Risk Factors for Severe Brain Injury in Preterm Infants with Gestational Age <32 Weeks Receiving Inhaled Nitric Oxide: A Propensity Score-Matched Analysis

Background Intracranial hemorrhage (IVH) and periventricular leukomalacia (PVL) are common complications in preterm infants with a gestational age (GA) < 32 weeks. Severe IVH (Grades 3–4) and PVL can lead to long-term neurological sequelae, including cerebral palsy, epilepsy, and intellectual disabilities. The safety and efficacy of inhaled nitric oxide (iNO) in infants with GA < 32 weeks remains controversial. Some studies suggest that iNO can improve oxygenation but may affect coagulation and increase the risk of IVH. Objective This study aimed to identify the factors influencing the occurrence of severe brain injury (sBI) in preterm infants with GA < 32 weeks receiving iNO treatment, using propensity score matching (PSM) analysis. Methods A multicenter retrospective cohort study was conducted, including preterm infants born at GA < 32 weeks who received iNO treatment for more than 3 hours across eight hospitals in China between 2013 and 2022. Infants were divided into two groups based on the occurrence of sBI. PSM was used to match the infants in a 1:1 ratio based on covariates such as GA, birth weight, and gender. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for sBI. Repeated-measures ANOVA and mediation analysis were used to assess the significance of risk factors and their potential mediating effects on the occurrence of sBI. Results After matching, baseline characteristics between the sBI and non-sBI groups were balanced. Univariate and multivariate analyses showed that reduced platelet count was an independent risk factor for sBI. The total invasive high-frequency mechanical ventilation time, P/F ratio at 3 hours and 6 hours post-iNO treatment were statistically significant in univariate analysis but not in multivariate analysis. Mediation analysis revealed no mediating effect of mechanical ventilation time or P/F ratio on the relationship between platelet count and sBI. Repeated-measures ANOVA showed that iNO treatment significantly affected the P/F ratio, which improved over time. However, no significant difference in P/F ratio changes was observed between the sBI and non-sBI groups. Conclusion This study suggests that reduced platelet count is an independent risk factor for the occurrence of sBI in preterm infants with GA < 32 weeks receiving iNO treatment. Although total invasive high-frequency mechanical ventilation time and P/F ratio changes may also affect sBI occurrence, they do not mediate the relationship between platelet count and sBI.