Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Neuroprotective Therapeutic Hypothermia

Acknowledgments Our work reported in this chapter is supported by the Health Research Council of New Zealand, the National Institutes of Health, the Lottery Health Board of New Zealand, the Auckland Medical Research Foundation, and the Neurological Foundation of New Zealand. Introduction Moderate to severe hypoxic-ischemic encephalopathy (HIE) continues to be a significant cause of acute neurologic injury at birth, occurring in approximately 1 to 2…

Cellular and Molecular Mechanisms of Neonatal Brain Injury and Neuroprotection

Acknowledgments We thank Drs. Billie Short, Nickie Andescavage, and Nneka Nzegwu (Division of Neonatology, Children’s National Hospital); Dr. Taeun Chang (Neonatal Neurology Program, Division of Epilepsy, Neurophysiology & Critical Care, Children’s National Hospital); and Dr. Hideo Jinno (Center for Neuroscience Research, Children’s National Hospital and Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences) for critically reading this chapter. The research program…

Pathophysiology of Neonatal White Matter Injury

White Matter Injury in the Preterm Neonate Preterm birth is a major public health issue affecting an estimated 13 million babies worldwide; one in eight deliveries in the United States are now preterm. Over the past two decades, improved neonatal intensive care unit (NICU) therapies have reduced the mortality and increased the survival of preterm newborns. Despite these advances in neonatal intensive care, preterm birth remains…

Intraventricular Hemorrhage in the Neonate

Introduction Germinal matrix hemorrhage–intraventricular hemorrhage (IVH) is the commonest form of intracranial hemorrhage in the newborn and is characteristic of the premature infant. The incidence of IVH in premature infants was documented to decline from very high rates of 34% to 49% in the 1970s to approximately 20% in the late 1980s. , There has also been a modest reduction in the rates of severe IVH…

Electroencephalography in the Preterm and Term Infant

Introduction Despite the evolution of new technologies for assessing neonatal brain function, electroencephalography (EEG) remains one of the most valuable diagnostic and prognostic tools. It is considered the gold standard for distinguishing epileptic seizures from nonepileptic paroxysmal events and for detecting subclinical seizure activity in high-risk babies. In babies who are severely ill, EEG is a more efficient predictive test than the neurologic examination. Background patterns,…

Cerebellar Development—The Impact of Preterm Birth and Comorbidities

Introduction It is well known that preterm birth is associated with increased risks of brain injury and impaired brain development resulting in impairments in motor, cognitive, and behavioral function. However, the focus has traditionally been on brain injury patterns in the cerebrum, such as intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). In recent years, it has become evident that the cerebellum is another major target for…

Developmental Aspects of Pain

Acknowledgments Ruth Grunau’s research is supported by the Canadian Institute of Health Research (CIHR) and a Senior Scientist salary award from the BC Children’s Hospital Research Institute. Simon Beggs’ research is supported by the Medical Research Council (MRC, UK) and National Institute of Academic Anaesthesia (NIAA). Introduction Pain is an intrinsic experience which is processed early in life by the maturing nervous system. However, for an…

Trophic Factor, Nutritional, and Hormonal Regulation of Brain Development

Introduction This chapter reviews advances in our understanding of the roles of neurotrophic proteins, retinoids, folate, lipids, and thyroid and steroid hormones in neural development. These molecules play central roles in the regulation of neuronal and glial lineages; when they are not maintained at optimal levels in the developing nervous system, neural structural abnormalities and permanent neurologic dysfunction may result. For example, maternal folate deficiency increases…

Development of the Blood-Brain Barrier

Acknowledgments Some of the work on which this chapter is based was supported by National Institutes of Health (NIH) grants R01-HD34618 and 1R01-HD-057100. Introduction The blood-brain barrier (BBB) is a selective diffusion barrier that maintains central nervous system (CNS) homeostasis and limits the entry of substances that could potentially alter neuronal function. The main anatomic substrate of the BBB is the specialized cerebral microvascular endothelium. It…

Mechanisms of Cell Death in the Developing Brain

Introduction When the brain is exposed to stress, a number of adaptive responses can act to reestablish homeostasis. However, when the stress is severe and/or the endogenous protective processes are not sufficiently effective, the cell will die. , Cell death can be initiated by numerous organelles (e.g., nucleus, mitochondrion, endoplasmic reticulum/lysosome, cytoskeleton, plasma membrane) and mitochondria, in particular, play a key role in the initiation and…

Development of the Nervous System

Introduction The human brain arises from a restricted population of embryonic cells to become the most complex organ system known during the brief 280 days of human gestation. The newborn brain is comprised of billions of neurons and glia arranged and interconnected in an exquisitely precise three-dimensional network. Unfortunately, minor changes have profound implications for postnatal development and function. Overlapping genetic and epigenetic events during neurodevelopment…

Neonatal Pulmonary Host Defense

Introduction Like the skin and gastrointestinal (GI) tract, the lung is a mucosal organ with a large surface area exposed to the external environment. Unlike the skin and GI tract, the lung is considered to be largely sterile below the glottis, whereas the skin and GI tract are colonized with bacteria termed commensal flora. Despite the lower airway being sterile, the upper airway becomes rapidly colonized…

Immunology of Human Milk

Introduction In 1891, it was discovered in experimental animals that immunity was transmitted through breast-feeding. , In the second decade of the 20th century, the incidence of diarrheal diseases was found to be much lower in breast-fed infants than cow’s milk-fed infants. Those observations were confirmed in developing and industrialized countries. Subsequently it was discovered that breast-feeding protected against many bacterial and viral enteric pathogens. Three…

Cytokines and Inflammatory Response in the Fetus and Neonate

Clinical Relevance of Inflammation in the Fetus and Neonate Thanks to skilled clinicians and cutting-edge technologies, care of the critically ill neonate has advanced significantly since the inception of neonatology. However, interventions presently employed by neonatologists to sustain patients’ lives, including ventilators, antibiotics, and vasoactive medications, to name a few, represent only types of supportive care. Mounting evidence suggests that disturbed homeostasis of the immune system…

The Complement System of the Fetus and Newborn

Introduction The complement system is composed of more than 30 soluble proteins, cell surface regulatory factors, and receptors that work together to accomplish a wide variety of functions. These are important not only in host defense and inflammatory responses but also in normal physiologic homeostasis. By facilitating proper disposal of apoptotic cells and antigens from infectious agents, complement plays an important role in preventing autoimmune and…

Normal and Abnormal Neutrophil Physiology in the Newborn

Introduction The response of the immune-competent host to invasive pathogens includes a variety of local and systemic mechanisms. Among these are humoral elements, such as complement or immunoglobulins (Igs), as well as cellular defenses that involve both innate (nonspecific but immediate) and adaptive (antigen-specific, programmed) immune responses. Neutrophils, or polymorphonuclear cells, comprise a critical arm of the innate immune system (reviewed by Nauseef and colleagues and…

Mononuclear Phagocyte System

Overview of the Mononuclear Phagocyte System The mononuclear phagocyte system (MPS) refers to a network of cells that share the ability to engulf (i.e., internalize) and digest large particles such as whole microbes (e.g., bacteria, fungi, and viruses) or dying cells, but also tumor cells and toxic metabolic products. Mononuclear cells have a single, round nucleus. Neutrophils and other granulocytes also share phagocytic functions, but they…

B-Cell Development

Acknowledgments The authors would like to acknowledge Tucker LeBien for portions of this chapter derived from the previous edition. Introduction Mammalian b-cell development occurs via a series of sequential developmental transitions that culminate in the establishment of a protective antibody repertoire that is essential for the host’s immunity to microbial pathogens. Primary antibody deficiencies can result from mutations in genes that are expressed in B-lineage cells…

T-Cell Development

Acknowledgment The authors wish to thank Marcia McDuffie, MD, Anthony R. Hayward, MD, PhD, and Luigi Notarangelo, MD, PhD, who contributed exceptionally to previous editions of this chapter in the third edition of Fetal and Neonatal Physiology . Introduction Hematopoietic stem cells give rise to committed progenitors of multiple lineages. Whereas maturation along myeloid, erythroid, and megakaryocytic cell lineages occurs within the bone marrow, and differentiation…

Host Defense Mechanisms Against Viruses

Overview of Innate and Adaptive Antiviral Immunity Viral host defense mechanisms of humans depend on a combination of tightly integrated innate and adaptive immune mechanisms. Key innate immune mechanisms include antiviral and proinflammatory cytokines, such as type I interferon (IFN), IFN-γ, and tumor necrosis factor (TNF)-α, which have pleiotropic immunoregulatory effects and multiple potential cellular sources, including mononuclear phagocytes, dendritic cells (DCs), and natural killer (NK)…