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Genetic Variants and Neonatal Disease

Introduction Infants with complex phenotypes and infants born at early gestational age are two of the most challenging groups of patients cared for in neonatal intensive care units (NICUs). Since the initial reports of the sequence of the human genome, , clinicians have hoped that the “genomic revolution” would lead to increasing likelihood of diagnoses for infants with complex phenotypes and identification of common variants associated…

Pathophysiology of Genetic Neonatal Disease

Introduction Genetic diseases are a leading cause of neonatal morbidity and mortality. Estimates of the incidence of genetic disease in neonates admitted to intensive care units have historically been based on targeted genetic testing of cohorts selected to have a high pretest probability, such as those with multiple congenital anomalies. However, the neonatal presentation of many thousands of genetic diseases overlaps with common, typically nongenetic conditions…

Pathophysiology of Chorioamnionitis: Host Immunity and Microbial Virulence

Introduction Approximately 1% to 10% of all births in the United States are complicated by chorioamnionitis, but the incidence varies significantly by study population, gestational age at presentation, and diagnostic criteria. Histologic chorioamnionitis is a pathologic term that refers to an influx of maternal inflammatory cells (neutrophils, macrophages, and T cells) into the placental membranes. The term clinical chorioamnionitis is used when overt signs of intraamniotic…

Pathophysiology of Preterm Birth

Introduction Although clinically managed as if it were a single disease, preterm birth is increasingly recognized as a syndrome secondary to multiple causative mechanisms and etiologies. In this chapter, we discuss the epidemiology of preterm birth, the endocrinology and physiology of parturition, and current practice in prediction and prevention of preterm labor (PTL). Epidemiology of Preterm Birth PTL is defined as the onset of labor before…

Pathophysiology of Preeclampsia

Introduction Preeclampsia is a multiorgan disease specific to pregnancy most often characterized by hypertension and proteinuria occurring after 20 weeks gestation. It is among the most common medical complication of pregnancy and is a leading cause of maternal/fetal morbidity and mortality highest in the developing nations. Although the eclamptic convulsion may have been recognized 4000 years ago and the term “eclampo” signifying “lightning” used to describe…

Pathophysiology of NeuralTube Defects

Acknowledgments The authors’ research on neurulation and NTDs is supported by grants from the Medical Research Council, Wellcome, NC3Rs, Sparks, Newlife, Action Medical Research, the Bo Hjelt Spina Bifida Foundation, Great Ormond Street Hospital Children’s Charity, and the National Institute for Health Research, Biomedical Research Centre, at Great Ormond Street Hospital for Children, NHS Foundation Trust, and University College London. Introduction Neural tube defects (NTDs) are…

Pathophysiology of Neonatal Acute Bacterial Meningitis

Bacterial Meningitis Meningitis is a life-threatening infection of the central nervous system (CNS) that affects the pia mater, the arachnoid, and the subarachnoid space. The microorganisms can activate the host immune response, and both inflammatory mediators and microorganisms can break down the blood-brain barrier, allowing the influx of fluid and solutes into the brain, triggering the brain edema. This infection is a significant cause of morbidity…

Pathophysiology of Neonatal Hypoxic-Ischemic Brain Injury

Acknowledgment This work was partially supported by NIH grants NS 100850, NS 099109, NS 088197. Introduction The pathophysiology of neonatal hypoxic-ischemic (HI) brain injury or hypoxic-ischemic encephalopathy (HIE) defines the response of central nervous system (CNS) to ischemia and reperfusion. Neonatal HI brain injury usually occurs due to a collapse of systemic circulation at or near birth or during the neonatal period. If not interrupted, HI…

Pathophysiology of Retinopathy of Prematurity

Acknowledgments The authors thank Maria Isabel Gomez for her expert help in organization and formatting the manuscript. Introduction Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide and is increasing in emerging countries able to save premature infants but without resources to provide optimal care. , ROP, first identified as retrolental fibroplasia (RLF) in the United States, was reported by Terry as…

Pathophysiology of Edema

Acknowledgment The editors thank David P. Carlton for his excellent work on this chapter in the fifth edition. It has been republished here essentially unchanged. General Considerations Edema is the clinical term used to describe excessive fluid accumulation in the adventitial tissue spaces of the body. Excess fluid accumulates when the net rate of transvascular fluid filtration from the microcirculation is exceeded by the rate of…

Pathophysiology of Neonatal AcuteKidney Injury

Introduction In recent years, there has been an exponential expansion of our understanding of the epidemiology and adverse outcomes associated with neonatal acute kidney injury (AKI). From a multitude of single-center studies and in the recent multicenter Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, AKI is now known to be associated with several adverse outcomes (increased length of stay, length of mechanical…

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…