Inhaled nitric oxide in preterm neonates with preterm prelabour rupture of membranes, a systematic review.

Aim: To perform a systematic literature review to determine the effect of inhaled nitric oxide (iNO) on oxygenation, mortality and morbidity in preterm neonates with preterm prelabour rupture of membranes (PPROM) and early hypoxaemic respiratory failure (HRF).

Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Zetoc and ProQuest were searched. Studies including neonates <34 weeks' gestation with PPROM, oligohydramnios or pulmonary hypoplasia and HRF in the first 28 days of life treated with iNO were included. Studies were critically appraised and assessed for potential risk of bias using standardised checklists.

Results: Six hundred and two records remained after duplicates were removed. Seven studies were included in the critical appraisal process. Quality of available evidence was very low to low. Six studies described an improvement in oxygenation after commencement of iNO. One hundred and three of 284 (36%) neonates exposed to iNO died. Seventy-seven of 92 (84%) neonates that had an echocardiogram performed before commencement of iNO had pulmonary hypertension (PH) present.

Conclusion: iNO may improve oxygenation when standard care fails. Improvement in oxygenation is likely associated with increase in survival. Survival may lead to an increase in morbidity. Efficacy of iNO in this cohort is likely secondary to relatively high prevalence of PH.