Neonatal encephalopathy (NE) outcomes have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. Although TH for NE in term and near-term infants has proven beneficial, 30–50% of infants with moderate-to-severe NE treated with TH still mourn the death or substantial impairments. Thus there is an urgent need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children. There are many potential candidates; however, it is unclear if these interventions provide other benefits when used with TH. 

Despite the importance of primary and delayed (secondary) brain injury in contributing to neurodisability, the very late evolution of tertiary brain injury likely requires different neurorestorative interventions. In addition to current trials combining erythropoietin, stem cells, and melatonin with TH, clinical trials are needed for seizure management and neuroprotection bundles.

Molloy EJ, El-Dib M, Juul SE. et al. Neuroprotective therapies in the NICU in term infants: present and future. Pediatr Res. 2022. https://doi.org/10.1038/s41390-022-02295-2