Downregulation of Umbilical Cord Blood Levels of miR-374a in Neonatal Hypoxic Ischemic Encephalopathy

Abstract

Objective: To investigate the expression profile of microRNA (miRNA) in umbilical cord blood from infants with hypoxic ischemic encephalopathy (HIE).

Study design: Full-term infants with perinatal asphyxia were identified under strict enrollment criteria. Degree of encephalopathy was defined using both continuous multichannel electroencephalogram in the first 24 hours of life and modified Sarnat score. Seventy infants (18 controls, 33 with perinatal asphyxia without HIE, and 19 infants with HIE [further graded as 13 mild, 2 moderate, and 4 severe]) were included in the study. MiRNA expression profiles were determined using a microarray assay and confirmed using quantitative real-time polymerase chain reaction.

Results: Seventy miRNAs were differentially expressed between case and control groups. Of these hsa-miR-374a was the most significantly downregulated in infants with HIE vs controls. Validation of hsa-miR-374a expression using quantitative real-time polymerase chain reaction confirmed a significant reduction in expression among infants with HIE compared with those with perinatal asphyxia and healthy controls (mean relative quantification [SD] = 0.52 [0.37] vs 1.10 [1.52] vs 1.76 [1.69], P < .02).

Conclusions: We have shown a significant step-wise downregulation of hsa-miR-374a expression in cord blood of infants with perinatal asphyxia and subsequent HIE.