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Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While 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 suffer death or significant impairments. There is therefore a critical 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 whether these interventions have additional benefits when used with TH. Although primary and delayed (secondary) brain injury starting in the latent phase after HI are major contributors to neurodisability, the very late evolving effects of tertiary brain injury likely require different interventions targeting neurorestoration. Clinical trials of seizure management and neuroprotection bundles are needed, in addition to current trials combining erythropoietin, stem cells, and melatonin with TH. Impact The widespread use of therapeutic hypothermia (TH) in the treatment of neonatal encephalopathy (NE) has reduced the associated morbidity and mortality. However, 30–50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. This review details the pathophysiology of NE along with the evidence for the use of TH and other beneficial neuroprotective strategies used in term infants. We also discuss treatment strategies undergoing evaluation at present as potential adjuvant treatments to TH in NE.

Therapeutic hypothermia (TH) has become the standard of care treatment to improve morbidity and mortality in infants with hypoxic-ischemic encephalopathy (HIE). Although TH has clearly proven to be beneficial, recent studies suggest optimization of respiratory management as an approach to prevent further damage and improve neurodevelopmental outcome. The ventilatory management of asphyxiated neonates presents a challenge because both the hypoxic insult and TH have an impact on respiratory functions. Although the danger of recurrence of hypocapnia is well recognized, a brief period of severe hyperoxia also can be detrimental to the previously compromised brain and have been shown to increase the risk of adverse neurodevelopmental outcomes. Therefore, judicious ventilatory management with rigorous monitoring is of particular importance in patients with HIE. In the present review, we provide an overview of the currently available evidence on pulmonary function, respiratory morbidities, and ventilation strategies in HIE and we highlight possible future research directions.

Background Neonatal neurocritical care (NNCC) is a rapidly advancing field with limited fellowship training available in locally developed, non-accredited programs. A standardized survey aimed to understand the training backgrounds of individuals practicing NNCC, the structure of existing clinical NNCC services/training programs, and suggested clinical competencies for new graduates. Methods We developed an anonymous survey electronically sent to members of societies related to NNCC. Using the survey results as a guide, we discuss a competence by design (CBD) curriculum as a complementary approach to traditional time-based training. Results There were 82 responses to the survey from 30 countries; 95% of respondents were physicians. Thirty-one (42%) institutions reported having an NNCC service, 24 (29%) individuals reported formal NNCC training, 81% reported “significant variability” across NNCC training programs, and 88% were both in favor of standardizing training programs and pursuing formal accreditation for NNCC in the next 5 years. Conclusions The survey results demonstrate international interest in standardizing NNCC training and development of an accreditation or certification process. We propose consideration of a CBD-type curriculum as a training approach to focus on the development of specific NNCC competencies, rather than assuming the acquisition of these competencies based on time as a surrogate. Impact Continued growth and development in the field of NNCC has led to increasing need for training programs suited to meet the diverse needs of trainees from varied backgrounds. We present the results of an international survey that assessed the structure of existing training programs and the priority areas in which graduates must demonstrate competence, highlighting the combination of CBD and time-based training as one approach to address these recommendations. The survey results support interest in translating published training competencies, existing expertise, and infrastructure across centers into a standardized curriculum for NNCC including certification opportunities.

In premature infants with an extremely low gestational age (ELGA, < 29 weeks GA), dysregulated changes in cerebral blood flow (CBF) are among the major pathogenic factors leading to germinal matrix/intraventricular hemorrhage (GM/IVH). Continuous monitoring of CBF can guide interventions to minimize the risk of brain injury, but there are no clinically standard techniques or tools for its measurement. We report the feasibility of the continuous monitoring of CBF, including measures of autoregulation, via diffuse correlation spectroscopy (DCS) in ELGA infants using CBF variability and correlation with scalp blood flow (SBF, served as a surrogate measure of systemic perturbations). In nineteen ELGA infants (with 9 cases of GM/IVH) monitored for 6–24 h between days 2–5 of life, we found a strong correlation between CBF and SBF in severe IVH (Grade III or IV) and IVH diagnosed within 72 h of life, while CBF variability alone was not associated with IVH. The proposed method is potentially useful at the bedside for the prompt assessment of cerebral autoregulation and early identification of infants vulnerable to GM/IVH.

Background and objective Hospitalized preterm infants experience reduced meaningful auditory exposures during a critical period of brain development. Music-based interventions (MBI) may be beneficial, though it remains unclear which stimuli optimally enhance infant stabilization. We investigated the relationship between three conceptually-different MBIs and short-term responses in hospitalized preterm infants. Study design This is a case-crossover pilot study including 21 preterm infants between 30 and 35 weeks postmenstrual age. Participants listened to three MBIs and ‘no music’; each condition was provided three times in random order. We monitored physiologic and behavioral parameters around each exposure and analyzed results using linear mixed models. Results Respiratory rates decreased after each MBI compared with ‘no music’ ( p  = 0.02). The most notable decrease occurred following exposure to a low, repetitive musical pattern resembling a lullaby ( p  = 0.01). We noted no significant changes for the remaining parameters. Conclusion Specific MBI characteristics may preferentially enhance physiologic stabilization in hospitalized preterm infants.

Preterm infants are exposed to frequent painful procedures and agitating stimuli over the many weeks of their hospitalization in the neonatal intensive care unit (NICU). The adverse neurobiological impact of pain and stress in the preterm infant has been well documented, including neuroimaging and neurobehavioral outcomes. Although many tools have been validated to assess acute pain, few methods are available to assess chronic pain or agitation (a clinical manifestation of neonatal stress). Both nonpharmacologic and pharmacologic approaches are used to reduce the negative impact of pain and agitation in the preterm infant, with concerns emerging over the adverse effects of analgesia and sedatives. Considering benefits and risks of available treatments, units must develop a stepwise algorithm to prevent, assess, and treat pain. Nonpharmacologic interventions should be consistently utilized prior to mild to moderately painful procedures. Sucrose may be utilized judiciously as an adjunctive therapy for minor painful procedures. Rapidly acting opioids (fentanyl or remifentanil) form the backbone of analgesia for moderately painful procedures. Chronic sedation during invasive mechanical ventilation represents an ongoing challenge; appropriate containment and an optimal environment should be standard; when indicated, low-dose morphine infusion may be utilized cautiously and dexmedetomidine infusion may be considered as an emerging adjunct.

As care of the most vulnerable infants in the neonatal intensive care unit (NICU) evolves, improved and real-time understanding of brain health becomes key. The availability of an in-NICU magnetic resonance imaging (MRI) scanner provides unique options to bedside care providers and researchers. We present our perspective on the 1-Tesla MRI unit in our NICU and its utilities and applications both in the clinical and research fields. We also discuss our experience with early and serial MRI in a cohort of infants with hypoxic-ischemic encephalopathy while undergoing therapeutic hypothermia, using a compatible cooling blanket and monitoring apparatus with special insight into the planning and organization between providers, and parental perspectives around early, detailed imaging.