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Encéfalo , Neuroimagen , Humanos , Recién Nacido , Neuroimagen/métodos , Encéfalo/diagnóstico por imagenRESUMEN
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.
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Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Unidades de Cuidado Intensivo Neonatal , Imagen por Resonancia Magnética , Neuroimagen , Humanos , Hipotermia Inducida/métodos , Recién Nacido , Imagen por Resonancia Magnética/métodos , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Neuroimagen/métodos , Sistemas de Atención de Punto , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria. METHODS: Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely. DISCUSSION: A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families. IMPACT: The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research. The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term 'Neonatal Encephalopathy'. A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience.
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OBJECTIVE: Identify feeding supports required among infants with neonatal encephalopathy and determine growth trajectories to 3 years. STUDY DESIGN: Single-center retrospective cohort study of 120 infants undergoing therapeutic hypothermia. Logistic regression and stratified analyses identified whether clinical factors, EEG-determined encephalopathy severity, and MRI-based brain injury predict feeding supports (nasogastric tube, oral feeding compensations) and growth. RESULTS: 50.8% of infants required feeding supports in the hospital, decreasing to 14% at discharge. Moderate-to-severe encephalopathy and basal ganglia injury predicted feeding support needs. Yet, 35% of mildly encephalopathic infants required gavage tubes. Growth trajectories approximated expected growth of healthy infants. CONCLUSION: Infants with neonatal encephalopathy-even if mild-frequently experience feeding difficulties during initial hospitalization. With support, most achieve full oral feeds by discharge and adequate early childhood growth. Clinical factors may help identify infants requiring feeding support, but do not detect all at-risk infants, supporting routine screening of this high-risk population.
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Nutrición Enteral , Hipotermia Inducida , Humanos , Recién Nacido , Hipotermia Inducida/métodos , Estudios Retrospectivos , Masculino , Femenino , Nutrición Enteral/métodos , Lactante , Imagen por Resonancia Magnética , Hipoxia-Isquemia Encefálica/terapia , Modelos Logísticos , Electroencefalografía , Intubación Gastrointestinal , Preescolar , Índice de Severidad de la EnfermedadRESUMEN
Neonatal meningoencephalitis caused by human parechovirus infection is being increasingly recognized in recent literature. While most cases are postnatally acquired, intrauterine infection is rare, presents early and has a more severe impact on brain health and development. We discuss here an infant born preterm at 34 weeks gestational age, with neonatal course remarkable for severe encephalopathy presenting on day 2 of life due to human parechovirus meningoencephalitis transmitted in utero. Early magnetic resonance brain imaging detected extensive white matter injury and subsequently evolved into multicystic leukoencephalopathy. Posthospital discharge, infant was noted to have early neurodevelopmental impairment at 4 months corrected age.
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Meningoencefalitis , Parechovirus , Infecciones por Picornaviridae , Humanos , Recién Nacido , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Recien Nacido Prematuro , Imagen por Resonancia Magnética/métodos , Meningoencefalitis/diagnóstico por imagen , Meningoencefalitis/patología , Neuroimagen , Infecciones por Picornaviridae/diagnóstico , Infecciones por Picornaviridae/patologíaRESUMEN
Infants born at an extremely low gestational age (ELGA, < 29 weeks) are at an increased risk of intraventricular hemorrhage (IVH), and there is a need for standalone, safe, easy-to-use tools for monitoring cerebral hemodynamics. We have built a multi-wavelength multi-distance diffuse correlation spectroscopy device (MW-MD-DCS), which utilizes time-multiplexed, long-coherence lasers at 785, 808, and 853â nm, to simultaneously quantify the index of cerebral blood flow (CBFi) and the hemoglobin oxygen saturation (SO2). We show characterization data on liquid phantoms and demonstrate the system performance on the forearm of healthy adults, as well as clinical data obtained on two preterm infants.
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Electroencephalogram (EEG) is an important biomarker for neonatal encephalopathy (NE) and has significant predictive value for brain injury and neurodevelopmental outcomes. Quantitative analysis of EEG involves the representation of complex EEG data in an objective, reproducible and scalable manner. Quantitative EEG (qEEG) can be derived from both a limited channel EEG (as available during amplitude integrated EEG) and multi-channel conventional EEG. It has the potential to enable bedside clinicians to monitor and evaluate details of cortical function without the necessity of continuous expert input. This is particularly useful in NE, a dynamic and evolving condition. In these infants, continuous, detailed evaluation of cortical function at the bedside is a valuable aide to management especially in the current era of therapeutic hypothermia and possible upcoming neuroprotective therapies. This review discusses the role of qEEG in newborns with NE and its use in informing monitoring and therapy, along with its ability to predict imaging changes and short and long-term neurodevelopmental outcomes. IMPACT: Quantitative representation of EEG data brings the evaluation of continuous brain function, from the neurophysiology lab to the NICU bedside and has a potential role as a biomarker for neonatal encephalopathy. Clinical and research applications of quantitative EEG in the newborn are rapidly evolving and a wider understanding of its utility is valuable. This overview summarizes the role of quantitative EEG at different timepoints, its relevance to management and its predictive value for short- and long-term outcomes in neonatal encephalopathy.
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Encefalopatías , Electroencefalografía , Humanos , Electroencefalografía/métodos , Recién Nacido , Encefalopatías/fisiopatología , Encefalopatías/terapia , Encefalopatías/diagnóstico , Hipotermia Inducida , Valor Predictivo de las Pruebas , Encéfalo/fisiopatología , Encéfalo/crecimiento & desarrollo , Pronóstico , BiomarcadoresRESUMEN
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.
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Estudios Cruzados , Recien Nacido Prematuro , Musicoterapia , Humanos , Proyectos Piloto , Recién Nacido , Masculino , Femenino , Musicoterapia/métodos , Frecuencia Respiratoria , MúsicaRESUMEN
OBJECTIVE: To evaluate the short-term outcomes and safety of therapeutic hypothermia (TH) for neonatal encephalopathy in preterm infants at 34-35 weeks of gestation. STUDY DESIGN: A matched retrospective cohort study of 20 preterm infants at 34-35 weeks of gestation and 40 infants at 36 weeks of gestation or more who received TH between the years 2015-2021. RESULT: Short-term outcomes of preterm infants at 34-35 weeks of gestation who received TH were comparable with infants at 36 weeks or more of gestation who received TH regarding seizures, intraventricular hemorrhage, blood transfusions, subcutaneous fat necrosis, brain injury on magnetic resonance imaging, and mortality. These findings were consistent when short-term outcomes were adjusted for birthweight. CONCLUSION: TH in preterm infants at 34-35 weeks of gestation is feasible and safe in our study population.
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Hipotermia Inducida , Enfermedades del Recién Nacido , Lactante , Recién Nacido , Humanos , Recien Nacido Prematuro , Edad Gestacional , Estudios Retrospectivos , Hemorragia Cerebral , Hipotermia Inducida/métodosRESUMEN
BACKGROUND: Neonatal encephalopathy (NE) continues to be a significant risk for death and disability. To address this risk, regional guidelines were developed with the support of a malpractice insurance patient safety organization. A NE registry was also established to include 14 centers representing around 50% of deliveries in the state of Massachusetts. The aim of this study was to identify areas of variation in practice that could benefit from quality improvement projects. METHODS: This manuscript reports on the establishment of the registry and the primary findings to date. RESULTS: From 2018 to 2020, 502 newborns with NE were evaluated for Therapeutic Hypothermia (TH), of which 246 (49%) received TH, representing a mean of 2.91 per 1000 live births. The study reports on prenatal characteristics, delivery room resuscitation, TH eligibility screening, and post-natal management of newborns with NE who did and did not receive TH. CONCLUSIONS: The registry has allowed for the identification of areas of variation in clinical practices, which have guided ongoing quality improvement projects. The authors advocate for the establishment of local and regional registries to standardize and improve NE patient care. They have made the registry data collection tools freely available for other centers to replicate this work. IMPACT: Malpractice insurance companies can take an active role in supporting clinicians in establishing clinical practice guidelines and regional registries. Establishing a collaborative regional neonatal encephalopathy (NE) registry is feasible. Data Collection tools for a NE registry have been made publicly available to be adopted and replicated by other groups. Establishing a regional NE registry allowed for the identification of gaps in knowledge, variations in practice, and the opportunity to advance care through quality improvement projects.
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Encefalopatías , Hipotermia Inducida , Enfermedades del Recién Nacido , Humanos , Recién Nacido , Encefalopatías/epidemiología , Encefalopatías/terapia , Enfermedades del Recién Nacido/terapia , Sistema de Registros , Massachusetts/epidemiologíaRESUMEN
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.
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Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Fármacos Neuroprotectores , Humanos , Recién Nacido , Fármacos Neuroprotectores/uso terapéutico , Neuroprotección , Lesiones Encefálicas/terapiaRESUMEN
BACKGROUND: Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH. METHODS: This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15). FINDINGS: Data quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (ß (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes. INTERPRETATION: Point of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE. FUNDING: This clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).