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OBJECTIVE: To study the association between the Sarnat exam (SE) performed before and after therapeutic hypothermia (TH) and outcomes at 2 years in infants with moderate or severe hypoxic-ischaemic encephalopathy (HIE). DESIGN: Secondary analysis of the High-dose Erythropoietin for Asphyxia and EncephaLopathy Trial. Adjusted ORs (aORs) for death or neurodevelopmental impairment (NDI) based on SE severity category and change in category were constructed, adjusting for sedation at time of exam. Absolute SE Score and its change were compared for association with risk for death or NDI using locally estimated scatterplot smoothing curves. SETTING: Randomised, double-blinded, placebo-controlled multicentre trial including 17 centres across the USA. PATIENTS: 479/500 enrolled neonates who had both a qualifying SE (qSE) before TH and a SE after rewarming (rSE). INTERVENTIONS: Standardised SE was used across sites before and after TH. All providers underwent standardised SE training. MAIN OUTCOME MEASURES: Primary outcome was defined as the composite outcome of death or any NDI at 22-36 months. RESULTS: Both qSE and rSE were associated with the primary outcome. Notably, an aOR for primary outcome of 6.2 (95% CI 3.1 to 12.6) and 50.3 (95% CI 13.3 to 190) was seen in those with moderate and severe encephalopathy on rSE, respectively. Persistent or worsened severity on rSE was associated with higher odds for primary outcome compared with those who improved, even when qSE was severe. CONCLUSION: Both rSE and change between qSE and rSE were strongly associated with the odds of death/NDI at 22-36 months in infants with moderate or severe HIE.

The survival of preterm infants has steadily improved thanks to advances in perinatal and neonatal intensive clinical care. The focus is now on finding ways to improve morbidities, especially neurological outcomes. Although antenatal steroids and magnesium for preterm infants have become routine therapies, studies have mainly demonstrated short-term benefits for antenatal steroid therapy but limited evidence for impact on long-term neurodevelopmental outcomes. Further advances in neuroprotective and neurorestorative therapies, improved neuromonitoring modalities to optimize recruitment in trials, and improved biomarkers to assess the response to treatment are essential. Among the most promising agents, multipotential stem cells, immunomodulation, and anti-inflammatory therapies can improve neural outcomes in preclinical studies and are the subject of considerable ongoing research. In the meantime, bundles of care protecting and nurturing the brain in the neonatal intensive care unit and beyond should be widely implemented in an effort to limit injury and promote neuroplasticity. IMPACT: With improved survival of preterm infants due to improved antenatal and neonatal care, our focus must now be to improve long-term neurological and neurodevelopmental outcomes. This review details the multifactorial pathogenesis of preterm brain injury and neuroprotective strategies in use at present, including antenatal care, seizure management and non-pharmacological NICU care. We discuss treatment strategies that are being evaluated as potential interventions to improve the neurodevelopmental outcomes of infants born prematurely.

BACKGROUND: An ancillary study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia examined the hypothesis that neonates randomized to receive erythropoietin (Epo) would have a lower seizure risk and burden compared with neonates who received placebo. METHODS: Electroencephalograms (EEGs) from 7/17 HEAL trial centers were reviewed. Seizure presence was compared across treatment groups using a logistic regression model adjusting for treatment, HIE severity, center, and seizure burden prior to the first dose. Among neonates with seizures, differences across treatment groups in median maximal hourly seizure burden were assessed using adjusted quantile regression models. RESULTS: Forty-six of 150 (31%) neonates had EEG seizures (31% in Epo vs 30% in placebo, p = 0.96). Maximal hourly seizure burden after the study drug was not significantly different between groups (median 11.4 for Epo, IQR: 5.6, 18.1 vs median 9.7, IQR: 4.9, 21.0 min/h for placebo). CONCLUSION: In neonates with HIE treated with hypothermia who were randomized to Epo or placebo, we found no meaningful between-group difference in seizure risk or burden. These findings are consistent with overall trial results, which do not support Epo use for neonates with HIE undergoing therapeutic hypothermia. IMPACT: In the HEAL trial of erythropoietin (Epo) vs placebo for neonates with encephalopathy presumed due to hypoxic-ischemic encephalopathy (HIE) who were also treated with therapeutic hypothermia, electrographic seizures were detected in 31%, which is lower than most prior studies. Epo did not reduce the proportion of neonates with acute provoked seizures (31% in Epo vs 30% in placebo) or maximal hourly seizure burden after the study drug (median 11.4, IQR 5.6, 18.1 for Epo vs median 9.7, IQR 4.9, 21.0 min/h for placebo). There was no anti- or pro-convulsant effect of Epo when combined with therapeutic hypothermia for HIE.

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.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). CONCLUSIONS: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

ObjectiveTo compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease.Study designThe Neonatal Seizure Registry is a multicenter, prospectively acquired cohort of neonates with clinical or electroencephalographic (EEG)-confirmed seizures. Cardiopulmonary disease was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous EEG monitoring strategy, seizure characteristics, seizure management, and outcomes for neonates with and without cardiopulmonary disease.ResultsWe evaluated 83 neonates with cardiopulmonary disease and 271 neonates without cardiopulmonary disease. Neonates with cardiopulmonary disease were more likely to have EEG-only seizures (40% vs 21%, P

ObjectiveTo evaluate the association of therapeutic hypothermia with magnetic resonance imaging (MRI) findings and 30-month neurodevelopment in term neonatal encephalopathy.Study designCross-sectional analysis of 30-month neurodevelopment (IQR 19.0-31.4) in a prospective cohort of mild-to-severe neonatal encephalopathy imaged on day 4 (1993-2017 with institutional implementation of therapeutic hypothermia in 2007). MRI injury was classified as normal, watershed, or basal ganglia/thalamus. Abnormal motor outcome was defined as Bayley-II psychomotor developmental index

Neuroimaging is widely used to aid in the diagnosis and clinical management of neonates with neonatal encephalopathy (NE). Yet, despite widespread use clinically, there are few published guidelines on neuroimaging for neonates with NE. This review outlines the primary patterns of brain injury associated with hypoxic-ischemic injury in neonates with NE and their frequency, associated neuropathological features, and risk factors. In addition, it provides an overview of neuroimaging methods, including the most widely used scoring systems used to characterize brain injury in these neonates and their utility as predictive biomarkers. Last, recommendations for neuroimaging in neonates with NE are presented.

ObjectiveTo determine whether screening continuous EEG monitoring (cEEG) is associated with greater odds of treatment success for neonatal seizures.MethodsWe included term neonates with acute symptomatic seizures enrolled in the Neonatal Seizure Registry (NSR), a prospective, multicenter cohort of neonates with seizures. We compared 2 cEEG approaches: (1) screening cEEG, initiated for indications of encephalopathy or paralysis without suspected clinical seizures; and (2) confirmatory cEEG, initiated for the indication of clinical events suspicious for seizures, either alone or in addition to other indications. The primary outcome was successful response to initial seizure treatment, defined as seizures resolved without recurrence within 30 minutes after initial loading dose of antiseizure medicine. Multivariable logistic regression analyses assessed the association between cEEG approach and successful seizure treatment.ResultsAmong 514 neonates included, 161 (31%) had screening cEEG and 353 (69%) had confirmatory cEEG. Neonates with screening cEEG had a higher proportion of successful initial seizure treatment than neonates with confirmatory cEEG (39% vs 18%; p < 0.0001). After adjusting for covariates, there remained a greater odds ratio (OR) for successful initial seizure treatment in the screening vs confirmatory cEEG groups (adjusted OR 2.44, 95% confidence interval 1.45-4.11, p = 0.0008).ConclusionsThese findings provide evidence from a large, contemporary cohort of neonates that a screening cEEG approach may improve odds of successful treatment of acute seizures.Classification of evidenceThis study provides Class III evidence that for neonates a screening cEEG approach, compared to a confirmatory EEG approach, increases the probability of successful treatment of acute seizures.

ObjectiveTo determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia.MethodsWe compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, "usual care" arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18-22 months adjusted for severity of HIE, center, and RCT.ResultsAmong 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86-3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92-4.53), respectively.ConclusionsPPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.

BACKGROUND: Neonatal seizures are associated with death and neurological morbidity; however, little is known about how neonates with seizures die. METHODS: This was a prospective, observational cohort study of neonates with seizures treated at seven sites of the Neonatal Seizure Registry. We characterized the mode of death, evaluated the association between infant characteristics and mode of death, and evaluated predictors of death or transfer to hospice. RESULTS: We enrolled 611 consecutive neonates with seizures, and 90 neonates (15%) died before hospital discharge at a median age of 11 days (range: 1 to 163 days); 32 (36%) died in the first postnatal week. An additional 19 neonates (3%) were transferred to hospice. The most common mode of in-hospital death was death after extubation amidst concerns for poor neurological prognosis, in the absence of life-threatening physiologic instability (n = 43, 48%). Only one infant died while actively receiving cardiopulmonary resuscitation. In an adjusted analysis, premature birth (odds ratio: 3.06, 95% confidence interval 1.59 to 5.90) and high seizure burden (odds ratio: 4.33, 95% confidence interval 1.88 to 9.95) were associated with increased odds of death or transfer to hospice. CONCLUSION: In a cohort of neonates with seizures, death occurred predominantly after decisions to withdraw or withhold life-sustaining intervention(s). Future work should characterize how these decisions occur and develop optimized approaches to support families and clinicians caring for newborns with seizures.

ObjectiveTo characterize and determine risk factors for key dimensions of well-being at hospital discharge in families of neonates with acute symptomatic seizures.Study designThis prospective, observational cohort study enrolled 144 parent-infant dyads among neonates with acute symptomatic seizures from 9 pediatric hospitals in the Neonatal Seizure Registry. One parent per family completed a discharge survey, which included measures of anxiety and depression, health-related quality of life, and impact on the family. Multivariable regression analyses adjusted for site were constructed to examine parent and infant characteristics associated with well-being.ResultsAt discharge, 54% of parents reported symptoms of anxiety and 32% reported symptoms of depression. Parents of infants with hypoxic-ischemic encephalopathy reported more depression and worse quality of life than parents of infants with other seizure etiologies. Parental quality of life was also lower with greater infant age at discharge. A higher level of maternal education was associated with greater impact on the family. All these differences were medium to large effect sizes, ranging from 0.52 to 0.78.ConclusionsSymptoms of anxiety and depression are common in parents of infants with neonatal seizures, and several parent and infant characteristics are associated with poorer parental quality of life and family well-being. These findings are a call to action to improve mental health screening and services for parents of infants with neonatal seizures.

In a prospective cohort of 534 neonates with acute symptomatic seizures, 66% had incomplete response to the initial loading dose of antiseizure medication (ASM). Treatment response did not differ by gestational age, sex, medication, or dose. The risk of incomplete response was highest for seizures due to intracranial hemorrhage and lowest for hypoxic-ischemic encephalopathy, although the difference was not significant after adjusting for high seizure burden and therapeutic hypothermia treatment. Future trial design may test ASMs in neonates with all acute symptomatic seizure etiologies and could target neonates with seizures refractory to an initial ASM.

BACKGROUND AND OBJECTIVES: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal morbidity and mortality. Therapeutic hypothermia (TH), a proven treatment of moderate-severe HIE, was first used clinically after 2006. We describe trends in HIE diagnosis and use of TH over a 10-year period in California. METHODS: We identified 62 888 infants, ≥36 weeks gestation, who were cared for in California Perinatal Quality Care Collaborative-participating NICUs between 2010 and 2019, and linked them to birth certificate data. We evaluated trends in HIE diagnosis and use of TH. RESULTS: Over time, rates of HIE diagnosis increased from 0.6 to 1.7 per 1000 live births, and use of TH increased from 26.5 to 83.0 per 1000 infants. Rates of moderate HIE increased more than mild or severe, although use of TH for mild HIE increased more than for moderate. Of those with moderate-severe HIE, 25% remain untreated. Treatment varied by NICU level of care. CONCLUSIONS: The rates of HIE and TH increased steadily. Some infants with moderate-severe HIE remain untreated, suggesting a need for ongoing education. Further evaluation of systems of care is needed to assure all qualifying infants are treated. [ABSTRACT FROM AUTHOR]

OBJECTIVE:To determine the characteristics of term infants with persistent pulmonary hypertension of the newborn (PPHN) associated with moderate or severe hypoxic ischemic encephalopathy (HIE). METHODS:We compared infants with and without PPHN enrolled in 2 randomized trials of therapeutic hypothermia: the induced hypothermia trial of cooling to 33.5°C for 72 hours vs normothermia, and the "usual-care" arm (33.5°C for 72 hours) of the optimizing cooling trial. RESULTS:Among 303 infants with HIE from these 2 studies, 67 (22%) had PPHN and 236 (78%) did not. We compared infants with PPHN with those without PPHN. The proportion of patients treated with therapeutic hypothermia was similar in PPHN and no-PPHN groups (66% vs 65%). Medication use during resuscitation (58% vs 44%), acidosis after birth (pH: 7.0 ± 0.2 vs 7.1 ± 0.2), severe HIE (43% vs 28%), meconium aspiration syndrome (39% vs 7%), pulmonary hemorrhage (12% vs 3%), culture-positive sepsis (12% vs 3%), systemic hypotension (65% vs 28%), inhaled nitric oxide therapy (64% vs 3%), and extracorporeal membrane oxygenation (12% vs 0%) were more common in the PPHN group. Length of stay (26 ± 21 vs 16 ± 14 days) and mortality (27% vs 16%) were higher in the PPHN group. CONCLUSIONS:PPHN is common among infants with moderate/severe HIE and is associated with severe encephalopathy, lung disease, sepsis, systemic hypotension, and increased mortality. The prevalence of PPHN was not different between those infants receiving therapeutic hypothermia at 33.5°C in these 2 trials (44/197 = 22%) compared with infants receiving normothermia in the induced hypothermia trial (23/106 = 22%).

BACKGROUND: The purpose of this study was to characterize seizures among preterm neonates enrolled in the Neonatal Seizure Registry, a prospective cohort of consecutive neonates with seizures at seven pediatric centers that follow the American Clinical Neurophysiology Societys neonatal electroencephalography monitoring guideline. STUDY DESIGN: Of 611 enrolled neonates with seizures, 92 (15%) were born preterm. Seizure characteristics were evaluated by gestational age at birth for extremely preterm (

This study aimed to characterize the circumstances of death in encephalopathic neonates treated with therapeutic hypothermia. Patients who died after or during treatment with therapeutic hypothermia between 2007-2014 were identified. Patient circumstance of death was characterized using an established paradigm. Thirty-one of 229 patients died (14%) at a median of 3 days of life. Most who died were severely encephalopathic on examination (90%) and had severely abnormal electroencephalographic (EEG) findings (87%). All those who had magnetic resonance images (n = 13) had evidence of moderate-severe brain injury; 6 had near-total brain injury. Cooling was discontinued prematurely in 61% of patients. Most patients (90%) were physiologically stable at the time of death; 81% died following elective extubation for quality of life considerations. Three patients (10%) died following withholding or removal of artificial hydration and nutrition. Characterization of death in additional cohorts is needed to identify differences in decision making practices over time and between centers.

We aimed to define determinants of duration of treatment for acute symptomatic neonatal seizures in a contemporary multicenter observational cohort study. After adjustment for potential confounders, only study site and seizure etiology remained significantly associated with the chance of continuing antiseizure medication after discharge to home.

ObjectiveTo determine the contemporary etiology, burden, and short-term outcomes of seizures in neonates monitored with continuous video-electroencephalogram (cEEG).Study designWe prospectively collected data from 426 consecutive neonates (56% male, 88% term) ≤44 weeks' postmenstrual age with clinically suspected seizures and/or electrographic seizures. Subjects were assessed between January 2013 and April 2015 at 7 US tertiary care pediatric centers following the guidelines of the American Clinical Neurophysiology Society for cEEG for at-risk neonates. Seizure etiology, burden, management, and outcome were determined by chart review by the use of a case report form designed at study onset.ResultsThe most common seizure etiologies were hypoxic-ischemic encephalopathy (38%), ischemic stroke (18%), and intracranial hemorrhage (11%). Seizure burden was high, with 59% having ≥7 electrographic seizures and 16% having status epilepticus; 52% received ≥2 antiseizure medications. During the neonatal admission, 17% died; 49% of survivors had abnormal neurologic examination at hospital discharge. In an adjusted analysis, high seizure burden was a significant risk factor for mortality, length of hospital stay, and abnormal neurological examination at discharge.ConclusionsIn this large contemporary profile of consecutively enrolled newborns with seizures treated at centers that use cEEG per the guidelines of the American Clinical Neurophysiology Society, about one-half had high seizure burden, received ≥2 antiseizure medications, and/or died or had abnormal examination at discharge. Greater seizure burden was associated with increased morbidity and mortality. These findings underscore the importance of accurate determination of neonatal seizure frequency and etiology and a potential for improved outcome if seizure burden is reduced.

ObjectiveTo determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy.MethodsIn a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar

Neonatal neurocritical care is an emerging subspecialty that combines the expertise of critical care medicine and neurology with that of nursing and other providers in an interprofessional team approach to care. Neurocritical care of the neonate has roots in adult and pediatric practice. It has been demonstrated that adults with acute neurologic conditions who are treated in a specialized neurocritical care unit have reduced morbidity and mortality, as well as decreased length of stay, lower costs, and reduced need for neurosurgical procedures. In pediatrics, neurocritical care has focused on various primary and secondary neurologic conditions complicating critical care that also contribute to mortality, morbidity, and duration of hospitalization. However, the concept of neurocritical care as a subspecialty in pediatric practice is still evolving, and evidence demonstrating improved outcomes is lacking. In the neonatal intensive care nursery, neurocritical care is also evolving as a subspecialty concept to address both supportive and preventive care and optimize neurologic outcomes for an at-risk neonatal patient population. To enhance effectiveness of this care approach, nurses must be prepared to appropriately recognize acute changes in neurologic status, implement protocols that specifically address neurologic conditions, and carefully monitor neurologic status to help prevent secondary injury. The complexity of this team approach to brain-focused care has led to the development of a specialized role: the neurocritical care nurse (neonatal intensive care nursery [NICN] nurse). This article will review key concepts related to neonatal neurocritical care and the essential role of nursing. It will also explore the emerging role of the NICN nurse in supporting early recognition and management of at-risk infants in this neonatal subspecialty practice.

The large randomized, controlled trials of therapeutic hypothermia for hypoxic-ischemic encephalopathy excluded neonates with congenital disorders. The objective of this study was to report our experience using hypothermia in neonates with signs of hypoxic-ischemic encephalopathy and a syndromic disorder or brain anomaly. Subjects were identified from a database of neonates admitted to the Neuro-Intensive Care Nursery at University of California, San Francisco. Of 169 patients fulfilling criteria for hypothermia, 8 (5%) had a syndromic disorder and were cooled per guidelines for nonsyndromic neonates. Perinatal characteristics of infants with and without syndromic disorder were not significantly different. Overall outcome was poor: 38% had evidence of acute hypoxic-ischemic injury, 3 subjects died, and 2 survivors had low developmental quotient (ie, 25). The risk versus benefit of therapeutic hypothermia for hypoxic-ischemic encephalopathy among neonates with congenital brain malformations or syndromic diagnoses is uncertain.

This cohort study examines medication use in term neonates with hypoxic-ischemic encephalopathy and seizures before and after implementation of a Neonatal Neurocritical Care Service (N = 108), which included increased seizure monitoring. Nearly all neonates received phenobarbital (96% pre- vs 95% post-Neonatal Neurocritical Care Service) and total loading dose did not vary among groups (33 [95% confidence interval 29-37] vs 30 [26-34] mg/kg). After adjustment for seizure burden, neonates managed during the Neonatal Neurocritical Care Service era, on average, received 30 mg/kg less cumulative phenobarbital (95% confidence interval 15-46 mg/kg) and were on maintenance 5 fewer days (95% confidence interval 3-8 days) than those who were treated prior to implementation of the service. In spite of the enhanced ability to detect seizures because of improved monitoring and increased vigilance by bedside practitioners, implementation of the Neonatal Neurocritical Care Service was associated with decreased use of potentially harmful phenobarbital treatment among neonates with hypoxic-ischemic encephalopathy.

ObjectivesTo determine the rate of magnetic resonance imaging (MRI)-detected noncystic white matter injury (WMI) in a prospective cohort of premature newborns, and to evaluate its associations with changes in clinical predictors of WMI over the study period.Study designA prospective cohort of premature newborns (

Neurocritical care is a multidisciplinary subspecialty that combines expertise in critical care medicine, neurology, and neurosurgery, and has led to improved outcomes in adults who have critical illnesses. Advances in resuscitation and critical care have led to high rates of survival among neonates with life-threatening conditions such as perinatal asphyxia, extreme prematurity, and congenital malformations. The sequelae of neurologic conditions arising in the neonatal period include lifelong disabilities such as cerebral palsy and epilepsy, as well as intellectual and behavioral disabilities. Centers of excellence have adapted the principles of neurocritical care to reflect the needs of the developing newborn brain, including early involvement of a neurologist for recognition and treatment of neurologic conditions, attention to physiology to help prevent secondary brain injury, a protocol-driven approach for common conditions like seizures and hypoxic-ischemic encephalopathy, and education of specialized teams that use brain monitoring and imaging to evaluate the effect of critical illness on brain function and development.

Animal studies suggest that hypothermia decreases seizure burden, whereas limited human data are inconclusive. This retrospective cohort study examines the relationship between therapeutic hypothermia and seizure in neonates with hypoxic-ischemic encephalopathy. Our center admitted 224 neonates from July 2004 to December 2011 who met institutional cooling criteria. Seventy-three neonates were born during the pre-cooling era, prior to November 2007, and 151 were born during the cooling era. Among neonates with moderate encephalopathy, the incidence of seizure in cooled infants was less than half the incidence in those not cooled (26% cooling, 61% pre-cooling era; risk ratio = 0.43, 95% confidence interval = 0.30-0.61). Among neonates with severe encephalopathy, there was no difference in the incidence (83% vs. 87%; risk ratio = 1.05, 95% confidence interval = 0.78-1.39). These results support animal data and suggest a mechanism by which neonates with moderate encephalopathy can benefit more from cooling than neonates with severe encephalopathy.

BackgroundErythropoietin is neuroprotective in animal models of neonatal hypoxic-ischemic encephalopathy. We previously reported a phase I safety and pharmacokinetic study of erythropoietin in neonates. This article presents the neurodevelopmental follow-up of infants who were enrolled in the phase I clinical trial.MethodsWe enrolled 24 newborns with hypoxic-ischemic encephalopathy in a dose-escalation study. Patients received up to six doses of erythropoietin in addition to hypothermia. All infants underwent neonatal brain magnetic resonance imaging (MRI) reviewed by a single neuroradiologist. Moderate-to-severe neurodevelopmental disability was defined as cerebral palsy with Gross Motor Function Classification System levels III-V or cognitive impairment based on Bayley Scales of Infant Development II mental developmental index or Bayley III cognitive composite score.ResultsOutcomes were available for 22 of 24 infants, at mean age 22 months (range, 8-34 months). There were no deaths. Eight (36%) had moderate-to-severe brain injury on neonatal MRI. Moderate-to-severe disability occurred in one child (4.5%), in the setting of moderate-to-severe basal ganglia and/or thalamic injury. Seven infants with moderate-to-severe watershed injury exhibited the following outcomes: normal (three), mild language delay (two), mild hemiplegic cerebral palsy (one), and epilepsy (one). All 11 patients with a normal brain MRI had a normal outcome.ConclusionsThis study is the first to describe neurodevelopmental outcomes in infants who received high doses of erythropoietin and hypothermia during the neonatal period. The findings suggest that future studies are warranted to assess the efficacy of this new potential neuroprotective therapy.

BackgroundPerinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy.MethodsThis study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index

OBJECTIVE: To assess the risk factors for electrographic seizures among neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). METHODS: Three-center observational cohort study of 90 term neonates treated with hypothermia, monitored with continuous video-EEG (cEEG) within the first day of life (median age at onset of recording 9.5 hours, interquartile range 6.3-14.5), and continued for >24 hours (total recording 93.3 hours, interquartile range 80.1-112.8 among survivors). A pediatric electroencephalographer at each site reviewed cEEGs for electrographic seizures and initial EEG background category. RESULTS: A total of 43 (48%) had electrographic seizures, including 9 (10%) with electrographic status epilepticus. Abnormal initial EEG background classification (excessively discontinuous, depressed and undifferentiated, burst suppression, or extremely low voltage), but not clinical variables (including pH

ObjectiveTo assess the risk factors for electrographic seizures among neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE).MethodsThree-center observational cohort study of 90 term neonates treated with hypothermia, monitored with continuous video-EEG (cEEG) within the first day of life (median age at onset of recording 9.5 hours, interquartile range 6.3-14.5), and continued for >24 hours (total recording 93.3 hours, interquartile range 80.1-112.8 among survivors). A pediatric electroencephalographer at each site reviewed cEEGs for electrographic seizures and initial EEG background category.ResultsA total of 43 (48%) had electrographic seizures, including 9 (10%) with electrographic status epilepticus. Abnormal initial EEG background classification (excessively discontinuous, depressed and undifferentiated, burst suppression, or extremely low voltage), but not clinical variables (including pH