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Children
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Neurological and Developmental Outcomes following Neonatal Encephalopathy
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Neurological and Developmental Outcomes following Neonatal Encephalopathy

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Neurology & Neurodevelopmental Disorders".

Deadline for manuscript submissions: closed (10 January 2025) | Viewed by 4698

Special Issue Editors

Dr. Kalpashri Kesavan

E-Mail Website
Guest Editor
Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Interests: developmental outcomes in NICU graduates; neonatal neuroprotection; neonatal sedation and analgesia
Dr. Jennifer Burnsed

E-Mail Website
Guest Editor
Department of Pediatrics, University of Virginia, Charlottesville, VA 22908-0386, USA
Interests: developmental outcomes in NICU graduates; neonatal neuroprotection; neonatal sedation and analgesia

Special Issue Information

Dear Colleagues,

Neonatal Encephalopathy (NE) is a clinical syndrome of disturbed neurologic function characterized by an altered level of consciousness, seizures, depressed tone and reflexes and disordered breathing control. NE remains one of the leading causes of neonatal morbidity and mortality in an infant ≥35 weeks of gestation. NE can occur as a result of a wide variety of antenatal, perinatal or genetic conditions. Broadly, maternal factors, genetic predisposition, placental abnormalities, hypoxic ischemic encephalopathy (HIE), infections, platelet and coagulation defects, and metabolic disorders have been implicated in the pathogenesis of NE.

An array of atypical developmental outcomes, such as cognitive deficits and motor deficits including cerebral palsy, can arise after NE. Therapeutic hypothermia remains the only effective evidence-based treatment of NE, especially the HIE subgroup. Early recognition of the underlying etiology of NE can help guide appropriate investigations, i.e., metabolic or sepsis or coagulopathy workups to ensure timely and optimal management. Furthermore, honing-in on the etiopathogenesis may aid in the development of targeted adjunctive therapies and develop preventative strategies that may have the potential to improve neurodevelopmental outcomes.

In this Special Issue, we aim to understand the different etiologies and pathogenesis of NE, early biomarkers of NE (clinical, laboratory and imaging studies) that may have therapeutic implications and later outcomes, preventative strategies and therapies that have the potential to modify neurodevelopmental outcomes in this vulnerable population.

We welcome original manuscripts, reviews and other types of papers on NE, early biomarkers of neurologic outcomes after NE, evidence-based diagnostic and management strategies for NE, neonatal seizure management, preventive strategies and promising adjunctive therapies to improve developmental outcomes after NE and lastly, short- and long-term outcomes after NE and developmental monitoring to optimize outcomes in this vulnerable population.

Dr. Kalpashri Kesavan
Dr. Jennifer Burnsed
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neonatal brain injury
  • neonatal seizures
  • hypoxic ischemic encephalopathy
  • therapeutic hypothermia
  • adjunctive therapies
  • developmental outcomes and early intervention

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Published Papers (3 papers)

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Research

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8 pages, 984 KiB  
Article
Motor Learning Deficits in a Neonatal Mouse Model of Hypoxic-Ischemic Injury
by Maria Marlicz, Weronika Matysik, Emily Zucker, Sarah Lee, Hannah Mulhern and Jennifer Burnsed
Children 2025, 12(1), 27; https://doi.org/10.3390/children12010027 - 27 Dec 2024
Viewed by 671
Abstract
Background/Objectives: Motor deficits following neonatal brain injury, from cerebral palsy to subtle deficits in motor planning, are common yet underreported. Rodent models of motor deficits in neonatal hypoxia–ischemia (HI) allow improved understanding of the underlying mechanisms and neuroprotective strategies. Our goal was to [...] Read more.
Background/Objectives: Motor deficits following neonatal brain injury, from cerebral palsy to subtle deficits in motor planning, are common yet underreported. Rodent models of motor deficits in neonatal hypoxia–ischemia (HI) allow improved understanding of the underlying mechanisms and neuroprotective strategies. Our goal was to test motor performance and learning in a mouse model of neonatal HI. Methods: We induced HI in postnatal day (p)10 C57/Bl6 mice through unilateral carotid ligation followed by 60 min of 8% oxygen exposure, or a sham procedure. At p30, we assessed complex motor performance and learning using the accelerating rotarod and complex running wheel tasks. Results: In the rotarod task, HI mice performed worse than sham mice, with shorter latencies to fall (n = 6 sham, 9 HI; day 1, p = 0.033; day 2, p = 0.013; day 3, p = 0.023). Sham mice demonstrated improved performance across days (p = 0.005), and HI mice did not (p = 0.44). During the simple running wheel task, we observed no difference in wheel rotation and speed between groups (n = 5/group; day 1, p = 0.67; day 4, p = 0.53). However, when navigating a wheel with a random pattern of spokes removed (complex task), HI mice took longer than sham mice to reach a plateau in performance (n = 5/group; day 1, p = 0.02; day 4, p = 0.77). Conclusions: Our findings demonstrate that young adult mice exposed to HI exhibit significant deficits and delayed learning in complex motor performance compared to sham mice. HI mice do not show deficits in gross motor performance; however, more subtle impairments are present in complex motor performance and learning. This HI model exhibits subtle motor deficits relevant to findings in humans and may be a useful tool in testing further neuroprotective strategies. Full article
(This article belongs to the Special Issue Neurological and Developmental Outcomes following Neonatal Encephalopathy)
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Review

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13 pages, 244 KiB  
Review
Sedation and Pain Management in Neonates Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy
by Artemiy Kokhanov and Peggy Chen
Children 2025, 12(2), 253; https://doi.org/10.3390/children12020253 - 19 Feb 2025
Viewed by 730
Abstract
Hypoxic-ischemic encephalopathy (HIE) is a common cause of significant neonatal morbidity and mortality. The stronghold of the treatment for moderate-to-severe HIE is therapeutic hypothermia (TH) which provides a neuroprotective effect. However, it also is associated with pain and stress. Moreover, neonates with HIE [...] Read more.
Hypoxic-ischemic encephalopathy (HIE) is a common cause of significant neonatal morbidity and mortality. The stronghold of the treatment for moderate-to-severe HIE is therapeutic hypothermia (TH) which provides a neuroprotective effect. However, it also is associated with pain and stress. Moreover, neonates with HIE are subjected to a significant number of painful procedures. Untreated pain during the early neonatal period may entail future challenges such as impaired brain growth and development as well as impaired pain sensitivity later in life. Hereby, the provision of adequate sedation and alleviation of pain and discomfort is essential. There are currently no universally accepted guidelines for sedation and pain management for this patient population. In this review, we highlight non-pharmacologic and pharmacologic methods currently in use to provide comfort and sedation to patients with HIE undergoing TH. Full article
(This article belongs to the Special Issue Neurological and Developmental Outcomes following Neonatal Encephalopathy)
13 pages, 289 KiB  
Review
Ultrasound Diagnosis and Near-Infrared Spectroscopy in the Study of Encephalopathy in Neonates Born under Asphyxia: Narrative Review
by Simeon N. Lavrentev, Anastasia S. Petrova, Olga F. Serova, Polina Vishnyakova, Maxim V. Kondratev, Anastasia S. Gryzunova, Nina I. Zakharova, Victor V. Zubkov and Denis N. Silachev
Children 2024, 11(5), 591; https://doi.org/10.3390/children11050591 - 14 May 2024
Viewed by 2486
Abstract
Brain injury resulting from adverse events during pregnancy and delivery is the leading cause of neonatal morbidity and disability. Surviving neonates often suffer long-term motor, sensory, and cognitive impairments. Birth asphyxia is among the most common causes of neonatal encephalopathy. The integration of [...] Read more.
Brain injury resulting from adverse events during pregnancy and delivery is the leading cause of neonatal morbidity and disability. Surviving neonates often suffer long-term motor, sensory, and cognitive impairments. Birth asphyxia is among the most common causes of neonatal encephalopathy. The integration of ultrasound, including Doppler ultrasound, and near-infrared spectroscopy (NIRS) offers a promising approach to understanding the pathology and diagnosis of encephalopathy in this special patient population. Ultrasound diagnosis can be very helpful for the assessment of structural abnormalities associated with neonatal encephalopathy such as alterations in brain structures (intraventricular hemorrhage, infarcts, hydrocephalus, white matter injury) and evaluation of morphologic changes. Doppler sonography is the most valuable method as it provides information about blood flow patterns and outcome prediction. NIRS provides valuable insight into the functional aspects of brain activity by measuring tissue oxygenation and blood flow. The combination of ultrasonography and NIRS may produce complementary information on structural and functional aspects of the brain. This review summarizes the current state of research, discusses advantages and limitations, and explores future directions to improve applicability and efficacy. Full article
(This article belongs to the Special Issue Neurological and Developmental Outcomes following Neonatal Encephalopathy)
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