Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review

Bronchopulmonary dysplasia (BPD) is usually diagnosed in preterm infants at least 28 days after birth. Great interest lies in the potential to identify biomarkers that predict development of the disease and future neurodevelopmental outcomes. We have reviewed the existing literature on early biomarkers as predictors for BPD in preterm infants. Two reviewers independently searched the databases of PubMed, EMBASE, and Google Scholar for studies pertaining to biomarkers for BPD. Studies were assessed using Quality Assessment of Diagnostic Accuracy Studies criteria. We identified 46 relevant articles that are summarized in the review. These studies assessed over 30 potential biomarkers. Sensitivity and specificity of biomarkers were reported or could be calculated for only 16 articles, and ranged from 0 to 100 %. Based on the nine highest quality studies, serum KL-6, CC16, neutrophil gelatinase-associated lipocalin, and end-tidal carbon monoxide (etCO) perform extremely well in predicting the early diagnosis of established BPD, highlighting these biomarkers as promising candidates for future research. Published data from studies on serum biomarkers and etCO suggest that biomarkers may have great potential to predict the subsequent BPD and neurodevelopmental outcomes. These biomarkers need validation in larger studies, and the generalizability of biomarkers for predicting BPD, as well as the neurodevelopmental outcomes, needs to be further explored.