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Background/Objectives: Motor deficits following neonatal brain injury, from cerebral palsy to subtle deficits in motor planning, are common yet underreported. Rodent models of motor deficits in neonatal hypoxia–ischemia (HI) allow improved understanding of the underlying mechanisms and neuroprotective strategies. Our goal was to test motor performance and learning in a mouse model of neonatal HI. Methods: We induced HI in postnatal day (p)10 C57/Bl6 mice through unilateral carotid ligation followed by 60 min of 8% oxygen exposure, or a sham procedure. At p30, we assessed complex motor performance and learning using the accelerating rotarod and complex running wheel tasks. Results: In the rotarod task, HI mice performed worse than sham mice, with shorter latencies to fall (n = 6 sham, 9 HI; day 1, p = 0.033; day 2, p = 0.013; day 3, p = 0.023). Sham mice demonstrated improved performance across days (p = 0.005), and HI mice did not (p = 0.44). During the simple running wheel task, we observed no difference in wheel rotation and speed between groups (n = 5/group; day 1, p = 0.67; day 4, p = 0.53). However, when navigating a wheel with a random pattern of spokes removed (complex task), HI mice took longer than sham mice to reach a plateau in performance (n = 5/group; day 1, p = 0.02; day 4, p = 0.77). Conclusions: Our findings demonstrate that young adult mice exposed to HI exhibit significant deficits and delayed learning in complex motor performance compared to sham mice. HI mice do not show deficits in gross motor performance; however, more subtle impairments are present in complex motor performance and learning. This HI model exhibits subtle motor deficits relevant to findings in humans and may be a useful tool in testing further neuroprotective strategies. [ABSTRACT FROM AUTHOR]

Objective Hypoxic–ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in neonates. Therapeutic hypothermia (TH) has improved outcomes and mortality in infants with >36 weeks' gestational age (GA) with moderate-to-severe HIE. There are limited data on the safety and efficacy of TH in preterm infants with HIE. This study describes our experience and examines the safety of TH in neonates with <36 weeks' GA. Study Design A single-center, retrospective study of preterm neonates born at <36 weeks' GA with moderate-to-severe HIE and treated with TH, compared to a cohort of term neonates with HIE (≥37 weeks' GA), was conducted. The term cohort was matched for degree of background abnormality on electroencephalogram, sex, inborn versus outborn status, and birth year. Medical records were reviewed for pregnancy and delivery complications, need for transfusion, sedation and antiseizure medications, electroencephalography and imaging findings, and in-hospital mortality. Results Forty-two neonates born at <36 weeks' GA with HIE received TH between 2005 and 2022. Data from 42 term neonates were analyzed for comparison. The average GA of the preterm cohort was 34.6 weeks and 39.3 weeks for the term cohort. Apgar scores, degree of acidosis, and need for blood product transfusions were similar between groups. Preterm infants were more likely to require inotropic support (55 vs. 29%, p = 0.026) and hydrocortisone (36 vs. 12%, p = 0.019) for hypotension. The proportion of infants without evidence of injury on magnetic resonance imaging was similar in both groups: 43 versus 50% in preterm and term infants, respectively. No significant difference was found in mortality between groups. Conclusion In this single-center cohort, TH in preterm infants appears to be as safe as in term infants, with no significant increase in intracranial bleeds or mortality. Preterm infants more frequently required inotropes and steroids for hypotension. Further research is needed to determine efficacy of TH in preterm infants. Key Points TH is used off-protocol in preterm infants. Preterm and term infants have similar mortality. Preterm cohort required more inotropic support. [ABSTRACT FROM AUTHOR]

Objective: To examine acute seizure activity and neuronal damage in a neonatal mouse model of inflammation-sensitized hypoxic-ischemic (IS-HI) brain injury utilizing continuous electroencephalography (cEEG) and neurohistology. Methods: Neonatal mice were exposed to either IS-HI with Escherichia coli lipopolysaccharide (LPS) or HI alone on postnatal (p) day 10 using unilateral carotid artery ligation followed by global hypoxia (n = 10 [5 female, 5 male] for IS-HI, n = 12 [5 female, 7 male] for HI alone). Video cEEG was recorded for the duration of the experiment and analyzed for acute seizure activity and behavior. Brain tissue was stained and scored based on the degree of neuronal injury in the hippocampus, cortex, and thalamus. Results: There was no significant difference in acute seizure activity among mice exposed to IS-HI compared to HI with regards to seizure duration (mean = 63 ± 6 seconds for HI vs mean 62 ± 5 seconds for IS-HI, p = 0.57) nor EEG background activity. Mice exposed to IS-HI had significantly more severe neural tissue damage at p30 as measured by neuropathologic scores (mean = 8 ± 1 vs 23 ± 3, p < 0.0001). Interpretation: In a neonatal mouse model of IS-HI, there was no significant difference in acute seizure activity among mice exposed to IS-HI compared to HI. Mice exposed to IS-HI did show more severe neuropathologic damage at a later age, which may indicate the presence of chronic inflammatory mechanisms of brain injury distinct from acute seizure activity. [ABSTRACT FROM AUTHOR]

Understanding the type and frequency of current neonatal intensive care unit (NICU) therapy services and predictors of referral for therapy services is a crucial first step to supporting positive long-term outcomes in very preterm infants. This study enrolled 83 very preterm infants (<32 weeks, gestational age mean 26.5 ± 2.0 weeks; 38 male) from a longitudinal clinical trial. Race, neonatal medical index, neuroimaging, and frequency of therapy sessions were extracted from medical records. The Test of Infant Motor Performance and the General Movement Assessment were administered. Average weekly sessions of occupational therapy, physical therapy, and speech therapy were significantly different by type, but the magnitude and direction of the difference depended upon the discharge week. Infants at high risk for cerebral palsy based on their baseline General Movements Assessment scores received more therapy sessions than infants at low risk for cerebral palsy. Baseline General Movements Assessment was related to the mean number of occupational therapy sessions but not physical therapy or speech therapy sessions. Neonatal Medical Index scores and Test of Infant Motor Performance scores were not predictive of combined therapy services. Medical and developmental risk factors, as well as outcomes from therapy assessments, should be the basis for referral for therapy services in the neonatal intensive care unit. [ABSTRACT FROM AUTHOR]

Characterize breast milk cell populations at the single cell level, determine the heterogeneity of its population and assess the proportion of cells that display stem cell features. Breast milk stem cells as a new source for stem cells therapy in neonatal brain injury B Cornaz Buros S b SP 1 sp , Fernandes Trigo N SP 3 sp , Steinlin M SP 1 sp , Schöberlein A SP 2 sp , Ganal S SP 3 sp , Klein A SP 1 sp I SP 1 sp Neuropediatrics, Kinderklinik, Inselspital, Bern, Switzerland, SP 2 sp Departement Geburtshilfe und Gynäkologie, Labor für Pränatale Medizin & Geburtshilfe und Feto-maternale Medizin, Inselspital, Bern, Switzerland, SP 3 sp Department for BioMedical Research, Inselspital, Bern, Switzerland i B BACKGROUND AND PURPOSE: b Human Breast milk is universally recognized as the best-adapted food for infants and toddlers. 2014; 5(6): 770-778. doi: 10.3945/an.114.006924 FGF21 therapy alters hippocampal CA2 proteins in a murine model of perinatal asphyxia B Jackson T b SP 1 sp , Herrmann J SP 2 sp , Gorse K SP 1 sp , Vagni V SP 2 sp , Janesko-Feldman K SP 2 sp , Kochanek P SP 2 sp I SP 1 sp USF Health Heart Institute, University Of South Florida, Tampa, United States, SP 2 sp Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, United States i B BACKGROUND/PURPOSE: b The cold-stress hormone fibroblast growth factor 21 (FGF21) is neuroprotective in the Rice-Vannucci model of perinatal asphyxia (PA) and improves long-term neurological outcome [1]. These cells would constitute ideal candidates for stem cell therapy in newborn but are still partly characterized. [Extracted from the article]

Infants born very preterm (VPT; ≤29 weeks of gestation) are at high risk of developmental disabilities and abnormalities in neural white matter characteristics. Early physical therapy interventions such as Supporting Play Exploration and Early Development Intervention (SPEEDI2) are associated with improvements in developmental outcomes. Six VPT infants were enrolled in a randomised clinical trial of SPEEDI2 during the transition from the neonatal intensive care unit to home over four time points. Magnetic resonance imaging scans and fixel-based analysis were performed, and fibre density (FD), fibre cross-section (FC), and fibre density and cross-section values (FDC) were computed. Changes in white matter microstructure and macrostructure were positively correlated with cognitive, motor, and motor-based problem solving over time on developmental assessments. In all infants, the greatest increase in FD, FC, and FDC occurred between Visit 1 and 2 (mean chronological age: 2.68–6.22 months), suggesting that this is a potential window of time to optimally support adaptive development. Results warrant further studies with larger groups to formally compare the impact of intervention and disparity on neurodevelopmental outcomes in infants born VPT. [ABSTRACT FROM AUTHOR]

Objective  Infants with a history of neonatal hypoxic-ischemic encephalopathy (HIE) are at risk for oral motor dysfunction. Previous studies have associated the need for gastrostomy tube at neonatal intensive care unit discharge with brainstem injury on magnetic resonance imaging (MRI). However, the factors associated with time to full oral feeds in this population have not been previously described. This study aimed to study factors associated with time to full oral feeds in this population. Study Design  This is a single-center, retrospective study that examined these factors using Cox regression. Results  A total of 150 infants who received therapeutic hypothermia from 2011 to 2017 were included in this study. The single clinical factor significantly associated with time to full oral feeds was the severity of background abnormality on electroencephalogram in the first 24 hours of age (severe vs. mild 95% confidence interval [CI]: 0.34–0.74; moderate vs. mild 95% CI: 0.19–0.45). Brainstem injury on MRI was the factor most highly associated with need for gastrostomy tube placement (p  = 0.028), though the overall incidence of need for gastrostomy tube feeds in this population was low (5%). Conclusion  These findings may help clinicians counsel families on what to expect in neonates with HIE and make decisions on the need for and timing to pursue gastrostomy tube in this population. Key Points The overall incidence of the need for assisted feeding at NICU discharge is low in this population. MRI brainstem injury was most highly associated with need for gastrostomy tube placement. Worsening severity of background abnormality on EEG was associated with longer time to oral feeds. [ABSTRACT FROM AUTHOR]

Cutaneous mucormycosis is a rare, often fatal fungal infection that most commonly affects patients with underlying immunosuppression but also can occur in premature neonates. We report the case of an extremely premature boy (<25 weeks) who developed primary cutaneous mucormycosis shortly after birth. Although surgical debridement has been a mainstay of treatment in combination with antifungal therapy, our patient was successfully treated with amphotericin B alone—the management only reported in three other cases to date. We present this case to highlight that prompt initiation of treatment with amphotericin B alone may be an appropriate alternative to surgical intervention, particularly in patients with non‐angioinvasive disease who are poor surgical candidates. [ABSTRACT FROM AUTHOR]

Objective: Evaluate longitudinal changes in brain microstructure and volumes in very preterm infants during the first year of life with and without intervention. Design: Descriptive pilot study. Methods: Five preterm infants in a three-arm clinical trial, one SPEEDI Early, two SPEEDI Late, and two usual care. Brain structural and diffusion MRI's were acquired within 72 hours after neonatal intensive care unit discharge (n = 5), three months post-baseline (n = 5), and six months post-baseline (n = 3). Fractional anisotropy (FA), Mean diffusivity (MD), and volume metrics were computed for five brain regions. Results: More than 60% of eligible participants completed 100% of the scheduled MRIs. FA and volume increased from baseline to six months across all brain regions. Rate of white matter volume change from baseline to six months was highest in SPEEDI Early. Conclusions: Non-sedated longitudinal MRI is feasible in very preterm infants and appears to demonstrate longitudinal changes in brain structure and connectivity. [ABSTRACT FROM AUTHOR]

Date Presented 03/21/24 Emotions around the neonatal intensive care unit (NICU) experience and transition home were explored. Fear was expressed equally for NICU and home, and happiness was discussed twice as often for home experiences. Professionals need to consider parent emotions during this period. Primary Author and Speaker: Audrey Kane Contributing Authors: Christine M. Spence, Corri Stuyvenberg, Rachel Gaston, Jennifer Burnsed, Karen D. Hendricks-Muñoz, Richard D. Stevenson, Stacey Dusing [ABSTRACT FROM AUTHOR]

Objective The aim of this project is to study the effect of a physical therapist intervention provided in the first months of life on developmental outcomes of infants born very preterm. Secondary aims are to investigate the impact of intervention timing on the efficacy and impact of the intervention on infants with and without cerebral palsy. Methods This study is a multisite longitudinal controlled trial comparing developmental outcomes from infants in the Supporting Play, Exploration, and Early Development Intervention (SPEEDI)_Late or SPEEDI_Early group to a usual care group. Settings are urban Urban and rural areas surrounding 2 academic medical centers. There will be 90 preterm infants enrolled in this study born at <29 weeks of gestation. SPEEDI is a developmental intervention provided by collaboration between a physical therapist and parent to support a child's motor and cognitive development. The primary outcome measure is the Bayley Scale of Infant and Toddler Development Cognitive and Gross Motor Scaled Scores. Secondary measures include behavioral coding of early problem solving skills, the Gross Motor Function Measure, and Test of Infant Motor Performance. Impact More than 270,000 infants are born very preterm in the United States each year, 50% of whom will have neurological dysfunction that limits their ability to keep pace with peers who are typically developing. This study is a step toward understanding the impact that intensive developmental intervention could have in this population in the first months of life. [ABSTRACT FROM AUTHOR]

We aimed to report our institution's experience with gabapentin therapy to manage agitation and pain in the neonatal intensive care unit (NICU) setting. This was a retrospective, single-center study of NICU patients admitted between January 2015 and December 2017, who received gabapentin. Data on neonatal agitation, pain, Neonatal Pain, Agitation and Sedation Scale (N-PASS) scores, neurosedative medications, and adverse events were collected. Gabapentin was initiated in 16 patients at a corrected gestational age of 44 weeks (range 36.2-75wks) for agitation (n=9), pain (n=6), and movement disorders (n=1). A neurological diagnosis was present in 13 patients. Neonatal agitation, pain, and N-PASS scores and the need for other neurosedatives were significantly decreased 14 days after treatment initiation. Gabapentin is well tolerated in neonates and infants; it is associated with decreased pain scores and decreased need for multiple neurosedative medications 2 weeks after initiation. WHAT THIS PAPER ADDS: Gabapentin is well tolerated in neonates and infants. Gabapentin decreases pain scores and the need for other neurosedative medications in neonates and infants. [ABSTRACT FROM AUTHOR]

Objective: To identify circuits active during neonatal hypoxic-ischemic (HI) seizures and seizure propagation using electroencephalography (EEG), behavior, and whole-brain neuronal activity mapping.Methods: Mice were exposed to HI on postnatal day 10 using unilateral carotid ligation and global hypoxia. EEG and video were recorded for the duration of the experiment. Using immediate early gene reporter mice, active cells expressing cfos were permanently tagged with reporter protein tdTomato during a 90-minute window. After 1 week, allowing maximal expression of the reporter protein, whole brains were processed, lipid cleared, and imaged with confocal microscopy. Whole-brain reconstruction and analysis of active neurons (colocalized tdTomato/NeuN) were performed.Results: HI resulted in seizure behaviors that were bilateral or unilateral tonic-clonic and nonconvulsive in this model. Mice exhibited characteristic EEG background patterns such as burst suppression and suppression. Neuronal activity mapping revealed bilateral motor cortex and unilateral, ischemic somatosensory cortex, lateral thalamus, and hippocampal circuit activation. Immunohistochemical analysis revealed regional differences in myelination, which coincide with these activity patterns. Astrocytes and blood vessel endothelial cells also expressed cfos during HI.Interpretation: Using a combination of EEG, seizure semiology analysis, and whole-brain neuronal activity mapping, we suggest that this rodent model of neonatal HI results in EEG patterns similar to those observed in human neonates. Activation patterns revealed in this study help explain complex seizure behaviors and EEG patterns observed in neonatal HI injury. This pattern may be, in part, secondary to regional differences in development in the neonatal brain. ANN NEUROL 2019;86:927-938. [ABSTRACT FROM AUTHOR]

Aim: Therapeutic hypothermia is standard of care in term infants with moderate-to-severe hypoxic-ischaemic encephalopathy (HIE). The goal of this survey was to explore the attitudes of U.S. neonatologists caring for infants with HIE who fall outside of current guidelines.Methods: Case-based survey administered to members of the Section on Neonatal-Perinatal Medicine of the American Academy of Pediatrics.Results: A total of 447 responses were analysed, a response rate of 19%. We found significant variability amongst U.S. neonatologists with regard to the use of therapeutic hypothermia for infants with HIE who fall outside standard inclusion criteria. Scenarios with the most variability included HIE in a late preterm infant and HIE following a postnatal code. Provision of therapeutic hypothermia outside of standard guidelines was not influenced by number of years in practice, neonatal intensive care type (NICU) or NICU size.Conclusion: Significant variability in practice exists when caring for infants with HIE who do not meet standard inclusion criteria, emphasizing the need for continued and rigorous research in this area. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia is standard of care for infants with hypoxic ischemic encephalopathy. Murine models of hypoxic-ischemic injury exist; however, a well-established mouse model of therapeutic hypothermia following hypoxic-ischemic injury is lacking. The goal of this study was to develop a full-term-equivalent murine model of therapeutic hypothermia after hypoxia-ischemia and examine magnetic resonance imaging, behavior, and histology in a region and sex specific manner. Hypoxic-ischemic injury was induced at postnatal day 10 in C57BL6 mice using a modified Vannucci model. Mice were randomized to control, hypothermia (31˚C for 4h), or normothermia (36˚C) following hypoxic-ischemic injury and stratified by sex. T2-weighted magnetic resonance imaging was obtained at postnatal day 18 and 30 and regional and total cerebral and cerebellar volumes measured. Behavioral assessments were performed on postnatal day 14, 21, and 28. On postnatal day 18, normothermic mice had smaller cerebral volumes (p < 0.001 vs. controls and p = 0.009 vs. hypothermia), while at postnatal day 30 both injured groups had smaller volumes than controls. When stratified by sex, only normothermia treated male mice had smaller cerebral volumes (p = 0.001 vs. control; p = 0.008 vs. hypothermia) at postnatal day 18, which persisted at postnatal day 30 (p = 0.001 vs. control). Female mice had similar cerebral volumes between groups at both day 18 and 30. Cerebellar volumes of hypothermia treated male mice differed from control at day 18, but not at 30. Four hours of therapeutic hypothermia in this murine hypoxic-ischemic injury model provides sustained neuroprotection in the cerebrum of male mice. Due to variable degree of injury in female mice, response to therapeutic hypothermia is difficult to discern. Deficits in female behavior tests are not fully explained by imaging measures and likely represent injury not detectable by volume measurements alone. [ABSTRACT FROM AUTHOR]