Pulmonary Hypoplasia (PH) is a decrease in the size and volume of the lungs due to reduced number of cells, alveoli and airways.1 As amniotic fluid is essential for foetal lung development, mid-trimester anhydramnios/oligohydramnios can contribute to the development of PH. PH resulting from preterm premature rupture of membranes (PPROM) is associated with high mortality and co-morbidities.2 Definite diagnosis of PH can only be established at post-mortem using lung body ratio.3 As a surrogate, a presumed diagnosis of PH could be made using clinical indicators such as difficult ventilation, low lung volume on chest radiograph and pulmonary hypertension on echocardiography. Inhaled Nitric oxide (iNO), a specific pulmonary vasodilator, acts via the cyclic guanosine phosphate on the endothelial cells of pulmonary vessels leading to muscle relaxation and reduction in the pulmonary artery pressures, hence reversing the hypoxia and pulmonary hypertension.4 The Cochrane systematic review by Barrington et al5 found that use of early rescue iNO did not improve mortality rates in preterm infants of <35 weeks of gestation with respiratory failure complicated by persistent pulmonary hypertension (PPHN). However, the review does not specifically reflect on subgroup of infants with PH and PPHN secondary to PPROM. In clinical practice, iNO is often used in this subgroup of patients, although the evidence is sparse in literature. Ellsworth et al6 conducted a retrospective cohort study with propensity score matching to determine whether iNO treatment within first week of life was associated with improved survival in extremely preterm infants. For this analysis, from the 302 matched neonates included in the original study, only the 210 belonging to the subgroup of infants with PH and PPHN were considered. Fifty-two per cent (n = 110) of the infants in this subgroup had PPROM. From this subgroup, a 33% reduced risk of in-hospital mortality was observed in infants who received iNO compared to matched referents was observed. However, this difference was not statistically significant. Propensity score matching would enable to reduce the differing baseline characteristics of the exposed and the referent groups. There were no defining criteria for either the PH or PPHN diagnosis, and the presence or absence of these conditions was at the discretion of the treating neonatologist. The doses of iNO, oxygenation indices and the echocardiography findings were not taken into account. The sample size of the subgroup is small, and therefore, the effect of iNO therapy may have been underestimated. The other limitations of the study include presence of confounding factors and incomplete representation of infants in subgroup analysis leading to ascertainment bias. Among the PH with PPHN and PH without PPHN subgroups, no significant difference in mortality has been found in group exposed to iNO and referent group. A large prospective randomised study, powered for iNO treatment analysis with clear defining criteria of PH and PPHN, could establish the effect of using iNO in this group of infants with PPROM, PH and PPHN and help to tease out characteristics of those infants who may or may not benefit from iNO. None. URL TO THE FULL REVIEW ON THE EBNEO WEBSITEhttps://ebneo.org/2020/11/inhaled-nitric-oxide-pulmonary-hypoplasia/