Advancements in Biomarkers and Machine Learning for Predicting of Bronchopulmonary Dysplasia and Neonatal Respiratory Distress Syndrome in Preterm Infants

Seyedehelham Shams ¹ Reza Bahrami ^2* Seyed Alireza Dastgheib ² Maryam Yeganegi ³ Sepideh Azizi ⁴ Mahsa Danaie ⁴ Mohammad Golshan-Tafti ⁵ Ali Masoudi ⁶ Amirhossein Shahbazi ⁷ Amirmasoud Shiri ² Kazem Aghili ⁶ Mahmood Noorishadkam ⁶ Hossein Neamatzadeh ⁶

• ¹ Hamadan University of Medical Sciences, Hamedan, Hamadan, Iran
• ² Shiraz University of Medical Sciences, Shiraz, Iran
• ³ Iranshahr University of Medical Sciences, Iranshahr, Sistan and Baluchestan, Iran
• ⁴ Iran University of Medical Sciences, Tehran, Tehran, Iran
• ⁵ Islamic Azad University, Yazd, Yazd, Yazd, Iran
• ⁶ Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Yazd, Iran
• ⁷ Medical University of Ilam, Ilam, Ilam, Iran

Recent advancements in biomarker identification and machine learning have significantly enhanced the prediction and diagnosis of Bronchopulmonary Dysplasia (BPD) and neonatal respiratory distress syndrome (nRDS) in preterm infants. Key predictors of BPD severity include elevated cytokines like Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α), as well as inflammatory markers such as the Neutrophil-to-Lymphocyte Ratio (NLR) and soluble gp130. Research into endoplasmic reticulum stress-related genes, differentially expressed genes, and ferroptosis-related genes provides valuable insights into BPD's pathophysiology. Machine learning models like XGBoost and Random Forest have identified important biomarkers, including CYYR1, GALNT14, and OLAH, improving diagnostic accuracy. Additionally, a five-gene transcriptomic signature shows promise for early identification of at-risk neonates, underscoring the significance of immune response factors in BPD. For nRDS, biomarkers such as the lecithin/sphingomyelin (L/S) ratio and oxidative stress indicators have been effectively used in innovative diagnostic methods, including attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and high-content screening for ABCA3 modulation. Machine learning algorithms like Partial Least Squares Regression (PLSR) and C5.0 have shown potential in accurately identifying critical health indicators. Furthermore, advanced feature extraction methods for analyzing neonatal cry signals offer a non-invasive means to differentiate between conditions like sepsis and nRDS. Overall, these findings emphasize the importance of combining biomarker analysis with advanced computational techniques to improve clinical decision-making and intervention strategies for managing BPD and nRDS in vulnerable preterm infants.