MicroRNA changes persist in newborn blood after neonatal encephalopathy

Babies with neonatal encephalopathy, a serious brain condition around the time of birth, carry distinctive changes in their blood microRNA levels that persist for at least the first 48 hours after delivery, according to a study published in Pediatric Research. The finding, reported by researchers working at Cork University Maternity Hospital, suggests that these molecular signatures could eventually support earlier bedside detection of the condition through minimally invasive sampling.

Neonatal encephalopathy affects term infants and is associated with severe neurological morbidity, yet reliable biochemical markers for early diagnosis and timely intervention remain lacking. Earlier work by the same research community had identified altered microRNA expression in umbilical cord blood from affected infants. The new study asked a clinically important follow-up question: do those alterations remain detectable after birth, in whole blood drawn from the newborn, where they could inform care decisions in the crucial first days of life?

The research team recruited term infants with neonatal encephalopathy and matched healthy controls, all born at Cork University Maternity Hospital between 2017 and 2020. Rather than relying on conventional venous blood draws, the investigators used dried blood spot microsampling, collecting whole blood within the first 6 hours after delivery, again at 24 hours, and once more at 48 hours. The severity of encephalopathy in each affected infant was graded as mild, moderate or severe using the modified Sarnat staging system assessed at one hour of age.

In the laboratory, the team measured 19 candidate microRNAs together with three housekeeping microRNAs used for normalization, applying the 2−ΔΔCt quantification method across all infants.

In total, 66 neonates were included in the analysis: 53 with encephalopathy, comprising 25 mild, 22 moderate and 6 severe cases, and 13 controls. Across the three postnatal timepoints, 105 whole blood samples were collected and analyzed, giving the study a longitudinal view of how the microRNA signal behaved over the first two days of life rather than a single snapshot.

Comparing infants with neonatal encephalopathy against controls at the earliest timepoint confirmed alteration of eight microRNAs, including one, miR-205-5p, newly identified in this postnatal context. When the researchers then tracked the encephalopathy group across all three timepoints, they found that four microRNAs remained persistently altered from 0 to 48 hours after birth. The persistence of the signal is the study’s central observation: the molecular differences are not confined to cord blood at delivery but continue to be measurable in the newborn’s circulating blood.

The authors also examined expression patterns by disease severity, contrasting mild cases with moderate and severe cases against healthy controls, and the published figures present these group-level comparisons at the first timepoint.

The researchers emphasize that the alterations were detectable through less invasive methods, and they describe the microRNA profiles as showing promise as potential markers for rapid detection of neonatal encephalopathy at the bedside. Building on the previous cord blood findings, the postnatal results extend the window in which such a signature could be sought, spanning the first two days after birth. Because the analysis involved a modest number of infants from a single maternity hospital, and the datasets are available only from the corresponding author on reasonable request, broader validation in independent cohorts would be needed before any clinical use. For now, the study establishes that the postnatal microRNA signal exists, persists, and can be captured with a simple microsampling approach.

Subject of Research: Persistent postnatal microRNA expression changes in neonatal encephalopathy detected via dried blood spot sampling

Article Title: Persistent postnatal alterations in microRNA expression in neonatal encephalopathy

Article References: Walls, E. A., O’Sullivan, M. P., Garvey, A. A., Pavel, A. M., Dempsey, E. M., Boylan, G. B., & Murray, D. M. (2026). Persistent postnatal alterations in microRNA expression in neonatal encephalopathy. Pediatric Research. https://doi.org/10.1038/s41390-026-05262-3

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05262-3

Keywords: neonatal encephalopathy, microRNA, biomarkers, dried blood spot, newborns, Pediatric Research, Sarnat staging, cord blood, gene expression, Cork University Maternity Hospital, Persistent, postnatal