miR223, miR30e, and miR30a show associations with perinatal metabolic acidosis in neonates with hypoxic–ischemic encephalopathy

Hypoxic-Ischemic Encephalopathy (HIE) is a leading cause of neonatal death and long-term disabilities, leading researchers to explore novel candidate biomarkers to improve early diagnosis and guide treatment strategies. miR223, miR30a and miR30e have attracted attention as potential biomarkers for HIE due to its involvement in key cellular processes like inflammation, cell death, and neuroprotection. The rationale of this study was to examine longitudinal maternal and infant circulating miRNA blood levels from T0–T3 to 48 h of life in relation to perinatal metabolic acidosis and neonatal hypoxic–ischemic encephalopathy status. A prospective observational cohort study involving newborns born from September 2023 to September 2024 was carried out. Healthy newborns were assigned as control group (CG), those with pH < 7.12 without inclusion criteria for hypothermic treatment were assigned to no hypothermic treatment group (NHTG) those that met inclusion criteria for hypothermic treatment were included in the hypothermic treatment group (HTG). Blood samples of the newborns were collected by umbilical cord artery along with maternal venous blood at birth (T0), at 3 (T3) and 48 (T48) hours after birth, the latter were collected from capillary blood. Our results demonstrated consistent upregulation of miR223, miR30e and miR30a at T0 and T3 in NHTG and HTG. Interestingly, miR223 and miR30a were upregulated also in samples obtained by NHTG and HTG mother blood. In this exploratory analysis, miR223, miR30e, and miR30a were found to be associated with perinatal metabolic acidosis and acute hypoxic stress, as defined by cord blood pH and clinical HIE status at presentation, supporting their role as candidate markers of early postnatal response. NCT05986994, Identification of a Pool of MiRNA to Improve Early Management of Perinatal Asphyxia and Hypoxic Ischemic Encephalopathy Prospectively Registered on 14 August 2023.