Expression and significance of miR-9-5p and GCH1 in neonates with bronchopulmonary dysplasia.

BACKGROUND

Bronchopulmonary dysplasia (BPD) is one of the most common respiratory disorders in preterm infants, associated with short- and long-term complications involving the respiratory, cardiovascular, and nervous systems, posing a major challenge in neonatal medicine. miR-9-5p has recently garnered attention for its role in lung diseases, including asthma and acute lung injury. The pathogenesis of these two diseases shares similarities with that of BPD, particularly regarding inflammatory responses and oxidative stress mechanisms. However, there are currently no clinical studies exploring the role of miR-9-5p in BPD. This study aimed to explore the potential of miR-9-5p and guanosine triphosphate cyclohydrolase 1 (GCH1) as early diagnostic biomarkers for BPD.

METHODS

From January 2024 to September 2025, 90 preterm infants born at <32 weeks of gestation and birth weight <1,500 g admitted to the Neonatal Department of Affiliated Hospital of Nantong University were enrolled. After excluding 8 neonates with major congenital malformations, genetic metabolic diseases, death within 28 days of life, or parental withdrawal from all treatment, 82 infants were included and divided into a BPD group (n=30) and a non-BPD group (n=52). General characteristics and clinical features including comorbidities and treatments were compared between two groups. Multiple logistic regression analysis was conducted to investigate postnatal risk factors. Peripheral blood plasma miR-9-5p expression was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), and GCH1 levels were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

In terms of comorbidities, the BPD group had significantly higher proportions of neonatal asphyxia, neonatal pneumonia, neonatal sepsis, retinopathy of prematurity (ROP), and neonatal anemia (all P<0.05). After correcting for confounding factors using multiple regression, neonatal asphyxia and neonatal sepsis were identified as independent risk factors for BPD (both P<0.05). In terms of treatments, the BPD group had significantly higher proportions of invasive ventilator use, red blood cell transfusion, higher exposure to oxygen concentrations >30%, longer duration of invasive/non-invasive ventilation, and longer days of oxygen inhalation (all P<0.05). Compared with the non-BPD group, BPD infants exhibited significantly higher miR-9-5p expression (0.0087±0.0021 vs. 0.0064±0.0025, P<0.001) and markedly lower GCH1 levels (0.0732±0.0074 vs. 0.2356±0.0609, P<0.001). Receiver operating characteristic (ROC) curve analysis showed that miR-9-5p had superior predictive value for BPD with an area under the curve (AUC) of 0.833 [95% confidence interval (CI): 0.742-0.924], while GCH1 yielded an AUC of 0.737 (95% CI: 0.629-0.845). Spearman correlation analysis revealed a strong negative correlation between miR-9-5p and GCH1 levels in peripheral blood of BPD neonates (r=-0.8967, P<0.001).

CONCLUSIONS

miR-9-5p, with an AUC of 0.833, is a promising early diagnostic biomarker for BPD, providing new insights into disease pathogenesis and informing strategies for early detection and intervention.