Part 1. The Field of Neonatal-Perinatal Medicine
1. Growth of Neonatal-Perinatal Medicine—A Historical Perspective
The High-Risk Fetus and Perinatal Obstetrics
Midwives and Perinatal Care
Neonatal Resuscitation: Tales of Heroism and Desperations
Apgar and the Language of Asphyxia
Foundling Asylums and Infant Care
Saving Infants to Man the Army
An Ingenious Contrivance, the Couveuse, and Premature Baby Stations
Incubators, Baby Shows, and Origins of Neonatal Intensive Care Units
Supportive Care and Oxygen Therapy
Ventilatory Care: “Extended Resuscitation”
Supportive Care: Intravenous Fluid and Blood Transfusions
Tools and Supplies for Neonatal Intensive Care Units
Pediatric Surgery: Not for Rabbits Anymore
Medical Errors and “Patient Safety” as a New Discipline
Controlled Clinical Trials, Evidence-Based Medicine, and Research Networks
Some Recent Advances and New Frontiers for Research
Some Famous High-Risk Infants
2. Epidemiology for Neonatologists
Common Epidemiologic Concepts
Health Statistics and Data Sources
3. Big Data for the Smallest Patients—What We Can Learn From Neonatal Database Research
Introduction: Neonatal Database Research
The Scope of Research Using Neonatal Databases
Interpretation of Neonatal Database Studies
The Future of Big Data in Neonatology
4. Medical Ethics in Neonatal Care
Principles in Medical Ethics
Clinical Applications in Specific Moral Problems
Ethical Responsibilities of Neonatal Physicians
5. Improving the Quality, Safety, and Equity of Neonatal Intensive Care for Infants and Families
Brief History of Industrial Quality Improvement
Definitions and Conceptual Frameworks for Quality
Data and Methods for Quality Improvement
Quality and Safety Applied
6. Importance of Simulation in Neonatology
Simulation-Based Training in Health Care
Simulation in Low-Resourced Areas
Simulation-Based Research and In Situ Simulation
7. Perinatal and Neonatal Care in Developing Countries
Global Initiatives to Reduce Infant Mortality Rate and Neonatal Mortality Rate
Global Burden of Maternal and Neonatal Deaths
Causes of Global Maternal and Neonatal Mortality
Burden of Neonatal Sepsis
Evidence-Based Interventions to Reduce Maternal Mortality Rates, Neonatal Mortality Rates, and Infant Mortality Rates
Strategies to Improve Global Perinatal and Neonatal Outcomes
8. Social and Economic Contributors to Neonatal Outcome in the United States
Epidemiology of Health Disparities in Neonatal and Perinatal Medicine
Interventions to Reduce Neonatal Health Outcome Disparities
9. Genetic Aspects of Perinatal Disease and Prenatal Diagnosis
Principles of Inheritance
Congenital Anomalies and Ultrasonography
Role of Prenatal Magnetic Resonance Imaging
Screening Modalities to Identify Genetic Disorders
Noninvasive Screening and Diagnosis: Current Controversies
Screening for Multifactorial Disorders
Technical Advances in Molecular Cytogenetics
Future Directions for Prenatal Diagnostic Testing
Assisted Reproductive Technologies
Genetic Evaluation and Counseling
Applications of Ultrasound Studies
Ultrasound-Guided Procedures
Fetal Well-Being Assessment
Ultrasound Examination for Fetal Abnormalities in the Second or Third Trimester
11. Estimation of Fetal Well-Being
Antepartum Fetal Surveillance
Evaluation of the Intrapartum Fetus
12. Surgical Treatment of the Fetus
Anesthetic Considerations
Anomalies Amenable to Fetal Surgery
13. Adverse Exposures to the Fetus
Exposures Not Concurrent With Pregnancy
Maternal Exposures Concurrent With Pregnancy
Pathways of Fetal Exposure
14. Fetal Growth Restriction: A Complex Interplay Between the Intrauterine and Maternal Environment
Definitions and Terminology
The Health Burden of Fetal Growth Restriction
Classification of Fetal Growth Restriction
Etiology of Fetal Growth Restriction
Antenatal Screening and Prenatal Management
Postnatal Evaluation of Fetal Growth Restriction
Long-Term Consequences of Fetal Growth Restriction
15. Developmental Origins of Health and Disease
Fetal Origins of Adult Disease Concept
Postnatal Growth and Nutrition
Placental Abnormalities and Association With Adult Disease
Gestational Diabetes and Long-Term Metabolic Effects on Offspring
Developmental Impact of Toxins, Endocrine Disrupters, and Air Pollution (See Also Chapter 13)
Translation to Neonatology
Part 3. Pregnancy Disorders and Their Impact on the Fetus
16. Hypertensive Disorders of Pregnancy
Classification of Hypertensive Disorders of Pregnancy
Epidemiology of Preeclampsia
Clinical Presentation of Preeclampsia
Other Hypertensive Disorders of Pregnancy
17. Pregnancy Complicated by Diabetes Mellitus
Gestational Diabetes Mellitus
Timing and Mode of Delivery
Postpartum Maternal Management
Pregestational Diabetes Mellitus
Implications for the Neonate
Breastfeeding in Women With Gestational Diabetes Mellitus
18. Obstetric Management of Prematurity
19. Fetal Effects of Autoimmune Disease
Placental Transfer: General Remarks
Fetal-Neonatal Consequences of Maternal Antinuclear Antibodies
Fetal-Neonatal Consequences of Maternal Antiphospholipid Antibodies
20. Multiple Gestation: Fetal and Maternal Considerations
Classification of Twin Pregnancies
First Trimester Assessment of Multiple Gestations (11+0 to 13+6 Weeks Scans)
Complications of Monochorionic Twins
Antenatal Steroids in Twin Pregnancies
Estimated Gestational Age
Incidence of Post-Term Pregnancy
Neonatal Risks of Post-Term Pregnancy
Long-Term Complications of Post-Term Pregnancy
22. Immune and Nonimmune Hydrops Fetalis
Nonimmune Hydrops Fetalis
23. Amniotic Fluid Volume
Measurement of Amniotic Fluid Volume
Normal Volume and the Singleton Pregnancy
Abnormalities of Amniotic Fluid Volume and Their Management
Management of Fluid Abnormalities in Multifetal Pregnancies
24. Perinatal Infections and Chorioamnionitis
Definitions and Epidemiology
Areas for Future Investigation
Optimal Use of Pathology Service
Structure, Function, and Pathologic Reaction Patterns
Part 4. The Delivery Room
26. Anesthesia for Labor and Delivery
Labor Pain Characteristics and Challenges
Techniques That Modify Pain
Delivery Modes and Anesthetic Techniques
27. Physical Examination of the Healthy Newborn
Detailed Neurologic Assessment
Interpretation of the Neurologic Examination
Limitations of the Routine Examination
Health Promotion, Screening, and Prevention
Injuries to the Neck, Shoulder Girdle, and Chest
Injuries to the Spine and Spinal Cord
Injuries to Intra-Abdominal Organs
Injuries to the Extremities
Injuries Related to Intrapartum Fetal Monitoring
Injuries Related to Trauma During Pregnancy
General Clinical Approach
Epidemiology and Etiology
Diagnostic Testing and Indications
Educational Resources and Support Organizations
Part 5. Resuscitation of the Newborn
30. Overview and Initial Management of Delivery Room Resuscitation
Causes of Depression and Asphyxia
Preparation for Resuscitation
Umbilical Cord Blood Gases
Elements of a Resuscitation
31. Role of Positive Pressure Ventilation in Neonatal Resuscitation
Normal Transition and Initial Spontaneous Breathing
Delayed Transition and Need for Respiratory Support
Basics of Positive Pressure Support
Application of Noninvasive Positive Pressure Support
Applying Positive Pressure Support
Peak Inflation Pressures and Tidal Volumes
Positive End-Expiratory Pressure
Inflation Rate and Duration
32. Oxygen Therapy in Neonatal Resuscitation
Use of Oxygen in Perinatal Asphyxia and Resuscitation
Room Air Versus Pure Oxygen for Resuscitation of the Newborn
Oxygen Supplementation in the Delivery Room in Extremely Low Gestational Age Neonates
Room Air Versus 100% Oxygen—Or Something Else
33. Chest Compression, Medications, and Special Problems in Neonatal Resuscitation
Importance of Effective Ventilation
When to Discontinue Resuscitation Efforts
Immediate Care After Establishing Adequate Ventilation and Circulation
Special Problems During Resuscitation
Screening for Congenital Defects
34. Role of Umbilical Cord Management in Neonatal Resuscitation
Concerns Related to Delayed Cord Clamping
Cord Management Strategies
Part 6. The Physical Environment in Neonatal Care
35. Thermal Environment of the Intensive Care Nursery
Thermal Aspects of the Care Environment
Recommendations for Practice
36. Optimization of the Neonatal Intensive Care Unit Environment
Neurobehavioral Maturation
Behavioral/Sleep States and Neonatal Intensive Care Unit Environment
Sensory Functions and Neonatal Intensive Care Unit Environment
Circadian Rhythm and Neonatal Intensive Care Unit Environment
Sensory Functions and Pain
Muscle Tone, Movements, and Reflexes
Environmental Support of Growth
Environmental Protection From Infections
Environmental Support of Parent–Infant Interaction
Neurobehavioral Assessment Tools
Neonatal Intensive Care Unit Design
Health Care Team Perspectives
Part 7. Provisions for Neonatal Care
37. Neonatal Cardiorespiratory Monitoring
38. Diagnostic Imaging of the Neonate
Digital Radiography, Fluoroscopy, and Computed Tomography
Magnetic Resonance Imaging
39. Anesthesia in the Neonate
Safety and Challenges of Neonatal Anesthesia
Preoperative Evaluation and Preparation
Neonatal Physiology and Specific Anesthetic Concerns
40. Care of Periviable Micropreemies: The Japanese Perspective
Care for the Improvement of Outcomes Among Preterm Infants
In the Neonatal Intensive Care Unit
41. The Late Preterm Infant
Hospitalizations and Rehospitalizations After Discharge
Long-Term Neurodevelopmental Outcomes
42. Nutritional Support for the Preterm Infant
Growth in the Neonatal Intensive Care Unit
Growth and Neurodevelopmental Outcomes
Provision of Nutritional Support
43. Support for the Family
Normal Mother-Infant Attachment
Formation of Mother-Infant Attachment
Attachment Challenges With Sick or Premature Infants
Parental Mental Health Issues
44. Perinatal Palliative Care
What Is Perinatal Palliative Care?
Providing Perinatal Palliative Care
Components of Perinatal Palliative Care
Anticipatory Guidance for End of Life
What the Future Looks Like
Part 8. Developmental Pharmacology
45. Principles of Drug Use in the Fetus and Neonate
Neonatal Drug Disposition
46. Principles of Drug Use During Lactation
Passage of Exogenous Compounds From Maternal Blood to Milk
Delivery of Compounds to and Disposition by the Infant
Conclusions Concerning Breastfeeding and Maternal Drug Therapy
47. Pharmacokinetics in Neonatal Medicine
Drug Disposition Explains Drug Exposure Over Time: Absorption, Distribution, Metabolism, and Excretion
Pharmacokinetic Models Describe Concentration of Drug Over Time
Important Factors That Impact Pharmacokinetics
48. Infants of Substance-Using Mothers
Prenatal and Perinatal Considerations
Benzodiazepines and Barbiturates
Part 9. The Immune System
49. Developmental Immunology
Overview of Hematopoiesis
Evaluation of Host Defenses in Neonates
Immunomodulation and Future Directions
50. Postnatal Bacterial Infections
Bacterial Infections by Organ System
51. Fungal and Protozoal Infections of the Neonate
Pathogenesis and Pathophysiology
Antifungal Prophylaxis Summary
Invasive Candida Infection Summary
Aspergillus, Mucormycosis, Malassezia, and Trichosporon Infections in the Neonatal Intensive Care Unit
Chapter 52. Viral Infections in the Neonate
Human Immunodeficiency Virus
Enteroviruses and Parechoviruses
Coronavirus: Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, and Coronavirus Disease 2019 (COVID-19)
Part 10. The Central Nervous System
53. Normal and Abnormal Brain Development
Neural Induction and Neurulation
Neuronal Migration and Cortical Lamination
Central Nervous System Organization
Brain Vascular Development
Abnormal Brain Development and Disorders
54. Cerebral White Matter Damage and Encephalopathy of Prematurity
Neuropathology of White Matter Injury
Models of Encephalopathy of Prematurity: Implications for Pathogenesis
Neuroimaging of White Matter Injury
Impairment of Brain Growth and Long-Term Development
55. Intracranial Hemorrhage and Stroke in the Neonate
Germinal Matrix Hemorrhage–Intraventricular Hemorrhage
56. Hypoxic-Ischemic Encephalopathy
Perinatal Hypoxic-Ischemic Brain Damage
Brain-Oriented Management
Specific Neuroprotective Strategies
The Association Between Hypoxic-Ischemic Encephalopathy and Less Severe Neurodisability
Pathophysiology of Newborn Seizures—Unique Maturational Features Increasing the Likelihood of Seizures in the Newborn
Biochemical and Physiologic Consequences of Seizures in the Immature Brain—Implications for the Clinician
Classification of Seizures in the Newborn
58. Hypotonia and Neuromuscular Disease in the Neonate
Neonatal Neuromuscular Disorders
Hereditary Motor and Sensory Neuropathies
Hereditary Sensory and Autonomic Neuropathies
Neuromuscular Junction Disorders
Congenital Muscular Dystrophy
Congenital Myotonic Dystrophy
Other Muscular Dystrophies
Metabolic and Multisystem Disorders
59. Disorders in Head Shape and Size
Prenatal Screening and Prevention
61. Hearing Loss in the Newborn Infant
Normal/Typical Hearing and Hearing Loss
Early Intervention Services
Medical Workup for Hearing Loss and Care Coordination
Stress and Impact on the Family
62. Early Childhood Neurodevelopmental Outcomes of High-Risk Neonates
Neurodevelopmental Outcome
Methodologic Considerations in Neurodevelopmental Outcome Studies
Children Born at the Threshold of Viability
Part 11. The Respiratory System
63. Lung Development and Maturation
Lung Structural Development
Other Disorders of Lung Development
Lethal Pulmonary Disorders
Physiologic Effects of Surfactant in the Preterm Lung
64. Assessment of Neonatal Pulmonary Function
Cardiorespiratory Assessment
65. Respiratory Distress Syndrome in the Neonate
Heritability of Respiratory Distress Syndrome
Prevention: Pharmacologic Acceleration of Pulmonary Maturation
66. Assisted Ventilation and Its Complications
Continuous Positive Airway Pressure and Noninvasive Ventilation
Indications for Assisted Ventilation
General Principles of Assisted Ventilation
Classification of Mechanical Ventilators
Suggested Ventilatory Management Guidelines
Monitoring of Ventilated Infants
Complications of Assisted Ventilation
67. Spectrum of Neonatal Respiratory Disorders
Acquired Neonatal Pulmonary Diseases
Extracorporeal Membrane Oxygenation for Respiratory Failure
68. Apnea, Bradycardia, Hypoxemia, and the Foundation of Respiratory Control
Postnatal Development of Respiratory Control
Neonatal Apnea, Bradycardia, and Hypoxemia
Brief, Resolved, Unexplained Events
69. Upper Airway Lesions in the Neonate
Nasal and Nasopharyngeal Lesions
Oral and Oropharyngeal Lesions
70. Bronchopulmonary Dysplasia in the Neonate
Epidemiology of Bronchopulmonary Dysplasia
Prediction of Bronchopulmonary Dysplasia
Prevention of Bronchopulmonary Dysplasia
Management of Established Bronchopulmonary Dysplasia
71. Postneonatal Respiratory Morbidity
Postneonatal Pulmonary Hypertension
Prevalence of the Problem
Reactive Airways Disease in Infants and Children Born Preterm
Neonatal Effects on Long-Term Adult Lung Function
Part 12. The Cardiovascular System
Overview of Normal Heart Development
Scientific Basis of Cardiogenesis
73. Pulmonary Vascular Development
Fetal Pulmonary Vascular Development
Pulmonary Vascular Transition
Vasoactive Mediators of the Pulmonary Vascular Transition
Abnormalities of Pulmonary Vascular Development
Clinical Therapy of Pulmonary Hypertension of the Newborn
74. Prenatal Diagnosis of Congenital Heart Disease
Overview of Fetal Circulation and Cardiac Adaptation at Birth
Indications for Fetal Echocardiogram
Performance of a Fetal Echocardiogram
Parental Counseling After Fetal Diagnosis of Congenital Heart Disease
Impact of Prenatal Diagnosis
Limitations of Fetal Echocardiograms
Novel Approaches to Prenatal Diagnosis of Congenital Heart Disease
75. Patent Ductus Arteriosus
76. Congenital Defects of the Cardiovascular System
Cyanotic Heart Defects: Mixing-Dependent
Cyanotic Heart Defects: Restricted Pulmonary Blood Flow
Cyanotic Heart Defects: Complete Mixing
Cyanotic Heart Defects: Variable Physiology
Obstructive Heart Defects
77. Unique Neonatal Cardiovascular Problems
Cardiac Malposition and Abnormalities of Abdominal Situs
Arteriovenous Malformations
Myocardial Diseases: Cardiomyopathy and Myocarditis
Vascular Rings and Slings
The Premature Infant With Congenital Heart Disease
78. Disorders of Cardiac Rhythm and Conduction in Newborns
Normal Sinus Rhythm and Sinus Node Dysfunction
Atrioventricular Conduction Disturbances
79. Neonatal Management of Congenital Heart Disease
Part 13. The Blood and Hematopoietic System
80. The Hemostatic System
Neonatal Platelet Disorders
Neonatal Coagulation Disorders
Neonatal Thrombotic Disorders
81. Red Blood Cell Disorders in the Fetus and Neonate
Human Hematopoietic Development
82. White Blood Cells and Immune Disorders
83. Neoplasms in the Neonate
Teratomas and Other Germ Cell Tumors
84. Blood Component Therapy for the Neonate
Special Considerations for Transfusion Therapy in the Neonate
Risks of Transfusion Therapy
Special Topics in Neonatal Transfusion
Part 14. The Gastrointestinal Tract
85. Development of the Neonatal Gastrointestinal Tract
Duodenum, Pancreas, and Biliary System
86. Gastrointestinal Reflux and Motility in the Neonate
Physiology of Gastroesophageal Reflux
Gastroesophageal Reflux Disease
87. Disorders of Digestion in the Neonate
Diagnostic Testing for Disorders of Digestion
Disorders of Digestion, Absorption, and Secretion
88. Selected Gastrointestinal Anomalies in the Neonate
Congenital Diaphragmatic Hernia
Spontaneous Intestinal Perforation
Hypertrophic Pyloric Stenosis
Duodenal Atresia and Stenosis
Gastrointestinal Duplications
Malrotation and Midgut Volvulus
Jejunoileal Atresia and Stenosis
89. Neonatal Necrotizing Enterocolitis
Definition of Necrotizing Enterocolitis
Pathophysiology of Necrotizing Enterocolitis
Some Imposters of Necrotizing Enterocolitis
Part 15. Metabolic and Endocrine Disorders
90. Disorders of Carbohydrate Metabolism in the Neonate
Placental Transport of Nutrients: Maternal-Fetal Relationship
Fetal Hormones Mediating Growth
Glucose Metabolism After Birth—Transitional Neonatal Hypoglycemia
Diabetes Mellitus in the Newborn
91. Disorders of Calcium, Phosphorus, and Magnesium Metabolism in the Neonate
Calcium, Phosphorus, and Magnesium Physiology
Hormonal Regulation of Mineral Metabolism
Clinical Conditions Associated With Calcium Disturbances
Clinical Conditions Associated With Magnesium Disturbances
Osteopenia of Prematurity
92. Thyroid Disorders in the Neonate
Physiologic Action of Thyroid Hormones
Synthesis, Release, Transport, and Metabolism of Thyroid Hormones
Laboratory Tests Used to Assess Thyroid Function
Thyroxine-Binding Globulin
Congenital Hypothyroidism
Defects in TSH or Thyroid Hormone Action
Other Conditions Associated With Congenital Hypothyroidism or Abnormal Thyroid Function Testing in the Neonate
Transient Disorders of Thyroid Function
Familial Abnormalities of Thyroxine-Binding Proteins
93. Disorders of Sex Development
Fetal Sexual Determination and Differentiation
A Clinical Approach to the Infant With Suspected Disorder of Sex Development
Disorders of Sex Development
94. Inborn Errors of Metabolism
Screening for Inborn Errors of Metabolism
The Critically Ill Newborn Infant: Clinical Phenotypes
The Abnormal Newborn Infant: Laboratory Phenotypes
Part 16. Neonatal Jaundice and Liver Disease
95. Neonatal Jaundice and Liver Disease
“Conjugated” Versus “Direct” Bilirubin
Equilibrium Between Bilirubin Production and Elimination Processes—The Major Determinant of TB Levels
Genetic Control of Bilirubin Production
Genetic Control of Uptake of Bilirubin into the Hepatocyte
Co-Expression of Genes Modulating the Risk of Neonatal Hyperbilirubinemia
Bilirubin-Induced Neurologic Disorders
Newer Methods of Diagnosis
Conjugated Hyperbilirubinemia
Part 17. The Kidney and Urinary Tract
96. Fluid, Electrolytes, and Acid-Base Homeostasis
Fluid and Electrolyte Management
97. The Kidney and Urinary Tract of the Neonate
Kidney and Urinary Tract Development
Evaluation of the Neonate With Kidney Disease
Congenital Anomalies of Kidney and Urinary Tract
98. The Skin of the Neonate
The Structural Biology of Fetal and Neonatal Skin
Disorders and Diseases of Fetal and Neonatal Skin
Principles of Newborn Skin Care
99. Examination and Common Problems in the Neonatal Eye
Hyperthyroid Exophthalmos
Retina and Vitreous Diseases
Congenital Disc Anomalies
Neuromuscular Abnormalities
Eye Findings in Chromosomal Syndromes
Eye Findings in Craniofacial Syndromes
Eye Findings in Neurocutaneous Disorders (Phakomatoses)
Neonatal Ocular Infections
Other Ocular Tumors in Infants
Ocular Manifestations of Maternal Substance Abuse
100. Retinopathy of Prematurity
Clinical Course and Screening
Recommendations for Examination Schedule
Part 20. Neonatal Orthopedics
101. Musculoskeletal Disorders in Neonates
Overview of Musculoskeletal Chapters
Etiology of Congenital Disorders
102. Bone and Joint Infections in Neonates
103. Congenital Abnormalities of the Upper and Lower Extremities and Spine
Appendix A. Therapeutic Agents
Appendix B. Tables of Normal Values
