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. 2025 Feb;114(2):428-436.
doi: 10.1111/apa.17457. Epub 2024 Nov 5.

Altered sleep and inflammation are related to outcomes in neonatal encephalopathy

Tim Hurley  1   2   3   4 , Philip Stewart  1   2   3 , Robert McCarthy  1   2   3 , Mary O'Dea  1   2   3   5   6 , Lynne Kelly  1   2   3 , Mandy Daly  4   7 , John Butler  8 , Rob McCarthy  1   2   3 , Jan Miletin  5 , Deirdre Sweetman  9 , Angela Byrne  10 , Gabrielle Colleran  11 , Megan Ni Bhroin  12   13 , Arun L W Bokde  14 , Eleanor J Molloy  1   2   3   4   5   6   13
Affiliations

Altered sleep and inflammation are related to outcomes in neonatal encephalopathy

Tim Hurley et al. Acta Paediatr. 2025 Feb.

Abstract

Aim: Immune dysregulation and delayed onset of sleep wake cycling (SWC) are associated with worse outcome in neonatal encephalopathy (NE), however the association between sleep and immune dysfunction in NE remains unclear. Aimed to evaluate association of sleep and systemic inflammation with outcomes in NE.

Methods: Amplitude-integrated electroencephalography (aEEG) recordings were collected on infants undergoing therapeutic hypothermia (TH). Duration to onset of (SWC) and sleep quality (SQ) were examined. Blood samples collected during the first 2 days of life. Thirteen pro- and anti-inflammatory serum cytokines were quantified. Adverse outcome defined as death or abnormal MRI brain.

Results: Earlier onset of SWC and better SQ had less adverse outcomes. SQ provided better prognostic value and showed better interobserver agreement compared to duration to SWC. Better SQ associated with lower cytokines EPO and interleukin (IL)-1β. In infants with unfavourable outcome, shorter duration to SWC was associated with higher EPO and better SQ was associated with lower TNF-α.

Conclusion: Earlier onset of SWC or better SQ showed less systemic inflammation and fewer adverse outcomes. SQ during TH provided better prognostic information than time of onset of SWC. Modulation of circadian rhythm in infants with NE may have an immunomodulatory role, leading to improved outcomes.

Keywords: brain injury; cytokines; inflammation; neonatal encephalopathy; neuroimaging; sleep.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Differences in time to sleep wake cycling (SWC) and sleep quality (SQ) in infants with neonatal encephalopathy and good outcome (survived & normal MRI) or adverse outcome (died or abnormal MRI) (n = 44). Differences between groups were significant in time to onset of SWC (p = 0.009) (A) with infants with adverse outcome taking longer to achieve SWC. Differences between groups were significant in SQ score (p = 0.002) (B) with infants with adverse outcome having lower SQ score.
FIGURE 2
FIGURE 2
Correlation between time to onset of sleep wake cycling (SWC) and MRI scoring systems in infants with neonatal encephalopathy. There is a significant positive correlation between longer time to onset of SWC and higher Barkovich score (p = 0.005, r s = 0.454) (A), NICHD (p = 0.001, r s = 0.526) (B) and de Vries scores (p = 0.001, r s = 0.536) (C).
FIGURE 3
FIGURE 3
Correlation between time to onset of sleep quality (SQ) and MRI scoring systems in infants with neonatal encephalopathy. There was a significant negative correlation between lower SQ score and higher Barkovich (p = <0.001, r s = −0.642) (A), NICHD (p = <0.001, r s = −0.688) (B) and de Vries scores (p = <0.001, r s = −0.658) (C).
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