HE4 and KL-6 as Promising Biomarkers for Diagnosis of Preterm Infants with Bronchopulmonary Dysplasia: A Diagnostic Prospective Cohort Study

Abstract

Background: Diagnosis of preterm infants with bronchopulmonary dysplasia (BPD) at an early stage may improve their quality of life. However, there is no proper diagnostic method. Therefore, a specific and objective marker is critically required. Here, we aim to evaluate the predictive characteristics of human epididymis protein 4 (HE4) and krebs von den lungen-6 (KL-6) as diagnostic biomarkers for preterm infants with BPD. Methods: A prospective cohort study was performed on 11 preterm infants with BPD and 21 preterm infants without BPD. Plasma levels of HE4 and KL-6 were measured and compared at 1, 14, and 28 days after birth. The correlation of HE4 and KL-6 with the clinical characteristics of preterm infants was also evaluated by Pearson’s correlation coefficient. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficiency in identifying BPD. Results: Interestingly, plasma HE4 and KL-6 levels were significantly increased in preterm infants with BPD at 1, 14, and 28 days after birth, and these levels were significantly correlated with gestational age, the weight of preterm infants, Apgar score (1 min), Apgar score (5 min), and invasive ventilation. ROC curve analysis showed that HE4 or KL-6 was highly capable of differentiating preterm infants with BPD from preterm infants without BPD. Notably, the combination of HE4 and KL-6 showed higher discriminatory capacity than HE4 or KL-6 alone. Conclusions: Plasma HE4 and KL-6 levels could serve as potential biomarkers for predicting BPD, and the combination of HE4 and KL-6 could also function as an efficient diagnostic marker.