Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group.

A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.

Effects of exogenous surfactant therapy on dynamic compliance during mechanical breathing in preterm infants with hyaline membrane disease.

In a prospective, randomized, controlled clinical trial, the immediate and the longitudinal effects of exogenous surfactant therapy on pulmonary mechanics were evaluated in extremely premature infants during mechanical respiration. Ninety-four infants weighing between 600 and 1250 gm received either exogenous surfactant or sham (air) therapy in the delivery room and up to three additional doses in the first 48 hours of life if they were ventilator-dependent, had fractional inspiratory oxygen requirements greater than or equal to 0.30, and radiographic findings consistent with hyaline membrane disease. Each infant underwent pulmonary mechanics assessment (dynamic compliance, total pulmonary resistance, tidal volume) immediately before and 1 hour after each dose, and at 24, 48, and 72 hours and 7 days of age. There were no significant differences in dynamic compliance, total pulmonary resistance, and tidal volume in the surfactant (n = 47) and control (n = 47) groups before and 1 hour after each dose. However, dynamic compliance was 50% greater in the surfactant group at 24 hours of age (p less than or equal to 0.009); this difference steadily increased to 94% at 7 days of age (p less than or equal to 0.009). Oxygenation, assessed by the ratio of alveolar to arterial oxygen pressure, was significantly greater in the surfactant group during the first 72 hours of life; the greatest difference was noted at 24 hours (p less than or equal to 0.001). Mean airway pressure requirements in the surfactant group were significantly less than in the control group at all times during the first week. We conclude that exogenous surfactant therapy, administered at birth and during the first 48 hours of life in extremely premature infants with hyaline membrane disease, improves dynamic compliance and gas exchange during mechanical breathing.

Changing outcome of extremely premature infants (less than or equal to 26 weeks' gestation and less than or equal to 750 gm): survival and follow-up at a tertiary center.

Management of extremely premature infants is controversial because limits of viability are not established. From 1981 to 1987, 175 infants were admitted to the neonatal intensive care unit at Minneapolis Children's Medical Center with gestational ages less than or equal to 26 weeks and birth weights less than or equal to 750 gm. To assess current prognosis and to analyze trends over time, survival data and developmental characteristics of surviving infants were reviewed. During the study period, antenatal obstetric management was assertive, with liberal indications for tocolysis and expectant management for preterm prolonged membrane rupture, with the goal of delivery of infants in a nonasphyxiated condition. Ninety-one percent of infants were inborn and were managed aggressively after birth with full neonatal support. Survival increased from 21% in 1981-1982 to greater than 50% in 1986-1987 and occurred as early as 23 weeks' gestation. Seventy-one percent of all deaths occurred within 48 hours of birth, and late death (greater than 28 days) was uncommon. At follow-up, 23% of survivors were impaired, a proportion that remained relatively constant during the study period. Improvements in survival were not associated with an increased proportion of impaired infants. Survival with good outcome is attainable at gestational ages and birth weights previously considered nonviable. For obstetricians, neonatologists, and parents, knowledge of such current data can play an important role in making appropriate management decisions for both mother and infant.

Prematurity prevention programs: an analysis of successes and failures.

OBJECTIVE: Our purpose was to assess the long-term results of established prematurity prevention programs. STUDY DESIGN: A population cohort of pregnant women from two major urban health care organizations were examined. Rates and cost-benefit analysis of prematurity and patient, system, or physician failures were analyzed. During 1990 1143 pregnant women were prospectively reviewed. RESULTS: A total of 11.8% of the mothers were high risk and responsible for 108 (50.2%) of the preterm deliveries. The preterm birth rate of all enrollees was 4.6%. One percent of the preterm neonates required level III care for complications. The average charge for a 35 week infant was 18 times, and a 36 week infant was five times more costly than a term infant. Patient, physician, and health care system failures occurred at different rates. CONCLUSIONS: This preterm prevention program resulted in low preterm birth rates. Potentially preventable preterm births most often occurred as a result of patient and physician failures.

Survival and follow-up of infants born at 23 to 26 weeks of gestational age: effects of surfactant therapy.

Little information is available regarding the effect of surfactant on outcome for infants born at or before 26 weeks of gestation. We addressed this issue by reviewing records of 310 infants born at gestational ages of 23 through 26 weeks who were admitted to our nursery from 1986, when surfactant was introduced, through 1990. Surfactant was administered to 154 infants (5 during a single-dose prevention study, 25 during a multiple-dose prevention study, 124 while receiving a Food and Drug Administration treatment investigational new drug); 156 infants were not treated with surfactant. Seventy-three percent of the treated infants survived, compared with 55% of the nontreated infants. Increased survival occurred at all gestational ages between 23 and 26 weeks but were greatest in infants born at 23 and 24 weeks. At follow-up, no differences in neurologic outcome were detected between surfactant-treated and nontreated infants. We conclude that surfactant use in extremely premature infants improves survival rates without increasing the proportion of impaired survivors.

New prospective studies of the association of Ureaplasma urealyticum colonization and chronic lung disease.

This study examined the association between Ureaplasma urealyticum colonization and the development of chronic lung disease (CLD) in 93 premature infants who were treated with surfactant and who had birth weights < 1251 g. Nasopharyngeal and tracheal cultures for U. urealyticum were obtained at 2 +/- 1 and at 14 +/- 1 days after birth and were positive in 17 (18%) of 93 patients. Infants born vaginally were 4.5 times more likely to be colonized than were those born by cesarean section. Colonization with U. urealyticum was associated with 1.66 (95% confidence interval, 1.24-2.20, P = .024) times the risk of developing CLD and with a greater incidence of > or = 2+ polymorphonuclear leukocytes in the tracheal aspirate at 2 +/- 1 days of age compared with uncolonized infants (P = .025). We conclude that U. urealyticum colonization is associated with CLD even after surfactant treatment. The presence of U. urealyticum is also associated with inflammatory cells in the tracheal aspirate.