Association between nitric oxide treatment and intraventricular hemorrhage among extremely preterm neonates in Switzerland, 2012–2020

Inhaled nitric oxide (iNO) treatment is routinely used to treat newborns suffering from severe respiratory distress syndrome (RDS). While the treatment is established for term born infants, its safety and efficacy remain controversial among preterm born infants. A 2017 meta-analysis focusing on this population reported a nonsignificant increase in the occurrence of severe intraventricular hemorrhage (sIVH) if infants were treated with iNO. sIVH is a dreaded complication of extreme premature birth that impairs long-term neurodevelopment. In this study, we hypothesize that iNO treatment is associated with the occurrence of sIVH among extremely preterm born infants. We investigated the Swiss population of infants born extremely preterm (< 28 weeks gestation) from 2012-2020 in a retrospective manner. The association between the treatment and sIVH was investigated by multivariable logistic regression analysis. A sensitivity analysis was performed by stratifying of the population according to the presence or absence of pulmonary hypertension of the newborn (PPHN). A total of 2101 neonates were included in the study. Among 251 patients in whom iNO treatment was applied, 62 (24.7%) suffered from sIVH, compared to 232 of the 1850 (12.5%) patients without iNO. We found no significant association between iNO treatment and the occurrence of sIVH in the presence of PPHN. It remains unclear whether the treatment is associated with the occurrence of sIVH in the absence of PPHN.Trial registration number: BASEC-ID 2022-00,403.