Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia.

We performed a randomized, double-blind, controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to receive either 2000 IU retinyl palmitate (n = 27) or saline placebo (n = 22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48%, placebo group 55%; p = 0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 micrograms/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease.

Results of laboratory surveillance of very low birth weight infants treated with a synthetic surfactant.

During two randomized, controlled trials comparing single prophylactic doses of air placebo and a synthetic surfactant, Exosurf Neonatal, many routine laboratory measurements were made in small premature infants during the first week of life. Values for serum electrolytes, urea, creatinine, phospholipid, cholesterol, glucose, calcium, bilirubin, and liver enzymes, as well as for hemoglobin, leukocyte and platelet counts, and urinalysis, did not differ between the placebo- and surfactant-treated infants. There was no evidence that prophylactic administration of this synthetic surfactant causes alterations in standard laboratory tests in small premature infants.

Improved outcome at 28 days of age for very low birth weight infants treated with a single dose of a synthetic surfactant.

Two identical double-blind, controlled, randomized trials were initiated to determine whether the administration of a single 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal), soon after the delivery of infants with birth weights 700 to 1350 gm, would improve rates of survival without bronchopulmonary dysplasia. Both trials were terminated before enrolling their planned sample sizes because of the availability of Exosurf under the provisions of a Treatment Investigational New Drug program. We report the combined results of these trials. Study infants were stratified according to birth weight and gender before random assignment to a treatment regimen. One hundred ninety-two infants received Exosurf and 193 received an air placebo. The study groups were similar when a variety of demographic features describing the mothers, their pregnancies, the circumstances of the births, and the infants were compared. Exosurf-treated infants required significantly less oxygen and respiratory support during the first 3 days of life in comparison with the air-treated infants. Fewer infants in the Exosurf group had pulmonary interstitial emphysema (26 vs 13; p = 0.028). In the Exosurf group, there was a significant reduction in the combined outcome, neonatal death or survival with bronchopulmonary dysplasia (57 vs 39; p = 0.042), and there was a significant increase in rates of survival without this disease (128 vs 137; p = 0.042). There were no differences between treatment groups in the incidences of a variety of complications of prematurity, including apnea, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. We conclude that improvements in respiratory physiology after a single prophylactic dose of Exosurf result in an increased likelihood of neonatal survival without bronchopulmonary dysplasia.