Prediction models of bronchopulmonary dysplasia: a systematic review and meta-analysis with validation

Introduction Neonatal bronchopulmonary dysplasia (BPD) is associated with lifelong respiratory and neurological sequalae. Prediction models could identify infants at greatest risk of BPD and allow targeted preventative strategies. We performed a systematic review and meta-analysis with external validation of identified models. Methods Studies using predictors available before day 14 of life to predict BPD in very preterm infants were included. Two reviewers assessed 7,628 studies for eligibility. Meta-analysis of externally validated models was followed by validation using 62,864 very preterm infants in England and Wales. Results 64 studies using 53 prediction models were included totalling 274,407 infants (range 32–156,587/study). 35 (55%) studies predated 2010; 39 (61%) were single-centre studies. 46 (87%) models were developed for the first week of life. Overall, 97% of studies had a high risk of bias, especially in the analysis domain. Internal (25%) and external (30%) validation were performed infrequently in the 44 model derivation studies. Following meta-analysis of 22 BPD and 11 BPD/death composite models, Laughon’s day one model was the most promising in predicting BPD and death with a fair C-statistic of 0.76 (95% CI 0.70–0.81) and good calibration. Six models were externally validated in our cohort with a C-statistic between 0.70 to 0.90 but with poor calibration. Conclusion Few BPD prediction models were developed with contemporary populations, underwent external validation, or had calibration and impact analyses. To reduce the adverse impact of BPD, we need contemporary, validated, and dynamic prediction models to allow targeted preventative strategies. What is the key question? This review aims to provide a comprehensive assessment of all BPD prediction models developed to address the clinical uncertainty of which predictive model is sufficiently valid and generalisable for use in clinical practice and research. What is the bottom line? Published BPD prediction models are mostly outdated, single centre and lack external validation. Why read on? Laughon’s 2011 model is the most promising but more robust models, using contemporary data with external validation are needed to support better treatments. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This research received no specific funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was granted by the Sheffield Research Ethics Committee (REC reference 19/YH/0115). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors