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Therapeutic hypothermia for hypoxic-ischemic encephalopathy after perinatal sentinel events: less brain injury on MRI and improved neurodevelopmental outcome at 18–36 months



To study the association between perinatal sentinel events (PSE) and brain MRI/neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH).


This is a retrospective single-center study. Data collection included perinatal history, brain MRI, and neurodevelopmental outcome.


Out of the 182 neonates, 53 (29%) neonates had PSE and 129 (71%) neonates did not have PSE. Neonates with PSE had more normal MRIs (76%) compared with neonates without PSE (55%), p = 0.01. PSE was associated with favorable motor (p = 0.02), language outcome (p = 0.03), and trend to better cognitive scores (p = 0.13). In PSE, favorable motor outcome persisted (OR for impairment 0.15 (0.003–0.84), p = 0.03) after adjusting for the degree of encephalopathy and brain MRI injury. Injury on brain MRI despite TH after PSE was associated with unfavorable neurodevelopmental outcome (p < 0.001).


Neonates with HIE receiving TH after PSE had less severe injury on brain MRI after rewarming, and improved motor and language outcomes at 18–36 months.

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Data availability

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.


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Author information




BG and AES made the conception and design of the study; they were responsible for acquisition of data, data analysis and interpretation, search and review of literature, and drafting of this paper. LGL, VC, HMB, SB, and DW helped with the acquisition of data, data interpretation, and critical review of this paper. KR performed all statistical analyses of the study and critically revised the paper. HW supervised conception and design of the study, data analysis and interpretation, search and review of literature, and critical review of this paper. All authors have read and approved the final paper.

Corresponding author

Correspondence to Beate Grass.

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The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

Data collection and evaluation for this study were approved by the Research and Ethics Board (REB) at The Hospital for Sick Children, Toronto, Canada, REB file number: 1000041535. Consent for publication is entailed in the approval. Written consent for the standard medical care given to the neonate as described in this observational study was obtained from the parents.

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Grass, B., El Shahed, A., Ly, L.G. et al. Therapeutic hypothermia for hypoxic-ischemic encephalopathy after perinatal sentinel events: less brain injury on MRI and improved neurodevelopmental outcome at 18–36 months. J Perinatol 40, 633–639 (2020).

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