Alterations in Cord Blood microRNAs May Predict Hypoxic-Ischemic Encephalopathy

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In this analysis, investigators examined alterations in the expression of umbilical cord whole-blood miRNAs.

Alterations in the expression of 3 microRNAs (miRNAs), including miR-374a-5p, miR-376c-3p, and mir-181b-5p, are common in the umbilical cord blood of neonates with hypoxic-ischemic encephalopathy (HIE) and perinatal asphyxia (PA) and may be predictive of these disorders in infants. Findings were published in JAMA Neurology.

Researchers from Ireland and Sweden included a total of 160 neonates across 2 cohorts. The first group, the discovery cohort, included healthy control infants (n=22) as well as full-term infants with PA and HIE who were enrolled in the Biomarkers in Hypoxic-Ischemic Encephalopathy (BiHiVE1) study (2009-2011) in Cork, Ireland, at birth (n=68). The second validation group, the BiHiVE2 cohort, was composed of infants with PA, infants with HIE, and healthy control patients (n=80), all of whom were studied to validate BiHiVE1 findings. In this analysis, investigators examined alterations in the expression of umbilical cord whole-blood miRNAs.

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The median age of neonates in both cohorts was 40 weeks (interquartile range [IQR], 39-41 weeks). A total of 7 candidate miRNAs found in the BiHiVE1 were chosen for validation in the BiHiVE2 trial. Only 3 miRNAs demonstrated consistent alteration in umbilical cord blood in the validation trial. Compared with healthy control patients, infants with HIE had significantly decreased miR-374a-5p (median relative quantification, 0.38 [IQR, 0.17-0.77] vs 0.95 [IQR, 0.68-1.19]; P =.009). In addition, miR-376c-3p was lower among infants with PA vs healthy infants (median, 0.42 [IQR, 0.21-0.61] vs 0.90 [IQR, 0.70-1.30]; P =.004). Finally, investigators noticed significantly lower miR-181b-5p in infants eligible for therapeutic hypothermia (median, 0.27 [IQR, 0.14-1.41] vs 1.18 [IQR, 0.70-2.05]; P =.02).

Limitations of this analysis include its small sample size, as well as the reliance on whole blood vs serum or plasma, the latter of which may have obscured “altered expression seen in extracellular miRNA owing to abundant levels of cellular miRNA in whole blood.”

Despite the limitations, the findings have validated that decreased expression of miR-374a and miR-376c may be predictive of PA and HIE in infants, and they believe their study “may bring [miRNA 181b] forward as a quantifiable noninvasive biomarker with a reliable [negative predictive value] to aid in identifying those infants who will not require intervention.”


O’Sullivan MP, Looney AM, Moloney GM, et al. Validation of altered umbilical cord blood microrna expression in neonatal hypoxic-ischemic encephalopathy [published online December 28, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.4182