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Pathophysiology of Respiratory Distress Syndrome

Introduction Respiratory distress syndrome (RDS) in preterm infants is the disease most identified with the development of neonatal intensive care. Before the late 1960s, the only therapy for preterm infants who developed progressive respiratory failure shortly after birth was supplemental oxygen; most of these infants died. At autopsy the lungs were atelectatic and had epithelial injury with hyaline membranes, resulting in the name hyaline membrane disease…

Pathophysiology of Apnea of Prematurity

Epidemiology and Definition of Apnea Definition Apnea is an almost universal manifestation of immature respiratory control in premature infants. Such infants may experience respiratory pauses of varying duration, with decreasing gestational age increasing vulnerability to such events. Short respiratory pauses may be self-limiting, while longer episodes may necessitate intervention, especially in the most immature infants. Apnea has traditionally been defined as a respiratory pause lasting at…

Pathophysiology of Shock in theFetus and Neonate

Introduction Cardiovascular compromise in the fetus and neonate often leads to severe organ injury or death, and the success of therapeutic interventions is limited by difficulties with accurate and timely detection of the condition, especially in the fetus, and the sensitivity of the developing organism to alterations in blood and oxygen (O 2 ) supply. Studies using animal models of fetal or neonatal shock have investigated…

Pathophysiology of Persistent Pulmonary Hypertension ofthe Newborn

Introduction Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of failed circulatory adaptation at birth, which is seen in about 2 in 1000 live-born infants; the incidence has not changed significantly over the last 20 years. , The syndrome is characterized by a sustained elevation of pulmonary vascular resistance (PVR) and is often associated with normal or low systemic vascular resistance (SVR). Consequently these…

Pathophysiology of Cardiomyopathies

Introduction Cardiomyopathies constitute a group of heterogenous disorders in which the muscle of the heart (myocardium) remodels and becomes structurally and functionally abnormal. This pathophysiology can potentially lead to progressive systolic and/or diastolic heart failure, thus representing a cause of morbidity and mortality during the neonatal period. , Cardiomyopathies are frequently caused by pathogenic gene variants, in addition to other triggers such as the presence of…

Pathophysiology of Neonatal Hypoglycemia

Introduction Hypoglycemia in neonates has been a topic of major concern and of controversy for many decades. These arise from two competing clinical issues. On the one hand, for a small number of infants born with persistent forms of hypoglycemia, there is the serious risk of seizures and permanent brain injury if not detected early and treated adequately. For example, over half of the children with…

Pathophysiology of Neonatal Sepsis

Acknowledgment I am indebted to Professor Hector Wong for his assistance with the prior iteration of this chapter. Introduction A successful immune response is critically necessary to eradicate infectious challenges and prevent dissemination of the infection throughout the host. However, if inflammation is not limited and becomes generalized, it can result in the constellation of signs and symptoms of a systemic inflammatory response syndrome (SIRS). If…

Physiology of Neonatal Resuscitation

Introduction The transition to newborn life represents one of the greatest physiologic challenges that humans face during their lives. Before birth, the future airways of the lungs are liquid-filled and the lungs play no role in gas exchange. Instead, gas exchange occurs across the placenta and the majority of right ventricular output bypasses the lungs and passes through the ductus arteriosus (DA) to enter the descending…

The Pathophysiology of Twin-Twin Transfusion Syndrome, Twin-Anemia Polycythemia Sequence, and Twin-Reversed Arterial Perfusion

Introduction Twin pregnancies account for 3.7% of all births in the United States, and the incidence has increased over the past decades. From a developmental and genetic perspective, twins are characterized either as dizygotic , arising from two eggs fertilized by two different sperm, or monozygotic , resulting from the division of one zygote, whereby both halves generally carry the same genetic information and are of…

Differentiation of the Ovary

Development of a Functional Ovary The follicle—the functional unit of the ovary—consists of an oocyte in the late prophase of the first meiotic division surrounded by granulosa cells enclosed by a basement membrane. Later, during follicle growth, it will become surrounded by theca cells. Human gonads of both sexes are established at week 4 post conception (pc) and are intimately connected to the mesonephros throughout early…

Genetics of Sex Determination and Differentiation

Introduction The classical paradigm of mammalian, including human, sexual development postulates an initially “indifferent” (sexually undifferentiated) state that is transformed, in two major stages, into the sexually dimorphic male and female forms. The two stages are called primary, relating to the gonad, and secondary, referring to all other genital organs. In the first stage, primary sex determination, specific sex-determining genetic factors that are present from conception…

Fetal and Neonatal Thyroid Physiology

Introduction Normal embryonic development in vertebrates requires the highly coordinated action of thyroid hormones. In mammals, these iodothyronine hormones (T3 and T4) are derived from both maternal and fetal sources and regulate the proliferation, differentiation, and apoptosis of developing tissues in a temporally and anatomically precise manner. During most of gestation, extracellular concentrations of active thyroid hormones in the fetus are low (as compared with maternal…

Fetal and Neonatal Adrenocortical Physiology

Acknowledgment The editors wish to thank the authors for their valuable contributions to this chapter in the 5th edition. The chapter has been republished here virtually unchanged. Introduction The adrenal cortex undergoes remarkable growth and unique metamorphosis during the fetal and neonatal period. Its morphology, functions, and secretory product profiles are distinctly different during fetal and postnatal life. The major products of the fetal adrenal cortex,…

Development of the Hypothalamus-Pituitary-Adrenal Axis in the Fetus

Introduction The development of the hypothalamus-pituitary-adrenal (HPA) axis begins early in gestation. Corticotropin-releasing hormone (CRH) is synthesized and secreted into the hypophyseal portal circulation by the paraventricular nucleus of the hypothalamus. CRH acts on corticotroph cells in the anterior pituitary gland to regulate the secretion of adrenocorticotropic hormone (ACTH). ACTH, in turn, stimulates cortisol secretion from the zona fasciculata of the adrenal cortex. ACTH is also…

Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in the Fetus and Newborn Infant

Acknowledgments Research work in the senior author’s (TRK) laboratory is supported in part by the National Institutes of Health (AG056046, HD081162, AG029531, AG062319, HD097202) and The Makowski Family Endowment. Introduction The pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), influence the function of the differentiated gonad in utero and regulate gonadal function in later life. LH and FSH are glycoprotein hormones secreted by the same…

Growth Hormone, Prolactin, and Placental Lactogen in the Fetus and Newborn

Introduction and Background In the fully developed organism, growth hormone (GH), a 22-kDa molecule of 191 amino acids, is synthesized by acidophil cells in the anterior pituitary gland under the direction of hypothalamic GH-releasing hormone, which binds to its G protein–coupled receptor to stimulate GH secretion, and via somatotropin release–inhibiting factor, also known as somatostatin, an inhibitor of GH release in a “dominant negative” manner. The…

Growth Factor Regulation of Fetal Growth

Introduction Growth during fetal life is characterized by an early period of cell division and organogenesis, followed by a more prolonged period of growth and refinement of organ development. Growth factors are peptides or proteins that serve as key regulators of cell proliferation and differentiation that exert their effects by binding to specific receptors, which mediate signal transduction across cell membranes. This binding triggers a cascade…

Hypothalamus: Neuroendometabolic Center

Acknowledgment The editors wish to thank authors Adda Grimberg and Jessica Katz Kutikov for their excellent contribution to this text in the fifth edition. This chapter has been reproduced here in the sixth edition essentially unchanged. Introduction Enabled by its strategic anatomy, the hypothalamus uniquely serves the interface between the neural and endocrine systems. It is at the same time a part of the brain, an…

Ontogenesis of Striated Muscle

Introduction Embryology is the basis for understanding the intimate relation between structures in different organ systems, such as the nervous system and muscle, and is primordial for understanding pathogenesis in disorders of development that in the human may present as one of the congenital myopathies. Demonstration of a defective gene provides an etiology but does not define morphogenesis. The timing and sequence of striated muscle maturation…