Elsevier

Clinics in Perinatology

Volume 43, Issue 3, September 2016, Pages 485-500
Clinics in Perinatology

Neonatal Encephalopathy: Update on Therapeutic Hypothermia and Other Novel Therapeutics

https://doi.org/10.1016/j.clp.2016.04.007Get rights and content

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Key points

  • Although limited in number, the available long-term follow-up studies of neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH) demonstrate sustained benefits through middle childhood.

  • Neonates with severe NE remain at high risk for death and disability despite treatment with TH, emphasizing the need for adjunctive neuroprotective treatments.

  • Clinical trials of erythropoietin neuroprotection have raised no safety concerns, and suggest that erythropoietin treatment

Clinical trials of the benefits of therapeutic hypothermia for neonatal encephalopathy

Numerous RCTs have investigated the benefit of TH for improving outcomes of newborns with NE.11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 TH methods for NE include whole body and selective head cooling, with both methods demonstrating similar effects regarding long-term neurologic outcomes based on metaanalysis.22

A recent Cochrane systematic metaanalysis review by Jacobs and colleagues23 included 11 RCTs, comprising 1505 term and late preterm infants with moderate to severe encephalopathy and

Erythropoietin

Erythropoietin (Epo), a glycoprotein originally identified for its role in erythropoiesis, has remarkable neuroprotective and reparative effects in the central nervous system.32, 33, 34, 35, 36, 37 Epo functions by binding to its homodimeric cell surface receptor. Epo receptors are expressed by multiple cell types in the central nervous system,38, 39 including neuronal progenitor cells,35 subsets of mature neurons,40 astrocytes,41 oligodendrocytes,41, 42, 43 microglia,44 and endothelial cells.35

Summary

Preventing NE related brain injury remains a monumental problem, because there is currently no way to predict whom NE will affect or when they will be affected. Although animal models often demonstrate effective prenatal pharmacologic treatments, this approach is often not feasible because NE is a postinjury event diagnosis. Whether safe and effective treatments (eg, melatonin) could be administered prophylactically to all pregnant mothers requires further investigation. Deciding which infants

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    • Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia

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      Citation Excerpt :

      Hypothermia is the only approved therapeutic intervention currently available to treat hypoxic ischemic encephalopathy (HIE) in newborn infants. However, this therapeutic modality is only partially protective (McAdams and Juul, 2016; Perrone et al., 2012; Shankaran, 2012; Shankaran et al., 2012), can only be used to treat full term infants who have been exposed to HIE (Shankaran, 2012; Shankaran et al., 2012) and cannot be used to treat premature infants with HI related brain injury. Although hypothermia has been shown to improve neurological outcomes in human neonates with moderate HIE, it has much more limited efficacy in infants exposed to severe HIE (Edwards et al., 2010; Xu et al., 2020).

    • FIRS: Neonatal considerations

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    • In clinical practice, cerebral MRI in newborns is highly predictive of neurodevelopmental outcome after therapeutic hypothermia

      2020, European Journal of Paediatric Neurology
      Citation Excerpt :

      Hypoxic ischaemic encephalopathy (HIE) remains an important cause of morbidity and mortality with an incidence of approximately 1.5 per 1000 live births [1]. Potential long term sequelae include cerebral palsy, and language and cognitive impairment [2]. Therapeutic hypothermia (TH) has been shown to be safe and effective in reducing death and disability in HIE survivors with numbers needed to treat of 7 [3].

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    The authors have no conflict of interest, financial support, or other potential conflicts of interest to declare.

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