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Pathophysiology of Kernicterus

Introduction Jaundice is a common transitional phenomenon in newborn infants and may have been first described in the Chinese textbook On the Origins and Symptoms of Diseases written in CE 610. It is not clear when the association between neonatal jaundice and yellow staining of the brain was first noticed, but the staining phenomenon later known as kernicterus was first described in 1875 by Johannes Orth,…

Pathophysiology and Prevention of Neonatal Necrotizing Enterocolitis

Introduction Neonatal necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease that primarily afflicts premature neonates after the initiation of enteral feeding. , Despite the significant morbidity and mortality associated with NEC, the pathophysiology has remained poorly understood. The disease is seen clinically in premature neonates with variable signs, including intestinal bleeding, emesis, abdominal distension and tenderness, lethargy, apnea and bradycardia, thrombocytopenia, metabolic acidosis, respiratory…

Pathophysiology of Gastroesophageal Reflux

Acknowledgments Dr. Jadcherla’s efforts are supported in part by NIH grants RO1 DK 068158 and PO1 DK 068051. We are grateful to Kathryn Hasenstab, BS, BME, for assistance with manuscript submission, and creating figures and artwork. Introduction Gastroesophageal reflux (GER) is defined as a retrograde movement of gastric contents into the esophagus; it is a normal physiologic phenomenon across the age spectrum. Importantly, the physical and…

Pathophysiology of Ventilator-Dependent Infants

General Considerations The respiratory system comprises an organ for gas exchange (the lung) and structures that move air into the lung (the respiratory pump). The lung includes the airways, alveoli, and blood vessels. The respiratory pump contains the respiratory muscles, the central nervous system and peripheral chemoreceptors that modulate pump output, and the structural tissues of the chest wall, including the ribs, cartilage, spine, and abdominal…

Pathophysiology of Bronchopulmonary Dysplasia

Introduction More than half a century after its first description by Northway and colleagues, bronchopulmonary dysplasia (BPD) continues to be the most common respiratory morbidity in extremely preterm infants surviving after different modes of respiratory support. Over the years, the epidemiologic, clinical, and pathologic picture of this condition has changed remarkably. In its current form, BPD is the end result of various antenatal and postnatal factors…

Pathophysiology of Meconium Aspiration Syndrome

Introduction Meconium aspiration syndrome (MAS) follows fetal hypoxic/ischemic stress that leads to intestinal peristalsis, meconium release, contamination of the amniotic fluid, and gasping respirations, which causes aspiration of noxious meconium-stained fluid deep into the fetal lung. Aspiration of meconium manifests as airway obstruction with trapping of gas in the lung during exhalation, chemical pneumonitis, and surfactant inactivation with decreased lung compliance. The newborn typically presents with…

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,…