Towards the “Baby Connectome”: Mapping the Structural Connectivity of the Newborn Brain

Defining the structural and functional connectivity of the human brain (the human “connectome”) is a basic challenge in neuroscience. Recently, techniques for noninvasively characterizing structural connectivity networks in the adult brain have been developed using diffusion and high-resolution anatomic MRI. The purpose of this study was to establish a framework for assessing structural connectivity in the newborn brain at any stage of development and to show how network properties can be derived in a clinical cohort of six-month old infants sustaining perinatal hypoxic ischemic encephalopathy (HIE). Two different anatomically unconstrained parcellation schemes were proposed and the resulting network metrics were correlated with neurological outcome at 6 months. Elimination and correction of unreliable data, automated parcellation of the cortical surface, and assembling the large-scale baby connectome allowed an unbiased study of the network properties of the newborn brain using graph theoretic analysis. In the application to infants with HIE, a trend to declining brain network integration and segregation was observed with increasing neuromotor deficit scores

Predictive Performance of a Gentamicin Population Pharmacokinetic Model in Neonates Receiving Full-Body Hypothermia

Population pharmacokinetic (popPK) models derived from small PK studies in neonates are often underpowered to detect clinically important characteristics that drive dosing. External validation of such models is crucial. In this study, the predictive performance of a gentamicin popPK model in neonates receiving hypothermia was evaluated

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The Neurointensive Care Nursery and Evolving Roles for Nursing

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 Neurointensive Care Nursery and Evolving Roles for Nursing.

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

Neonatal seizures and therapeutic hypothermia for hypoxic-ischemic encephalopathy.

Neonatal seizures are associated with morbidity and mortality. Hypoxic-ischemic encephalopathy (HIE) is the most common cause of seizures in newborns. Neonatal animal models suggest that therapeutic hypothermia can reduce seizures and epileptiform activity in the setting of hypoxia-ischemia, however data from human studies have conflicting results. In this research highlight, we will discuss the findings of our recent study that demonstrated a decreased seizure burden in term newborns with moderate HIE treated with hypothermia

Interdisciplinary approach to neurocritical care in the intensive care nursery.

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

Lower incidence of seizure among neonates treated with therapeutic hypothermia.

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

Every 36-h gentamicin dosing in neonates with hypoxic-ischemic encephalopathy receiving hypothermia

Objective:To examine the impact of a change in the empiric gentamicin dose from 5 mg kg -1 every 24 h (Q24 h period) to 5 mg kg every 36 h (Q36 h period) on target drug concentration achievement in neonates with hypoxic ischemic encephalopathy (HIE) recei

Outcome After Therapeutic Hypothermia in Term Neonates With Encephalopathy and a Syndromic Diagnosis.

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