Introduction Of Surfactant Therapy Research Articles

Geographical Differences and Temporal Improvements in Forced Expiratory Volume in 1 Second of Preterm-Born Children

Although preterm birth is associated with later deficits in lung function, there is a paucity of information on geographical differences and whether improvements occur over time, especially after surfactant was introduced. To determine deficits in percentage predicted forced expiratory volume in 1 second (%FEV1) in preterm-born study participants, including those with bronchopulmonary dysplasia (BPD) in infancy, when compared with term-born control groups. Eight databases searched up to December 2021. Studies reporting spirometry for preterm-born participants with or without a term-born control group were identified. Data were extracted and quality assessed by 1 reviewer and checked by another. Data were pooled using random-effects models and analyzed using Review Manager and the R metafor package. Deficits in %FEV1 between preterm-born and term groups. Associations between deficits in %FEV1 and year of birth, age, introduction of surfactant therapy, and geographical region of birth and residence were also assessed. From 16 856 titles, 685 full articles were screened: 86 with and without term-born control groups were included. Fifty studies with term controls were combined with the 36 studies from our previous systematic review, including 7094 preterm-born and 17 700 term-born participants. Of these studies, 45 included preterm-born children without BPD, 29 reported on BPD28 (supplemental oxygen dependency at 28 days), 26 reported on BPD36 (supplemental oxygen dependency at 36 weeks' postmenstrual age), and 86 included preterm-born participants. Compared with the term-born group, the group of all preterm-born participants (all preterm) had deficits of %FEV1 of -9.2%; those without BPD had deficits of -5.8%, and those with BPD had deficits of approximately -16% regardless of whether they had BPD28 or BPD36. As year of birth increased, there was a statistically significant narrowing of the difference in mean %FEV1 between the preterm- and term-born groups for the all preterm group and the 3 BPD groups but not for the preterm-born group without BPD. For the all BPD group, when compared with Scandinavia, North America and western Europe had deficits of -5.5% (95% CI, -10.7 to -0.3; P = .04) and -4.1% (95% CI, -8.8 to 0.5; P = .08), respectively. Values for the measure %FEV1 were reduced in preterm-born survivors. There were improvements in %FEV1 over recent years, but geographical region had an association with later %FEV1 for the BPD groups.

Prediction of lung function and lung density of young adults who had bronchopulmonary dysplasia.

COPD risk is jointly determined by fetal lung development, lung growth rate and lung growth duration leading to the maximally attained level of lung function in early adulthood. Bronchopulmonary dysplasia (BPD) is considered a developmental arrest of alveolarisation. Long-term outcome studies of adult survivors born before the introduction of surfactant therapy (“old BPD”) showed impaired lung function. We aimed to predict adult lung function and lung density in a cohort of premature infants born in the surfactant era, representing “new BPD”.We studied a cohort of young adults born between 1987 and 1998, with (n=36) and without (n=28) BPD, treated in a single centre. Their perinatal characteristics and pulmonary function in infancy were studied by regression analysis for correlation with adult lung function and tissue lung density, all expressed by z-scores, at a mean age of 19.7±1.1 and 21±2.2 years, respectively.Although BPD adults had on average lower forced expiratory volume in 1 s (zFEV1)/forced vital capacity (FVC) and zFEV1 than those without, 55% of the BPD group had zFEV1/FVC values above the lower limit of normal (LLN). Moreover, above LLN values of diffusing capacity of the lung for carbon monoxide (zDLCO) was present in 89% of BPD adults and lung density in 71%. Only higher oxygen supply (FIO2) at 36 weeks post-conception of BPD subjects had a trend with lower zFEV1 (B=−6.4; p=0.053) and lower zDLCO (B=−4.1; p=0.023) at adulthood.No statistically significant predictors of new BPD were identified.

Emergency Neonatal Chest Imaging: "Challenges and Peculiarities"

: The neonatal chest and lung abnormalities can be divided into congenital and acquired or iatrogenic disorders, mostly causing respiratory distress. Congenital lesions include various types of abnormalities such as congenital diaphragmatic hernia, congenital cystic adenoid malformation (CCAM), bronchopulmonary sequestration, lobar emphysema and others. Such conditions are frequently associated with other additional organ malformations. The primary acquired neonatal pulmonary diseases are hyaline membrane disease of premature neonate, meconium aspiration syndrome, transient tachypnea of newborn and neonatal pneumonia. Both congenital and acquired pulmonary disorders in the neonatal period mostly need interventional therapy with the use of mechanical ventilation, oxygen therapy or high frequency ventilation. All these procedures may be complicated by pulmonary air leakage with various intra- and extrapulmonary changes, initially, mostly as interstitial emphysema followed by pneumothorax, pneumomediastinum, pneumopericardium and pneumoretroperitoneum. Such events are always complicated with recurrent atelectasis, acidosis and hypoxemia resulting mostly in chronic lung disease (bronchopulmonary dysplasia). Together with the pulmonary infection, sepsis and other extrapulmonary problems such as intraventricular hemorrhage and necrotizing enterocolitis they result in a high mortality and morbidity rate in this group of infants. The introduction of surfactant therapy in respiratory distress syndrome contributed largely to the reduction of complications in neonatal pulmonary diseases. The imaging of congenital intrathoracic malformations is now frequently recognized by antenatal sonography or MRI if available. The conventional chest X-ray after birth is the first step in the diagnosis of all congenital and acquired neonatal lung disorders for the detection of intrathoracic complications. The prevention of iatrogenic incidents is especially a challenge to the radiologist in this field. The aim of this workshop will be a systematic interpretation of the typical and atypical neonatal chest films including congenital and acquired diseases. Special attention should be paid to the various pulmonary and extrapulmonary complications demonstrated by different pathological signs. Additionally, the radiological signs of patent ductus Botalli on the chest film and the different types and development of chronic lung disease (bronchopulmonary dysplasia) will be shown.

Response to Dr Egan’s letter

Thank you for the opportunity to respond to the letter from Dr Edmund A Egan, Chief Medical Officer of ONY, Inc., manufacturer of Infasurf (Calfactant, (CA)). In the letter by Dr Egan, he refers to the studies presented as abstracts in 2007 (ref. 1,2 in his letter) and our study published electronically as a peer reviewed manuscript in 2011 and included in this print issue. These are different studies, in which different protocols, different timeframes (abstract 2007: Jan 2003 to June 2006; full publication 2011:Jan 2005 to Dec 2009) different infants, different number of patients and different statistical models were used. Dr Egan discusses the increased length of stay (LOS) resulting from improvement in mortality due to surfactant therapy in studies comparing surfactant vs placebo. Based on evidence, the introduction of surfactant therapy has led to significantly decreased mortality and morbidity without increasing resource utilization. The statements of Dr Egan regarding inverse correlation between mortality and LOS are based on a very old study (ref. 3 in his letter) comparing surfactant with placebo in a different ‘era’ of neonatology, where respiratory distress syndrome (RDS) was the major cause of death and had a major influence on LOS. Most important is the fact that surfactant therapy compared with placebo has shown decrease in cost both in infants who survived as well as in infants who died. Subsequent studies on resource utilization are clearly different and these have reported LOS in patients who received one of the three animal-derived surfactants.1, 2 Baroutis et al.3 reported decreased mortality and significantly shorter LOS with poractant alfa (PA), when compared to alveofact or beractant (BE) in a randomized, controlled trial. Fujii et al.4 reported a nonsignificant decrease in mortality (8 vs 19%) and shorter LOS in a PA-treated group compared with that in the BE-treated group (87 vs 97 days, P=0.179). In two randomized, controlled trials comparing PA and BE, incidence of patent ductus arteriosus (PDA), as well as the need for medical or surgical ligation of PDA, were significantly less in patients treated with PA,4, 5 which might therefore contribute to shorter LOS. In a study comparing high vs low dose surfactant therapy, LOS was shorter in the high dose group when compared with low dose group (82 vs 99 days).6 A recently published systematic review and meta-analysis,7 demonstrated a good correlation between higher surfactant efficacy (mortality reduction) and reduced LOS with poractant alfa (PA). Indeed, in the meta-analysis, PA was associated with both a significant reduced risk of death vs BE (P=0.02) and a significantly shorter LOS (weighted mean difference: −26.3 [95% CI: −36.5 to −16.07]; P<0.00001). In the most recent randomized trial comparing PA with BE, LOS was not increased in PA group despite a 50% reduction in mortality rate in the PA-treated group (9.8 vs 20%).8

Improved Survival Rates With Increased Neurodevelopmental Disability for Extremely Low Birth Weight Infants in the 1990s

Advances in perinatal care have resulted in increased survival rates for extremely low birth weight children. We sought to examine the relative changes in rates of survival and neurodevelopmental impairment at 20 months of corrected age among 500- to 999-g birth weight infants born at our perinatal center during 2 periods, before and after the introduction of surfactant therapy in 1990. Four hundred ninety-six infants with birth weights of 500 to 999 g were born at our perinatal center during period I (1982-1989) (mean body weight: 762 g; mean gestational age: 25.8 weeks) and 682 during period II (1990-1998) (mean body weight: 756 g; mean gestational age: 25.5 weeks). Rates of death and survival with and without neurodevelopmental impairment at 20 months of corrected age for the 2 periods were compared with logistic regression analyses, with adjustment for gestational age. Survival rates increased from 49% during period I to 67% during period II. Neonatal morbidity rates also increased during period II, including rates of sepsis (from 37% to 51%), periventricular leukomalacia (from 2% to 7%), and chronic lung disease, defined as oxygen dependence at 36 weeks of corrected age (from 32% to 43%). Rates of severe cranial ultrasound abnormalities were similar (22% vs 22%). Among children monitored, the rate of neurologic abnormalities, including cerebral palsy, increased from 16% during period I to 25% during period II and the rate of deafness increased from 3% to 7%. The overall rate of neurodevelopmental impairment (major neurosensory abnormality and/or Bayley Mental Developmental Index score of <70) increased from 26% to 36%. Compared with period I, in period II there were decreased rates of death (odds ratio [OR]: 0.3; 95% confidence interval [CI]: 0.2-0.4) and increased rates of survival with impairment (OR: 2.3; 95% CI: 1.7-3.3) but also increased rates of survival without impairment (OR: 1.7; 95% CI: 1.3-2.2). Compared with period I, for every 100 infants with birth weights of 500 to 999 g born in period II, 18 additional infants survived, of whom 7 were unimpaired and 11 were impaired. The improved survival rates in the 1990s occurred with an increased risk of significant neurodevelopmental impairment. Prospective parents of extremely low birth weight infants should be advised of this substantial risk, to facilitate decision-making in the delivery room.

Ethical considerations in the management of infants born at extremely low gestational age

With ongoing improvements in technology and the understanding of neonatal physiology, there has been increasing debate regarding the gestational age and birth weight limits of an infants’ capability of sustaining life outside the womb and how this is to be determined. The objective of this review was to address this issue with an analysis of current data (following the introduction of surfactant therapy in 1990) from published studies of survival in extremely low gestational age infants. We found that survival was possible at 22 completed weeks of gestation but only in < 4% of live births reported. Survival increased from 21% at 23 weeks gestational age to 46% at 24 weeks gestational age. Historically, despite continual advances in neonatology, the mortality at 22 weeks has not improved over the past three decades. Combining the data from studies on survival with evidence from developmental biology, we believe that it is not worthwhile to pursue aggressive support of infants born at < 23 weeks gestational age. Given the complicated issues related to morbidity and mortality in infants born at 22 to 25 weeks gestational age and the ethical implications of the available evidence, we propose the need for a consensus derived framework to help in decision-making.

Historical Perspectives

When pharmacologic closure of patent ductus arteriosus (PDA) in the preterm infant using indomethacin was introduced in 1976, there was a paucity of knowledge about the factors controlling the caliber of the ductus arteriosus both before and after birth. Additionally, mortality and morbidity of prematurity (associated with what was then usually referred to as hyaline membrane disease) was remarkably high in the early 1970s. As early as the 1950s, some neonatologists recognized PDA as a complication of what later became designated as “respiratory distress syndrome” (RDS), although it was not until the advent of intermittent mandatory ventilation (IMV) and continuous positive airway pressure (CPAP) that the concept gained prominence. Patency of the ductus appeared to be a major complication, especially in the smallest of preterm babies (at that time, < 1,350 g]) and usually carried a terminal prognosis. The advent of IMV and CPAP kept these small babies alive for a sufficient period of time for the patent ductus to become recognized progressively as a distinct clinical entity and an important early complication of preterm birth. Observant neonatologists noted that babies who had RDS often improved up to a point, beyond which they worsened. The usual story was that the baby experienced ventilatory failure, was treated with mechanical ventilation, and began to improve, with lower inspired oxygen requirements. After a few days, when discussions ensued about taking the baby off the ventilator, the infant’s improvement would cease. The radiographic picture changed from a clearing of the initial ground glass appearance coupled with a relatively small heart to an enlarging heart and the pulmonary edema of congestive heart failure due to a left-to-right shunt across the PDA. Beginning in the mid-1960s, aggressive surgeons advocated operative closure of the PDA in these small preterm infants, but multiple centers consistently reported unacceptably high …

Longitudinal, 15-year follow-up of children born at less than 29 weeks gestation after introduction of surfactant therapy into a region: neurological, cognitive, and educational outcomes.

SANDLER, ADRIAN D. M.D.Editor(s): TEPLIN, STUART W. M.D., Editor; GRUS, CATHERINE L. Ph.D.; SANDLER, ADRIAN D. M.D.; REIFF, MICHAEL I. M.D. Author Information

Longitudinal, 15-year follow-up of children born at less than 29 weeks' gestation after introduction of surfactant therapy into a region: neurologic, cognitive, and educational outcomes.

To measure the primary and secondary school-age neurologic, cognitive, and educational outcomes in a cohort of extremely premature infants born after the introduction of exogenous surfactant therapy in a circumscribed region. Two hundred thirteen infants born at <29 weeks' gestation were cared for at a regional referral center during 1985-1987. At primary school age, neurologic and cognitive outcomes, educational achievement, school placement, health status, and socioeconomic status were determined by follow-up visit. At secondary school age, school placement and health status were evaluated by telephone interview. One hundred thirty-two infants survived to school age, of whom 127 (96%) were evaluated in 1992-1995 and 126 (95%) were evaluated in 2000. Mean ages were 7.0 years at first follow-up and 14.1 years at second follow-up. At primary-school age follow-up, 19 children (15%) had cerebral palsy, 24 (19%) had a general cognitive index <70, and 41 (32%) were placed in a self-contained, special classroom. Thirty-nine children (31%) had no physical or educational impairment, whereas 27 (21%) had at least 1 severe disability. At secondary school age, cerebral palsy incidence remained unchanged, whereas 36 children (29%) were placed in a special classroom. Fifty-one children (41%) had no physical or educational impairment, whereas 24 (19%) had at least 1 severe disability. Neonatal intraventricular hemorrhage and low socioeconomic status were the strongest predictors of adverse outcomes. Premature infants born in the surfactant era remain at high risk of neurodevelopmental compromise. Although many of these children do well, a significant minority will require intensive special educational services through secondary school age.

Trend in mortality from respiratory distress syndrome in the United States, 1970-1995

Objective: We examined the trend in mortality caused by respiratory distress syndrome (RDS) and its impact on changes in infant and neonatal mortality rates (IMR, NMR) in the United States. Study design: Data on infant deaths in the United States for the period 1970 through 1995 were used to compare RDS-specific IMR to other cause-specific IMR. Data from the U.S. birth cohorts of 1985 through 1991 were used to examine birth weight- and RDS-specific NMRs. Results: IMR from RDS declined from 2.6 per 1000 live births in 1970 to 0.4 per 1000 in 1995. More than three quarters of this decline occurred between 1970 and 1985. RDS-specific NMR declined by 13% between 1985 and 1988 and by more than twofold greater, that is, 28%, between 1988 and 1991. There was also a significant reduction in postneonatal mortality from chronic lung diseases between 1988 and 1991. Conclusions: Most of the reduction in mortality from RDS occurred before the introduction of surfactant therapy. The recent accelerated reduction in mortality from RDS between 1988 and 1991 was temporally associated with widespread use of surfactant therapy and was the single most important factor for reduction in overall NMR in the United States.(J Pediatr 1999;134:434-40)

Severe Pulmonary Hemorrhage in the Premature Newborn Infant: Analysis of Presurfactant and Surfactant Eras

We undertook a case-control study of premature infants who developed clinically significant, severe pulmonary hemorrhage (PH) in the presurfactant and surfactant eras to learn more about the cause of severe PH and whether the pathogenesis of severe PH has changed with the advent of surfactant therapy. Severe PH was defined as an acute onset of severe endotracheal bleeding with an acute drop in hematocrit and the development of multilobar infiltrates on chest radiograph. Eleven premature infants from the presurfactant era population and 17 premature infants from the surfactant era population met the criteria for severe PH, all with gestational ages <32 weeks and birth weights <1,500 g (very low birth weight infants). These were each matched by gestational age, date of birth, birth order (for twins), and birth weight to 2 controls. The incidence of severe PH in infants of gestational age <32 weeks was similar in the two eras (1.8% in the presurfactant era and 3.0% in the surfactant era). Severe PH was not associated with maternal characteristics such as drug use or prenatal care, pregnancy complications, evidence of intrauterine anoxia, hyaline membrane disease, frequency of endotracheal suctioning, or patent ductus arteriosus. Premature infants suffering from severe PH in the presurfactant era required more delivery room resuscitation and had more severe early respiratory disease during the first 12 h of life as compared with their controls. However, these differences were not present in the group from the surfactant era. Infants with severe PH were more likely to have birth weights below the third percentile for gestation (severe intrauterine growth restriction). The proportion of infants receiving surfactant, and the number of surfactant doses used, did not differ between severe-PH infants and their controls in the surfactant era group. We conclude that severe intrauterine growth restriction represents a risk factor for severe PH in very low birth weight infants. The introduction of surfactant therapy has not altered the incidence of severe PH, even though it has apparently helped remove the severity of early lung disease as a risk factor. The physiological basis of severe PH requires further investigation.

Trends in Infant Mortality Among Infants Admitted to Four NICUs in North Carolina † 1212

OBJECTIVE: This study examined race specific trends in the mortality of very-low-birth-weight (VLBW) infants over two time periods among newborns admitted to four neonatal intensive care units (NICUs) in North Carolina. METHODS: Data for this study were obtained from the NC-NICU statewide database from 1988-1995. Eleven hospitals in North Carolina contribute clinical data on all admissions to their NICUs to a central computerized database. Four tertiary level NICUs which have contributed data consistently to this database were selected for study based on the similar number of admissions per year and the similar services available at each medical center. Data for all 2,535 VLBW infants (500-1500 grams) admitted to the four centers were merged and mortality rates for the two time periods were compared. The time periods selected for analysis were Pre-Surfactant, the period before each NICU began using surfactant, and Post-Surfactant, the period following the introduction of surfactant use at each of the four NICUs. Multiple logistic regression was used to determine the effect of surfactant therapy and race on mortality while controlling for infants' sex, birth weight and NICU. RESULTS: Since the introduction of surfactant therapy, the mortality rate has decreased by 33 percent for VLBW infants of both races in our study population. The reduction was similar for white (-34.2%) and black (-26.2%) infants. Multiple logistic regression found that VLBW infants of both races were significantly less likely to die in the post-surfactant than the pre-surfactant time period controlling for sex, race, birth weight and NICU (odds ratio = 0.54, 95% CI= 0.40, 0.73). The findings were similar when separate models were run for white infants (odds ratio = 0.56, 95% CI= 0.38, 0.81) and black infants (odds ratio= 0.50, 95% CI= 0.31, 0.82). CONCLUSION: Since the introduction of surfactant therapy in four North Carolina NICUs, mortality rates for black as well as white VLBW infants have decreased significantly. This differs from the conclusion of Hamvas et al. (N Eng J Med 1996;334:1635-40), who found that the mortality rate for black infants did not change significantly in the post-surfactant era.

Physiology and pathophysiology of lung development

Summary Over the past few years, there has been a considerable improvement in our understanding of the normal development of the fetal lung and its regulation. These advances have occurred mostly through increased knowledge of molecular biological mechanisms of growth and differentiation. These advances have also resulted in an improvement in our comprehension of the pathological basis of various pulmonary diseases. As a result of this new and improved knowledge, new and innovative therapeutic modalities are being introduced into clinical practice. The introduction of surfactant therapy into the clinical setting was one such milestone in neonatal respiratory management. Pulmonary surfactant is responsible for stabilising alveoli during normal respiration, thereby preventing atelectasis or alveolar flooding. Disease processes which result in an insufficiency in surfactant, such as respiratory distress syndrome (RDS) or congenital diaphragmatic hernia (CDH), generally carry a very high mortality rate. Exogenous surfactant administration reduces both the mortality and morbidity associated with RDS and its sequelae, and its efficacy in the treatment of CDH is now being evaluated clinically. Moreover, laboratory studies suggest that surfactant therapy may be used in combination with other treatments, such as tracheal occlusion to promote lung growth in CDH, in order to achieve a maximal effect in these complex, multifactorial lung diseases.

Surfactant Therapy: More Evidence of Effectiveness

In the August 1993 issue of Pediatrics Horbar et al1 reported an 8% decrease in mortality of 601 to 1300 preterm neonates after the introduction of surfactant therapy at eight neonatal intensive care units (NICUs) in the Neonatal Research Network. Even after adjusting for perinatal risk factors and time trend, a 27% reduction in the risk of death was found among infants for whom surfactant treatment was available (adjusted odds ratio = 0.73; 95% confidence interval: 0.55, 0.95).

Extensive intraalveolar pulmonary hemorrhage in infants dying after surfactant therapy

To assess the possible relationship between exogenous surfactant therapy and pulmonary hemorrhage in premature infants, we compared autopsy findings in 15 infants treated with exogenous surfactant and in 29 who died before the introduction of surfactant therapy. Infants who met the following criteria were included: birth weight 501 to 1500 gm, survival 4 hours to 7 days, and no congenital anomalies. Average birth weight, gestational age, and age at death were equivalent for the two groups. High rates of pulmonary hemorrhage were present in both groups (treated 80% vs untreated 83%). The untreated group had higher incidences of interstitial hemorrhage and lung hematomas and significantly more large interstitial hemorrhages: 31% untreated versus 0% treated (p < 0.05). The overall rate of intraalveolar hemorrhage was similar in the two groups, but surfactant-treated infants were more likely to have extensive intraalveolar hemorrhage: 53% versus 14% (p < 0.05). Most surfactant-treated infants who survived more than 24 hours had extensive intraalveolar hemorrhage (8/9). Patients who had extensive intraalveolar hemorrhage, with or without prior surfactant therapy, frequently had clinically significant pulmonary hemorrhage (7/12). These findings indicate that infants who die after surfactant therapy have higher rates of a specific type of pulmonary hemorrhage--extensive intraalveolar hemorrhage.

Decreasing Mortality Associated With the Introduction of Surfactant Therapy: An Observational Study of Neonates Weighing 601 to 1300 Grams at Birth

Objective. To determine whether the introduction of surfactant therapy was associated with decreased mortality for high-risk preterm neonates weighing 601 to 1300 g at birth. Design. Before-after observational study. Setting. Eight tertiary care neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Patients. The outcomes for neonates with birth weight 601 to 1300 g admitted in the 2 years before surfactants became available (n = 2780) were compared with those of neonates admitted in the year beginning 2 months after surfactants became available (n = 1413). Main outcome measures. The primary outcome measure was in-hospital mortality; secondary outcome measures included durations of assisted ventilation, length of hospitalization, and neonatal morbidity. Results. Forty percent of neonates in the postsurfactant group received surfactant (range 28% to 69% at the centers). Mortality decreased from 27.8% before to 19.9% after surfactant therapy was introduced (Mantel-Haenszel x 2 = 31.4, P = .001). The adjusted odds ratio for mortality after surfactants became available was 0.73 (95% confidence interval 0.55 to 0.95). The duration of assisted ventilation and length of hospitalization increased after surfactants were introduced ( P = .0001 for both outcomes). Conclusion. Mortality for neonates weighing 601 to 1300 g decreased after surfactant therapy was introduced, suggesting that the efficacy of surfactants demonstrated in randomized controlled trials will translate into effectiveness in routine clinical care.

Decreasing Mortality Associated With the Introduction of Surfactant Therapy: An Observational Study of Neonates Weighing 601 to 1300 Grams at Birth

Objective. To determine whether the introduction of surfactant therapy was associated with decreased mortality for high-risk preterm neonates weighing 601 to 1300 g at birth. Design. Before-after observational study. Setting. Eight tertiary care neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Patients. The outcomes for neonates with birth weight 601 to 1300 g admitted in the 2 years before surfactants became available (n = 2780) were compared with those of neonates admitted in the year beginning 2 months after surfactants became available (n = 1413). Main outcome measures. The primary outcome measure was in-hospital mortality; secondary outcome measures included durations of assisted ventilation, length of hospitalization, and neonatal morbidity. Results. Forty percent of neonates in the postsurfactant group received surfactant (range 28% to 69% at the centers). Mortality decreased from 27.8% before to 19.9% after surfactant therapy was introduced (Mantel-Haenszel x2 = 31.4, P = .001). The adjusted odds ratio for mortality after surfactants became available was 0.73 (95% confidence interval 0.55 to 0.95). The duration of assisted ventilation and length of hospitalization increased after surfactants were introduced (P = .0001 for both outcomes). Conclusion. Mortality for neonates weighing 601 to 1300 g decreased after surfactant therapy was introduced, suggesting that the efficacy of surfactants demonstrated in randomized controlled trials will translate into effectiveness in routine clinical care.