Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral infections in etiopathogenesis. The aim of this study was to summarize the relationship between viral infections and BPD through a systematic review and meta-analysis. We searched PubMed, Embase, the Web of Science Core Collection, and the Cochrane Database on December 19, 2023. We included observational studies that examined the association between viral infections and BPD in preterm infants. We extracted data on study methods, participant characteristics, exposure assessment, and outcome measures. We assessed study risk of bias using the Newcastle-Ottawa Scale (NOS). We included 17 and 15 studies in the qualitative review and meta-analysis, respectively. The meta-analysis showed a significant association between viral infection and BPD diagnosed at 36 weeks postmenstrual age (odds ratio (OR): 2.42, 95% confidence interval: 1.89–3.09, 13 studies, very low certainty of evidence). In a subgroup analysis of specific viruses, cytomegalovirus (CMV) proved to be significantly associated with BPD diagnosed at 36 weeks postmenstrual age (OR: 2.34, 95% confidence interval: 1.80–3.05, 11 studies). We did not find an association between viral infection and BPD diagnosed on the 28th day of life, probably due to the small sample size of the included prospective studies.  Conclusion: Viral infections, especially CMV, are associated with an increased risk of BPD in preterm infants. Methodologically reliable prospective studies with large samples are needed to validate our conclusions, and high-quality randomized controlled studies are needed to explore the effect of prevention or treatment of viral infections on the incidence of BPD. What is Known:• Studies have attempted to identify viral infections and bronchopulmonary dysplasia in preterm infants; however, results have been inconsistent. What is New:• Systematic demonstration that viral infections, particularly cytomegalovirus, are positively associated with bronchopulmonary dysplasia diagnosed in preterm infants at the 36th week of postmenstrual age.• The importance of screening for viral infections in preterm infants, especially cytomegalovirus. More high-quality studies should be produced in the future to investigate the causal relationship between viral infections and bronchopulmonary dysplasia.

Introduction Bronchopulmonary dysplasia (BPD) is one of the most common and significant complications of preterm birth. It ultimately leads to a decrease in the quality of life for preterm infants and impacts their long-term health. Early prediction and timely intervention are crucial to halting the development of BPD. This study aims to identify the biomarkers that can predict the early occurrence and development of BPD by screening serum metabolites in preterm infants. This will provide strong support for the early prediction of BPD and targeted interventions in future research. Methods and analysis This is a prospective, multicentre, open-label, observational cohort study spanning 3 years. It will be conducted in six major neonatal intensive care units in Shenzhen, China, involving preterm infants born at gestational ages <32 weeks. Demographic data and treatment information will be collected prospectively. Serum samples will be collected at five distinct time points: within 24 hours after birth, at 1 week, 2 weeks, 28 days and at 36 weeks postmenstrual age. These samples will undergo analysis using liquid chromatography-tandem mass spectrometry for untargeted metabolomics studies. Participants will be categorised into BPD and non-BPD groups based on their final diagnosis, and metabolite differences between these groups will be analysed. The study aims to enrol 1500 preterm infants with gestational ages <32 weeks over 3 years. A three-step analysis strategy—discovery, validation and clinical testing—will be used to identify and validate the clinical utility of novel biomarkers. Additionally, a nested case-control study will be conducted, matching participants 1:1 with a control group sharing similar BPD risk factors. Ethics and dissemination Our protocol has been approved by the Medical Ethics Committees of all participating hospitals, including Peking University Shenzhen Hospital, Shenzhen People’s Hospital, Shenzhen Baoan Women’s and Children’s Hospital, Longgang District Maternity and Child Healthcare Hospital, Nanshan Maternity and Child Healthcare Hospital and Shenzhen Luohu People’s Hospital. We will disseminate our study results through academic conferences and peer-reviewed public journals. Trial registration number ChiCTR2400081615.

Introduction: 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. Methods and analysis: 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. Ethics and dissemination: 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. Trial registration number: ChiCTR2400094994.