Bovine surfactant replacement therapy in neonates of less than 30 weeks' gestation: a randomized controlled trial of prophylaxis versus treatment. Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial. Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial. Porcine surfactant replacement therapy in newborns of 25-31 weeks' gestation: a randomized, multicentre trial of prophylaxis versus rescue with multiple low doses. The French Collaborative Multicentre Study Group. Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Randomized, placebo-controlled trial of human surfactant given at birth versus rescue administration in very low birth weight infants with lung immaturity. Early CPAP versus surfactant in extremely preterm infants. A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation. [Administration of exogenous surfactant in premature very low birth weight infants with RDS].
The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age). Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All treated neonates were eligible to receive up to three additional doses during the first 5 days of life. The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours. There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001). Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age). There were no differences between early and late surfactant groups in any of these parameters. The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005). Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters. It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS) To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.
                Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.
                Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.
                Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies. The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management.
                Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6.
                At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality.
                Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria. The aim of the study was to determine if prophylaxis with multiple low doses of porcine surfactant would increase survival, without bronchopulmonary dysplasia, compared with rescue therapy, for respiratory distress syndrome in newborns of 25-31 weeks' gestation. Compared with rescue therapy (n = 122), prophylaxis (n = 134) decreased the need for oxygenation and ventilatory support within 3-72 h. It did not, however, increase survival without bronchopulmonary dysplasia (60% versus 46%) (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 0.90-2.61). Furthermore, prophylaxis decreased the incidence of severe peri-intraventricular haemorrhage (3% versus 16%) (OR = 0.28, 95% CI = 0.09-0.84) and retinopathy of prematurity (2% versus 11%) (OR = 0.18, CI = 0.04-0.78). We conclude that prophylaxis did not increase survival without bronchopulmonary dysplasia. The decreased incidence of severe peri-intraventricular haemorrhage and retinopathy of prematurity after prophylaxis requires further study. Although numerous trials have demonstrated the efficacy of exogenous surfactant for prophylaxis or treatment of neonatal respiratory distress syndrome (RDS), optimum timing of administration remains controversial. One previous study showed that administration of calf lung surfactant extract immediately following birth, to neonates born before 30 weeks postconceptional age, was preferable to delaying administration until after development of RDS. The current study was designed to test a similar hypothesis for babies born between 29 and 32 weeks gestational age.
                One thousand three hundred ninety-eight neonates with obstetric estimates of 29 through 32 weeks' gestation were randomized to receive CLSE at birth or to wait until development of mild RDS. After exclusions for malformations and other factors, data from 1248 were analyzed.
                Prophylaxis was associated with less development of moderate RDS (7% vs 12%), less need for retreatment (5% vs 9%), less need for mechanical ventilation or supplemental oxygen during the first 4 days, and fewer deaths or less requirement for supplemental oxygen at 28 days (5% vs 9%). Although 1-minute Apgar scores were significantly lower in the prophylaxis group, the difference disappeared by the 5-minute score and there was no difference in the incidence of asphyxia-related complications. Sixty percent of the neonates assigned to early treatment received endotracheal intubation and 43% received calf lung surfactant extract at a median age of 1.5 hours. When data were analyzed by gestational age and birth weight subgroups, most of the differences could be attributable to babies born at 30 weeks or less or weighing less than 1500 g, probably because of the higher incidence of surfactant deficiency in this more immature subgroup. We designed a multicenter randomized trial to compare 3 approaches to the initial respiratory management of preterm neonates: prophylactic surfactant followed by a period of mechanical ventilation (prophylactic surfactant [PS]); prophylactic surfactant with rapid extubation to bubble nasal continuous positive airway pressure (intubate-surfactant-extubate [ISX]) or initial management with bubble continuous positive airway pressure and selective surfactant treatment (nCPAP).
                Neonates born at 26 0/7 to 29 6/7 weeks' gestation were enrolled at participating Vermont Oxford Network centers and randomly assigned to PS, ISX, or nCPAP groups before delivery. Primary outcome was the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age.
                648 infants enrolled at 27 centers. The study was halted before the desired sample size was reached because of declining enrollment. When compared with the PS group, the relative risk of BPD or death was 0.78 (95% confidence interval: 0.59-1.03) for the ISX group and 0.83 (95% confidence interval: 0.64-1.09) for the nCPAP group. There were no statistically significant differences in mortality or other complications of prematurity. In the nCPAP group, 48% were managed without intubation and ventilation, and 54% without surfactant treatment.
                Preterm neonates were initially managed with either nCPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation. An approach that uses early nCPAP leads to a reduction in the number of infants who are intubated and given surfactant. A randomized, placebo-controlled trial of human surfactant given intratracheally at birth (prophylactic) versus rescue administration after the onset of severe respiratory distress syndrome (RDS) was conducted among preterm infants born at 24 to 29 weeks of gestation. Singleton fetuses were randomly assigned to receive (1) placebo (air), (2) prophylactic surfactant treatment, or (3) rescue surfactant treatment; infants of multiple births received either (1) prophylactic or (2) rescue treatment. Of 282 potentially eligible fetuses, 246 infants received treatments at birth and 200 infants had RDS. Outcomes are presented both as an intention-to-treat analysis (including infants who met exclusion criteria at or after birth) and as a full treatment protocol analysis for those infants with RDS and likely to benefit from surfactant. Preterm infants (mean 1.0 kg birth weight, 27 to 28 weeks of gestational age) randomly assigned to receive prophylactic treatment received surfactant soon after birth; those assigned to receive rescue surfactant had instillation at a mean age of 220 minutes if the lecithin-sphingomyelin ratio was less than or equal to 2.0 and no phosphatidylglycerol was detected in either amniotic fluid or initial airway aspirate, oxygen requirements were a fraction of inspired oxygen of greater than 0.5, and mean airway pressure was greater than or equal to 7 cm H2O from 2 to 12 hours after birth. Up to four treatment doses (or air) were permitted within 48 hours; approximately 60% of surfactant-treated infants required two or more doses. Surfactant-treated infants had significantly less pulmonary interstitial emphysema than placebo-treated infants (p = 0.02), but there were no other significant differences in mortality rates or morbidity. Indexes of oxygenation and ventilation were improved in surfactant recipients during the first 24 hours. An intention-to-treat analysis found no significant differences between infants given placebo and surfactant-treated infants or between prophylactic- and rescue-treated infants; an improved total mortality rate (p = 0.002) was found among surfactant-treated infants in Helsinki but not in San Diego. Among infants with RDS, the total mortality rate was significantly improved (p = 0.004) with surfactant treatment but not the proportion alive and without bronchopulmonary dysplasia at 28 days (p = 0.052), or the proportion alive and without bronchopulmonary dysplasia at 38 weeks of postconceptional age (p = 0.18) to adjust for differences in prematurity. Deaths caused by RDS or bronchopulmonary dysplasia were significantly reduced among surfactant recipients (p = 0.0001). Neither among singletons nor among multiple-birth infants was there a selective advantage to prophylactic versus rescue treatment.(ABSTRACT TRUNCATED AT 400 WORDS) There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants.
                We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen).
                A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups.
                The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)
                2010 Massachusetts Medical Society Exogenous pulmonary surfactants are administered into the trachea either to prevent respiratory distress syndrome in premature infants or to treat it. In a randomized, multicenter trial, we compared the results of surfactant therapy initiated as prophylaxis with the results of rescue therapy with surfactant.
                Before birth, 479 infants with an estimated gestational age of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis (n = 235) or rescue therapy (n = 244). The infants in the prophylaxis group received a 90-mg intratracheal dose of an exogenous calf-lung surfactant extract at the time of delivery, whereas the infants in the rescue-therapy group received 90 mg of the surfactant several hours after delivery if the fractional inspiratory oxygen concentration was at least 0.40 or if the mean airway pressure was at least 0.686 kPa (7 cm of water), or both. Infants in both groups received additional doses of surfactant at intervals of 12 to 24 hours if these criteria were met.
                The proportion of infants surviving until discharge to their homes was significantly higher in the prophylaxis group than in the rescue-therapy group (88 vs. 80 percent, P = 0.028). This difference was due primarily to the longer survival of very premature infants (less than or equal to 26 weeks' gestation) in the prophylaxis group than in the rescue-therapy group (75 vs. 54 percent, P = 0.006). According to proportional-hazards regression analysis, the distribution of survival times was better for all infants in the prophylaxis group (P = 0.007) and for the subgroup of infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier (P = 0.0048). Infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier had a lower incidence of pneumothorax than similar infants in the rescue-therapy group (7 vs. 18 percent, P = 0.03).
                We found a significant advantage to the administration of the initial dose of surfactant as prophylaxis rather than as rescue therapy in very premature infants. A retrospective study is carried out with the aim of establishing the effect from surfactant therapy on pulmonary function, survival and complication from intensive therapy on VLBWI with RDS. 67 premature infants below 1500 grams are included in the study divided in 3 groups: I gr.--27 babies treated with Corosurf; II gr.--16 babies treated with Exosurf; III gr.--24 control babies without surfactant. The results show that in spite of relatively lower gestational age and higher incidence of inborn infection in group I, Curosurf treated babies spend shortest time on mechanical ventilation and oxygen therapy showing lower incidence of BPD, IVH and mortality rate.
Although the early trials of prophylactic surfactant administration to infants judged to be at risk of developing RDS compared with selective use of surfactant in infants with established RDS demonstrated a decreased risk of air leak and mortality, recent large trials that reflect current practice (including greater utilization of maternal steroids and routine post delivery stabilization on CPAP) do not support these differences and demonstrate less risk of chronic lung disease or death when using early stabilization on CPAP with selective surfactant administration to infants requiring intubation.