A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants

Abstract

Objective Bronchopulmonary dysplasia (BPD) is the most common cause of pulmonary morbidity in premature infants and is associated with life-long morbidities. Developing drugs for the prevention of BPD would improve public health. We sought to determine characteristics of favorable randomized controlled trials (RCTs) of drugs for BPD prevention. Evidence review We searched MEDLINE and EMBASE from 1992–2014 using the MeSH terms “BPD” and “respiratory distress syndrome, newborn.” We included a Cochrane Library search to ensure inclusion of all available RCTs. We identified RCTs with BPD as a primary or secondary outcome and determined the definition of BPD used by the study. We determined whether a phase I or phase II study—to determine drug safety, efficacy, or optimal dose—was performed prior to the RCT. Finally, we searched the Cochrane Library for meta-analyses for each drug and used the results of available meta-analyses to define a favorable versus unfavorable RCT. Findings We identified 2026 articles; 47 RCTs met our inclusion criteria encompassing 21 drugs; 5 of the drugs reduced the incidence of BPD. We found data from phase I or II studies for 16 of the drugs, but only 1 demonstrated a reduction of BPD. Conclusions and relevance The majority of the drugs studied in RCTs failed to reduce the incidence of BPD. Performing early-phase studies prior to phase III trials might provide necessary information on drugs and drug doses capable of preventing BPD, thus informing the development of future RCTs.

Displasia broncopulmonar: incidencia y factores de riesgo

“…Además, si bien la DBP es infrecuente en RN que no han recibido soporte ventilatorio mecánico, actualmente, se reconoce su desarrollo en pacientes sin enfermedad pulmonar grave inicial. [3][4][5][6][7][8][9][10]24 El exceso de volumen corriente en cada ciclo conduce al denominado "volutrauma", caracterizado por una sobredistensión de la membrana alveolocapilar, desarrollo de una reacción inflamatoria, edema intersticial e inactivación de surfactante. 22 En nuestro estudio, tanto la utilización de oxígeno como el requerimiento de ventilación asistida y surfactante pulmonar (como expresión de gravedad del síndrome de dificultad respiratoria inicial) se asociaron a DBP en el análisis univariado.…”

“…6 Un reconocido estudio que aleatorizó a más de 2000 prematuros a recibir cafeína o placebo encontró que no administrarla cuando estaba indicada aumentaba el riesgo de desarrollar DBP. 27 Se suele concluir que la cafeína debe darse a todo RN prematuro para prevenir DBP, lo cual es una interpretación errónea del estudio citado.…”

“…), nuevas modalidades ventilatorias, control de la infección nosocomial, mejora de los aspectos nutricionales, etc. [5][6][7] Al ser la causa más frecuente de morbilidad respiratoria en RN prematuros que sobreviven al período neonatal, resulta de interés conocer su incidencia en las unidades neonatales, además de identificar los factores 7,8 Si bien la bibliografía disponible en este campo es amplia y muy extensa, 3,[8][9][10][11] realizar una revisión periódica de la incidencia y los factores de riesgo asociados a DBP en cada unidad neonatal resulta importante a la hora de reevaluar las estrategias de prevención.…”

Animal models of bronchopulmonary dysplasia. The preterm baboon models

“…The incorporation of this perinatal infection into the primate model of preterm birth and BPD has been perhaps the most important new addition to models of BPD over the past decade. The major role of perinatal infection in the very preterm human may be one of the key reasons that most singular therapeutic agents found to be useful for the prevention or treatment of BPD in animal models have had relatively little clinical effect in very preterm humans (9,12). Incorporating infection as an element of animal modeling will more closely mirror the human phenotype and should further our understanding of the pathophysiology of BPD and lead to more effective treatment options.…”

Bronchopulmonary dysplasia: incidence and risk factors

“…), new ventilation modes, management of nosocomial infections, improved nutritional aspects, etc. [5][6][7] Given that BPD is the most common cause of respiratory morbidity among preterm NBIs surviving the neonatal period, it is very interesting to establish its incidence in neonatal units and also identify risk factors in these infants. However, both the incidence of BPD and its associated risk factors may change over time, once strategies mentioned here are …”