dynamic compliance, ventilatory efficiency indices, and saturated phosphatidylcholine levels (all p < 0.05). Umbilical cord plasma cortisol and catecholamine levels, white blood cells and differentials, cardiac output, regional blood flow, and kidney function did not differ between the groups. However, at 120 min after delivery, the cortisol levels for IL-1α-treated animal were higher than for controls. Single intra-amniotic IL-1α treatment increases surfactant pool size and improves dynamic compliance in the absence of an inflammatory response or differences in other indicators of fetal or newborn organ function.

The purpose of this study was to analyze the impact of neonatal care practices on the efficacy of exogenous human surfactant. Two hundred newborns (gestational age 24.0 to 29.9 weeks, lecithin-sphingomyelin ratio less than 2 or absent phosphatidylglycerol, and requirement of mechanical ventilation at birth) participated in a randomized bicenter trial of human surfactant substitution. In only one of the two sites (site 2) surfactant substitution decreased the severity of respiratory failure and increased neonatal survival without bronchopulmonary dysplasia. For analysis of three-way association, continuous variables describing patient characteristics and treatment were dichotomized at the median. The following variables were significantly associated with good outcome in site 1 and 2 and with surfactant substitution in site 2: low oxygen requirement during first three neonatal days, low mean airway pressure during second and third day, low Paco2 during first two neonatal days, and no ligation of ductus arteriosus. Low fluid intake during the first three days and low colloid intake during the first two days of life were associated with good outcome in both sites. The ratio between mean airway pressure and the oxygen requirement was higher in site 2 than in site 1 during the first day of life. Fluid intake and ventilatory management may influence the efficacy of exogenous surfactant.