Mortality Risk Factors in Actively Resuscitated 22-Week Preterm Infants: A Case-Control Study Focusing on NEC and Maternal Hospitalization

Background: Infants born at 22 weeks’ gestation represent one of the most vulnerable populations in neonatal care. Despite increasing survival rates with active resuscitation, variability in outcomes remains significant. This study aimed to identify risk factors associated with in-hospital mortality in actively resuscitated infants born at 22 weeks’ gestation. Methods: A retrospective case-control study was conducted at Kagoshima City Hospital between January 2006 and December 2023. Fifty-seven live-born infants at 22 weeks’ gestation who received active resuscitation were included. Clinical characteristics and outcomes were compared between survivors and non-survivors. Univariable and multivariable logistic regression analyses were performed. Firth’s correction and cross-validation were used to address small sample size and model robustness. Results: Of the 57 infants included, 19 (33.3%) died during hospitalization. Necrotizing enterocolitis (NEC, stage ≥ II) and maternal hospitalization ≤5 days prior to delivery were independently associated with mortality (adjusted odds ratios: 5.4 and 6.4, respectively). Only non-survivors experienced tension pneumothorax or were born outside of tertiary centers. Bacteremia within 10 days and intraventricular hemorrhage grade III–IV were also associated with mortality in univariable analyses. Model performance after sensitivity analyses yielded an AUC of 0.892 and improved calibration. Conclusions: NEC and short maternal hospitalization are significant independent predictors of mortality in infants born at 22 weeks of gestation. Delivery at tertiary centers and timely maternal transfer may improve survival. Further studies are needed to establish preventive strategies for NEC, sepsis, and respiratory complications in this high-risk group . Trial registration: Not applicable