473 - MicroRNA-223 and MicroRNA-30e as Potential Diagnostic Biomarkers for Neonatal Asphyxia and Hypoxic Encephalopathy

Publication Number: 473.5862

Giuseppe De Bernardo, Ospedale Buon Consiglio Fatebenefratelli, Napoli, Campania, Italy; Matteo Miele, Ospedale Fate Bene Fratelli Napoli, Napoli, Campania, Italy; Maurizio Giordano, University of Naples Federico II, Naples, Campania, Italy; Rohan mahesh Patil, University of Naples Federico II, Napoli, Campania, Italy; GIUSEPPE PIGNATARO, FEDERICO II UNIVERSITY OF Naples, NAPOLI, Campania, Italy

Background: Hypoxic-Ischemic Encephalopathy (HIE) is a serious neurological condition that affects 1.5-2.5% of live newborns in developed nations. It is caused by oxygen deprivation (hypoxia) and decreased blood flow (ischemia) to the brain in the first few hours of birth. It is a prominent cause of infant mortality and long-term disability, prompting researchers to investigate new biomarkers to enhance early detection and guiding treatment techniques. miRNA-223 has been identified as a possible biomarker for HIE due to its participation in essential physiological processes such as inflammation, cell death, and neuronal damage. Similarly, miR-30a and miR-30e have parts in apoptotic pathways and neurodevelopment, implying that changed levels could indicate neuronal stress caused by hypoxia.

Objective: The rationale of this study was to evaluate maternal and infant miRNA levels to early detect the brain injury caused by oxygen deprivation.

Design/Methods: A prospective experimental cohort study involving newborns born at Buonconsiglio Fatebenefratelli Hospital in Naples from September 2023 to September 2024. The study was approved by Ethics Committee Lazio 1. They were enrolled newborns > 35 weeks of gestational age and >1800 g and mothers without pregnancy complications, infections, fever, positive vaginal-rectal swabs and early rupture of membranes. Healthy newborns were assigned as control group (Group A), while those with pH < 7,12 were indicated as case group. Case group was composed of newbornsby newborns with asphyxia did not practice therapeutic hypothermia (Group B1) and newborns with HIE and that practiced therapeutic hypothermia. At birth (T0), blood samples of the newborn were collected by umbilical cord artery along with maternal venous blood. At 3 (T3) and 48 (T48) hours after birth, they 0.2 ml was.

Results: Our results demonstrated consistent upregulation of all three miRNAs at birth (T0) and after 3 hours (T3), except for miR-30a. Notably, miR-30e normalized to control levels by T3, while miR-223 and miR-30a remained upregulated in asphyxia and HIE cases, respectively, as illustrated in Figure 1 and Figure 2.

Conclusion(s): The findings from this study demonstrate miRNA-223 & miRNA-30e as a promising biomarker for the early detection of fetal metabolic acidosis, with elevated levels suggesting its involvement in neonatal asphyxia and hypoxia. However, it is equally important to consider miRNA-30a levels at T48 for the recovery of the damage as miRNA-30a is involved in neurogenesis.

Figure 1
The volcano plot for specific miRNAs were plotted as log2FC (x-axis) against -log10(P-value) (y-axis). Only significant p-values (e.g., p < 0.05) were included in this study as potential biomarkers in both hypoxic encephalopathy and asphyxia.

Figure 2
Figure 2: Barr plot with error bars show miRNA profiles of mothers and newborns at three time points of the study. Hsa-miR: homo sapiens miRNA; HIE: Hypoxic-Ischemic Encephalopathy; T0: at birth; T3: at 3 hours of life; T48: At 48 hours of life. *p <0,05;**p <0,01;***p <0,001