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BackgroundMild hypoxic-ischemic encephalopathy (HIE) is increasingly recognized as a risk factor for neonatal brain injury. We examined the timing and pattern of brain injury in mild HIE.MethodsThis retrospective cohort study includes infants with mild HIE treated at 9 hospitals. Neonatal brain MRIs were scored by 2 reviewers using a validated classification system, with discrepancies resolved by consensus. Severity and timing of MRI brain injury (i.e., acute, subacute, chronic) was scored on the subset of MRIs that were performed at or before 8 days of age.ResultsOf 142 infants with mild HIE, 87 (61%) had injury on MRI at median age 5 (IQR 4-6) days. Watershed (23%), deep gray (20%) and punctate white matter (18%) injury were most common. Among the 125 (88%) infants who received a brain MRI at ≤8 days, mild (44%) injury was more common than moderate (11%) or severe (4%) injury. Subacute (37%) lesions were more commonly observed than acute (32%) or chronic lesions (1%).ConclusionSubacute brain injury is common in newborn infants with mild HIE. Novel neuroprotective treatments for mild HIE will ideally target both subacute and acute injury mechanisms.ImpactAlmost two-thirds of infants with mild HIE have evidence of brain injury on MRI obtained in the early neonatal period. Subacute brain injury was seen in 37% of infants with mild HIE. Neuroprotective treatments for mild HIE will ideally target both acute and subacute injury mechanisms.

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.).

IntroductionMRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms.Methods and analysisNeonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans.Ethics and disseminationIRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor.Trial registration numberNCT02811263; Pre-result.

Objective This study aimed to determine neonatal neurodevelopmental follow-up (NDFU) practices across academic centers. Study Design This study was a cross-sectional survey that addressed center-specific neonatal NDFU practices within the Children's Hospitals Neonatal Consortium (CHNC). Results Survey response rate was 76%, and 97% of respondents had a formal NDFU program. Programs were commonly staffed by neonatologists (80%), physical therapists (77%), and nurse practitioners (74%). Median gestational age at birth identified for follow-up was ≤32 weeks (range 26–36). Median duration was 3 years (range 2–18). Ninety-seven percent of sites used Bayley Scales of Infant and Toddler Development, but instruments used varied across ages. Scores were recorded in discrete electronic data fields at 43% of sites. Social determinants of health data were collected by 63%. Care coordination and telehealth services were not universally available. Conclusion NDFU clinics are almost universal within CHNC centers. Commonalities and variances in practice highlight opportunities for data sharing and development of best practices. Key Points Neonatal NDFU clinics help transition high-risk infants home. Interdisciplinary neonatal intensive care unit follow-up brings together previously separated outpatient service lines. This study reviews the current state of neonatal NDFU in North America. [ABSTRACT FROM AUTHOR]

Objective Infants with neonatal opioid withdrawal syndrome (NOWS) have disrupted neurobehavior that requires hospitalization and treatment. This article aimed to evaluate electroencephalography (EEG) abnormalities using amplitude-integrated EEG (aEEG) in NOWS. Study Design Eighteen term born infants with NOWS were recruited prospectively for an observational pilot study. aEEG monitoring was started within 24 hours of recruitment and twice weekly through discharge. aEEG data were analyzed for background and seizures. Severity of withdrawal was monitored using the modified Finnegan scoring (MFS) system. Results Fifteen neonates had complete datasets. Thirteen (87%) had continuous aEEG background in all recordings. None had sleep–wake cyclicity (SWC) at initial recording. Brief seizures were noted in 9 of 15 (60%) infants. Lack of SWC was associated with higher MFS scores. At discharge, 8 of 15 (53%) had absent or emerging SWC. Conclusion aEEG abnormalities (absent SWC) are frequent and persist despite treatment at the time of discharge in the majority of patients with NOWS. Brief electrographic seizures are common. Neonates with persistent aEEG abnormalities at discharge warrant close follow-up. Key Points EEG abnormalities are common and persist after clinical signs resolve in patients with NOWS. Short subclinical seizures may be seen. aEEG may identify neonates who need follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Comprehensive genetic testing with whole-exome (WES) or whole-genome (WGS) sequencing facilitates diagnosis, can optimize treatment, and may improve outcomes in critically ill neonates, including those requiring extracorporeal membrane oxygenation (ECMO) for respiratory failure. Our objective was to describe practice variation and barriers to the utilization of comprehensive genetic testing for neonates on ECMO. Methods: We performed a cross-sectional survey of Level IV neonatal intensive care units in the United States across the Children's Hospitals Neonatal Consortium (CHNC). Results: Common indications for WES and WGS included concerning phenotype, severity of disease, unexpected postnatal clinical course, and inability to wean from ECMO support. Unexpected severity of disease on ECMO was the most common indication for rapid genetic testing. Cost of utilization was the primary barrier to testing. If rapid WES or WGS were readily available, 63% of centers would consider incorporating universal screening for neonates upon ECMO cannulation. Conclusion: Despite variation in the use of WES and WGS, universal testing may offer earlier diagnosis and influence the treatment course among neonates on ECMO. Cost is the primary barrier to utilization and most centers would consider incorporating universal screening on ECMO if readily available. [ABSTRACT FROM AUTHOR]