Hypoxic-ischaemic encephalopathy (HIE), a leading cause of neurological disability in neonates, is managed with therapeutic hypothermia, yet systematic data on its aetiology and prognosis are lacking, particularly in China. Herein, our study addresses this gap by establishing a prospective registry in Shenzhen and aims to clinically characterise HIE, identify its risk factors and document its long-term outcomes. We will recruit 200 neonates with HIE from 10 hospitals in Shenzhen, China, between January 2025 and December 2028. In parallel, clinical data will be collected during hospitalisation, with supplemental referral information obtained from birth hospitals via an online, specialised HIE database. We will include HIE severity, survival status and the incidence of serious complications, such as arrhythmias, pulmonary haemorrhage, neonatal acute respiratory distress syndrome, persistent pulmonary hypertension of the newborn and disseminated intravascular coagulation, to assess key outcomes of HIE in neonates.Longitudinal follow-up is scheduled for 18, 24 and 36 months, involving assessments using physical developmental scales, video-electroencephalogram (VEEG) recordings, the Chinese version of the Bayley Infant and Toddler Developmental Scale, Fourth Edition and cranial MRI at 18 months. The primary objectives of this study are to determine survival status, track loss-to-follow-up rates and evaluate neurodevelopmental outcomes at 3 years, with the ultimate goal of enhancing our understanding of HIE risk factors, hypothermia therapy and prognosis to reduce HIE-related morbidity and disability. This study protocol has been approved by the Medical Ethics Committee of Shenzhen Children's Hospital (Ethics No. 2024096), and the findings will be disseminated through presentations at national academic conferences and publication in peer-reviewed paediatric journals. ChiCTR2400094994.

Key clinical features of neonatal acute respiratory distress syndrome (NARDS) are broadly comparable to those observed in pediatric and adult ARDS; however, evidence is insufficient to recommend high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) as the preferred first-line therapy. To evaluate whether HFOV is superior to CMV in reducing bronchopulmonary dysplasia (BPD) and other neonatal adverse outcomes, including death, among preterm infants (≤34 weeks' gestational age) with NARDS. This single-center randomized clinical trial conducted from August 1, 2019, to December 31, 2023, enrolled preterm infants born between 25 weeks 0 days and 34 weeks 6 days of gestation with NARDS who were stabilized with CMV. Data were analyzed from October to December 2024. Participants were randomly assigned to continue CMV or transition to elective HFOV. The primary outcome was BPD, assessed using 2 definitions: definition 1, that of the 2001 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and definition 2, one based on 2019 research. Secondary outcomes included death, retinopathy of prematurity (higher than stage 2), necrotizing enterocolitis (stage 2 or higher), intraventricular hemorrhage (grade 3 or higher), air leak, and hemodynamically significant patent ductus arteriosus. Modified Poisson regression, ordinal regression, and Cox proportional hazards regression were applied for outcome risk assessment where applicable. A total of 386 preterm infants (230 male [59.6%]; mean [SD] maternal age, 29.9 [4.8] years) were randomized: 181 to elective HFOV and 205 to CMV. Overall, 154 (39.9%) and 83 (21.5%) developed BPD according definitions 1 and 2, respectively. Elective HFOV reduced the risk of BPD by 8.0% (34.3% vs 44.9%; relative risk, 0.92; 95% CI, 0.86-0.99) according to definition 1 and by 32.0% (17.1% vs 25.4%; relative risk 0.68; 95% CI, 0.45-1.00) according to definition 2 compared with CMV. No significant between-group differences were observed for death, higher than stage 2 retinopathy of prematurity, stage 2 or higher necrotizing enterocolitis, grade 3 or higher intraventricular hemorrhage, air leak, or hemodynamically significant patent ductus arteriosus. Sensitivity analysis excluding 44 participants who crossed over between treatment groups did not significantly attenuate the estimates. This randomized clinical trial found that elective HFOV reduced the incidence of BPD in preterm infants born at 34 weeks' gestation or earlier with NARDS compared with CMV. The results of this study suggest that elective HFOV is a promising strategy for preventing BPD in this high-risk population, especially the more severe forms linked to increased long-term morbidity and mortality. ClinicalTrials.gov Identifier: NCT03591796.

Preterm premature rupture of membranes (PROM) is a major cause of extremely preterm birth. Intrauterine infection and inflammation markedly increase the risk of neonatal acute respiratory distress syndrome (NARDS), particularly moderate or severe cases associated with poor outcomes. This study developed and validated a prediction model for moderate or severe NARDS in this population using inflammatory biomarkers. This single center retrospective cohort study included 243 extremely preterm infants with PROM from 2015 to 2024. The primary outcome was moderate or severe NARDS occurring within 72 hours after delivery, diagnosed according to Montreux criteria. Patients were grouped by NARDS severity. Predictive variables were screened using LASSO regression and incorporated into a multivariable logistic model to build a nomogram. Model performance was assessed through receiver operating characteristic curves (ROC), calibration plots and decision curve analysis (DCA). The primary outcome incidence was 20.2% (49/243). Multivariable analysis identified elevated C-reactive protein (CRP) (OR=1.04, 95% CI:1.01-1.07), decreased platelet count (OR=0.99, 95% CI:0.988-0.998), decreased albumin (OR=0.87, 95% CI:0.80-0.95), and decreased arterial pH (OR=0.01, 95% CI:0.001-0.041) as independent predictors. The nomogram integrating these four parameters demonstrated excellent discrimination with an area under the curve (AUC) of 0.824. Internal validation demonstrated good robustness (C-index=0.795). To enhance clinical translation, we developed an interactive web calculator for real time risk assessment to guide pediatricians' clinical decision making. DCA established a 30% risk threshold to inform early interventions. The validated model containing CRP, platelets, albumin and pH effectively identifies high risk PROM infants. The web based interface enables practical bedside application for early detection of critical cases. Patients with predicted probabilities reaching 30% should be considered for preventive lung protection measures. Additional multicenter studies are needed to verify wider applicability and enhance clinical implementation protocols.

Research on the infection-related etiologies of neonatal acute respiratory distress syndrome (NARDS) remains limited. This study aimed to investigate mortality risk differences in NARDS attributed to distinct infection origins (sepsis of extrapulmonary origin or pulmonary infection origin). Subjects were derived from a multicenter retrospective study organized by the Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network. It included neonates with NARDS who initiated invasive mechanical ventilation (IMV) within 72 h of birth. A total of 268 from 1275 NARDS cases with infectious etiologies were enrolled. Multivariate Cox regression found a significant difference in the survival prognosis (sepsis of extrapulmonary origin, adjusted hazard ratio (HR): 3.93, 95% CI 1.79-8.62, log-rank test: P < 0.001]. Further multi-model and sensitivity analysis confirmed the robustness. Between early-onset and late-onset NARDS, the subgroup analysis showed no significant differences in the mortality risk, whether it was pulmonary infection origin (HR 1.69, 95% CI 0.61-4.64) or sepsis of extrapulmonary origin (HR 0.50, 95% CI 0.17-1.51). Restricted cubic spline also exhibited that the onset time of NARDS was not related to the mortality risk. This study suggests that for sepsis of extrapulmonary origin, we should be more vigilant about the mortality risk it brings and deal with the risk factors more actively and prudently. • Limited research has systematically investigated the association between infection origin and mortality risk in neonatal acute respiratory distress syndrome (NARDS). • Our study found that sepsis of extrapulmonary origin was associated with an increased mortality risk in neonates with gestational age > 34 weeks, with robust results from multivariate Cox modeling and sensitivity analyses. • It highlights the need for heightened vigilance and proactive management of extrapulmonary sepsis-related NARDS to mitigate mortality risk in neonates.