Eight RCTs (612 randomised newborns) fulfilled the inclusion criteria.
Three of the included RCTs scored 12 out of a maximum 13 points for methodological quality, the remaining 5 RCTs scored 11 points.
PPHN without congenital diaphragmatic hernia.
Death during hospitalisation: the meta-analysis included 5 studies (513 newborns). There were 31 (11%) deaths in the NO group and 26 (12%) in the control group. There was no difference in mortality between the groups (OR 1.04, 95% CI: 0.59, 1.82).
Requirements for ECMO (5 studies with 537 newborns): fewer patients from the NO group needed ECMO, 101 out of 305 (33%), compared with 115 of the 232 (50%) controls (RR 0.73, 95% CI: 0.6, 0.9).
Systemic oxygenation: in all but one of the 7 trials in which this outcome was analysed, it was concluded that NO improved oxygenation. The meta-analysis supported the superiority of NO for this outcome.
Disturbances of the central nervous system (3 studies with 420 newborns): there was no difference between the NO-treated and control groups (OR 0.83, 95% CI: 0.50, 1.37).
Development of chronic pulmonary disease during hospitalisation (2 trials with 378 infants): no difference between the NO-treated and control groups was found for this outcome (OR 1.3, 95% CI: 0.69, 2.46).
PPHN with congenital diaphragmatic hernia.
Death or ECMO requirement: one trial (53 infants) showed there was no significant difference between the groups (RR 1.17, 95% CI: 0.97, 1.41).
Systemic oxygenation: 2 trials examined this outcome, neither of which found NO to be superior to control.
Disturbances of the central nervous system: one study (53 newborns) showed no difference between the number of events in each group (OR 1.14, 95% CI: 0.26, 5.07).
Development of chronic pulmonary disease: one trial (53 newborns) found no benefit for inhaled NO (RR 0.62, 95% CI: 0.24, 1.61).