Background and Aims
Inhaled nitric oxide (iNO) is widely used to treat neonatal hypoxaemic respiratory failure, complicated by persistent pulmonary hypertension of the newborn (PPHN). There is emerging evidence that PPHN physiology confirmed echocardiographically, is a key determinant of response to iNO therapy and short and longer term outcomes. We systematically reviewed the clinical and echocardiographic criteria used for the definition of PPHN in RCTs of iNO.

Method
A systematic review using various databases, including PubMed and the Cochrane Library, were searched for randomised trials evaluating iNO therapy in neonates. The included studies were reviewed independently and categorised by clinical and ultrasound criteria used to define PPHN.

Results
998 potentially eligible trials were identified in total, of which 33 trials were included in our review. 24 were trials of iNO versus placebo/no treatment and 9 were comparative trials. There was wide variation in the criteria used for the diagnosis of PPHN, which was made primarily on the basis of clinical criteria alone (n=13), a combination of clinical and echocardiographic parameters (n=19) and a combination of clinical and chest X-ray changes (n=1).

Conclusion
This systematic review found a wide variation in the definition of PPHN in RCTs of iNO, with specific echocardiographic criteria being rarely used. The lack of an accepted standardised definition of PPHN makes comparison of studies difficult. Establishing an international consensus on the definition of PPHN would help to design and interpret future trials in this area.

THE DEFINITION OF PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN IN RANDOMISED CONTROLLED TRIALS: A SYSTEMATIC LITERATURE REVIEW