Abstract
BackgroundPreterm infants requiring assisted ventilation are at significant risk of both pulmonary and cerebral injury. Inhaled Nitric Oxide, an effective therapy for pulmonary hypertension and hypoxic respiratory failure in the full term infant, has also been studied in preterm infants. The most recent Cochrane review of preterm infants includes 11 studies and 3,370 participants. The results show a statistically significant reduction in the combined outcome of death or chronic lung disease (CLD) in two studies with routine use of iNO in intubated preterm infants. However, uncertainty remains as a larger study (Kinsella 2006) showed no significant benefit for iNO for this combined outcome. Also, trials that included very ill infants do not demonstrate significant benefit. One trial of iNO treatment at a later postnatal age reported a decrease in the incidence of CLD. The aim of this individual patient meta-analysis is to confirm or refute these potentially conflicting results and to determine the extent to which patient or treatment characteristics may explain the results and/or may predict benefit from inhaled Nitric Oxide in preterm infants.Methods/DesignThe Meta-Analysis of Preterm Patients on inhaled Nitric Oxide (MAPPiNO) Collaboration will perform an individual patient data meta-analysis to answer these important clinical questions. Studies will be included if preterm infants receiving assisted ventilation are randomized to receive inhaled Nitric Oxide or to a control group. The individual patient data provided by the Collaborators will be analyzed on an intention-to-treat basis where possible. Binary outcomes will be analyzed using log-binomial regression models and continuous outcomes will be analyzed using linear fixed effects models. Adjustments for trial differences will be made by including the trial variable in the model specification.DiscussionThirteen (13) trials, with a total of 3567 infants are eligible for inclusion in the MAPPiNO systematic review. To date 11 trials (n = 3298, 92% of available patients) have agreed to participate. Funding was successfully granted from Ikaria Inc as an unrestricted grant. A collaborative group was formed in 2006 with data collection commencing in 2007. It is anticipated that data analysis will commence in late 2009 with results being publicly available in 2010.
Highlights
Preterm infants requiring assisted ventilation are at significant risk of both pulmonary and cerebral injury
Thirteen (13) trials, with a total of 3567 infants are eligible for inclusion in the MAPPiNO systematic review
The results showed there was a marginally significant reduction in death or chronic lung disease (CLD) at 36 weeks with a relative risk of 0.91 in studies with routine use of inhaled NO (iNO) in intubated preterm infants
Summary
A recently updated meta-analysis [27] showed that inhaled Nitric Oxide marginally reduced the incidence of death or CLD as well as severe brain damage in two studies where iNO was used routinely for mildly sick preterm infants. The best way to answer these remaining questions is to utilize existing individual patient data from all infants enrolled in these trials. This approach has been described as the 'gold standard' of systematic review methodology as it allows for more powerful and flexible analysis of both subgroups and outcomes. The MAPPiNO Collaboration has been formed to undertake a systematic review of all available trials, with meta-analysis based on individual patient data, to answer these important clinical questions. Authors' contributions LMA participated in the design and coordination of the study and drafted the manuscript. MV participated in the design of the study, performed the statistical analysis and helped to draft the manuscript.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
