Antileukotrienes for the prevention and treatment of chronic lung disease in very preterm newborns: a systematic review

Abstract

Background Very preterm infants are at high risk of developing chronic lung disease, which requires respiratory support and might have long-term sequelae. As lung inflammation plays an important role in pathogenesis, antileukotrienes have been explored in both clinical and animal studies. We aimed to assess the benefits and harms of antileukotrienes for the prevention and treatment of respiratory morbidity and mortality in very preterm newborns. Methods In this systematic review, we included randomized trials and non-randomized studies in humans and animals reporting the effects of antileukotrienes in very preterm infants or other mammals within 10 days of birth. Our pre-specified primary outcomes were all-cause mortality and any harm, and, for the clinical studies, incidence of chronic lung disease. Included studies underwent risk of bias-assessment and data extraction performed by two authors independently. There were no language restrictions. Results Fifteen studies totally met our inclusion criteria: one randomized trial and four non-randomized studies in humans and 10 animal studies (five in rodents, two in lambs and one in either guinea pigs, rabbits or caprinae). All five clinical studies used montelukast and had a small sample size, ranging from 4 to 77 infants. The randomized trial (n = 60) found no difference in the incidence of chronic lung disease between the groups. Only one clinical study, which enrolled four very preterm infants and had a critical overall risk of bias, reported long-term outcomes. All other studies had unclear or greater overall risk of bias and meta-analyses were therefore deemed unfeasible. Eight of ten animal studies used leukotriene receptor antagonists as antileukotriene (montelukast in three of ten studies) and seven had an experimental study design (i.e. some animals were not exposed to antileukotrienes but no randomization). Three of the ten animal studies assessed different doses. Animal studies found no effect on the outcomes mortality, growth, or lung function related surrogate outcomes. Conclusions Use of antileukotrienes in very preterm infants to prevent or treat chronic lung disease is not supported by the available evidence. Large randomized trials focusing on outcomes relevant to patients, including long-term outcomes, are needed. Studies should also minimize risk of bias.

Montelukast Sodium to Prevent and Treat Bronchopulmonary Dysplasia in Very Preterm Infants: A Quasi-Randomized Controlled Trial

“…Jukema et al conducted a system analysis reporting the effects of antileukotrienes in very preterm infants or other mammals within 10 days of birth. They concluded that there is not enough evidence to support the use of antileukotrienes in very preterm infants for the prevention or treatment of chronic lung disease [47]. However, the research results of Rupprecht et al [26] show that montelukast can significantly improve the survival rate in preterm infants born between 23 and 27 weeks of gestation suffering from severe BPD; therefore, this treatment is recommended in severe cases of BPD in infants at high risk of death.…”