Persistent postnatal alterations in microRNA expression in neonatal encephalopathy

Despite causing severe neurological morbidity, neonatal encephalopathy (NE) lacks reliable biochemical markers for early diagnosis and intervention. This study investigated if alterations in microRNA (miRNA) expression, previously identified in umbilical cord blood in NE, remain altered in postnatal whole blood samples.

Term infants with NE (and matched controls) born in Cork University Maternity Hospital (CUMH) between 2017 and 2020 were recruited. Whole blood was collected within the first 6 (T0), 24 (T24) and 48 (T48) hours after delivery via dried blood spot microsampling. Encephalopathy grade (mild, moderate, or severe) was determined based on modified Sarnat at 1 h. 19 candidate and three housekeeping miRNAs were analyzed in all infants via the 2^-ΔΔCt method.

66 neonates were included in the study; 53 with encephalopathy; (25 mild, 22 moderate and 6 severe), and 13 controls. 105 whole blood samples were taken across the three timepoints. Comparing NE (n = 28) with controls (n = 13) at T0 confirmed alteration of eight miRNAs, including newly identified miR-205-5p. Comparison of NE infants across the three timepoints found the persistent alteration of four miRNAs.

Persistent miRNA alterations are seen in NE 0-48 h postnatally and are detectable through minimally invasive microsampling.

Altered microRNA expression can be detected in the blood of neonates with neonatal encephalopathy when compared to healthy controls. These changes in expression are detectable in the postnatal period, up to 48 h after birth. Alterations can be detected through less invasive methods, showing promise that these microRNA profiles may serve as potential markers for the rapid detection of neonatal encephalopathy at the bedside. This follows on from previous research showing changes in microRNA expression in umbilical cord samples in encephalopathic infants, providing a longer window for potential detection spanning post-natally.