One-year follow-up of 89 infants with birth weights of 500 to 749 grams and respiratory distress syndrome randomized to two rescue doses of synthetic surfactant or air placebo

doi:10.1016/S0022-3476(95)70008-0

The Journal of Pediatrics

Volume 126, Issue 5, Supplement, May 1995, Pages S53-S60

https://doi.org/10.1016/S0022-3476(95)70008-0 Get rights and content

Abstract

Double-blind neurodevelopmental and physical evaluations were conducted at 1-year adjusted age in 89 infants with birth weights of 500 to 749 gm who had respiratory distress syndrome in the neonatal period and were randomized to receive two rescue doses of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co., Research Triangle Park, N.C.) or air placebo. The trial used a common protocol and was conducted at 13 hospitals; patients were entered in the trial between February 1988 and September 1990. Ninety-five percent of surviving infants were assessed. Growth and development in the two groups were equivalent. Mean Bayley Scales of Infant Development scores were comparable (mental development index, 79 ± 22 vs 87 ± 20; psychomotor development index, 73 ± 18 vs 81 ± 19 for air placebo and synthetic surfactant, respectively). The incidence of severe retinopathy of prematurity was significantly decreased in the surfactant group compared with the air placebo group (15% vs 34%; relative risk 0.428; 95% confidence interval 0.2 to 0.9). Overall, administration of surfactant appeared to increase the probability of a favorable outcome. Confirmation of the trends observed in this study would provide a strong rationale for the rescue use of synthetic surfactant in extremely low birth weight infants with respiratory distress syndrome even if overall mortality is not reduced. (J P EDIATR 1995;126:S53-60)

Section snippets

Study design

The trial was designed as a multicenter, prospective, double-blind, randomized, parallel comparison of the effects of two 5 ml/kg endotracheal doses (each 5 ml/kg dose given 12 hours apart) of either synthetic surfactant (colfosceril palmitate, cetyl alcohol, and tyloxapol, Exosurf Neonatal, Burroughs Wellcome Co., Research Triangle Park, N.C.) or air placebo. The trial involved a common protocol and was conducted at 13 hospitals in Canada; participating principal investigators are listed in

RESULTS

This report describes results from data collected from day 29 through 1-year adjusted age. During the enrollment period, 224 patients entered the trial. A total of 111 patients in the air placebo group and 113 patients in the surfactant group were treated ( Table I). At 1-year adjusted age, a total of 89 survivors, 42 (95%) in the placebo group and 47 (96%) in the surfactant group, were assessed. Two patients who received the air placebo and two patients treated with surfactant were lost to

DISCUSSION

The present multicenter study was designed to evaluate outcome at 1-year adjusted age after two rescue doses of synthetic surfactant or air placebo in neonates with RDS whose birth weights were greater than or equal to 500 gm and less than 750 gm. Ninety-five percent of surviving infants in the air placebo group and 96% in the synthetic surfactant group completed the 1-year evaluation. The risk of disability or other adverse outcomes between 29 days postnatal and 12-months adjusted age was not

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Cited by (23)

Outcomes of children of extremely low birthweight and gestational age in the 1990s
2000, Seminars in Neonatology
Advances in perinatal care have improved the chances for survival of extremely low birthweight (<800 grams) and gestational age (<26 weeks) infants. A review of the world literature reveals that among regional populations, survival at 23 weeks' gestation ranges from 2 to 35%, at 24 weeks' gestation 17 to 62% and at 25 weeks' gestation 35 to 72%. These wide variations may be accounted for by differences in population descriptors, in the criteria used for starting or withdrawing treatment, in the reported duration of survival and differences in care. Major neonatal morbidity increases with decreasing gestational age and birthweight. At 23 weeks' gestation, chronic lung disease occurs in 57 to 86% of survivors, at 24 weeks in 33 to 89% and at 25 weeks' gestation in 16 to 71% of survivors. The rates of severe cerebral ultrasound abnormality range from 10 to 83% at 23 weeks' gestation, 9 to 64% at 24 weeks and 7 to 22% at 25 weeks' gestation Of 77 survivors at 23 weeks' gestation, 26 (34%) have severe disability (defined as subnormal cognitive function, cerebral palsy, blindness and/or deafness). At 24 weeks' gestation, the rates of severe neurodevelopmental disability range from 22 to 45%, and at 25 weeks' gestation 12 to 35%. When compared with children born prior to the 1990s, the rates of neurodevelopmental disability have, in general, remained unchanged. We conclude that, with current methods of care, the limits of viability have been reached. The continuing toll of major neonatal morbidity and neurodevelopmental handicap are of serious concern.
Outcomes of children of extremely low birthweight and gestational age in the 1990's
1999, Early Human Development
Advances in perinatal care have improved the chances for survival of extremely low birthweight (<800 g) and gestational age (<26 weeks) infants. A review of the world literature and our own experience reveals that at 23 weeks gestation survival ranges from 2% to 35%. At 24 weeks gestation the range is 17% to 58%, and at 25 weeks gestation 35% to 85%. Differences in population descriptors, in the initiation and withdrawal of treatment and the duration of survival considered may account for the wide variations in the reported ranges of survival. Major neonatal morbidity increases with decreasing gestational age and birthweight. The rates of severe cerebral ultrasound abnormality range at 23 weeks gestation from 10% to 83%, at 24 weeks from 17% to 64% and at 25 weeks gestation from 10% to 22%. At 23 weeks gestation, chronic lung disease occurs in 57% to 70% of survivors, at 24 weeks in 33% to 89%, and at 25 weeks gestation in 16% to 71% of survivors. When compared to children born prior to the 1990's, the rates of neurodevelopmental disability have, in general, remained unchanged. Of 30 survivors reported at 23 weeks gestation nine (30%) are severely disabled. At 24 weeks gestation the rates of severe neurodevelopmental disability (including subnormal cognitive function, cerebral palsy, blindness and deafness) range from 17% to 45%, and at 25 weeks gestation 12% to 35% are similarly affected. In Cleveland, Ohio, we compared the outcomes of 114 children with birthweight 500–749 g born 1990–1992 to 112 infants born 1993–1995. Twenty month survival was similar (43% vs 38%). The use of antenatal and postnatal steroids increased (10% vs 54% and 43% vs 84%, respectively, P<0.001), however the rates of chronic lung disease increased from 41% to 63% (P=0.06). There was a significant increase in the rate of subnormal cognitive function at 20 months corrected age (20% vs 48%, P<0.02) and a trend to an increase in the rate of cerebral palsy (10% vs 16%) and neurodevelopmental impairment. We conclude that, with current methods of care, the limits of viability have been reached. The continuing toll of major neonatal morbidity and neurodevelopmental handicap are of serious concern.
Symposium on Synthetic Surfactant II: Perspective and commentary
1995, The Journal of Pediatrics
Double-blind, randomized, placebo-controlled Canadian multicenter trial of two doses of synthetic surfactant or air placebo in 224 infants weighing 500 to 749 grams with respiratory distress syndrome
1995, The Journal of Pediatrics
In a multicenter, double-masked, placebo-controlled rescue trial conducted at 12 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 224 infants with birth weights of 500 to 749 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio of less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to the infants continuing to receive mechanical ventilation. Infants were stratified at study entry by birth weight and gender. Infants receiving synthetic surfactant showed significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7. In the group randomized to synthetic surfactant, significant improvements were seen in oxygen requirements at the first time point measured (2 hours; p = 0.02), in the alveolar-arterial oxygen tension gradient by the second time point measured (6 hours; p = 0.03), and in mean airway pressure after 6 hours. Overall mortality at 28 days was not significantly different in the two groups (50% vs 46%, air placebo group vs synthetic surfactant group; p = 0.586). Similarly, neither the incidence of bronchopulmonary dysplasia (37% vs 30%, air placebo group vs synthetic surfactant group; p = 0.089) nor the incidence of survival without BPD through 28 days (17% vs 26%, respectively; p = 0.070) was significantly different in the two groups. No significant differences in the incidence of safety-related outcomes or in adverse effects such as apnea or pulmonary hemorrhage were noted. These findings indicate that rescue therapy with synthetic surfactant results in physiologic improvements in very tiny premature infants, but improvements in overall mortality or other complications of respiratory distress syndrome were not documented in the sample evaluated. (J P EDIATR 1995;126:S81-9)
Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials
1995, The Journal of Pediatrics
Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% [92 of 745] for the air placebo group vs 11% [86 of 771] for the synthetic surfactant group; severe impairment, 15% [114 of 745] for the air placebo group vs 13% [102 of 771] for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced. (J P EDIATR 1995;126:S43-52)
Two-year neurodevelopmental outcome of preterm born children ≤750 g at birth
2011, Archives of Disease in Childhood: Fetal and Neonatal Edition

View all citing articles on Scopus

^☆: From the Departments of Pediatrics, Children's Hospital, University of Manitoba, Winnipeg, Canada; University of Saskatchewan, Saskatoon, Canada; University of Ottawa, Ontario, Canada; British Columbia Children's Hospital, Vancouver, Canada; McMaster University, Hamilton, Ontario, Canada; University of Dalhousie, Halifax, Nova Scotia, Canada; the University of North Carolina at Chapel Hill; and participating centers

^☆☆: Reprint requests: Oscar Casiro, MD, Children's Hospital, 840 Sherbrook St., CK261, Winnipeg, Manitoba, Canada R3A 1S1.

^★: 0022-3476/95/$3.00 + 0 9/0/61827

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One-year follow-up of 89 infants with birth weights of 500 to 749 grams and respiratory distress syndrome randomized to two rescue doses of synthetic surfactant or air placebo☆,☆☆,★

Abstract

Section snippets

Study design

RESULTS

DISCUSSION

J P EDIATR

J P EDIATR

J P EDIATR

Early Hum Dev

J P EDIATR

J P EDIATR

J P EDIATR

J P EDIATR

A controlled trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome

N Engl J Med

Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial

Pediatrics

Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome

Pediatrics