MiR-181a, IL-6, and TNF-α: Biomarkers for Diagnosis and Long-Term Neurodevelopmental Prognosis in Neonatal Sepsis

Jialin Shen, Min Yu, Shirui Zhu, Mei Xue Department of Neonatology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of ChinaCorrespondence: Mei Xue, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, No. 366, Taihu Road, Hailing District, Taizhou City, Jiangsu Province, People’s Republic of China, Email [email protected]: To investigate the value of serum microRNA-181a (miR-181a), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in early prediction of neonatal sepsis and their correlation with long-term neurodevelopmental outcomes.Methods: A retrospective analysis of 131 septic and 129 non-infected neonates from January 2023 to August 2024 assessed serum miR-181a, TNF-α, and IL-6 levels, with neurodevelopmental outcomes evaluated at 12 months. Multivariate logistic regression was employed to identify risk factors for sepsis and adverse neurodevelopmental outcomes. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of each indicator for sepsis and poor neurodevelopmental outcomes.Results: The septic group had lower miR-181a and higher IL-6 and TNF-α levels (P < 0.0001), with an AUC of 0.860 for sepsis diagnosis. Among septic neonates, 31.30% had neurodevelopmental abnormalities, linked to lower miR-181a and higher IL-6 and TNF-α levels (P < 0.01), with an AUC of 0.850 for predicting these abnormalities. Multivariable logistic regression identified miR-181a as a protective factor for neonatal sepsis, while IL-6, TNF-α, and NLR were independent risk factors. For long-term adverse neurodevelopmental outcomes, miR-181a and gestational age served as protective factors, whereas IL-6, TNF-α, and prenatal inflammation were independent risk factors.Conclusion: Serum miR-181a, IL-6, and TNF-α are sensitive indicators for the early prediction of neonatal sepsis. Low expression of miR-181a and high expression of IL-6 and TNF-α are closely associated with adverse neurodevelopmental outcomes. Combined detection of these three markers holds significant clinical value for prognostic assessment, facilitating early identification of high-risk infants and enabling timely intervention.Keywords: neonatal sepsis, miR-181a, interleukin-6, tumor necrosis factor-alpha, neurodevelopmental outcomes