Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns / Comparação de dois esquemas posológicos de ibuprofeno para o fechamento do canal arterial em recém-nascidos pré-termo

Abstract Objective: To compare the efficacy of intravenous ibuprofen at high (20-10-10 mg/kg/dose) and low doses (10-5-5 mg/kg/dose) the closure of patent ductus arteriosus in preterm newborns. Methods: A cohort study with historical control of newborns that received high- and low-dose intravenous ibuprofen, from 2010 to 2013 in a neonatal intensive care unit, for closure of the patent ductus arteriosus, documented by echocardiography. Secondary outcomes included the number of ibuprofen cycles, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, changes in renal function, and death. Results: Seventy-seven patients received three doses of ibuprofen for the treatment of patent ductus arteriosus, with 33 receiving high-dose and 44 low-dose therapy. The ductus closed after the first cycle in 25 (56.8%) low-dose patients and in 17 (51.5%) high-dose patients (p > 0.99). Sixteen patients received a second cycle of ibuprofen, and the ductus closed in 50% after low-dose and in 60% after high-dose therapy (p > 0.99). Seven patients required surgery for ductus closure, 13.6% in the low-dose group and 3% in the high-dose group (p = 0.22). Thirty-nine patients developed bronchopulmonary dysplasia, 50% in the low-dose group and 51.5% in the high-dose group (p > 0.99). Twenty-two (50%) low-dose patients died vs. 15 (45.5%) high-dose patients (p = 0.86). Conclusions: There was no difference in closure of the ductus arteriosus or occurrence of adverse effects between the two dose regimens.

Resumo Objetivo: Comparar a eficácia do ibuprofeno endovenoso em doses altas (20, 10 e 10 mg/kg/dose) e em doses baixas (10, 5 e 5 mg/kg/dose) para o fechamento do canal arterial em recém-nascidos pré-termo. Métodos: Estudo de coorte com controle histórico que pesquisou recém-nascidos que receberam ibuprofeno endovenoso, de 2010 a 2013, na unidade de internação neonatal, em doses altas e baixas para o fechamento do canal arterial, documentado por ecocardiograma. Como desfechos secundários foram avaliados o número de ciclos de ibuprofeno feitos, a incidência de displasia broncopulmonar, enterocolite necrosante, alteração de função renal e óbito. Resultados: Receberam três doses de ibuprofeno para tratamento do canal arterial 77 pacientes, 33 dose alta e 44 dose baixa; 25 (56,8%) dos que receberam dose baixa fecharam o canal após o 1° ciclo e 17 (51,5%) fecharam após receberem dose alta (p > 0,99); 16 pacientes receberam o 2° ciclo e 50% fecharam o canal após uso de dose baixa e 60% após o uso de dose alta (p > 0.99); sete pacientes foram à cirurgia para fechamento do canal, 13,6% do grupo que recebeu dose baixa e 3% dose alta (p = 0,22); 39 pacientes desenvolveram displasia broncopulmonar, 50% do grupo de dose baixa e 51,5% do grupo de dose alta (p > 0,99); 22 (50%) dos pacientes do grupo dose baixa evoluíram a óbito versus 15 (45,5%) dos pacientes do grupo de dose alta (p = 0,86). Conclusão: Não encontramos diferença em relação ao fechamento do canal arterial, assim como ocorrência de efeitos adversos, quando comparamos os dois esquemas posológicos.

Reviewing the use of corticosteroids in bronchopulmonary dysplasia / Revendo o uso dos corticosteroides em displasia broncopulmonar

Abstract Objective: Review the risks and benefits of postnatal corticosteroid use for the treatment of bronchopulmonary dysplasia, considering that there is not a more effective therapy. Data sources: The literature review was carried out in the BIREME database, using the terms "bronchopulmonary dysplasia and corticosteroid" in the LILACS, IBECS, MEDLINE, Cochrane Library, and SciELO databases, selecting the most relevant articles on the subject, with emphasis on recent literature published in the last five years. Summary of the data: In preterm infants, bronchopulmonary dysplasia is still a common problem and remains without a specific therapy, despite knowledge of the several risk factors. The treatment essentially consists of supportive measures, but in the past, corticosteroids were widely used, as they are the only medications that have an impact on disease progression. However, the emergence of cerebral palsy associated with the indiscriminate use of corticosteroids has prevented the prescription of this drug in the last 15 years. Since then, no new measures have been taken, and the incidence of the disease tended to increase during this period, creating the need for a review of corticosteroid use and, possibly, more restricted indications. Conclusions: The association between risks and benefits of corticosteroid use in preterm infants needs to be considered due to the fact that some infant subpopulations may show more benefits than risks, such as those using mechanical ventilation with difficult weaning.

Resumo Objetivo: Revisar os riscos e benefícios do uso do corticoide pós-natal para o tratamento da displasia broncopulmonar, uma vez que ainda não há outra terapia mais eficaz. Fontes de dados: A revisão da literatura foi feita pelo banco de dados da Bireme, com os termos bronchopulmonary dysplasia and corticosteroid nos sistemas Lilacs, Ibecs, Medline, Biblioteca Cochrane e SciELO. Foram selecionados os artigos de maior relevância sobre o tema, com ênfase na literatura dos últimos cinco anos. Síntese dos dados: Em recém-nascidos prematuros, a broncodisplasia ainda é um problema frequente e sem terapêutica específica, apesar do conhecimento dos vários fatores de risco. O tratamento, basicamente, é feito por medidas de suporte, mas o corticoide no passado foi largamente usado por se tratar da única medicação com impacto na evolução da doença. Porém, o aparecimento de paralisia cerebral associada ao uso indiscriminado do corticoide inviabilizou a prescrição da droga nos últimos 15 anos. Desde então, nenhuma nova medida foi tomada, a incidência da doença tendeu a um aumento nesse período e criou a necessidade da revisão do uso do corticoide e de possíveis indicações mais restritas. Conclusões: A relação do risco e benefício dos corticoides usados em recém-nascidos prematuros precisa ser ponderada diante de algumas subpopulações de bebês que podem ter mais benefícios do que riscos, como naqueles em ventilação mecânica e com desmame difícil.

Actualización en displasia broncopulmonar / Bronchopulmonary displasia update

Bronchopulmonary dysplasia is one of the most common pediatric chronic lung diseases. In the recent decades the advances made in perinatal care and the increase survival of extreme preterm have shown an overall change in the characteristics of this disease giving rise to the concept of new dysplasia. In the development of the disease is essential the exposure of the immature lung to various factors such as nutritional deficiency, pre and post-natal infections, persistent ductus arteriosus, and genetic susceptibility. This article reviews the most important characteristics of this disease, treatment and follow-up.

La displasia broncopulmonar (DBP) es una de las enfermedades pulmonares crónicas frecuentes en pediatría. Los avances experimentados en las últimas décadas en cuidados perinatales y la sobrevida de prematuros cada vez más extremos han demostrado un cambio global en las características de esta enfermedad dando lugar al concepto de nueva displasia, en cuyo desarrollo son fundamentales la exposición del pulmón inmaduro a diversos factores como deficiencia nutricional, infecciones pre y post-natales, ductus arterioso persistente, y susceptibilidad genética. El presente articulo revisa las características más relevantes de esta patología, su enfrentamiento global, manejo y seguimiento ambulatorio.

Respiratory Syncytial Virus Related Readmission in Preterm Infants Less than 34 weeks' Gestation Following Discharge from a Neonatal Intensive Care Unit in Korea

This study was done to evaluate respiratory syncytial virus (RSV) related readmission (RRR) and risk factors of RRR in preterm infants 1 yr after discharge from the NICU, were enrolled. The average GA and birth weight of the infants was 30(+5) +/- 2(+5) weeks and 1,502 +/- 474 g, respectively. The RRR rate of enrolled infants was 8.4% (96/1,140), and RSV accounted for 58.2% of respiratory readmissions of infants who had laboratory tests confirming etiological viruses. Living with elder siblings (odd ratio [OR], 2.68; 95% confidence interval [CI], 1.68-4.28; P < 0.001), and bronchopulmonary dysplasia (BPD) (OR, 2.95; 95% CI, 1.44-6.04; P = 0.003, BPD vs. none) increased the risk of RRR. Palivizumab prophylaxis (OR, 0.06; 95% CI, 0.03-0.13; P < 0.001) decreased the risk of RRR. The risk of RRR of infants of 32-33 weeks' gestation was lower than that of infants < 26 weeks' gestation (OR, 0.11; 95% CI, 0.02-0.53; P = 0.006). This was a nationwide study that evaluated the rate and associated risk factors of RRR in Korean preterm infants. Preterm infants with BPD or living with siblings should be supervised, and administration of palivizumab to prevent RRR should be considered.

Efficacy of Surfactant-TA, Calfactant and Poractant Alfa for Preterm Infants with Respiratory Distress Syndrome: A Retrospective Study

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.

Efficacy of Surfactant-TA, Calfactant and Poractant Alfa for Preterm Infants with Respiratory Distress Syndrome: A Retrospective Study

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.

Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1alpha in a Rat Model of Bronchopulmonary Dysplasia

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1alpha is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1alpha inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1alpha and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1alpha was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1alpha in human small airway epithelial cells and to promote the expression of HIF-1alpha target genes. Our data suggest that DFX induces and activates HIF-1alpha, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.

Early Caffeine Use in Very Low Birth Weight Infants and Neonatal Outcomes: A Systematic Review and Meta-Analysis

The use of caffeine citrate for treatment of apnea in very low birth weight infants showed short-term and long-term benefits. A systematic review and meta-analysis of the literature was undertaken to document the effect providing caffeine early (0-2 days of life) compared to providing caffeine late (> or =3 days of life) in very low birth weight infants on several neonatal outcomes, including bronchopulmonary dysplasia (BPD). We searched MEDLINE, the EMBASE database, the Cochrane Library, and KoreaMed for this meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Jadad's scale. Studies were included if they examined the effect of the early use of caffeine compared with the late use of caffeine. Two reviewers screened the candidate articles and extracted the data from the full-text of all of the included studies. We included a total of 59,136 participants (range 58,997-59,136; variable in one study) from a total of 5 studies. The risk of death (odds ratio [OR], 0.902; 95% confidence interval [CI], 0.828 to 0.983; P=0.019), bronchopulmonary dysplasia (BPD) (OR, 0.507; 95% CI, 0.396 to 0.648; P<0.001), and BPD or death (OR, 0.526; 95% CI, 0.384 to 0.719; P<0.001) were lower in the early caffeine group. Early caffeine use was not associated with a risk of necrotizing enterocolitis (NEC) and NEC requiring surgery. This meta-analysis suggests that early caffeine use has beneficial effects on neonatal outcomes, including mortality and BPD, without increasing the risk of NEC.

Rosiglitazone, a Peroxisome Proliferator-Activated Receptor-gamma Agonist, Restores Alveolar and Pulmonary Vascular Development in a Rat Model of Bronchopulmonary Dysplasia

PURPOSE: We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-gamma agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS: A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia (80% for 7 days). RGZ (3 mg/kg/d, i.p.) or vehicle was given daily to rat pups for 14 days. This model included four experimental groups: No BPD+vehicle (V), No BPD+RGZ, BPD+V, and BPD+RGZ. On D14, alveolarization, lung vascular density, and right ventricular hypertrophy (RVH) were evaluated. RESULTS: Morphometric analysis revealed that the BPD+RGZ group had significantly smaller and more complex airspaces and larger alveolar surface area than the BPD+V group. The BPD+RGZ group had significantly greater pulmonary vascular density than the BPD+V group. Western blot analysis revealed that significantly decreased levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 by the combined exposure to intra-amniotic LPS and postnatal hyperoxia were restored by the RGZ treatment. RVH was significantly lesser in the BPD+RGZ group than in the BPD+V group. CONCLUSION: These results suggest that RGZ can restore alveolar and pulmonary vascular development and lessen pulmonary hypertension in a rat model of BPD.

Incidence of Bronchopulmonary Dysplasia in Korea

A nationwide survey was conducted to determine the incidence of bronchopulmonary dysplasia (BPD) in Korea and the intercenter differences in survival and BPD rates among preterm infants. Questionnaires were sent to all registered neonatal intensive care units (NICUs). The questionnaires inquired about the survival and BPD rates of very low birth weight (VLBW, < 1,500 g) infants who had been admitted to each NICU from 2007 to 2008. BPD was defined as requiring oxygen at 36 weeks' postmenstrual age. Almost all level III NICUs replied. During the study period, 3,841 VLBW infants were born in the NICUs that responded to the survey. The survival rate was 81% and the BPD rate was 18%. Combined outcome of BPD or death rate was 37%. The BPD rate and combined outcome of BPD or death rate varied considerably from 5% to 50% and 11% to 73%, respectively across the centers. There was no significant correlation between the survival rate and the BPD rate across the centers. In conclusion, the incidence of BPD among VLBW infants in Korea during the study period was 18%, and a considerable intercenter difference in BPD rates was noted.

[Postnatal corticosteroid and chronic lung disease]

Cortieosteroids can be used postnatally to prevent or treat chronic lung disease. Controversy exists, however, about its effects on long term survival infants. Systematic reviews of randomised controlled trials of postnatal corticosteroids in the Chochrane Library were examined to determine the cost-benefit ratios of treatment. Beneficial effects include earlier extubation, reduced chonic lung disease and avoidance of late steroids. However, there are significant adverse short-term effects such as hyperglycaemia, hypertension, hypertrophic cardiomyopathy, gastrointestinal bleeding and growth failure. More important are long-term adverse effects of cerebral palsy, developmental delay. These adverse effects are more pronounced with early [<96 h] treatment but probably also occur when steroids are given later in the postnatal peroid. Postnatal steroids should be avoided if at all possible. More trials should be undertaken with a long term follow-up

Use of corticosteroids and the outcome of infants with bronchopulmonary dysplasia

Ventilator-dependent premature infants are often treated with dexamethasone. Several trials showed that steroids while improve pulmonary compliance and facilitate extubation, some treated infants may have adverse effects, such as alterations of growth curves. We conducted this retrospective study to evaluate the effects of steroids on mechanical ventilation, oxygen therapy, hospital length stay and mortality, in ventilator-dependent infants with bronchopulmonary dysplasia (BPD) (defined as the need of oxygen supplementation at 28 days of life). Twenty-six newborns with BPD were evaluated during 9 3/4 42 days postpartum (mean = 31 days) and were divided into two groups: Group I - 14 newborns that did not receive dexamethasone, and Group II - 12 newborns that received dexamethasone at 14 3/421 days of life. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously for 3 days, after which the dose was tapered. RESULTS: There were no statistically significant differences in the mean length of mechanical ventilation (Group I - 37 days, Group II - 35 days); oxygen supplementation (Group I - 16 days, Group II - 29 days); hospital stay (Group I - 72 days, Group II - 113 days); mortality (Group I - 35.7 percent, Group II - 41.6 percent). At birth, Group II was lighter (BW: Group I - 1154 grams +/- 302, Group II - 791 grams +/- 165; p<0.05) and smaller (height: Group I - 37.22 cm +/- 3.3, Group II - 33.5 +/- 2.4; <0.05) than Group I. At 40 weeks, there were no statistically significant differences between groups in relation to anthropometric measurements. CONCLUSIONS: The use of corticosteroids in bronchopulmonary dysplasic infants may influence the somatic growth during its use. However, after its suspension, a recovery seems to occur, suggesting that its influence could be transitory.

Estrategias en prevención de displasia broncopulmonar / Prevention strategies of bronchopulmonar dysplasia

La displasia broncopulmonar se ha constituído en la morbilidad más frecuentemente asociada a la enfermedad de membrana hialina y la causa más común de enfermedad pulmonar crónica del lactante. Afecta alrededor del 25-30 por ciento de los recién nacidos de muy bajo peso (<1.500 g) y hasta un 75 por ciento en menores de 1.000 g. de peso al nacer. Es causa frecuente de morbilidad y rehospitalizaciones durante los primeros años de vida. En su etiología actuarían múltiples factores como la inmadurez pulmonar, el empleo de ventilación mecánica, la oxigenoterapia, carencias de nutrientes y antioxidantes. Debido a la patogénesis multifactorial de la displasia broncopulmonar, se han realizado múltiples ensayos terapéuticos en diversas áreas destinados a disminuir su incidencia o atenuar su gravedad. El propósito de este artículo es revisar el estado actual de algunas de estas terapias, con especial énfasis en la administración muy precoz de corticoides, tema sobre el cual nuestra Unidad ha venido desarrollando estudios durante los últimos años

Budesonida inhalada en tratamiento de displasia broncopulmonar en neonatos / Inhaled budesonine in the treatment of bronchopulmonary displasia

Objetivo. Evaluar la efectividad de un esteroide inhalado(budesodina) con otro por vía sistémica (dexametasona) en el tratamiento de displasia broncopulmonar (DBP).Diseño. Estudio clínico prospectivo, al azar.Poblacion. 30 recién nacidos diagnosticados con DBP. Metodología. El grupo de recién nacidos se dividió en dos grupos. El grupo A (n=20) fue tratado con budesonida inhalada (0.5 mgs, tres veces al día) y el grupo B (n=10) con dexametasona (0.5 mgs/kg, tres veces al día). Se compararon los resultados en base a medición de la paCO2, necesidad de oxígeno y complicaciones. Resultados. La edad gestacional promedio fue de 36ñ2 semanas y la media de peso de 1,780 ñ 400 gms. El 85 de los pacientes del grupo de budesonida prescindieron del oxígeno al terminar el tratamiento y en el grupo de dexametasona el 30 (p=0.0004). La PaCO2 disminuyó a valores normales en el 100 de los tratados con busesonida y en el 40 en el grupo con esteroides (p=0.0003). El 60 de pacientes del grupo con dexametasona presentó cuadro de hiperglicemia al tratamiento. Conclusiones. La budesonida inhalada es segura y efectiva en el tratamiento de displasia broncopulmonar del neonato

Respiratory and systemic effects of inhaled dexamethasone on ventilator dependant preterm infants at risk for bronchopulmonary dysplasia.

Short-term inhaled dexamethasone therapy was evaluated in a double blind placebo controlled trial in 36 ventilator dependent preterm neonates (BW < 1500 gm, postnatal age > 7 days) who were at risk for bronchopulmonary dysplasia. Pulmonary and systemic effects were compared at early (day 3), late (7-10 days) and post (14 days after initiation) phases of therapy. Airflow mechanics improved as demonstrated by a net 101% improvement in pulmonary resistance (a decrease from 139 to 101 cm H2O/L/s in the dexamethasone treated infants as compared to an increase from 153 to 267 cmH2O/L/s in the placebo treated infants during the early phase of therapy); this was associated with a 45% increase in inspiratory airflow (1.29 +/- 0.43 to 1.87 +/- 0.978 L/min; p < 0.01), and 37% increase in expiratory airflow. These changes resulted in a significant reduction in the work of breathing such that the mean tidal driving pressure significantly decreased from 13.6 cmH2O to 9.4 cm H2O with inhaled steroid administration. Though the brief duration of therapy did not result in cessation of ventilatory support, the level of support was significantly reduced (decreased values of oxygen supplementation, mean airway pressure and oxygenation index and increased ventilatory efficiency index). The inhaled dexamethasone therapy was also associated with systemic absorption of the drug as evidenced by transient but apparently reversible reduction in serum cortisol levels. No systemic side effects of hypertension, hyperglycemia or nosocomial sepsis were observed. These data demonstrate beneficial effects of short-term inhaled dexamethasone on the resistive airflow properties of preterm infants at risk for BPD and may provide adjunctive means to facilitate weaning in the ventilator dependent neonates.

Terapia con surfactante exógeno en recién nacidos con enfermedad de membrana hialina / Exogenous surfactant therapy in newborns with hyaline membrane disease

Con el propósito de evaluar el impacto del empleo del surfactante exógeno (colfosceril palmitato con alcohol cetílico y tiloxapol para suspensión intratraqueal) en la letalidad y morbilidad de los recién nacidos con enfermedad de membrana hialina (EMH), se compararon 73 niños atendidos en tres unidades de neonatología de hospitales asociados con universidades de Santiago, Chile (grupo tratado, 1 de diciembre de 1990 a 30 de noviembre de 1991), cuyas medias de peso al nacer y edad gestacional fueron 1.471 g y 30,5 semanas, con 77 niños (grupo control 1 de diciembre de 1989 a 30 de noviembre de 1990) cuyas medias de peso al nacer y edad gestacional eran de 1.493 g y 30,7 semanas. Entre ambas muestras no había diferencias significativas poblacionales ni cambios sustanciales en las variables de tratamiento, normas de manejo e infraestructura de las unidades aistenciales. En el grupo tratado con surfactante artificial se registró disminución de significativa de letalidad (30,1 por ciento ante 57,1 por ciento; p=0,0009), especialmente entre los niños cuyo peso al nacer era entre 1.000 y 1.499 g (27,6 por ciento ante 76,7 por ciento; p=0,004); significativamente mayor proporción de sobrevivientes sin displasia broncopulmonar (53,4 por ciento ante 35,1 por ciento; p=0,03). Los promedios de los días en ventilación mecánica y oxigenoterapia fue similar entre ambos grupos, como tambien la incidencia de rotura alveolar. En morbilidad asociada, sólo se encontró mayor incidencia de apnea en el grupo tratado (21,9 por ciento ante 3,9 por ciento; p=0,0009). Se comprueba que el tratamiento de los recién nacidos con enfermedad de membrana hialina disminuye la letalidad y aumenta la proporción de sobrevivientes libres de displasia broncopulmonar