Clinical trajectory and determinants of pulmonary hemorrhage in neonates: a 10-year case–control study

BACKGROUND: Pulmonary hemorrhage remains a life-threatening condition in neonates. This study aimed to identify factors associated with pulmonary hemorrhage, characterize the clinical trajectory during the 24 h preceding the event, and evaluate factors associated with mortality. METHODS: In this 10-year single-center case-control study with frequency-matched control selection, neonates with pulmonary hemorrhage were compared with controls matched at the sampling stage according to gestational age, birth weight, and admission period. Perinatal and postnatal variables were analyzed together with clinical characteristics observed during the 24 h preceding pulmonary hemorrhage. Multivariate logistic regression was used to evaluate associations between clinical variables, pulmonary hemorrhage, and mortality. A sensitivity analysis restricted to a recent cohort was performed to assess the robustness of the findings. RESULTS: A total of 120 neonates (60 cases, 60 controls) were included. Antenatal corticosteroid exposure was associated with a lower likelihood of pulmonary hemorrhage (OR 0.39, 95% CI 0.17-0.93, p = 0.035). Postnatal steroid exposure was associated with pulmonary hemorrhage (OR 4.59, 95% CI 1.01-20.78, p = 0.048). However, this finding likely reflects underlying disease severity, survivor bias, and confounding by indication rather than a direct causal effect. PDA diameter was not independently associated with pulmonary hemorrhage after multivariable adjustment (OR 3.14, 95% CI 0.82-12.07, p = 0.09). Affected neonates frequently exhibited progressive clinical deterioration characterized by increasing ventilatory support requirements, inotropic support, and fluid imbalance during the 24 h preceding pulmonary hemorrhage. Rescue surfactant administration during or shortly after the hemorrhagic episode was associated with mortality among affected neonates (OR 11.20, 95% CI 1.55-80.9, p = 0.017), although this finding should be interpreted cautiously because it may reflect underlying disease severity. Findings were consistent in sensitivity analyses. CONCLUSIONS: Pulmonary hemorrhage was associated with a recognizable pattern of progressive cardiorespiratory deterioration rather than isolated static clinical characteristics. Increasing respiratory support requirements, hemodynamic instability, and signs of fluid imbalance were common clinical features preceding the hemorrhagic event. These findings highlight a potential period of evolving clinical instability before pulmonary hemorrhage and provide a foundation for future prospective studies aimed at improving risk recognition and clinical monitoring in vulnerable neonates.