Nearly all infants are exposed to repeated but usually short periods of compromised gas exchange before and during labor, and yet only a remarkably small proportion of newborns develop hypoxic–ischemic encephalopathy (HIE). Indeed, even severe metabolic acidosis at birth is associated with HIE in less than half of cases. Similarly, experimental studies typically report that cerebral injury occurs only in a very narrow temporal window between survival with complete recovery and death. In part, this reflects the remarkable efficacy of fetal adaptations that maintain perfusion to the essential organs. However, it also reflects a fine balance between injurious events triggered by hypoxia–ischemia and countervailing endogenous protective processes that help limit neural injury. These processes may be modified, raising the possibility of treating acute encephalopathy.

Birth asphyxia and the resulting neonatal encephalopathy (NE) in neonates remains a critical condition causing significant mortality and long-term morbidities, including cerebral palsy, epilepsy, and global developmental delay. The incidence of birth asphyxia is approximately 2–4 cases per 1,000 live births in high-income countries (HICs), and up to 30 per 1,000 live births in low- and middle-income countries (LMICs). Currently, therapeutic hypothermia (TH) is the only proven treatment for NE in HICs, but its role in LMICs remains debated. However, up to 29% of these treated neonates still develop abnormal outcome. Research on adjunct treatments is ongoing to improve the outcome of these neonates. In the meantime, to prevent or limit further brain injury, supportive therapies and maintenance of homeostasis remain a cornerstone of the daily management of these neonates.

We must consider how care in the NICU is delivered to improve outcomes for infants and their families. Cultures and practices that support brain maturation, aim to prevent injury, aid in recovery, support the role of the family, and optimize the environment are referred to as developmental, neuroprotective, or neuropromotive care models and are important strategies to optimize the neurodevelopment of vulnerable infants. Neurosupportive care and its full impact on the developing brain has been hard to define due to the range of approaches and confounding factors; therefore, it has been underfunded and underexplored. We review what is known, but there is urgent need for broader recognition of and investment into the many opportunities to improve our care models. We discuss evidence-based care practices that have been shown to impact developmental outcomes, including use of specific care contexts and cultures, a focus on partnerships with families, use of a multidisciplinary team, reduction of pain and stress, and enhancing the sensory environment. Paradigms that adopt an “All Care is Brain Care” approach, center families’ engagement and experience, and employ intentional brain-focused strategies to protect and promote brain development can create a neuroprotective care culture.

Acute hypoxic–ischemic brain injury occurring around the time of birth is a major cause of death and disability. The exact timing and the preceding course of events are often not known but play a crucial role in the pathogenesis, regional susceptibility, and injury severity in humans, requiring different treatment approaches. The dynamic nature of the developing brain requires the use of age-appropriate models to advance our understanding of both the injurious mechanisms and the means to ameliorate injury and enhance repair. Key factors that modulate the risk and pattern of injury to the immature brain caused by experimental hypoxia–ischemia or focal stroke in animals, include the brain maturity, blood flow regulation and energy metabolism, inflammation, and intracellular injury mechanisms and neuronal death. We will review emerging concepts in the cellular and molecular basis of injury, including the status of the neurovascular unit and blood–brain barrier, neuroinflammation, adaptive intracellular mechanisms, neuroprotection, growth factors and brain repair.

Prematurity is a major contributor to perinatal morbidity and mortality in the United States and around the world. This chapter highlights the prevalence, risk factors, and causes of preterm birth, provides a brief overview of the physiology of the preterm infant brain, and reviews current literature on preterm birth prevention strategies. We discuss the diagnostic approach for a pregnant person at risk of preterm birth, as well as how to best care for and safely transport the pregnant person or neonate to a tertiary care center. We also review fetal monitoring approaches, management of labor and delivery, and antenatal interventions to prevent neonatal brain injury including use of antenatal corticosteroids and magnesium sulfate.

Hypoxic–ischemic encephalopathy (HIE) is a form of brain damage in infants caused by reduced blood and oxygen supply to the brain, occurring in about 1–3 infants per 1,000 live term births in America and Western Europe. Damage can be mild, moderate, or severe and can cause death or long-term neurological, cognitive, and behavioral disabilities. Worldwide nearly 1 million infants die each year from HIE after perinatal asphyxia. Hypothermia (HT) is the only approved treatment for neonatal HIE in western countries. However, about one third of the infants who receive whole-body or head cooling still have moderate-to-severe impairments in executive, visuospatial, and motor functions, language, and emotional maturity years later. A better understanding of the process of neonatal brain degeneration and the mechanisms of HT neuroprotection and persistence of injury will help to develop additional therapeutics. We explore four key mechanistic aspects of neonatal brain injury to potentially catalyze progress: connectivity or connectomics; proteinopathy; cell death; and the proteasome. In this chapter we discuss these four aspects of neonatal brain injury and their possible interrelations.

Perinatal brain injury is a significant contributor to cerebral palsy, epilepsy, and other neurological disorders, occurring from 20 weeks’ gestation to 28 days postnatally. Approximately 40% of cases are associated with premature birth, whereas 11% result from acute intrapartum hypoxia–ischemia (HI). Despite improvements in neonatal care, the incidence remains stable, underscoring the need for better early detection methods. There is a critical “window of opportunity” for therapeutic intervention postinsult, with therapeutic hypothermia being the only established neuroprotective therapy for term infants. However, its efficacy is limited, as many infants continue to suffer disabilities despite treatment. The development of robust biomarkers is essential to identify infants at risk for significant brain injury and to evaluate the effectiveness of treatments. This chapter explores existing and novel biomarkers for assessing injury, determining treatability, and predicting long-term outcomes after HI, ultimately aiming to enhance management strategies for affected infants and improve prognostic abilities in clinical practice.

After the initial resuscitation of a depressed or encephalopathic infant, the extended management of the patient becomes critical in order to prevent or ameliorate secondary injury. There are many different management protocols that are acceptable, and it is not the intent of this chapter to review all used for the various conditions encountered in neonatal intensive care. Rather, we focus on the early transitional period following birth and resuscitation for both the premature and term infant, during which the condition of the depressed infant can be substantially improved by expert care.

Neonatal encephalopathy (NE) encompasses a range of disorders presenting with altered brain function in neonates, often leading to long-term neurodevelopmental deficits. Characterized by symptoms such as altered consciousness, poor tone, and seizures, NE occurs in 1–6 per 1,000 live term births and is a major cause of neurodevelopmental disabilities. Although many cases relate to hypoxic–ischemic injury, other causes include metabolic disorders, infections, and congenital anomalies. The introduction of therapeutic hypothermia (TH) has improved outcomes for infants with hypoxic–ischemic encephalopathy (HIE), significantly reducing the incidence of severe neurodevelopmental disabilities. However, variations in practices and results persist, and adjunct therapies such as erythropoietin have not shown effective benefits. The chapter discusses the spectrum of neurocognitive impairments following HIE, predictors of outcomes based on brain injury patterns, and highlights ongoing research to understand the long-term impact of these interventions on affected individuals.

This chapter provides an outline of the areas of paediatric intensive care relevant to an anaesthetist. The chapter examines current epidemiology in critical care and the characteristics of children requiring transfer from local hospitals to specialist centres. It reviews differences between adult and paediatric respiratory physiology, outlines an approach to medications used in intubation and discusses respiratory support for critically unwell children. The chapter provides key basic guidance on the use of high-frequency oscillatory ventilation (HFOV) in children. Maintenance fluid and inotrope selection are also reviewed. The chapter also reviews presentations commonly encountered on paediatric intensive care units (PICU) across respiratory, cardiovascular, gastrointestinal, renal, neurological, metabolic and infectious conditions. Neuroprotection criteria are provided, with key relevance to anaesthetists who may need to undertake time-critical transfers from their usual place of work to neurosurgical centres. Organ donation and non-accidental injury are also discussed.

Until recently, only five medicines have been approved for treatment of patients with Alzheimer’s disease (AD). Unfortunately, these agents offer just mild and temporary symptomatic improvement, without slowing progression of the disease itself. The Harrington Discovery Institute of University Hospitals Health System in Cleveland addresses this problem through a unique model that advances a diversified portfolio of new medicines for both treatment and prevention of AD. The institute identifies academic scientists in the USA, UK, and Canada who have made exceptionally innovative basic science discoveries related to AD and provides them with both financial support and critical programmatic direction. This latter contribution entails guidance and oversight from eminent drug developers whose collective expertise would normally only be available within a large pharmaceutical company. This enables academic scientists to bridge the “valley of death” between their scientific discoveries and development of medicines. As a result, HDI is bringing new medicines with novel mechanisms of action into the clinic for Alzheimer’s disease.