Averys Diseases of The Newborn 10th Edition 2018

Avery's Diseases of the Newborn 10th Edition----:---- Page # 1
Front Matter----:---- Page # closed----:---- Page # 52

Avery's Diseases of the Newborn----:---- Page # 52
Copyright----:---- Page # closed----:---- Page # 54
Copyright Page----:---- Page # 54
Dedication----:---- Page # closed----:---- Page # 55
Dedication----:---- Page # 55
Contributors----:---- Page # closed----:---- Page # 56
Contributors----:---- Page # 56
Preface----:---- Page # closed----:---- Page # 70
Preface----:---- Page # 70
History----:---- Page # 70
What’s New and Improved About This Edition?----:---- Page # 70
Acknowledgments and Gratitude----:---- Page # 71
Video Contents----:---- Page # closed----:---- Page # 72
Video Contents----:---- Page # 72
Part XV\: Hematologic System and Disorders of Bilirubin
Metabolism----:---- Page # 72
79 Neonatal Bleeding and Thrombotic Disorders----:---- Page # 72
1 Neonatal and Perinatal Epidemiology----:---- Page # closed----:---- Page # 73
I Overview----:---- Page # 73
1 Neonatal and Perinatal Epidemiology----:---- Page # 73
Health Disorders of Pregnancy and the Perinatal Period----:----
Page # 73
Key Population Mortality Rates----:---- Page # 73
Sources of Information on Mortality–Vital Data----:----
Page # 74
Time Trends in Mortality Rates of the Perinatal Period in
the United States----:---- Page # 74
International Comparisons----:---- Page # 78
Health Disparities in the Perinatal Period----:---- Page #
78
Major Causes of Death----:---- Page # 78
Major Morbidities Related to the Perinatal Period----:----
Page # 79
Factors Affecting Perinatal Health----:---- Page # 80
Health States in Pregnancy----:---- Page # 80
Health Behaviors----:---- Page # 80
Perinatal Medical Care----:---- Page # 80
Epidemiologic Study Designs in the Perinatal Period----:---- Page
# 80
Cohort Studies in Pregnancy/Birth----:---- Page # 80
Randomized Controlled Trials----:---- Page # 81
Summary and Conclusions----:---- Page # 81
Suggested Readings----:---- Page # 82
References----:---- Page # 83
2 Biomedical Informatics in Neonatology----:---- Page # closed----:---- Page # 85
2 Biomedical Informatics in Neonatology----:---- Page # 85
Background----:---- Page # 85
Biomedical and Health Informatics----:---- Page # 86
Databases----:---- Page # 87
Electronic Health Record----:---- Page # 89
Evaluating Therapeutic Recommendations----:---- Page # 91
Online Resources----:---- Page # 92
Future Directions----:---- Page # 93
3 Ethics, Data, and Policy in Newborn Intensive Care----:---- Page #
closed----:---- Page # 96
3 Ethics, Data, and Policy in Newborn Intensive Care----:---- Page # 96
Philosophy----:---- Page # 96
Getting Good Data----:---- Page # 96
Public Policy\: the Baby Doe Case----:---- Page # 97
Malpractice Cases Against Neonatologists----:---- Page # 97
Fetal Medicine Centers----:---- Page # 98
Expanded Newborn Screening----:---- Page # 98
Should Policy Dictate Resuscitation Practices?----:---- Page # 99
Summary----:---- Page # 99
4 Global Neonatal Health----:---- Page # closed----:---- Page # 102
4 Global Neonatal Health----:---- Page # 102
Global Newborn Health – History----:---- Page # 102
Global Newborn Health 2000–2015\: Addressing Cause-Specific Neonatal
Mortality----:---- Page # 103
Major Causes of Neonatal Mortality----:---- Page # 107
Birth Asphyxia----:---- Page # 107
Neonatal Sepsis----:---- Page # 107
Preterm Birth----:---- Page # 108
Antenatal Corticosteroids----:---- Page # 108
Continuous Positive Airway Pressure----:---- Page # 110
Surfactant----:---- Page # 110
Kangaroo Mother Care----:---- Page # 110
Global Newborn Health at the End of the Millennium Development Goals
Era----:---- Page # 110
Toward a “Grand Convergence”----:---- Page # 113
5 Development, Function, and Pathology of the Placenta----:---- Page #
closed----:---- Page # 119
II Fetal Growth and Development----:---- Page # 119
5 Development, Function, and Pathology of the Placenta----:---- Page #
119
Placental Origin----:---- Page # 119
Development of the Placenta----:---- Page # 120
Trophoblast Lineage Allocation----:---- Page # 120
Trophoblast Differentiation----:---- Page # 120
Trophoblast Invasion----:---- Page # 122
Placental Functions----:---- Page # 124
Transport----:---- Page # 124
Endocrine Function----:---- Page # 125
Steroid Hormones----:---- Page # 125
Progesterone----:---- Page # 125
Estrogens----:---- Page # 126
Glucocorticoids----:---- Page # 127
Pituitary-Like Hormones----:---- Page # 127
Human Chorionic Gonadotropin----:---- Page # 128
Human Chorionic Somatomammotropin----:---- Page # 128
Placental Growth Hormone Variant----:---- Page # 128
Insulin-Like Growth Factors----:---- Page # 129
Other Secreted Growth Factors----:---- Page # 129
Inhibin and Activin----:---- Page # 129
Proopiomelanocortin Hormones----:---- Page # 129
Hypothalamic-Like Hormones----:---- Page # 130
Gonadotropin-Releasing Hormone----:---- Page # 130
Corticotrophin-Releasing Hormone and
Urocortins----:---- Page # 130
Thyrotropin-Releasing Hormone----:---- Page # 130
Growth Hormone-Releasing Hormone, Somatostatin, and
Ghrelin----:---- Page # 130
Leptin----:---- Page # 130
Oxytocin----:---- Page # 130
Additional Placental Secreted Factors----:---- Page # 131
Vasoactive Peptides----:---- Page # 131
Endogenous Opioid Peptides----:---- Page # 131
Cytokines----:---- Page # 131
Eicosanoids----:---- Page # 131
Immunologic Function----:---- Page # 131
Fetal Programming----:---- Page # 132
Regulation of Placental Function----:---- Page # 132
Nutrient-Sensing Signaling Pathways----:---- Page # 132
Epigenetic Regulation in the Placenta----:---- Page # 132
Placental Diseases----:---- Page # 134
Placental Disorders of Pregnancy----:---- Page # 134
Preeclampsia----:---- Page # 134
Intrauterine Growth Restriction----:---- Page # 135
Preterm Birth----:---- Page # 135
Gestational Diabetes----:---- Page # 136
Central Nervous System Injury----:---- Page # 136
Evaluation of Placental Dysfunction----:---- Page # 136
Placental Histopathology----:---- Page # 136
Placental Imaging----:---- Page # 137
Serum Biomarkers of Placental Disease----:---- Page #
138
Serum Analytes----:---- Page # 138
Circulating Cell-Free Fetal DNA----:---- Page #
138
Extracellular Vesicles----:---- Page # 138
6 Abnormalities of Fetal Growth----:---- Page # closed----:---- Page # 148
6 Abnormalities of Fetal Growth----:---- Page # 148
Defining Fetal Growth----:---- Page # 148
Patterns of Altered Growth----:---- Page # 149
Fetal Causes of Growth Restriction----:---- Page # 150
Placental Causes of Growth Restriction----:---- Page # 150
Maternal Causes of Growth Restriction----:---- Page # 151
Maternal Smoking----:---- Page # 152
Short-Term Outcomes of Fetal Growth Restriction----:---- Page # 152
Developmental Outcomes of Fetal Growth Restriction\: Early
Childhood----:---- Page # 152
Long-Term Consequences of Fetal Growth Restriction\: the Developmental
Origins of Adult Disease----:---- Page # 153
Programming----:---- Page # 153
Epidemiology----:---- Page # 153
The Role of Catch-Up Growth----:---- Page # 153
Size at Birth, Insulin Secretion, and Insulin Action----:---- Page #
154
Epidemiologic Challenges----:---- Page # 154
Size at Birth Cannot Be Used as a Proxy for Fetal Growth----:---- Page
# 154
Genetics versus Environment----:---- Page # 154
Cellular Mechanisms of Developmental Programming----:---- Page # 154
Molecular Mechanisms of Developmental Programming\:
Epigenetics----:---- Page # 155
Macrosomia----:---- Page # 155
7 Multiple Gestations and Assisted Reproductive Technology----:---- Page #
closed----:---- Page # 160
7 Multiple Gestations and Assisted Reproductive Technology----:---- Page #
160
Epidemiology of Multiples----:---- Page # 160
Diagnosing Zygosity and Chorionicity----:---- Page # 161
The Effect of Chorionicity----:---- Page # 161
Increase in Monozygotic Twins With Assisted Reproductive
Technology----:---- Page # 162
Age----:---- Page # 163
Zona Pellucida Manipulation----:---- Page # 163
Blastocyst Transfer----:---- Page # 163
Ovulation Induction and Superovulation----:---- Page # 163
Fetal Complications Associated With Multiples----:---- Page # 163
Maternal Complications----:---- Page # 165
Psychosocial Factors----:---- Page # 165
Cost----:---- Page # 165
Decreasing the Risk of Multiples----:---- Page # 166
Multifetal Pregnancy Reduction----:---- Page # 166
Acknowledgment----:---- Page # 167
8 Prematurity and Stillbirth----:---- Page # closed----:---- Page # 172
8 Prematurity and Stillbirth----:---- Page # 172
Demographic Factors and Disparities----:---- Page # 173
Environmental Factors----:---- Page # 174
Nutrition and Maternal Body Weight----:---- Page # 174
Infection and Microbiota----:---- Page # 174
Genetic Factors----:---- Page # 174
Placental and Pregnancy Factors----:---- Page # 175
Prevention of Preterm Birth----:---- Page # 175
Stillbirth----:---- Page # 175
Looking Forward----:---- Page # 175
9 Nonimmune Hydrops----:---- Page # closed----:---- Page # 179
9 Nonimmune Hydrops----:---- Page # 179
Incidence----:---- Page # 179
Etiology----:---- Page # 179
Pathophysiology----:---- Page # 181
Normal Fluid Homeostasis----:---- Page # 181
Derangements in Fluid Homeostasis----:---- Page # 182
Elevated Central Venous Pressure----:---- Page # 182
Decreased Lymphatic Flow----:---- Page # 182
Decreased Oncotic Pressure----:---- Page # 182
Increased Capillary Leak----:---- Page # 182
Prenatal Diagnosis----:---- Page # 182
Prenatal Management----:---- Page # 183
Neonatal Evaluation----:---- Page # 184
Intensive Care of the Infant With Hydrops Fetalis----:---- Page # 184
Respiratory Management----:---- Page # 184
Fluid and Electrolyte Management----:---- Page # 185
Cardiovascular Management----:---- Page # 185
Lymphatic Evaluation and Interventions----:---- Page # 185
Clinical Course and Outcome----:---- Page # 185
10 Maternal Diabetes----:---- Page # closed----:---- Page # 189
III Maternal Health----:---- Page # 189
10 Maternal Diabetes----:---- Page # 189
Types of Diabetes----:---- Page # 189
Type 1 Diabetes----:---- Page # 189
Type 2 Diabetes----:---- Page # 189
Monogenic Diabetes----:---- Page # 189
Gestational Diabetes----:---- Page # 191
Diabetic Embryopathy----:---- Page # 191
Fetal Growth and Macrosomia----:---- Page # 193
Stillbirth and Perinatal Mortality----:---- Page # 194
Maternal Preeclampsia----:---- Page # 195
Obstetric Management of Diabetes in Pregnancy----:---- Page # 196
Preconception Care----:---- Page # 196
Medical Therapy for Diabetes in Pregnancy----:---- Page #
196
Antenatal Monitoring----:---- Page # 197
Delivery Planning----:---- Page # 197
Intrapartum Diabetes Management----:---- Page # 198
Maternal Obesity----:---- Page # 198
Neonatal Complications----:---- Page # 198
Hypoglycemia----:---- Page # 198
Respiratory Distress----:---- Page # 199
Antenatal Corticosteroids for Reduction in Risk of
Respiratory Distress Syndrome----:---- Page # 200
Hypertrophic Cardiomyopathy----:---- Page # 200
Hypocalcemia and Hypomagnesemia----:---- Page # 200
Polycythemia----:---- Page # 201
Hyperbilirubinemia----:---- Page # 201
Breastfeeding----:---- Page # 201
11 Maternal Medical Disorders of Fetal Significance----:---- Page # closed----:----
Page # 207
11 Maternal Medical Disorders of Fetal Significance----:---- Page # 207
General Principles in the Diagnosis and Management of Medical
Complications During Pregnancy----:---- Page # 207
Diagnostic Radiation----:---- Page # 207
Surgery During Pregnancy----:---- Page # 208
Medication Usage----:---- Page # 208
Autoimmune Disorders----:---- Page # 209
Systemic Lupus Erythematosus----:---- Page # 209
Antiphospholipid Antibody Syndrome----:---- Page # 210
Neonatal Lupus----:---- Page # 211
Immune Thrombocytopenia----:---- Page # 212
Heart Disease----:---- Page # 212
Cardiomyopathy----:---- Page # 212
Congenital Heart Disease----:---- Page # 213
Coronary Artery Disease----:---- Page # 213
Renal Disease----:---- Page # 213
Cancer----:---- Page # 214
Principles----:---- Page # 214
Chemotherapy----:---- Page # 214
Radiation Therapy----:---- Page # 215
Cervical Cancer----:---- Page # 216
Breast Cancer----:---- Page # 216
Ovarian Cancer----:---- Page # 216
Survivors of Childhood Cancer----:---- Page # 217
Maternal Seizure Disorders----:---- Page # 217
Perinatal Risk----:---- Page # 217
Fetal Hydantoin Syndrome----:---- Page # 218
Management----:---- Page # 218
Mental Health Disorders----:---- Page # 218
Depression----:---- Page # 218
Postpartum Psychosis----:---- Page # 220
Schizophrenia----:---- Page # 220
12 Hypertensive Complications of Pregnancy----:---- Page # closed----:---- Page #
225
12 Hypertensive Complications of Pregnancy----:---- Page # 225
Classification of Hypertensive Disorders of Pregnancy----:---- Page #
225
Chronic Hypertension----:---- Page # 226
Antihypertensive Treatment of Chronic Hypertension in
Pregnancy----:---- Page # 226
Antenatal Fetal Surveillance in Chronic Hypertension----:----
Page # 227
Gestational Hypertension----:---- Page # 227
Preeclampsia–Eclampsia----:---- Page # 228
Prediction----:---- Page # 229
Prevention----:---- Page # 229
Antepartum Management----:---- Page # 229
Preeclampsia and Fetal Risk----:---- Page # 230
Intrapartum Management----:---- Page # 230
Eclampsia----:---- Page # 231
13 Prenatal Drug Exposure----:---- Page # closed----:---- Page # 234
13 Prenatal Drug Exposure----:---- Page # 234
Epidemiology of Perinatal Substance Exposure----:---- Page # 234
Prevalence----:---- Page # 234
Health Policy----:---- Page # 235
Perinatal Exposure to Specific Substances (Tables 13.1–13.2)----:----
Page # 235
Alcohol----:---- Page # 235
History/Epidemiology----:---- Page # 235
Pharmacology and Biologic Actions----:---- Page # 235
Complications of Pregnancy----:---- Page # 236
Fetal Growth----:---- Page # 237
Fetal Alcohol Spectrum Disorders----:---- Page # 237
Cigarette Smoking and Nicotine----:---- Page # 239
Marijuana----:---- Page # 239
Long-Term Effects of Perinatal Cannabis Exposure----:----
Page # 240
Opioids (Including Prescription Painkillers)----:---- Page # 241
Long-Term Effects of Perinatal Opioid Exposure----:----
Page # 242
Cocaine----:---- Page # 242
Long-Term Effects of Perinatal Cocaine Exposure----:----
Page # 243
Amphetamines----:---- Page # 244
Long-Term Effects of Perinatal Amphetamine
Exposure----:---- Page # 245
Selective Serotonin Reuptake Inhibitors----:---- Page # 245
Identifying Pregnancies and Babies at Risk----:---- Page # 245
Pregnancies----:---- Page # 245
Babies----:---- Page # 246
Pregnancy Management----:---- Page # 246
Maternal Treatment for Opioid Addiction----:---- Page # 247
Methadone Maintenance----:---- Page # 247
Buprenorphine (Suboxone, Subutex)----:---- Page # 247
Human Immunodeficiency Virus and Other Viral Infections----:----
Page # 247
Neonatal Management After Gestational Substance Exposure----:---- Page
# 248
General----:---- Page # 248
Breastfeeding and Drug Exposure----:---- Page # 248
Neonatal Abstinence Syndrome----:---- Page # 249
Clinical Findings----:---- Page # 249
Treatment----:---- Page # 250
Sudden Infant Death Syndrome----:---- Page # 251
14 Antepartum Fetal Assessment----:---- Page # closed----:---- Page # 257
IV Labor and Delivery----:---- Page # 257
14 Antepartum Fetal Assessment----:---- Page # 257
General Principles----:---- Page # 257
Principles of Testing----:---- Page # 257
Fetal Physiology and Behavior----:---- Page # 257
Technology----:---- Page # 258
Indications and Timing----:---- Page # 258
Fetal Assessment in Low-Risk Pregnancies----:---- Page # 258
Ultrasound\: Pregnancy Dating----:---- Page # 258
Ultrasound\: Second and Third Trimesters----:---- Page #
259
Fetal Movement Counting----:---- Page # 260
Fetal Assessment in High-Risk Pregnancies----:---- Page # 260
Cardiotocography----:---- Page # 260
Nonstress Test----:---- Page # 261
Contraction Stress Test----:---- Page # 261
Ultrasound----:---- Page # 262
Growth Assessment----:---- Page # 263
Amniotic Fluid Assessment----:---- Page # 265
Biophysical Profile----:---- Page # 265
Doppler----:---- Page # 267
15 Complicated Deliveries----:---- Page # closed----:---- Page # 273
15 Complicated Deliveries----:---- Page # 273
Overview----:---- Page # 273
Vaginal Delivery----:---- Page # 273
Cesarean Section----:---- Page # 274
Operative Vaginal Delivery\: Obstetric Forceps and Vacuum
Extraction----:---- Page # 274
Description of the Obstetric Forceps----:---- Page # 274
Indications for Use of Obstetric Forceps----:---- Page # 275
Forceps and Potential Neonatal Morbidity----:---- Page # 275
Vacuum Delivery\: Indications, Uses, and Comparison With Forceps
Procedures----:---- Page # 276
Shoulder Dystocia----:---- Page # 278
Vaginal Breech Delivery----:---- Page # 280
Multifetal Delivery----:---- Page # 281
Twin Delivery----:---- Page # 281
Vertex–Vertex----:---- Page # 281
Vertex–Nonvertex----:---- Page # 282
Nonvertex–Nonvertex----:---- Page # 282
Monochorionic, Monoamniotic Twins----:---- Page # 282
Higher-Order Multiple Gestations----:---- Page # 282
Vaginal Birth After Cesarean\: Neonatal Concerns----:---- Page # 283
Cord Accidents----:---- Page # 283
16 Obstetric Analgesia and Anesthesia----:---- Page # closed----:---- Page # 287
16 Obstetric Analgesia and Anesthesia----:---- Page # 287
History of Obstetric Anesthesia----:---- Page # 287
Anatomy of Labor Pain----:---- Page # 287
Changes in Maternal Physiology and the Implications----:---- Page # 288
Maternal Circulatory System----:---- Page # 288
Maternal Airway and Respiratory Systems----:---- Page # 288
Maternal Gastrointestinal System----:---- Page # 288
Uterine and Fetal Circulation----:---- Page # 288
Analgesic Options for Labor and Vaginal Delivery----:---- Page # 289
Nonpharmacologic Analgesia----:---- Page # 289
Systemic Medications----:---- Page # 289
Inhaled Nitrous Oxide----:---- Page # 290
Neuraxial (Regional) Analgesia----:---- Page # 290
Neuraxial Local Anesthetics----:---- Page # 290
Neuraxial Opioids----:---- Page # 290
Neuraxial Techniques for Labor Analgesia----:---- Page # 291
Epidural Analgesia----:---- Page # 291
Effects on the Progress of Labor and Rate of Operative
Delivery----:---- Page # 292
Spinal Analgesia----:---- Page # 292
Combined Spinal–Epidural Analgesia----:---- Page # 292
Contraindications and Complications of Neuraxial
Techniques----:---- Page # 292
Paracervical Block----:---- Page # 293
Pudendal Block----:---- Page # 293
Anesthesia for Cesarean Delivery----:---- Page # 293
Epidural Anesthesia for Cesarean Delivery----:---- Page # 293
Spinal Anesthesia for Cesarean Delivery----:---- Page # 294
Local Anesthesia----:---- Page # 294
General Anesthesia----:---- Page # 294
Induction Agents----:---- Page # 294
Nitrous Oxide----:---- Page # 294
Inhaled Halogenated Anesthetics----:---- Page # 295
Neuromuscular Blocking Agents----:---- Page # 295
17 The Human Genome and Neonatal Care----:---- Page # closed----:---- Page # 299
V Genetics----:---- Page # 299
17 The Human Genome and Neonatal Care----:---- Page # 299
History of Mapping and Sharing the Genome----:---- Page # 299
Defining the Genome and Genomics----:---- Page # 300
Mitochondrial DNA----:---- Page # 300
Types of Variation in the Human Genome----:---- Page # 300
Single Nucleotide Polymorphisms----:---- Page # 300
Copy Number Variants----:---- Page # 301
Current Variant Counts----:---- Page # 301
Regulation of Gene Expression----:---- Page # 301
Connecting Genes to Diseases----:---- Page # 302
Identification of Disease-Related Genes----:---- Page # 302
Making a Diagnosis in the Human Genome Era----:---- Page #
303
Applying Exomes and Whole Genome Sequences in Clinical
Complex Common/Multigenic Diseases of Newborns----:----
Page # 306
Guidelines and Recommendations for Integration of Genomics Into
Practice----:---- Page # 308
Prenatal Identification of Genetic Disorders----:---- Page # 308
The Future----:---- Page # 308
18 Prenatal Diagnosis----:---- Page # closed----:---- Page # 311
18 Prenatal Diagnosis----:---- Page # 311
Principles of Prenatal Screening and Diagnosis----:---- Page # 311
Invasive Prenatal Diagnostic Procedures----:---- Page # 311
Midtrimester Genetic Amniocentesis----:---- Page # 311
Chorionic Villus Sampling----:---- Page # 312
Percutaneous Umbilical Cord Blood Sampling----:---- Page # 313
Genetic Testing of the Fetus----:---- Page # 314
Microarray Technology----:---- Page # 315
Exome Sequencing----:---- Page # 316
Noninvasive Prenatal Screening----:---- Page # 316
Maternal Serum Screening----:---- Page # 316
Prenatal Fetal Imaging----:---- Page # 317
Cell-Free DNA (Noninvasive Prenatal Testing)----:---- Page # 319
Preimplantation Genetic Diagnosis/Screening----:---- Page # 320
Preimplantation Genetics----:---- Page # 320
19 The Dysmorphic Infant----:---- Page # closed----:---- Page # 323
19 The Dysmorphic Infant----:---- Page # 323
Prenatal----:---- Page # 323
Birth----:---- Page # 323
Medical----:---- Page # 324
Pedigree Analysis and Family History----:---- Page # 324
Physical Examination for Dysmorphology----:---- Page # 325
Adjunct Studies----:---- Page # 328
Literature Review----:---- Page # 329
Specialized Laboratory Tests----:---- Page # 331
Diagnosis----:---- Page # 331
20 Chromosome Disorders----:---- Page # closed----:---- Page # 334
20 Chromosome Disorders----:---- Page # 334
Human Karyotype----:---- Page # 334
Trisomies----:---- Page # 336
Down Syndrome (Trisomy 21)----:---- Page # 336
Clinical Features----:---- Page # 336
Genetic Counseling----:---- Page # 337
Trisomy 18 (Edwards Syndrome)----:---- Page # 338
Trisomy 13 (Patau Syndrome)----:---- Page # 338
45,X (Turner Syndrome)----:---- Page # 339
Triploidy (69,XXX or 69,XXY)----:---- Page # 339
Deletion Syndromes----:---- Page # 339
Chromosome 1p Deletion Syndrome (1p–)----:---- Page # 339
Wolf–Hirschhorn Syndrome (4p–)----:---- Page # 340
Cri du Chat Syndrome (5p–)----:---- Page # 340
Chromosomal Microarrays----:---- Page # 340
Segmental Duplications and Microdeletion Syndromes----:---- Page # 341
Williams–Beuren Syndrome (7q11.2 Deletion)----:---- Page # 342
22q11.2 Deletion Syndrome----:---- Page # 343
Additional Microdeletion and Microduplication Syndromes----:---- Page #
344
Disorders of Imprinted Chromosomes----:---- Page # 344
Prader–Willi Syndrome----:---- Page # 344
Angelman Syndrome----:---- Page # 345
Beckwith–Wiedemann Syndrome----:---- Page # 345
Russell–Silver Syndrome----:---- Page # 346
21 Introduction to Metabolic and Biochemical Genetic Diseases----:---- Page #
closed----:---- Page # 349
VI Metabolic Disorders of the Newborn----:---- Page # 349
21 Introduction to Metabolic and Biochemical Genetic Diseases----:----
Page # 349
Classification of Inborn Errors of Metabolism----:---- Page # 350
Signs and Symptoms of Inborn Errors----:---- Page # 351
Emergency Treatment----:---- Page # 354
22 Inborn Errors of Carbohydrate, Ammonia, Amino Acid, and Organic Acid
Metabolism----:---- Page # closed----:---- Page # 355
22 Inborn Errors of Carbohydrate, Ammonia, Amino Acid, and Organic Acid
Carbohydrate Metabolism Disorders----:---- Page # 355
Galactosemia----:---- Page # 355
Epimerase Deficiency Galactosemia----:---- Page # 359
Galactokinase Deficiency----:---- Page # 359
Glycogen Storage Diseases----:---- Page # 359
Hepatic Glycogen Storage Diseases----:---- Page # 359
Muscular Glycogen Storage Diseases----:---- Page # 359
Fructose Metabolism----:---- Page # 361
Urea Cycle Disorders----:---- Page # 361
Transient Hyperammonemia of the Newborn----:---- Page # 363
Amino Acid Metabolism Disorders----:---- Page # 363
Maple Syrup Urine Disease----:---- Page # 363
Tyrosinemia Type 1----:---- Page # 365
Nonketotic Hyperglycinemia----:---- Page # 365
Hyperhomocystinemias and Remethylation Disorders----:---- Page #
366
Phenylketonuria----:---- Page # 366
Organic Acidemias----:---- Page # 367
Methylmalonic Acidemia----:---- Page # 367
Propionic Acidemia----:---- Page # 368
Isovaleric Acidemia----:---- Page # 369
Multiple Carboxylase Deficiency----:---- Page # 369
Glutaric Aciduria Type 1----:---- Page # 369
Fatty Acid Oxidation Disorders----:---- Page # 370
Medium-Chain Acyl-CoA Dehydrogenase Deficiency----:---- Page #
370
Very Long Chain Acyl-CoA Dehydrogenase Deficiency----:---- Page #
371
Short-Chain Acyl-CoA Dehydrogenase Deficiency----:---- Page # 371
Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency and
Trifunctional Protein Deficiency----:---- Page # 371
Primary Carnitine Transporter Deficiency----:---- Page # 371
Carnitine Palmitoyltransferase Type I Deficiency----:---- Page #
372
Carnitine Acylcarnitine Translocase Deficiency----:---- Page #
372
Carnitine Palmitoyltransferase Type II Deficiency----:---- Page #
372
Multiple Acyl-CoA Dehydrogenase Deficiency----:---- Page # 372
Ketone Metabolism Disorders----:---- Page # 373
Primary Lactic Acidosis----:---- Page # 373
Pyruvate Dehydrogenase Complex Deficiency----:---- Page # 374
Pyruvate Carboxylase Deficiency----:---- Page # 374
Electron Transport Chain Defects----:---- Page # 374
Benign Infantile Mitochondrial Myopathy, Cardiomyopathy, or
Both----:---- Page # 375
Lethal Infantile Mitochondrial Disease----:---- Page # 376
Leigh Disease\: Subacute Necrotizing Encephalomyelopathy----:----
Page # 376
Pearson Syndrome----:---- Page # 376
Barth Syndrome----:---- Page # 376
Early Lethal Lactic Acidosis----:---- Page # 376
23 Lysosomal Storage, Peroxisomal, and Glycosylation Disorders and Smith–Lemli–
Opitz Syndrome Presenting in the Neonate----:---- Page # closed----:---- Page # 382
23 Lysosomal Storage, Peroxisomal, and Glycosylation Disorders and Smith–
Lemli–Opitz Syndrome Presenting in the Neonate----:---- Page # 382
Lysosomal Storage Disorders----:---- Page # 384
Clinical Presentations----:---- Page # 387
Niemann–Pick A Disease (Acute, Sphingomyelinase
Deficient)----:---- Page # 387
Niemann–Pick C Disease----:---- Page # 388
Gaucher Disease Type 2 (Acute Neuropathic)----:---- Page #
389
Krabbe Disease (Globoid Cell Leukodystrophy)----:---- Page
# 389
GM1 Gangliosidosis----:---- Page # 389
Farber Lipogranulomatosis----:---- Page # 390
Sialidosis----:---- Page # 390
Galactosialidosis----:---- Page # 390
Wolman Disease----:---- Page # 391
Infantile Sialic Acid Storage Disease----:---- Page # 391
I-Cell Disease (Mucolipidosis Type II)----:---- Page # 391
Mucolipidosis Type IV----:---- Page # 391
Mucopolysaccharidosis Type VII (Sly Disease)----:---- Page
# 391
Diagnosis, Management, and Prognosis----:---- Page # 392
Congenital Disorders of Glycosylation----:---- Page # 393
Clinical Presentations----:---- Page # 393
N-Linked Protein Glycosylation Defects----:---- Page # 394
O-Linked Protein Glycosylation Defects----:---- Page # 394
Combined Glycosylation Defects----:---- Page # 395
Glycosylphosphatidylinositol Anchor Glycosylation
Defects----:---- Page # 395
Lipid Glycosylation Defects----:---- Page # 395
Treatment, Management, and Prognosis----:---- Page # 396
Peroxisomal Disorders----:---- Page # 396
Disorders of Peroxisomal Biogenesis----:---- Page # 396
Zellweger Syndrome----:---- Page # 397
Neonatal Adrenoleukodystrophy----:---- Page # 397
Infantile Refsum Disease----:---- Page # 397
Rhizomelic Chondrodysplasia Punctata----:---- Page # 397
Peroxisomal Fission Defects----:---- Page # 397
Single Peroxisomal Enzyme Defects----:---- Page # 398
D-Bifunctional Protein Deficiency----:---- Page # 398
Acyl Coenzyme A Oxidase Deficiency----:---- Page # 398
2-Methylacyl Coenzyme A Racemase Deficiency----:---- Page #
398
X-Linked Adrenoleukodystrophy----:---- Page # 398
Diagnosis, Management, and Prognosis----:---- Page # 398
Smith–Lemli–Opitz Syndrome----:---- Page # 399
24 Newborn Resuscitation----:---- Page # closed----:---- Page # 405
VII Basic Newborn Care----:---- Page # 405
24 Newborn Resuscitation----:---- Page # 405
Transition From Fetal to Extrauterine Life----:---- Page # 406
Environment and Preparation----:---- Page # 407
Transition and Resuscitation----:---- Page # 409
Recommendations and Evidence for Delayed Cord
Clamping----:---- Page # 409
Cord Milking----:---- Page # 409
Breathing During Delayed Cord Clamping----:---- Page # 410
Delivery Room Monitoring----:---- Page # 411
Assessment----:---- Page # 411
Heart Rate----:---- Page # 411
Airway Pressure----:---- Page # 411
Initial Steps\: Temperature Management and Maintaining the
Airway----:---- Page # 413
Assisting Ventilation----:---- Page # 413
Transitional Oxygenation and Oxygen Use----:---- Page # 415
Assisting Circulation----:---- Page # 416
Apgar Score----:---- Page # 418
Specific Problems Encountered During Resuscitation----:---- Page
# 418
Neonatal Response to Maternal Anesthesia/Analgesia----:----
Page # 418
The Use of Early Caffeine----:---- Page # 418
Conditions Complicating Resuscitation----:---- Page # 419
Limits of Viability----:---- Page # 419
Care After Resuscitation----:---- Page # 420
25 Newborn Evaluation----:---- Page # closed----:---- Page # 425
25 Newborn Evaluation----:---- Page # 425
Initial Newborn Evaluation\: Key Elements----:---- Page # 425
Physical Examination Considerations----:---- Page # 426
Examination at Birth and Delivery Room Disposition----:----
Page # 427
Nursery Admission Examination----:---- Page # 427
Targeted or Problem-Directed Evaluation----:---- Page # 427
Daily Follow-Up Encounter----:---- Page # 427
Nursery Discharge Examination----:---- Page # 427
Performance of Examination----:---- Page # 427
Approach to the Newborn Examination----:---- Page # 427
Environment----:---- Page # 427
Evaluation of Gestational Age----:---- Page # 428
Determination of Key Metrics----:---- Page # 428
Initial Observation----:---- Page # 428
Example Examination Sequence----:---- Page # 430
Detailed Physical Examination----:---- Page # 430
Skin----:---- Page # 430
Head----:---- Page # 436
Face----:---- Page # 438
Ears----:---- Page # 438
Eyes----:---- Page # 439
Nose----:---- Page # 439
Mouth and Oral Cavity----:---- Page # 439
Neck----:---- Page # 440
Chest Wall----:---- Page # 440
Lungs and Respiration----:---- Page # 440
Cardiovascular System----:---- Page # 441
Abdomen----:---- Page # 442
Genitalia and Perineum----:---- Page # 442
Back----:---- Page # 443
Musculoskeletal System----:---- Page # 443
Hips.----:---- Page # 443
Neurologic Examination----:---- Page # 443
Neonatal Reflexes.----:---- Page # 444
Brachial Plexus Injury.----:---- Page # 445
Cranial Nerves.----:---- Page # 445
Books----:---- Page # 446
Guidelines and Policy Statements----:---- Page # 446
Online Resources----:---- Page # 447
26 Newborn Nursery Care----:---- Page # closed----:---- Page # 449
26 Newborn Nursery Care----:---- Page # 449
Initial Assessment----:---- Page # 449
Routine Testing----:---- Page # 450
Glucose----:---- Page # 450
Newborn Metabolic Screening----:---- Page # 451
Hearing Screening----:---- Page # 451
Screening for Critical Congenital Heart Disease----:---- Page #
452
Prenatal Ultrasound Screening for Birth Defects----:---- Page #
452
Central Nervous System Findings----:---- Page # 452
Cardiac Findings----:---- Page # 453
Gastrointestinal Findings----:---- Page # 453
Urinary Tract Findings----:---- Page # 453
Car Seats and the Newborn Car Seat Challenge----:---- Page # 453
Routine and Common Medical Treatments----:---- Page # 453
Prevention of Ophthalmia Neonatorum and Conjunctivitis----:----
Page # 453
Vitamin K----:---- Page # 454
Circumcision----:---- Page # 455
Hepatitis B Vaccine----:---- Page # 456
Ongoing Care----:---- Page # 456
Umbilical Cords----:---- Page # 456
Umbilical Cord Variants----:---- Page # 456
Prevention of Omphalitis----:---- Page # 456
Delayed Cord Clamping----:---- Page # 456
Umbilical Cord Blood Banking----:---- Page # 456
Breastfeeding----:---- Page # 457
Benefits of Breastfeeding----:---- Page # 457
Support of Breastfeeding----:---- Page # 457
Breastfeeding Problems----:---- Page # 457
Supplementation of Breastfeeding----:---- Page # 459
Contraindications to Breastfeeding----:---- Page # 459
Bottle feeding----:---- Page # 459
Anticipatory Guidance----:---- Page # 460
Sleep Position----:---- Page # 461
Discharge and Follow-Up----:---- Page # 461
Common Problems During the Nursery Stay----:---- Page # 461
Hypothermia and Hyperthermia----:---- Page # 461
Hypothermia----:---- Page # 461
Hyperthermia----:---- Page # 462
Elimination----:---- Page # 462
Urination----:---- Page # 462
Defecation----:---- Page # 462
Jaundice----:---- Page # 462
Respiratory Complications----:---- Page # 464
Cardiovascular Issues----:---- Page # 465
Possible Neonatal Sepsis----:---- Page # 465
Group B Streptococcus Screening and Intrapartum Antibiotic
Prophylaxis----:---- Page # 466
Evaluation of Perinatal Risk Factors----:---- Page # 466
Clinical and Laboratory Evaluation----:---- Page # 467
27 Newborn Screening----:---- Page # closed----:---- Page # 475
27 Newborn Screening----:---- Page # 475
Screening Procedure----:---- Page # 476
Specimen----:---- Page # 476
Specimen Collection----:---- Page # 476
Timing of Collection----:---- Page # 476
Screening Tests----:---- Page # 479
Secondary Tests----:---- Page # 479
Physician Contact for Abnormal Results----:---- Page # 479
Screened Disorders----:---- Page # 481
Metabolic Disorders----:---- Page # 481
Amino Acid Disorders----:---- Page # 481
Homocystinuria----:---- Page # 482
Tyrosinemia----:---- Page # 482
Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency and
Other Fatty Acid Oxidation Disorders----:---- Page # 483
Organic Acid Disorders----:---- Page # 483
Biotinidase Deficiency----:---- Page # 484
X-Linked Adrenoleukodystrophy----:---- Page # 485
Endocrine Disorders----:---- Page # 485
Congenital Hypothyroidism----:---- Page # 485
Congenital Adrenal Hyperplasia----:---- Page # 485
Sickle Cell Disease----:---- Page # 486
Cystic Fibrosis----:---- Page # 486
Severe Combined Immunodeficiency----:---- Page # 486
Hearing Loss----:---- Page # 486
Critical Congenital Heart Disease----:---- Page # 486
Specific Issues in Newborn Screening----:---- Page # 487
Criteria for Newborn Screening----:---- Page # 487
False-positive Results----:---- Page # 487
Increased Detection by Screening----:---- Page # 488
Missed Cases----:---- Page # 488
The Future----:---- Page # 489
28 Neonatal Transport----:---- Page # closed----:---- Page # 493
VIII High-Risk Newborn Care----:---- Page # 493
28 Neonatal Transport----:---- Page # 493
Regionalization of Neonatal Care, Care in the Community, and
Transfer Agreements----:---- Page # 493
Historical Perspective----:---- Page # 493
Care in the Community and Back Transport----:---- Page #
494
Transfer Agreements----:---- Page # 494
Transport Communication----:---- Page # 494
Medical Supervision----:---- Page # 495
Mode of Transport----:---- Page # 495
Transport Personnel, Education, and Team Composition----:----
Page # 496
Quality Improvement----:---- Page # 497
Transport Administration----:---- Page # 497
Transport Safety----:---- Page # 498
Family-Centered Care----:---- Page # 498
Medical Legal Issues----:---- Page # 498
Patient Care During Transport----:---- Page # 499
Extreme Prematurity and the Limits of Viability----:----
Page # 499
Thermoregulation----:---- Page # 500
Hypoxic Respiratory Failure----:---- Page # 500
Neurologic Issues----:---- Page # 501
Supplemental Oxygen----:---- Page # 503
Prostaglandin E1 Therapy----:---- Page # 503
Vascular Access----:---- Page # 504
Surgical Emergencies----:---- Page # 504
Congenital Diaphragmatic Hernia----:---- Page # 504
Abdominal Wall Defects----:---- Page # 504
Esophageal Atresia and Tracheoesophageal
Fistula----:---- Page # 505
Midgut Volvulus----:---- Page # 505
Necrotizing Enterocolitis----:---- Page # 505
Meningomyelocele----:---- Page # 505
29 Temperature Regulation----:---- Page # closed----:---- Page # 512
29 Temperature Regulation----:---- Page # 512
Mechanisms of Heat Loss----:---- Page # 512
Evaporation----:---- Page # 512
Radiation----:---- Page # 513
Convection----:---- Page # 513
Conduction----:---- Page # 513
Mechanisms of Thermoregulation----:---- Page # 513
Nonshivering Thermogenesis----:---- Page # 514
Thermal Management Strategies----:---- Page # 515
Delivery Room Environment----:---- Page # 515
Care of the Extremely Low Birth Weight Infant----:---- Page # 515
Warming Babies----:---- Page # 515
Incubators Versus Radiant Warmers----:---- Page # 515
Weaning to an Open Crib----:---- Page # 516
Skin-to-Skin Care----:---- Page # 516
Additional Considerations----:---- Page # 516
Transport----:---- Page # 516
Hyperthermia----:---- Page # 517
Bathing----:---- Page # 517
30 Fluid, Electrolyte, and Acid–Base Balance----:---- Page # closed----:---- Page #
520
30 Fluid, Electrolyte, and Acid–Base Balance----:---- Page # 520
Fluid and Electrolyte Balance----:---- Page # 520
Developmental Changes Affecting Fluid and Electrolyte Balance in
the Fetus and Neonate----:---- Page # 520
Developmental Changes in Body Composition and Fluid
Compartments----:---- Page # 520
Changes During Intrauterine Development----:---- Page
# 520
Changes During Labor and Delivery----:---- Page # 520
Effect of Timing of Cord Clamping----:---- Page # 521
Changes in the Postnatal Period----:---- Page # 521
Physiology of the Regulation of Body Composition and Fluid
Regulation of the Intracellular Solute and Water
Compartment----:---- Page # 521
Regulation of the Intracellular–Extracellular
Interface\: the Interstitial Compartment----:---- Page # 522
Regulation of the Extracellular Solute and Water
Maturation of Organs Regulating Body Composition and Fluid
Maturation of the Cardiovascular System----:---- Page
# 523
Maturation of Renal Function----:---- Page # 523
Maturation of the Skin----:---- Page # 524
Maturation of End-Organ Responsiveness to Hormones
Involved in the Regulation of Fluid and Electrolyte Balance----:---- Page # 524
Renin–Angiotensin–Aldosterone System.----:----
Page # 524
Vasopressin.----:---- Page # 525
Atrial Natriuretic Peptide.----:---- Page # 525
Brain (or B-Type) Natriuretic Peptide.----:----
Page # 525
Prostaglandins.----:---- Page # 525
Prolactin.----:---- Page # 525
Management of Fluid and Electrolyte Homeostasis----:---- Page #
525
General Principles of Fluid and Electrolyte
Assessment of Fluid and Electrolyte Status----:----
Page # 525
Water Homeostasis and Management----:---- Page # 526
Water Losses----:---- Page # 526
Management of Water Requirements----:---- Page # 526
Treatment of Fluid Overload----:---- Page # 527
Treatment of Dehydration----:---- Page # 527
Sodium and Potassium Homeostasis and Management----:----
Page # 527
Hyponatremia----:---- Page # 527
Hypernatremia----:---- Page # 528
Treatment of Hypernatremia.----:---- Page # 530
Potassium Homeostasis and Management----:---- Page #
531
Hypokalemia.----:---- Page # 531
Treatment of Hypokalemia.----:---- Page #
531
Hyperkalemia.----:---- Page # 531
Treatment of Hyperkalemia.----:---- Page
# 531
Clinical Conditions Associated With Fluid and Electrolyte
Disturbances----:---- Page # 532
Extreme Prematurity----:---- Page # 532
Transient Tachypnea of the Newborn----:---- Page # 533
Bronchopulmonary Dysplasia----:---- Page # 533
Patent Ductus Arteriosus and Treatment With
Indomethacin/Ibuprofen----:---- Page # 534
Syndrome of Inappropriate Antidiuretic Hormone
Secretion----:---- Page # 534
Surgical Conditions----:---- Page # 534
Acid–Base Balance----:---- Page # 535
Physiology of Acid–Base Balance Regulation----:---- Page # 535
Disturbances of Acid–Base Balance in the Newborn----:---- Page #
536
General Principles----:---- Page # 536
Transitional Physiology After Birth----:---- Page # 537
Metabolic Acidosis----:---- Page # 537
Respiratory Acidosis----:---- Page # 540
Metabolic Alkalosis----:---- Page # 540
Respiratory Alkalosis----:---- Page # 541
31 Extremely Low-Birth-Weight Infants----:---- Page # closed----:---- Page # 546
31 Extremely Low-Birth-Weight Infants----:---- Page # 546
Perinatal Management----:---- Page # 547
Prenatal Consultation----:---- Page # 547
General Principles of Care Specific to Extremely Low Birth Weight
Infants----:---- Page # 549
First Hours----:---- Page # 549
Delivery Room----:---- Page # 549
Admission to the Neonatal Intensive Care Unit----:---- Page # 550
Vascular Access----:---- Page # 551
Skin Care----:---- Page # 551
Mechanical Ventilation and Noninvasive Respiratory
Support----:---- Page # 552
Noninvasive Ventilation----:---- Page # 552
Conventional Mechanical Ventilation----:---- Page # 553
High-Frequency Ventilation----:---- Page # 553
Postextubation Continuous Positive Airway Pressure and High-Flow
Nasal Cannula Therapy for Respiratory Distress Syndrome and Apnea----:---- Page #
554
Adjunctive Therapies to Prevent Bronchopulmonary
Dysplasia----:---- Page # 554
Vitamin A Supplementation----:---- Page # 554
Caffeine----:---- Page # 554
Inhaled Nitric Oxide----:---- Page # 554
Systemic Corticosteroids----:---- Page # 554
Nutritional Management----:---- Page # 555
Enteral Nutrition----:---- Page # 555
Early Parenteral Nutrition----:---- Page # 555
Management and Prevention of Infection----:---- Page # 556
Early-Onset Infections----:---- Page # 556
Late-Onset Infections----:---- Page # 557
Prevention of Nosocomial Infection----:---- Page # 557
Neurosensory Complications----:---- Page # 558
Developmental and Parental Care----:---- Page # 559
Suggested References----:---- Page # 559
32 Late Preterm Infants----:---- Page # closed----:---- Page # 566
32 Late Preterm Infants----:---- Page # 566
Definition----:---- Page # 567
Pathophysiology and Clinical Course----:---- Page # 568
Respiratory----:---- Page # 568
Gastrointestinal----:---- Page # 571
Nutrition----:---- Page # 571
Hyperbilirubinemia----:---- Page # 574
Infectious Diseases----:---- Page # 574
Thermoregulation----:---- Page # 574
Neurodevelopment----:---- Page # 575
Hospitalization of the Late Preterm Infant----:---- Page # 575
Recommendations----:---- Page # 576
Admission Criteria----:---- Page # 576
Discharge Criteria----:---- Page # 576
Follow-Up After Discharge----:---- Page # 577
Readmission to the Hospital----:---- Page # 577
Outcomes----:---- Page # 578
Future Research----:---- Page # 578
Definition, Epidemiology, and Background----:---- Page # 579
Pathophysiology and Clinical Course----:---- Page # 579
Long-Term Outcome----:---- Page # 579
33 Neonatal Pharmacology----:---- Page # closed----:---- Page # 582
33 Neonatal Pharmacology----:---- Page # 582
Principles of Neonatal Therapeutics----:---- Page # 582
Absorption----:---- Page # 582
Distribution----:---- Page # 583
Excretion----:---- Page # 584
Pharmacogenetics and Pharmacogenomics----:---- Page # 584
Pharmacokinetic Principles----:---- Page # 585
Apparent Volume of Distribution----:---- Page # 585
First-Order Kinetics----:---- Page # 586
Half-Life----:---- Page # 586
Multicompartment First-Order Kinetics----:---- Page # 586
Apparent Single-Compartment First-Order Kinetics----:---- Page #
587
Zero-Order Kinetics----:---- Page # 587
Noncompartmental Analysis----:---- Page # 587
Population Pharmacokinetics----:---- Page # 588
Target Drug Concentration Strategy----:---- Page # 588
Therapeutic Drug Monitoring----:---- Page # 588
Pharmacokinetic-Based Dosing----:---- Page # 588
Repetitive Dosing and the “Plateau Principle”----:---- Page # 589
Clearance----:---- Page # 589
Modeling and Simulations----:---- Page # 590
Clinical Applications of Pharmacokinetics----:---- Page # 591
How to Estimate Dose Adjustments----:---- Page # 591
Gentamicin----:---- Page # 591
Phenobarbital----:---- Page # 591
Drug-Induced Illness----:---- Page # 592
Illustrations of Drug-Induced Illnesses in Neonates----:---- Page
# 592
Reduction and Prevention of Medication Errors in Newborn
Care----:---- Page # 592
Drug Excretion in Breast Milk----:---- Page # 593
34 Neonatal Pain and Stress - Assessment and Management----:---- Page #
closed----:---- Page # 597
34 Neonatal Pain and Stress----:---- Page # 597
Historical Timeline----:---- Page # 597
Development of Public Policy----:---- Page # 598
Recent International Surveys of Clinical Practice----:---- Page # 598
Ontogeny and Development of Pain and Stress Responses----:---- Page #
599
Assessment of Neonatal Pain and Stress----:---- Page # 599
Assessment of the Neonatal Behavioral Responses to Pain----:----
Page # 599
Infant Pain Scores----:---- Page # 600
Bedside Noninvasive Neurophysiologic Measures to Evaluate Pain
and Stress----:---- Page # 601
Long-Term Consequences of Neonatal Pain and Stress----:---- Page # 602
Clinical Pain and Stress Management Strategies----:---- Page # 602
Surgical Anesthesia----:---- Page # 602
Fetal Surgery----:---- Page # 602
Neonatal Surgery----:---- Page # 602
Postoperative Pain Management Strategies----:---- Page # 603
Mechanical Ventilation----:---- Page # 603
Procedures----:---- Page # 604
Blood Sampling and Monitoring----:---- Page # 604
Tracheal Intubation----:---- Page # 604
Circumcision----:---- Page # 604
Other Invasive Procedures----:---- Page # 605
Pharmacologic Analgesia----:---- Page # 605
Nonopioid Analgesics----:---- Page # 605
Nonsteroidal Antiinflammatory Drugs (Indomethacin,
Ibuprofen, Ketorolac)----:---- Page # 605
Acetaminophen----:---- Page # 605
Opioid Analgesics----:---- Page # 605
Morphine----:---- Page # 606
Fentanyl----:---- Page # 606
Enterally Dosed Opioids----:---- Page # 606
Mixed Opioid Agonist–Antagonists----:---- Page # 606
Long-Term Effects of Neonatal Opioid Exposure----:---- Page # 607
Experimental Animal Studies----:---- Page # 607
Clinical Studies----:---- Page # 607
Topical and Local Anesthetics----:---- Page # 607
Sedatives----:---- Page # 608
Benzodiazepines----:---- Page # 608
Dexmedetomidine----:---- Page # 608
Nonpharmacologic Analgesia----:---- Page # 608
35 Palliative Care----:---- Page # closed----:---- Page # 617
35 Palliative Care----:---- Page # 617
What Is Palliative Care?----:---- Page # 617
Paradigms of Palliative Care----:---- Page # 617
Scope of the Problem----:---- Page # 618
Which Patients Benefit From Palliative Care in the Neonatal Intensive
Care Unit?----:---- Page # 618
Components of Palliative Care in the Neonatal Intensive Care
Unit----:---- Page # 619
Grief and Bereavement Support----:---- Page # 620
Timing of the News----:---- Page # 620
Early Prenatal Diagnosis----:---- Page # 620
Late Prenatal Diagnosis----:---- Page # 620
Postnatal Diagnosis----:---- Page # 620
End-of-Life Care----:---- Page # 621
Ethical Concerns----:---- Page # 622
Barriers to Palliative Care in the Neonatal Intensive Care
Unit----:---- Page # 622
Training in Neonatal–Perinatal Palliative Care----:---- Page # 622
Research Opportunities/Future Directions----:---- Page # 622
36 Immunology of the Fetus and Newborn----:---- Page # closed----:---- Page # 626
IX Immunology and Infections----:---- Page # 626
36 Immunology of the Fetus and Newborn----:---- Page # 626
Maternal and Placental Immunology----:---- Page # 626
Role of Regulatory T Cells in Pregnancy----:---- Page # 628
Role of the Microbiome----:---- Page # 629
Effect of Pregnancy Complications on the Developing Fetal
Immune System----:---- Page # 629
Developmental Fetal–Neonatal Immunology----:---- Page # 630
Innate Immunity----:---- Page # 630
Complement----:---- Page # 630
Antimicrobial Proteins and Peptides----:---- Page #
633
Innate Lymphoid Cells, Including Natural Killer
Cells----:---- Page # 633
Polymorphonuclear Neutrophils----:---- Page # 634
Monocytes, Macrophages, and Dendritic Cells----:----
Page # 635
Adaptive Immunity----:---- Page # 635
T Lymphocytes----:---- Page # 635
Thymocyte Development----:---- Page # 635
Recent Thymic Emigrants and the Naïve T-Cell
Naïve CD4 T-Cell Activation Into Effector Th1,
Th2, Th17, and Follicular Helper T Cells----:---- Page # 639
Effector CD4 T-Cell Response to Herpes Simplex
Virus Infection----:---- Page # 640
Naïve CD8 T-Cell Activation Into Cytolytic
Effector Cells----:---- Page # 640
Antigen-Specific Memory T-Cell
Responses----:---- Page # 640
Regulatory T Cells----:---- Page # 641
γδ T Cells----:---- Page # 641
Natural Killer T Cells----:---- Page # 641
Mucosal-Associated Invariant T Cells----:----
Page # 642
B Lymphocytes----:---- Page # 642
B-Cell Development----:---- Page # 642
B-Cell Preimmune Selection and
Maturation----:---- Page # 644
Fetal and Neonatal B-Cell Development and
Surface Phenotype----:---- Page # 644
B-Cell Activation, Somatic Hypermutation, and
Isotype Switching----:---- Page # 644
Neonatal Antibody Responses to T-Dependent and T-
Independent Antigens----:---- Page # 645
Immunoglobulins----:---- Page # 645
Immunoglobulin G----:---- Page # 646
Immunoglobulin M----:---- Page # 646
Immunoglobulin A----:---- Page # 647
Immunoglobulin E----:---- Page # 647
Immunoglobulin D----:---- Page # 647
Polyclonal Immunoglobulin Therapy for
Prevention or Treatment of Bacterial Infections----:---- Page # 647
Monoclonal Antibody Prophylaxis to Prevent
Infection----:---- Page # 648
Specific Immunologic Deficiencies of the Newborn and Their
Severe Combined Immunodeficiency----:---- Page # 648
DiGeorge Syndrome----:---- Page # 650
Combined Immune Disorders Involving T Cells and B
Cells----:---- Page # 651
B-Cell Immunodeficiencies----:---- Page # 651
Innate Immune Deficiency Disorders----:---- Page # 651
Immunization----:---- Page # 651
Maternal Immunization----:---- Page # 651
Immunization of the Prematurely Born Infant----:---- Page #
652
Neonatal Immunization----:---- Page # 653
Acknowledgments----:---- Page # 654
37 Viral Infections of the Fetus and Newborn----:---- Page # closed----:---- Page #
662
37 Viral Infections of the Fetus and Newborn----:---- Page # 662
General Diagnostic Approach----:---- Page # 662
Herpesviridae----:---- Page # 664
Herpes Simplex Virus Infections----:---- Page # 665
Virology, Epidemiology, and Clinical Manifestations of
Herpes Simplex Virus Disease----:---- Page # 665
Neonatal Herpes----:---- Page # 665
Treatment and Outcomes----:---- Page # 667
Prospects for Prevention----:---- Page # 671
Varicella–Zoster Virus----:---- Page # 671
Epidemiology of Maternal and Perinatal Varicella–Zoster
Virus Infection----:---- Page # 672
Pathogenesis and Clinical Manifestations----:---- Page #
672
Diagnostic Studies----:---- Page # 673
Cytomegalovirus----:---- Page # 674
Pathogenesis----:---- Page # 675
Clinical Presentation, Sequelae, and Prognosis----:----
Page # 675
Diagnosis and Infant Assessment----:---- Page # 677
Treatment\: Antiviral Intervention in the Newborn and the
Pregnant Patient----:---- Page # 677
Natal Acquisition of Cytomegalovirus Infection\:
Implications for the Premature Infant----:---- Page # 678
Human Herpesvirus 6 and 7----:---- Page # 680
Kaposi Sarcoma–Associated Herpesvirus and Epstein–Barr
Virus----:---- Page # 680
Human Parvovirus B19----:---- Page # 681
Clinical Spectrum----:---- Page # 682
Laboratory Evaluation----:---- Page # 682
Prognosis----:---- Page # 683
Rubella----:---- Page # 683
Treatment and Prognosis----:---- Page # 685
Lymphocytic Choriomeningitis Virus----:---- Page # 686
Enteroviruses----:---- Page # 688
Etiology and Pathogenesis----:---- Page # 688
Short-Term and Long-Term Prognosis----:---- Page # 690
Human Parechovirus----:---- Page # 690
Zika Virus----:---- Page # 691
Clinical Manifestations----:---- Page # 692
Laboratory Evaluation and Diagnostic Studies----:---- Page # 692
Clinical Evaluation and Prognosis----:---- Page # 693
Hepatitis Viruses----:---- Page # 693
Hepatitis B Virus----:---- Page # 693
Clinical Spectrum and Laboratory Evaluation----:---- Page #
695
Hepatitis C Virus----:---- Page # 696
Clinical Spectrum and Laboratory Evaluation----:---- Page #
697
Adenovirus----:---- Page # 698
Epidemiology and Clinical Manifestations----:---- Page # 698
Adenovirus Infections in Newborns----:---- Page # 698
Prevention and Intervention----:---- Page # 699
Respiratory Viruses----:---- Page # 699
Respiratory Syncytial Virus----:---- Page # 699
Gastrointestinal Viruses----:---- Page # 700
Human Immunodeficiency Virus Infection----:---- Page # 700
Introduction----:---- Page # 700
Prevention of Mother-to-Child Transmission of Human
Immunodeficiency Virus----:---- Page # 701
Antepartum----:---- Page # 701
Intrapartum----:---- Page # 702
Postpartum----:---- Page # 702
Treatment of the Human Immunodeficiency Virus–Exposed
Infant----:---- Page # 704
All Human Immunodeficiency Virus–Exposed Infants----:----
Page # 704
Human Immunodeficiency Virus–Infected Infant----:---- Page
# 705
38 Congenital Toxoplasmosis, Syphilis, Malaria, and Tuberculosis----:---- Page #
closed----:---- Page # 726
38 Congenital Toxoplasmosis, Syphilis, Malaria, and Tuberculosis----:----
Page # 726
Congenital Toxoplasmosis----:---- Page # 726
Pathogenesis, Clinical Presentation, and Natural History----:----
Page # 726
Therapy----:---- Page # 729
Congenital Syphilis----:---- Page # 731
Page # 731
Follow-Up----:---- Page # 737
Congenital Malaria----:---- Page # 737
Natural History, Pathogenesis, and Clinical Presentation----:----
Page # 739
Congenital Tuberculosis----:---- Page # 744
Page # 744
Treatment and Management----:---- Page # 748
Congenital Toxoplasmosis----:---- Page # 751
Congenital Syphilis----:---- Page # 751
Congenital Malaria----:---- Page # 751
Congenital Tuberculosis----:---- Page # 751
39 Newborn Sepsis and Meningitis----:---- Page # closed----:---- Page # 758
39 Newborn Sepsis and Meningitis----:---- Page # 758
Pathogenesis of Early-Onset Neonatal Bacterial Infections----:---- Page
# 758
Epidemiology of Early-Onset Bacterial Infections----:---- Page # 759
Bacterial Pathogens in Early-Onset Infections----:---- Page # 759
Group B Streptococcal Infections----:---- Page # 759
Transmission of Group B Streptococcus From Mothers to
Infants----:---- Page # 760
Chemoprophylaxis and Intrapartum Antibiotic
Intrapartum Antibiotic Prophylaxis----:---- Page # 760
Group B Streptococcal Sepsis in Neonates----:---- Page #
761
Escherichia Coli Infections----:---- Page # 761
Listeria Monocytogenes Infections----:---- Page # 762
Miscellaneous Bacterial Pathogens----:---- Page # 762
Clinical Signs of Bacterial Sepsis----:---- Page # 762
Laboratory Testing----:---- Page # 762
Microbiologic Cultures----:---- Page # 763
Blood Cultures----:---- Page # 763
Urine Cultures----:---- Page # 763
Cerebrospinal Fluid----:---- Page # 763
White Blood Cell Count and Neutrophil Indices----:---- Page # 763
Platelet Counts----:---- Page # 764
Acute-Phase Reactants and Erythrocyte Sedimentation Rate----:----
Page # 764
Intrapartum Management of Parturients----:---- Page # 765
Intravenous Immune Globulin for Prevention of Early-Onset
Sepsis----:---- Page # 766
Diagnostic Approach to Neonates With Suspected Sepsis----:---- Page #
766
Antimicrobial Therapy----:---- Page # 768
Immunologic Therapies for Early-Onset Sepsis----:---- Page # 768
Neonatal Bacterial Meningitis----:---- Page # 768
Pathology and Clinical Manifestations----:---- Page # 769
40 Health Care-Associated Infections----:---- Page # closed----:---- Page # 774
40 Health Care-Associated Infections----:---- Page # 774
Health Care–Associated Infection Surveillance and Data Sources----:----
Page # 774
Defining and Diagnosing Neonatal Health Care–Associated
Definitions of Central Line–Associated Bloodstream Infection,
Ventilator-Associated Pneumonia, and Catheter-Associated Urinary Tract
Challenges With Central Line–Associated Bloodstream Infection
Challenges With Ventilator-Associated Pneumonia
Challenges With Urinary Tract Infection Diagnosis----:---- Page #
776
Epidemiology of Health Care–Associated Infection----:---- Page # 776
Health Care–Associated Infection Epidemiology in the Newborn
Nursery----:---- Page # 776
Health Care–Associated Infection Epidemiology in the Neonatal
Intensive Care Unit----:---- Page # 776
Risk Factors for Development of Health Care–Associated
Risk Factors Related to Patient Characteristics----:----
Page # 779
Risk Factors Caused by Necessary Medical
Interventions----:---- Page # 779
Risk Factors Associated With the Neonatal Intensive Care
Unit and Hospital Environment----:---- Page # 780
Health Care–Associated Infection\: Distribution by
Pathogen----:---- Page # 781
Microbial Resistance----:---- Page # 781
Gram-Positive Bacteria----:---- Page # 781
Coagulase-Negative Staphylococci----:---- Page # 781
Staphylococcus aureus----:---- Page # 781
Enterococcus----:---- Page # 782
Group B Streptococcus----:---- Page # 782
Gram-Negative Bacteria----:---- Page # 782
Fungi----:---- Page # 782
Viruses----:---- Page # 782
Respiratory Syncytial Virus----:---- Page # 782
Influenza----:---- Page # 783
Rotavirus----:---- Page # 783
Enterovirus----:---- Page # 783
Adverse Outcomes Related to Health Care–Associated Infection----:----
Page # 783
Prevention of Health Care–Associated Infection----:---- Page # 784
Overall Approach to Infection Control----:---- Page # 784
Guidelines for Hand Hygiene Practices----:---- Page # 784
Guidelines for Gloves and Gowns----:---- Page # 785
Recent Quality Improvement Efforts at Reduction of Health Care–
Associated Infection in Neonatal Intensive Care Units----:---- Page # 785
Prevention of Central Line–Associated Bloodstream
Prevention of Health Care–Associated Pneumonia----:---- Page #
786
Other Aspects of Prevention and Management of Health Care–
Acquired Infections----:---- Page # 787
Skin Care----:---- Page # 787
Human Milk Feedings----:---- Page # 787
Catheter Removal Following Central Line–Associated
Bloodstream Infection----:---- Page # 787
Antibiotic and Adjunctive Therapies----:---- Page # 787
Conclusion----:---- Page # 787
41 Fungal Infections in the Neonatal Intensive Care Unit----:---- Page #
closed----:---- Page # 795
41 Fungal Infections in the Neonatal Intensive Care Unit----:---- Page # 795
Infections Caused by Candida Species----:---- Page # 796
Congenital Candidiasis----:---- Page # 796
Local Infections With Candida Species----:---- Page # 796
Diaper Dermatitis----:---- Page # 796
Funisitis----:---- Page # 796
Urinary Tract Infection----:---- Page # 796
Peritonitis----:---- Page # 796
Systemic Infection----:---- Page # 797
Candidemia Associated With Central Venous
Catheters----:---- Page # 797
Disseminated Candidiasis----:---- Page # 797
Antifungal Therapy for Systemic Infection----:---- Page # 797
Antifungal Prophylaxis----:---- Page # 798
Infections Ascribable to Other Fungi----:---- Page # 798
Invasive Fungal Dermatitis----:---- Page # 798
Line Infections Caused by Lipophilic Organisms----:---- Page #
798
Miscellaneous Fungal Infections----:---- Page # 799
Aspergillus Species----:---- Page # 799
Trichosporon beigelii----:---- Page # 799
42 Lung Development----:---- Page # closed----:---- Page # 802
X Respiratory System----:---- Page # 802
42 Lung Development----:---- Page # 802
Key Events in Lung Development----:---- Page # 802
Development of Airways and Gas Exchange Surfaces----:----
Page # 802
Composition of Airways and Alveoli----:---- Page # 804
Proximal Airways----:---- Page # 804
Distal Airways----:---- Page # 804
Alveolar Epithelium----:---- Page # 805
Development of the Pulmonary Vasculature----:---- Page #
807
Development of Pulmonary Host Defense----:---- Page # 807
Development of Detoxification Systems----:---- Page # 808
Mechanisms of Lung Development----:---- Page # 808
Branching Morphogenesis----:---- Page # 808
Stretch and Mechanotransduction----:---- Page # 809
Static Stretch\: Fetal Lung Fluid Production----:----
Page # 809
Cyclic Stretch\: Fetal Breathing Movements----:----
Page # 809
Alveolarization----:---- Page # 810
Interdependence of Alveolar and Vascular
Development----:---- Page # 810
Molecular Basis for Lung Development----:---- Page # 810
Growth Factors in Lung Development----:---- Page # 810
Transcription Factors in Lung Development----:---- Page #
812
Novel Concepts in Lung Development----:---- Page # 812
Stem/Progenitor Cells in the Lung----:---- Page # 812
Epithelial to Mesenchymal Transition----:---- Page # 812
Epigenetic Regulation of Lung Development and
Maturation----:---- Page # 814
43 Control of Breathing----:---- Page # closed----:---- Page # 818
43 Control of Breathing----:---- Page # 818
Animal Models of Control of Breathing----:---- Page # 818
Overview of Respiratory Control----:---- Page # 819
Muscles of Respiration----:---- Page # 819
Respiratory Rhythmogenesis----:---- Page # 819
Neuroanatomy of the Central Respiratory Network----:---- Page #
820
Neurochemical Control of Respiration----:---- Page # 821
Neurotransmitters----:---- Page # 821
Neuromodulators----:---- Page # 823
Genetic Mutations Affecting Respiratory Control----:---- Page #
823
Peripheral Inputs That Modulate the Central Respiratory
Network----:---- Page # 825
Bronchopulmonary Reflexes----:---- Page # 825
Slowly Adapting Stretch Receptors\: Major Modulators of
Respiratory Timing----:---- Page # 825
Rapidly Adapting Receptors\: Cough, Augmented
Breaths----:---- Page # 826
C-Fiber Receptors\: Apnea, Bronchoconstriction, Rapid
Shallow Breathing----:---- Page # 826
Laryngeal Reflexes----:---- Page # 827
Chemical Control of Breathing----:---- Page # 827
Central Chemosensitivity----:---- Page # 827
Maturation of CO2/H+ Sensitivity of Central
Chemoreceptors----:---- Page # 828
Peripheral Arterial Chemoreceptors----:---- Page # 829
Maturation of CO2/H+ Chemosensitivity of Peripheral
Arterial Chemoreceptors----:---- Page # 830
Maturation of O2 Sensitivity of Peripheral Arterial
Chemoreceptors----:---- Page # 830
Hypoxic Ventilatory Depression\: Consequences for the
Neonate----:---- Page # 830
Effect of Sleep State on Breathing----:---- Page # 831
Apnea of Prematurity----:---- Page # 831
Therapeutic Approaches----:---- Page # 832
Methylxanthines----:---- Page # 832
Gastroesophageal Reflux and Apnea of Prematurity----:---- Page #
833
Resolution and Consequences of Neonatal Apnea----:---- Page # 834
44 Neonatal Pulmonary Physiology----:---- Page # closed----:---- Page # 840
44 Neonatal Pulmonary Physiology----:---- Page # 840
Lung Mechanics and Lung Volumes----:---- Page # 840
Elastic Recoil----:---- Page # 840
Resistance----:---- Page # 841
Inertance----:---- Page # 842
Dynamic Interaction----:---- Page # 842
Work of Breathing----:---- Page # 842
Measurements of Respiratory System Mechanics----:---- Page # 842
Alveolar Ventilation----:---- Page # 845
Ventilation–Perfusion Relationships----:---- Page # 847
Heart–Lung Interaction----:---- Page # 848
Effects of the Lung on the Heart----:---- Page # 848
Effects of Changes in Intrathoracic Pressure on the
Heart----:---- Page # 848
Negative Intrathoracic Pressure----:---- Page # 848
Positive Intrathoracic Pressure----:---- Page # 849
Effect of Lung Inflation on Pulmonary Vascular
Resistance----:---- Page # 849
Effects of the Heart on the Lung----:---- Page # 850
Pulmonary Edema----:---- Page # 850
Increased Driving Pressure----:---- Page # 851
Increased Permeability----:---- Page # 851
Decreased Lymphatic Drainage----:---- Page # 851
Alveolar Space----:---- Page # 852
Symptoms of Pulmonary Edema----:---- Page # 852
Treatment of Pulmonary Edema----:---- Page # 853
45 Neonatal Respiratory Therapy----:---- Page # closed----:---- Page # 856
45 Neonatal Respiratory Therapy----:---- Page # 856
Respiratory Monitoring----:---- Page # 856
Breathing Frequency, Apnea, and Heart Rate Monitoring----:----
Page # 856
Ventilation Monitoring----:---- Page # 856
Blood Gas Monitoring----:---- Page # 857
Blood Gas Sampling----:---- Page # 857
Transcutaneous Blood Gas Monitoring----:---- Page # 857
End-Tidal Carbon Dioxide Monitoring----:---- Page # 857
Arterial Oxygen Saturation Measured by Pulse
Oximetry----:---- Page # 858
Oxygen Therapy----:---- Page # 858
Methods of Administration----:---- Page # 858
Treatment Strategies----:---- Page # 859
Noninvasive Respiratory Support----:---- Page # 860
Nasal Continuous Positive Airway Pressure----:---- Page # 860
Devices for Application of Nasal Continuous Positive Airway
Pressure----:---- Page # 861
Complications----:---- Page # 861
Noninvasive Ventilation----:---- Page # 861
Synchronization of Noninvasive Ventilation----:---- Page #
862
Potential Drawbacks----:---- Page # 862
High-Flow Nasal Cannula----:---- Page # 862
Drawbacks----:---- Page # 862
Invasive Mechanical Ventilation----:---- Page # 862
Indications----:---- Page # 862
Inspired Gas Conditioning----:---- Page # 863
Conventional Positive Pressure Ventilation----:---- Page # 864
Modes of Conventional Positive Pressure
Ventilation----:---- Page # 865
Intermittent Mandatory Ventilation----:---- Page #
865
Synchronized Intermittent Mandatory
Assist/Control Ventilation----:---- Page # 867
Pressure Support Ventilation----:---- Page # 868
Volume-Targeted Ventilation----:---- Page # 868
Volume-Controlled Ventilation.----:---- Page #
868
Pressure-Regulated Volume-Controlled
Ventilation.----:---- Page # 868
Volume Guarantee Ventilation.----:---- Page #
868
Proportional Assist Ventilation----:---- Page # 869
Neurally Adjusted Ventilatory Assist----:---- Page #
869
Targeted Minute Ventilation----:---- Page # 869
High-Frequency Ventilation----:---- Page # 869
Gas Transport During High-Frequency Ventilation----:----
Page # 869
Devices for High-Frequency Ventilation----:---- Page # 870
Ventilator Settings During High-Frequency
Clinical Use of High-Frequency Ventilation----:---- Page #
870
High-Frequency Ventilation in Respiratory Distress
Syndrome----:---- Page # 870
High-Frequency Ventilation in Persistent Pulmonary
Hypertension of the Newborn----:---- Page # 871
Other Indications for High-Frequency
Side Effects of High-Frequency Ventilation----:---- Page #
871
Weaning of Infants off Mechanical Ventilation----:---- Page # 871
Synchronized Patient-Triggered Ventilation for
Weaning----:---- Page # 871
Volume Monitoring and Volume-Targeted Ventilation During
Weaning----:---- Page # 872
Weaning of Infants off High-Frequency Ventilation----:---- Page #
872
Permissive Hypercapnia----:---- Page # 872
Dead Space Reduction----:---- Page # 872
Automated and Computer-Assisted Weaning----:---- Page # 872
Extubation----:---- Page # 872
Nasal Continuous Positive Airway Pressure and Noninvasive
Ventilation for Extubation----:---- Page # 873
Respiratory Stimulants for Extubation----:---- Page # 873
Acute Complications of Respiratory Support----:---- Page # 873
Pulmonary Gas Leaks----:---- Page # 873
Pulmonary Interstitial Emphysema----:---- Page # 873
Pneumothorax----:---- Page # 874
Pneumopericardium----:---- Page # 874
Pneumoperitoneum----:---- Page # 874
Intravascular Gas----:---- Page # 875
Airway Complications----:---- Page # 875
Ventilator-Associated Pneumonia----:---- Page # 875
Ventilator- and Oxygen-Associated Neurologic Sequelae----:----
Page # 875
46 Respiratory Disorders in the Preterm Infant----:---- Page # closed----:---- Page
# 883
46 Respiratory Disorders in the Preterm Infant----:---- Page # 883
Risk Factors----:---- Page # 883
Pathophysiology of Respiratory Distress Syndrome----:---- Page #
883
Purpose of Surfactant----:---- Page # 884
Origin and Composition of Surfactant----:---- Page # 886
Clinical Signs of Respiratory Distress Syndrome----:---- Page #
887
Differential Diagnosis----:---- Page # 888
Laboratory Features of Respiratory Distress Syndrome----:----
Page # 888
Radiographic Features of Respiratory Distress Syndrome----:----
Page # 888
Initial Diagnostic Evaluation for Possible Respiratory Distress
Treatment of Patients With Respiratory Distress Syndrome----:----
Page # 889
Respiratory Complications of Respiratory Distress
Prevention and Treatment of Respiratory Distress
Prevention of Asphyxia----:---- Page # 890
Exogenous Surfactant----:---- Page # 890
Historical Summary----:---- Page # 890
Types of Surfactants Available for Clinical
Use----:---- Page # 890
Surfactant Selection----:---- Page # 891
Timing of Surfactant Administration----:---- Page #
891
Combining and Comparing Surfactant Therapy With the
Use of Continuous Positive Airway Pressure----:---- Page # 891
Methods of Surfactant Dosing----:---- Page # 892
Number of Surfactant Doses and Dosing
Intervals----:---- Page # 892
Clinical Care After Dosing----:---- Page # 892
Pulmonary Hypoplasia----:---- Page # 892
Definition and Incidence----:---- Page # 892
Pathology----:---- Page # 893
Clinical Signs----:---- Page # 893
Radiographic Signs----:---- Page # 893
Prenatal Treatment----:---- Page # 895
Pneumonia----:---- Page # 895
Incidence and Etiology----:---- Page # 895
Clinical Signs----:---- Page # 895
Laboratory and Radiographic Signs----:---- Page # 895
Pulmonary Hemorrhage----:---- Page # 896
Incidence and Clinical Signs----:---- Page # 896
47 Respiratory Disorders in the Term Infant----:---- Page # closed----:---- Page #
900
47 Respiratory Disorders in the Term Infant----:---- Page # 900
Evaluation of the Term Newborn With Hypoxemia/Respiratory
Distress----:---- Page # 900
Physical Examination----:---- Page # 901
Interpretation of Pulse Oximetry Measurements----:---- Page # 901
Laboratory and Radiologic Evaluation----:---- Page # 902
Response to Supplemental Oxygen----:---- Page # 902
Echocardiography----:---- Page # 902
Persistent Pulmonary Hypertension of the Newborn----:---- Page # 903
Specific Pulmonary Conditions Causing Respiratory Distress in the Term
Newborn----:---- Page # 904
Transient Tachypnea of the Newborn----:---- Page # 904
Meconium Aspiration Syndrome----:---- Page # 904
Surfactant Protein Deficiency----:---- Page # 905
Surfactant-Associated Protein B Deficiency----:---- Page #
906
Surfactant-Associated Protein C Deficiency----:---- Page #
906
Adenosine Triphosphate–Binding Cassette Subfamily A Member
3 Deficiency----:---- Page # 906
Thyroid Transcription Factor 1 Gene Mutation----:---- Page
# 907
Surfactant-Associated Proteins A and D----:---- Page # 907
Interstitial Lung Disease----:---- Page # 907
Alveolar Capillary Dysplasia/Misalignment of Pulmonary
Veins----:---- Page # 907
Pulmonary Interstitial Glycogenosis----:---- Page # 907
Pulmonary Hypoplasia----:---- Page # 909
48 Bronchopulmonary Dysplasia----:---- Page # closed----:---- Page # 913
48 Bronchopulmonary Dysplasia----:---- Page # 913
Historical Overview----:---- Page # 913
Pathobiology----:---- Page # 914
Pathologic Findings in the “New” Form of the Disease----:----
Page # 915
Multifactorial Etiologic Factors----:---- Page # 915
Host Susceptibility and Genetic Predisposition----:---- Page #
915
Inflammation----:---- Page # 916
Neonatal Infection----:---- Page # 917
Oxygen Toxicity and Oxidative Stress----:---- Page # 917
Ventilation With Volutrauma----:---- Page # 918
Fluid Balance, Pulmonary Edema, and Patent Ductus
Arteriosus----:---- Page # 919
Pulmonary Vascular Abnormalities----:---- Page # 920
Inadequate Nutrition----:---- Page # 920
Surfactant Dysfunction----:---- Page # 920
Adrenal Insufficiency----:---- Page # 921
Inhibition of Normal Lung Development and Vascular
Preventive Factors----:---- Page # 922
Prenatal Steroids----:---- Page # 922
Surfactant Replacement Therapy----:---- Page # 922
Gentle Ventilation and Nasal Continuous Positive Airway
Pressure----:---- Page # 923
Vitamin A----:---- Page # 924
Systemic Postnatal Corticosteroids----:---- Page # 924
Inhaled/Instilled Corticosteroids----:---- Page # 925
Antioxidant Therapy----:---- Page # 926
Clinical Course and Treatment----:---- Page # 927
Nonpharmacologic Support\: Nutrition, Ventilation, Noninvasive
Respiratory Support, and Oxygen Saturation Targets----:---- Page # 927
Pharmacologic Strategies----:---- Page # 927
Diuretics----:---- Page # 928
Bronchodilator Therapy----:---- Page # 928
Postnatal Corticosteroids----:---- Page # 928
Pulmonary Hypertension----:---- Page # 928
Outcome----:---- Page # 929
49 Surgical Disorders of the Chest and Airways----:---- Page # closed----:---- Page
# 936
49 Surgical Disorders of the Chest and Airways----:---- Page # 936
Anomalies of the Airways----:---- Page # 936
Nasopharyngeal Obstructive Disorders----:---- Page # 936
Congenital Choanal Atresia----:---- Page # 936
Congenital Nasal Pyriform Aperture Stenosis----:---- Page #
937
Pierre Robin Syndrome (Robin Sequence)----:---- Page # 937
Glossoptosis–Apnea Syndrome----:---- Page # 937
Pharyngeal Incoordination----:---- Page # 937
Laryngeal Deformities----:---- Page # 937
Laryngomalacia (Congenital Laryngeal Stridor)----:---- Page
# 937
Vocal Cord Paralysis----:---- Page # 938
Laryngeal Atresia----:---- Page # 939
Congenital Subglottic Stenosis----:---- Page # 939
Congenital Subglottic Hemangioma----:---- Page # 939
Laryngotracheoesophageal Cleft (Congenital Laryngeal
Cleft)----:---- Page # 939
Tracheal Deformities and Other Tracheal Disorders----:---- Page #
939
Tracheal Agenesis----:---- Page # 939
Congenital Tracheal Stenosis----:---- Page # 940
Tracheobronchomalacia (Tracheomalacia)----:---- Page # 940
Tracheal Compression by Vascular Rings----:---- Page # 941
Tracheal Compression by Extrinsic Masses----:---- Page #
942
Congenital High Airway Obstruction Syndrome and the Ex
Utero Intrapartum Treatment Procedure----:---- Page # 942
Disorders of the Mediastinum----:---- Page # 942
Thymus----:---- Page # 942
Congenital Mediastinal Teratoma----:---- Page # 942
Congenital Bronchogenic Cysts----:---- Page # 943
Neurenteric Duplication Cysts----:---- Page # 943
Congenital Thoracic Neuroblastoma----:---- Page # 944
Disorders of the Chest Wall----:---- Page # 945
Skeletal Disorders----:---- Page # 945
Defects of Sternal Fusion----:---- Page # 945
Pectus Excavatum----:---- Page # 945
Poland Syndrome----:---- Page # 946
Thoracic Dystrophies----:---- Page # 946
Asphyxiating Thoracic Dystrophy (Jeune
Syndrome)----:---- Page # 946
Other Thoracic Dystrophies----:---- Page # 947
Neuromuscular Disorders----:---- Page # 947
Disorders of the Pleural Cavity----:---- Page # 948
Congenital Chylothorax----:---- Page # 948
Management of Chylothorax----:---- Page # 948
Congenital Thoracic Masses and Cysts----:---- Page # 949
Congenital Pulmonary Airway Malformation of the Lung----:----
Page # 949
Congenital Pulmonary Airway Malformation Types----:----
Page # 949
Fetal Diagnosis and Natural History----:---- Page #
951
Prenatal Management----:---- Page # 951
Postnatal Management----:---- Page # 952
Bronchopulmonary Sequestration----:---- Page # 953
Other Cystic Lesions----:---- Page # 954
Congenital Lobar Emphysema----:---- Page # 954
Pleuropulmonary Blastoma----:---- Page # 955
Postinfectious Pneumatoceles----:---- Page # 955
Hyperinflation and Emphysema in Chronic Lung
Disease----:---- Page # 955
Miscellaneous Cysts----:---- Page # 956
Disorders of the Diaphragm----:---- Page # 956
Prenatal Diagnosis and Management----:---- Page # 958
Postnatal Diagnosis and Management----:---- Page # 959
Long-Term Morbidity----:---- Page # 962
Hepatopulmonary Fusion----:---- Page # 963
Congenital Eventration of the Diaphragm----:---- Page # 963
Diaphragmatic Paresis----:---- Page # 963
Neonatal Scimitar Syndrome----:---- Page # 963
50 Developmental Biology of the Heart----:---- Page # closed----:---- Page # 974
XI Cardiovascular System----:---- Page # 974
50 Developmental Biology of the Heart----:---- Page # 974
Overview of Cardiac Developmental Anatomy----:---- Page # 974
Cell Types Within the Heart and Their Origins----:---- Page # 976
Formation of the Embryonic Cardiac Crescent and Heart
Tube----:---- Page # 977
Looping and Laterality of the Heart Tube----:---- Page # 978
Abnormalities in Cardiac Looping----:---- Page # 979
Ventricular Inlet Septation\: Endocardial
Cushions----:---- Page # 980
Ventricular Outflow Tract Septation\: Endocardial Cushions and
Neural Crest----:---- Page # 981
Separation of Aorta and Pulmonary Artery\: Normal
Dextroposition----:---- Page # 983
Cardiac Valve Formation----:---- Page # 983
Development of the Ventricles and Ventricular Septum----:----
Page # 984
Development of the Atria and Atrial Septum----:---- Page # 985
Systemic and Pulmonary Vein Development----:---- Page # 986
Aortic Arch Development----:---- Page # 987
Coronary Arteries----:---- Page # 987
Conduction System----:---- Page # 989
Physiology of Transition----:---- Page # 989
51 Cardiovascular Compromise in the Newborn----:---- Page # closed----:---- Page #
994
51 Cardiovascular Compromise in the Newborn----:---- Page # 994
Principles of Developmental Cardiovascular Physiology and
Pathophysiology, Phases, and Causes of Neonatal Shock----:---- Page # 996
Principles of Oxygen Delivery----:---- Page # 996
Developmental Regulation of Cardiac Output and Its
Determinants----:---- Page # 999
Preload----:---- Page # 999
Contractility----:---- Page # 999
Afterload----:---- Page # 999
Changes in Preload, Contractility, and Afterload During
Transition----:---- Page # 999
Developmental Regulation of Systemic Blood Pressure----:---- Page
# 1000
Developmental Regulation of Organ Blood Flow and Its
Autoregulation and Vital Organ Assignment----:---- Page # 1001
Cerebral Blood Flow Autoregulation----:---- Page # 1001
Vital Organ Assignment----:---- Page # 1001
Developmental Regulation of Cerebral Oxygen Demand–Delivery
Coupling----:---- Page # 1001
Phases of Shock----:---- Page # 1002
Pathogenesis of Neonatal Shock----:---- Page # 1002
Etiologic Factors----:---- Page # 1002
Hypovolemia----:---- Page # 1002
Myocardial Dysfunction----:---- Page # 1003
Abnormal Peripheral Vasoregulation----:---- Page #
1003
Clinical Presentations of Shock in Neonates Associated With Multiple
Etiologic Factors----:---- Page # 1003
Transitional Circulatory Compromise of the Very Preterm
Neonate----:---- Page # 1003
Low Preload and Immediate Umbilical Cord Clamping----:----
Page # 1003
Myocardial Dysfunction and High Afterload----:---- Page #
1004
Patent Ductus Arteriosus----:---- Page # 1004
Respiratory Support and Hemodynamics----:---- Page # 1004
Ischemia–Reperfusion----:---- Page # 1004
Vital Organ Assignment----:---- Page # 1006
Vasopressor-Resistant Hypotension----:---- Page # 1007
Sepsis----:---- Page # 1007
Pulmonary Hypertension With or Without Meconium Aspiration
Diagnosis of Circulatory Compromise----:---- Page # 1007
Heart Rate and Blood Pressure----:---- Page # 1007
Capillary Refill Time----:---- Page # 1009
Core–Peripheral Temperature Difference----:---- Page # 1009
Low Urine Output and Hyperkalemia----:---- Page # 1009
Lactic Acid, pH, and Base Excess----:---- Page # 1010
Organ Blood Flow----:---- Page # 1010
Near-Infrared Spectroscopy----:---- Page # 1010
Echocardiographic Systemic Blood Flow Measures----:---- Page #
1010
Measurement of Systemic Blood Flow by Electrical Impedance
Velocimetry----:---- Page # 1011
Treatment of Neonatal Shock----:---- Page # 1011
Association Between Systemic Hypotension, Hypoperfusion, and
Their Treatment and Mortality or Neurodevelopmental Impairment----:---- Page # 1011
Volume Administration----:---- Page # 1012
Dopamine and Dobutamine----:---- Page # 1013
Hemodynamic Effects of Dopamine----:---- Page # 1013
Hemodynamic Effects of Dobutamine----:---- Page # 1014
Dopamine Versus Dobutamine----:---- Page # 1014
Epithelial and Neuroendocrine Effects----:---- Page # 1015
Epinephrine, Norepinephrine, and Other Cardiovascular Agents and
Hormones----:---- Page # 1016
Epinephrine----:---- Page # 1016
Norepinephrine----:---- Page # 1016
Milrinone----:---- Page # 1016
Vasopressin----:---- Page # 1016
Steroid Administration----:---- Page # 1017
Steroid Administration as Primary or Rescue
Rationale for Hydrocortisone Treatment----:---- Page # 1017
Clinical Applications of Hydrocortisone----:---- Page #
1017
Short-Term Side Effects----:---- Page # 1018
Long-Term Side Effects----:---- Page # 1018
Supportive Measures----:---- Page # 1019
52 Persistent Pulmonary Hypertension----:---- Page # closed----:---- Page # 1027
52 Persistent Pulmonary Hypertension----:---- Page # 1027
Normal Fetal Pulmonary Vascular Development and Transition----:----
Page # 1027
Pathophysiology of Persistent Pulmonary Hypertension of the
Newborn----:---- Page # 1029
Other Causes of Neonatal Pulmonary Hypertension----:---- Page # 1031
Alveolar Capillary Dysplasia----:---- Page # 1031
Pulmonary Hypertension in Premature Infants----:---- Page # 1031
Clinical Evaluation of Persistent Pulmonary Hypertension of the
Newborn----:---- Page # 1032
General Management----:---- Page # 1033
Oxygen----:---- Page # 1035
Other Therapeutic Agents----:---- Page # 1035
Phosphodiesterase Inhibitors----:---- Page # 1035
Prostanoids----:---- Page # 1035
Endothelin Receptor Antagonists----:---- Page # 1036
Summary----:---- Page # 1037
53 Fetal and Neonatal Echocardiography----:---- Page # closed----:---- Page # 1041
53 Fetal and Neonatal Echocardiography----:---- Page # 1041
Application of Ultrasound to Cardiac Imaging----:---- Page # 1041
Physics of Ultrasound----:---- Page # 1041
Basic Imaging Components----:---- Page # 1041
M-Mode----:---- Page # 1041
Two-Dimensional Imaging----:---- Page # 1042
Doppler----:---- Page # 1042
Neonatal Echocardiography\: Goals of Imaging----:---- Page # 1044
Fetal-to-Neonatal Transitional Physiology\: Echocardiographic
Assessment----:---- Page # 1045
Suspected Congenital Heart Disease----:---- Page # 1045
Assessment of the Ductus Arteriosus----:---- Page # 1045
Evaluation of Persistent Pulmonary Hypertension----:---- Page #
1045
Neonatal Imaging Techniques----:---- Page # 1046
Limitations of Neonatal Echocardiography----:---- Page # 1047
Fetal Echocardiography\: Goals of Imaging----:---- Page # 1047
Fetal Imaging Techniques----:---- Page # 1047
Limitations of Fetal Echocardiography----:---- Page # 1049
Other Cardiovascular Imaging Modalities----:---- Page # 1049
Transesophageal Echocardiography----:---- Page # 1049
Intracardiac Echocardiography----:---- Page # 1049
Three-Dimensional Echocardiography----:---- Page # 1050
Computed Tomography and Magnetic Resonance Imaging----:---- Page
# 1050
Summary----:---- Page # 1050
54 Patent Ductus Arteriosus in the Preterm Infant----:---- Page # closed----:----
Page # 1052
54 Patent Ductus Arteriosus in the Preterm Infant----:---- Page # 1052
Regulation of Ductus Arteriosus Patency----:---- Page # 1053
Balance Between Vasoconstriction and Vasorelaxation----:---- Page
# 1053
In Utero Regulation----:---- Page # 1053
Postnatal Regulation----:---- Page # 1054
Developmental Regulation----:---- Page # 1055
Genetic Regulation----:---- Page # 1056
Anatomic Closure—Histologic Changes----:---- Page # 1056
Relationship Between Vasoconstriction and Anatomic
Closure----:---- Page # 1057
Hemodynamic and Pulmonary Alterations----:---- Page # 1058
Treatment Options for Closing a PDA----:---- Page # 1059
Indomethacin and Intracranial Hemorrhage----:---- Page # 1060
PDA and Neonatal Morbidity\: To Close or Not to Close----:----
Page # 1061
A Personalized Approach----:---- Page # 1061
55 Congenital Heart Disease----:---- Page # closed----:---- Page # 1069
55 Congenital Heart Disease----:---- Page # 1069
General Considerations----:---- Page # 1069
Fetal-to-Postnatal Transition----:---- Page # 1069
Nomenclature----:---- Page # 1070
Clinical Evaluation of the Newborn----:---- Page # 1071
Laboratory Assessment of the Neonate----:---- Page # 1071
Genetics and Congenital Heart Disease----:---- Page # 1072
Heart Transplantation----:---- Page # 1073
Ventricular Assist Devices----:---- Page # 1074
Murmurs in the Newborn—Congenital Cardiac Lesions----:---- Page # 1074
Patent Ductus Arteriosus and Aortopulmonary Window----:---- Page
# 1074
Ventricular Septal Defect----:---- Page # 1074
Atrial Septal Defects----:---- Page # 1076
Atrioventricular Septal Defects----:---- Page # 1077
Peripheral Pulmonic Stenosis----:---- Page # 1078
Pulmonic Stenosis----:---- Page # 1078
Aortic Stenosis----:---- Page # 1079
Cyanosis in the Newborn----:---- Page # 1079
Transposition of the Great Arteries----:---- Page # 1079
Double Outlet Right Ventricle----:---- Page # 1080
Truncus Arteriosus----:---- Page # 1080
Total Anomalous Pulmonary Venous Return----:---- Page # 1082
Tetralogy of Fallot----:---- Page # 1083
Tetralogy of Fallot Absent Pulmonary Valve----:---- Page # 1083
Pulmonary Atresia With Intact Ventricular Septum----:---- Page #
1084
Tricuspid Atresia----:---- Page # 1086
Ebstein Anomaly of the Tricuspid Valve----:---- Page # 1086
Lesions That Present Primarily With Heart Failure----:---- Page # 1087
Hypoplastic Left Heart Syndrome----:---- Page # 1087
Obstructed Total Anomalous Pulmonary Venous Return----:---- Page
# 1088
Cor Triatriatum----:---- Page # 1090
Mitral Stenosis----:---- Page # 1090
Critical Aortic Stenosis----:---- Page # 1091
Coarctation of the Aorta----:---- Page # 1091
Interrupted Aortic Arch----:---- Page # 1092
Anomalous Origin of the Left Coronary Artery From the Pulmonary
Artery----:---- Page # 1093
Systemic Arterial Malformations----:---- Page # 1093
Cardiomyopathy----:---- Page # 1094
56 Perinatal Arrhythmias----:---- Page # closed----:---- Page # 1098
56 Perinatal Arrhythmias----:---- Page # 1098
Conduction System of the Human Heart----:---- Page # 1098
Sinus Node----:---- Page # 1098
Atrioventricular Node----:---- Page # 1098
His–Purkinje System----:---- Page # 1099
Abnormalities in Cardiac Conduction----:---- Page # 1099
First-Degree Atrioventricular Block----:---- Page # 1099
Second-Degree Atrioventricular Block----:---- Page # 1099
Third-Degree Atrioventricular Block----:---- Page # 1099
Ventricular Preexcitation----:---- Page # 1099
Abnormalities in Cardiac Rhythm----:---- Page # 1099
Ectopic Beats----:---- Page # 1100
Premature Atrial Complexes----:---- Page # 1100
Premature Ventricular Complexes----:---- Page # 1100
Tachyarrhythmias----:---- Page # 1100
Orthodromic Reciprocating Tachycardia----:---- Page # 1100
Permanent Form of Junctional Reciprocating Tachycardia----:----
Page # 1102
Atrial Ectopic Tachycardia----:---- Page # 1102
Junctional Ectopic Tachycardia----:---- Page # 1103
Neonatal Atrial Flutter----:---- Page # 1103
Ventricular Tachycardia----:---- Page # 1103
Management Considerations for Neonatal Tachyarrhythmias----:---- Page #
1104
Bradyarrhythmias----:---- Page # 1105
Blocked Premature Atrial Complex----:---- Page # 1105
Long QT Syndrome----:---- Page # 1105
Congenital Complete Atrioventricular Block----:---- Page # 1106
Fetal Rhythms----:---- Page # 1107
Benign Arrhythmias----:---- Page # 1108
Management of Benign Arrhythmias----:---- Page # 1108
Fetal Tachycardias----:---- Page # 1108
Orthodromic Reentrant Tachycardia----:---- Page # 1108
Atrial Flutter----:---- Page # 1108
Sustained Ventricular Tachycardia----:---- Page # 1110
Rare Tachycardias----:---- Page # 1111
Sinus Tachycardia----:---- Page # 1111
Arrhythmia Medications----:---- Page # 1111
Fetal Bradycardia----:---- Page # 1111
Benign Fetal Bradycardia----:---- Page # 1111
Ion Channelopathies----:---- Page # 1111
Atrioventricular Block----:---- Page # 1112
57 Long-Term Neurologic Outcomes in Children With Congenital Heart Disease----:----
Page # closed----:---- Page # 1116
57 Long-Term Neurologic Outcomes in Children With Congenital Heart
Disease----:---- Page # 1116
Structural and Developmental Abnormalities of the Brain in Congenital
Heart Disease----:---- Page # 1116
Fetal Circulation in Congenital Heart Disease\: Effects on
Cerebral Blood Flow----:---- Page # 1116
Preoperative Evidence of Delayed Brain Development by Magnetic
Resonance Imaging----:---- Page # 1118
Fetal Brain Magnetic Resonance Imaging Identifies Developmental
Abnormalities in Congenital Heart Disease----:---- Page # 1118
Trajectory of Brain Development in Congenital Heart
Disease----:---- Page # 1119
Acquired Brain Injury With Congenital Heart Disease\: Characteristics
and Risk Factors----:---- Page # 1119
Risk Factors for Preoperative Brain Injury----:---- Page # 1119
Risk Factors for Intraoperative Brain Injury----:---- Page # 1119
Risk Factors for Postoperative Brain Injury----:---- Page # 1121
Brain Immaturity as a Risk Factor for Brain Injury----:---- Page
# 1122
Neurodevelopmental Outcomes----:---- Page # 1122
Immediate Neurologic Outcomes After Surgical Repair----:---- Page
# 1122
Short-Term and Long-Term Neurologic Outcomes After Surgical
Repair----:---- Page # 1122
Genetic Susceptibility to Neurodevelopmental
Abnormalities----:---- Page # 1122
Neurodevelopmental Signature of Congenital Heart Disease----:----
Page # 1123
Conclusions----:---- Page # 1123
58 Central Nervous System Development----:---- Page # closed----:---- Page # 1126
XII Neurologic System----:---- Page # 1126
58 Central Nervous System Development----:---- Page # 1126
Neuronal Production and Migration----:---- Page # 1126
Programmed Neuronal Death----:---- Page # 1128
Organization of the Central Nervous System----:---- Page # 1128
Subplate Neurons----:---- Page # 1128
Axonal and Dendritic Growth----:---- Page # 1128
Synaptogenesis----:---- Page # 1128
Glial Proliferation, Differentiation, and Myelination----:----
Page # 1129
Astrocytes----:---- Page # 1129
Oligodendrocytes and Myelination----:---- Page # 1129
Microglia----:---- Page # 1129
The Environment and Epigenetics----:---- Page # 1129
59 Congenital Malformations of the Central Nervous System----:---- Page #
closed----:---- Page # 1132
59 Congenital Malformations of the Central Nervous System----:---- Page #
1132
Prosencephalic Cleavage and Related Events----:---- Page # 1132
Normal Prosencephalic Development----:---- Page # 1132
Disorders of Structures Derived From the Prosencephalon----:---- Page #
1132
Aprosencephaly and Atelencephaly----:---- Page # 1132
Holoprosencephaly----:---- Page # 1133
Epidemiology and Etiology----:---- Page # 1135
Genotype–Phenotype Variability----:---- Page # 1135
Agenesis of the Corpus Callosum----:---- Page # 1135
Septo-Optic Dysplasia----:---- Page # 1136
Diagnosis and Prognosis----:---- Page # 1136
Absent Cavum Septi Pellucidi----:---- Page # 1138
Cortical Defects in Size and Organization----:---- Page # 1138
Cortical Defects in Proliferation and Neuronal Survival----:---- Page #
1138
Microcephaly----:---- Page # 1138
Macrocephaly and Megalencephaly----:---- Page # 1139
Cortical Defects in Migration----:---- Page # 1139
Heterotopia----:---- Page # 1139
Lissencephaly----:---- Page # 1140
Cobblestone Complex Syndromes----:---- Page # 1140
Polymicrogyria----:---- Page # 1141
Tubulinopathy-Related Dysgyria----:---- Page # 1142
Destructive Lesions----:---- Page # 1142
Malformations of Structures in the Posterior Fossa----:---- Page # 1143
Normal Midbrain and Hindbrain Development----:---- Page # 1143
Malformations With Major Cerebellar Involvement----:---- Page # 1144
Dandy–Walker Malformation----:---- Page # 1144
Clinical Features and Management----:---- Page # 1144
Rhomboencephalosynapsis----:---- Page # 1145
Malformations With Both Cerebellar and Brainstem Involvement----:----
Page # 1145
Joubert Syndrome and Related Disorders----:---- Page # 1145
Pontocerebellar Hypoplasia----:---- Page # 1145
Malformations With Brainstem Involvement----:---- Page # 1146
Moebius Sequence Disorders----:---- Page # 1146
HOXA1A Mutation Syndromes----:---- Page # 1147
Chiari Malformations----:---- Page # 1147
Neural Tube Defects and Spinal Cord Dysraphisms----:---- Page # 1148
Gene–Environment Association of Neural Tube Defects----:---- Page
# 1148
Fetal Diagnosis of Neural Tube Defects----:---- Page # 1148
Open Neural Tube Defects----:---- Page # 1150
Anencephaly----:---- Page # 1150
Myelomeningocele----:---- Page # 1150
Myeloschisis----:---- Page # 1151
Skin-Covered Neural Tube Defects----:---- Page # 1151
Encephalocele----:---- Page # 1151
Meningocele----:---- Page # 1152
Occult Spinal Dysraphisms----:---- Page # 1152
Clinical Features and Diagnosis----:---- Page # 1153
60 Brain Injury in the Preterm Infant----:---- Page # closed----:---- Page # 1159
60 Brain Injury in the Preterm Infant----:---- Page # 1159
General Principles of Preterm Brain Injury----:---- Page # 1159
Intraventricular and Periventricular Hemorrhage in the Preterm
Infant----:---- Page # 1160
Site, Incidence, and Timing of Hemorrhage----:---- Page # 1160
Clinical Presentation----:---- Page # 1161
Grading of Intraventricular Hemorrhage----:---- Page # 1161
Outcome and Prognosis----:---- Page # 1161
White Matter Injury----:---- Page # 1164
Spectrum of Human White Matter Injury----:---- Page # 1164
Physiologic Factors Related to the Pathogenesis of White Matter
Injury----:---- Page # 1168
Role of Hypoxia–Ischemia----:---- Page # 1168
Pressure-Passive Circulation----:---- Page # 1168
Factors That Influence the Distribution of White Matter
Injury----:---- Page # 1168
Clinical Factors Related to the Severity of White Matter
Injury----:---- Page # 1168
Pathogenesis of Chronic White Matter Injury----:---- Page # 1170
Emerging Roles for Myelin in Brain Development, Learning,
and Memory----:---- Page # 1170
Pathogenesis of Chronic Myelination Failure and Potential
Therapeutic Strategies----:---- Page # 1170
Preterm Cerebral Gray Matter Injury----:---- Page # 1172
Summary----:---- Page # 1176
61 Brain Injury in the Term Infant----:---- Page # closed----:---- Page # 1183
61 Brain Injury in the Term Infant----:---- Page # 1183
Hypoxic–Ischemic Encephalopathy----:---- Page # 1183
Birth History and Delivery Room Presentation----:---- Page
# 1183
Clinical Signs and Symptoms----:---- Page # 1183
Laboratory and Ancillary Studies----:---- Page # 1184
Electroencephalography----:---- Page # 1185
Neuroimaging----:---- Page # 1185
Brain Injury Patterns----:---- Page # 1185
Mechanisms of Injury----:---- Page # 1186
Management of Hypoxic–Ischemic Encephalopathy----:---- Page #
1187
Apgar Score----:---- Page # 1187
Seizures----:---- Page # 1187
Magnetic Resonance Imaging and Spectroscopy----:---- Page #
1187
Perinatal Arterial Ischemic Stroke----:---- Page # 1188
Cerebral Sinus Venous Thrombosis----:---- Page # 1190
Neonatal Hypoglycemia----:---- Page # 1190
Central Nervous System Infections----:---- Page # 1190
Meningitis----:---- Page # 1191
Herpes Simplex Virus----:---- Page # 1192
Toxoplasmosis----:---- Page # 1192
Cytomegalovirus----:---- Page # 1192
Zika Virus----:---- Page # 1193
Inborn Errors of Metabolism----:---- Page # 1193
Methylmalonic Acidemia----:---- Page # 1193
Bilirubin-Induced Neurologic Dysfunction and Kernicterus----:---- Page
# 1194
62 Neuroprotection Strategies for the Newborn----:---- Page # closed----:---- Page
# 1200
62 Neuroprotection Strategies for the Newborn----:---- Page # 1200
Mechanisms of Disease\: Identification of Targets for
Neuroprotection----:---- Page # 1200
Clastic Lesions----:---- Page # 1200
Interruption/Disruption of Normal Development----:---- Page #
1201
Therapeutic Approaches----:---- Page # 1201
Current Therapies for Preterm Infants\: Prenatal
Therapies----:---- Page # 1201
Steroids----:---- Page # 1201
Magnesium Sulfate----:---- Page # 1201
Delayed Cord Clamping----:---- Page # 1202
Kangaroo Care----:---- Page # 1202
Therapies on the Horizon for Preterm Infants----:---- Page # 1202
Melatonin----:---- Page # 1202
Erythropoietin Neuroprotection----:---- Page # 1203
Translational Trials of Neonatal Erythropoietin
Neuroprotection for Preterm Infants----:---- Page # 1203
Risks of Intervention----:---- Page # 1203
Future Outlook on Neuroprotection for Preterm Brain
Injury----:---- Page # 1204
Cell-Specific Targeting----:---- Page # 1204
Microglial Activation States----:---- Page # 1204
Tertiary-Phase Injury Processes----:---- Page # 1204
Paucity of Endogenous Protectors----:---- Page # 1205
Targeting Oligodendrocyte Maturation----:---- Page # 1205
Targeting Gray Matter Damage----:---- Page # 1205
Current Therapies for Term Infants----:---- Page # 1205
Therapeutic Hypothermia----:---- Page # 1205
Cooling Duration and Depth----:---- Page # 1206
Therapies on the Horizon for Term Infants----:---- Page # 1206
Adjunctive Neuroprotective Treatments Plus Therapeutic
Erythropoietin----:---- Page # 1206
Xenon----:---- Page # 1206
Argon----:---- Page # 1207
Melatonin----:---- Page # 1207
Stem Cells----:---- Page # 1207
Umbilical Cord Stem Cells.----:---- Page # 1207
Mesenchymal Stem Cells.----:---- Page # 1207
Embryonic Stem Cells.----:---- Page # 1207
Induced Pluripotent Stem Cells.----:---- Page #
1207
Neural Stem Cells.----:---- Page # 1210
Amniotic Fluid–Derived Stem Cells.----:----
Page # 1210
Clinical Management Strategies----:---- Page # 1210
Future Outlook on Term Brain Injury Neuroprotection----:---- Page
# 1210
Remote Ischemic Postconditioning----:---- Page # 1210
Targeting Inflammation----:---- Page # 1210
Targeting Autophagy----:---- Page # 1210
63 Neonatal Neuroimaging----:---- Page # closed----:---- Page # 1218
63 Neonatal Neuroimaging----:---- Page # 1218
Imaging Modalities----:---- Page # 1218
Cranial Ultrasonography----:---- Page # 1218
Computed Tomography----:---- Page # 1220
Magnetic Resonance Imaging----:---- Page # 1220
T1-Weighted and T2-Weighted Imaging----:---- Page # 1221
Diffusion Imaging----:---- Page # 1221
Angiography----:---- Page # 1223
Susceptibility-Weighted Imaging----:---- Page # 1224
Magnetic Resonance Spectroscopy----:---- Page # 1225
Preterm Neonates----:---- Page # 1226
Intraventricular Hemorrhage----:---- Page # 1226
White Matter Injury----:---- Page # 1230
Cerebellar Hemorrhage----:---- Page # 1233
Predicting Outcome With Imaging at Term Equivalent Age----:----
Page # 1234
Structural Magnetic Resonance Imaging----:---- Page # 1234
Diffusion Magnetic Resonance Imaging----:---- Page # 1236
Term Neonates----:---- Page # 1237
Neonatal Encephalopathy----:---- Page # 1237
Sinovenous Thrombosis----:---- Page # 1239
Stroke----:---- Page # 1239
Vein of Galen Malformation----:---- Page # 1239
Other Intracranial Hemorrhages----:---- Page # 1239
Subdural Hemorrhage----:---- Page # 1242
Subarachnoid Hemorrhage----:---- Page # 1242
Methods Not Yet in Clinical Use----:---- Page # 1244
Quantitative Interpretation of Magnetic Resonance Imaging
Studies----:---- Page # 1244
Cortical Cartography----:---- Page # 1245
Functional Magnetic Resonance Imaging----:---- Page # 1246
64 Neonatal Neuromuscular Disorders----:---- Page # closed----:---- Page # 1253
64 Neonatal Neuromuscular Disorders----:---- Page # 1253
Neonatal Neuromuscular Disorders----:---- Page # 1253
Primary Muscle Disorders----:---- Page # 1253
Congenital Muscular Dystrophies----:---- Page # 1253
α-Dystroglycanopathies----:---- Page # 1253
Walker–Warburg Syndrome----:---- Page # 1254
Muscle–Eye–Brain Disease----:---- Page # 1254
Fukuyama Congenital Muscular Dystrophy----:---- Page # 1254
Other α-Dystroglycanopathies----:---- Page # 1254
LAMA2-Related Muscular Dystrophy----:---- Page # 1254
Congenital Myotonic Dystrophy----:---- Page # 1254
Other Forms of Muscular Dystrophies----:---- Page # 1256
Type VI Collagen-Related Disorders----:---- Page # 1256
Congenital Myopathies----:---- Page # 1256
Nemaline Myopathy----:---- Page # 1256
Core Myopathies----:---- Page # 1256
Myotubular (Centronuclear) Myopathy----:---- Page # 1257
Motor Neuron Disorders----:---- Page # 1257
5q Spinal Muscular Atrophy----:---- Page # 1257
Non-5q Spinal Muscular Atrophies----:---- Page # 1258
Spinal Muscular Atrophy With Respiratory Distress----:----
Page # 1258
X-Linked Infantile Spinal Muscular Atrophy----:---- Page #
1258
Pontocerebellar Hypoplasia Plus Spinal Muscular
Atrophy----:---- Page # 1258
Transient Neonatal Myasthenia Gravis----:---- Page # 1259
Congenital Myasthenic Syndromes----:---- Page # 1259
Peripheral Neuropathies----:---- Page # 1259
Approach to Neonatal Neuromuscular Disorders----:---- Page # 1259
Creatine Phosphokinase----:---- Page # 1260
Electromyography----:---- Page # 1260
Muscle Biopsy----:---- Page # 1260
Genetic Testing----:---- Page # 1260
65 Neonatal Seizures----:---- Page # closed----:---- Page # 1264
65 Neonatal Seizures----:---- Page # 1264
Neonatal Seizures----:---- Page # 1264
Diagnosis of Seizures----:---- Page # 1264
Categorization of Seizures----:---- Page # 1264
Clonic Seizures (Focal and Multifocal)----:---- Page # 1265
Tonic Seizures----:---- Page # 1265
Myoclonic Seizures----:---- Page # 1265
Subtle Seizures----:---- Page # 1265
Nonepileptic Neonatal Movements----:---- Page # 1265
Tremulousness or Jitteriness----:---- Page # 1265
Myoclonus Without Electrographic Correlate----:---- Page # 1266
Dyskinesias----:---- Page # 1266
Neurophysiologic Diagnosis of Seizure----:---- Page # 1266
Electroencephalography----:---- Page # 1266
Neurophysiologic Definitions----:---- Page # 1266
Electroclinical Uncoupling----:---- Page # 1267
Amplitude-Integrated Electroencephalography----:---- Page # 1267
Interictal Abnormalities----:---- Page # 1267
Etiologies of Neonatal Seizures----:---- Page # 1267
Other Causes of Neonatal Encephalopathy----:---- Page # 1268
Cerebrovascular Lesions----:---- Page # 1268
Metabolic Derangements----:---- Page # 1269
Hypocalcemia----:---- Page # 1269
Hyponatremia and Hypernatremia----:---- Page # 1269
Drug Withdrawal and Intoxication----:---- Page # 1269
Congenital Brain Malformations----:---- Page # 1270
Progressive Neonatal Epilepsy Syndromes----:---- Page # 1271
Benign Familial Neonatal Seizures----:---- Page # 1271
Treatment of Seizures----:---- Page # 1271
Antiepileptic Drugs----:---- Page # 1271
Efficacy of Antiepileptic Drugs----:---- Page # 1272
Discontinuation of Antiepileptic Drugs----:---- Page # 1272
Postnatal Epilepsy----:---- Page # 1273
66 Risk Assessment and Neurodevelopmental Outcomes----:---- Page # closed----:----
Page # 1278
66 Risk Assessment and Neurodevelopmental Outcomes----:---- Page # 1278
Outcome Assessment in High-Risk Infants----:---- Page # 1278
Who Is the “High-Risk” Infant?----:---- Page # 1278
What Is Meant by “Outcomes”?----:---- Page # 1279
Early Neurodevelopmental Outcome Assessments----:---- Page # 1279
Motor Function----:---- Page # 1279
Cognitive Assessment----:---- Page # 1280
Hearing and Vision Outcomes----:---- Page # 1281
Neurodevelopmental Impairment—Difficulties and Realities of
a Composite Outcome----:---- Page # 1281
Limitations and Challenges to Interpreting Early
Neurodevelopmental Outcomes Studies----:---- Page # 1282
Focus on Functional Outcomes----:---- Page # 1282
Outcomes of Preterm Infants Across the Life Spectrum----:---- Page #
1283
Early Neurodevelopmental Outcomes of Extremely Preterm
Infants----:---- Page # 1283
The Victoria Infant Collaborative Study Group----:---- Page
# 1283
EPICure 2----:---- Page # 1283
Extremely Preterm Infants in Sweden Study----:---- Page #
1285
Japan Neonatal Research Network----:---- Page # 1285
Eunice Kennedy Shriver NICHD Neonatal Research Network
Follow-Up Study Group----:---- Page # 1286
Swiss National Extremely Preterm Cohort----:---- Page #
1286
School-Age Outcomes After Prematurity----:---- Page # 1286
Adolescent and Adult Outcomes After Prematurity----:---- Page #
1288
Risk Factors for Adverse Outcomes in Preterm Infants----:---- Page #
1288
Brain Injury----:---- Page # 1288
Cranial Ultrasound----:---- Page # 1288
Retinopathy of Prematurity----:---- Page # 1291
Growth and Nutrition----:---- Page # 1292
Socioeconomic Status----:---- Page # 1292
Summary----:---- Page # 1292
Other Infants at High Risk for Adverse Outcomes----:---- Page # 1292
Extracorporeal Membrane Oxygenation----:---- Page # 1294
Summary----:---- Page # 1294
Postdischarge Management of the High-Risk Infant----:---- Page # 1294
Discharge Planning for the High-Risk Infant----:---- Page # 1294
Multidisciplinary Follow-Up Care for the High-Risk
Infant----:---- Page # 1294
Referral for Early Intervention Services----:---- Page # 1295
Challenges to and Importance of Follow-Up----:---- Page # 1296
67 Breastfeeding----:---- Page # closed----:---- Page # 1305
XIII Nutrition----:---- Page # 1305
67 Breastfeeding----:---- Page # 1305
Rates of Breastfeeding in the United States----:---- Page # 1305
Interventions to Support Breastfeeding Initiation, Exclusivity,
and Continuation----:---- Page # 1306
The Evidence to Support Breastfeeding----:---- Page # 1308
Studies Supporting Benefits of Breastfeeding----:---- Page
# 1308
Nutritional Aspects----:---- Page # 1308
Nutritional Implications for the Premature Infant----:----
Page # 1310
Host Defense\: Prevention of Infections----:---- Page #
1310
Chronic Conditions of Childhood----:---- Page # 1313
Neurobehavioral Aspects----:---- Page # 1314
Infant and Childhood Mortality----:---- Page # 1314
Maternal Benefits----:---- Page # 1314
Societal Impact of Breastfeeding----:---- Page # 1315
Contraindications to Breastfeeding----:---- Page # 1315
Anatomy and Physiology of Lactation----:---- Page # 1315
Management of Breastfeeding----:---- Page # 1317
Hospital Care----:---- Page # 1317
Initial Management----:---- Page # 1317
Latch On----:---- Page # 1317
The First 2 Weeks to 2 Months----:---- Page # 1318
Growth of the Breastfed Infant----:---- Page # 1318
Tongue Tie----:---- Page # 1318
Breastfeeding the Late Preterm Infant----:---- Page # 1319
Breastfeeding the Very Low Birth Weight Premature
Infant----:---- Page # 1319
Maternal Breastfeeding Issues----:---- Page # 1319
Nipple Pain----:---- Page # 1319
Engorgement and Blocked Ducts----:---- Page # 1319
Mastitis----:---- Page # 1319
Low Milk Supply----:---- Page # 1319
Contraception----:---- Page # 1320
Maternal Employment Outside the Home----:---- Page # 1320
Jaundice and Breastfeeding----:---- Page # 1320
Breast-Nonfeeding Jaundice----:---- Page # 1320
Breast Milk Jaundice----:---- Page # 1321
Collection and Storage of Human Milk----:---- Page # 1321
Donor Human Milk----:---- Page # 1321
Suggested Educational Resources on the Web----:---- Page # 1322
68 Enteral Nutrition for the High-Risk Neonate----:---- Page # closed----:---- Page
# 1328
68 Enteral Nutrition for the High-Risk Neonate----:---- Page # 1328
Macronutrient Requirements----:---- Page # 1328
Protein----:---- Page # 1328
Energy----:---- Page # 1329
Carbohydrates----:---- Page # 1329
Fat----:---- Page # 1329
Micronutrients, Vitamins, Minerals, and Trace Element
Requirements----:---- Page # 1330
Calcium and Phosphorus----:---- Page # 1330
Magnesium----:---- Page # 1330
Trace Elements----:---- Page # 1330
Zinc----:---- Page # 1330
Copper----:---- Page # 1331
Selenium----:---- Page # 1331
Iron----:---- Page # 1331
Sodium and Potassium----:---- Page # 1331
Vitamins----:---- Page # 1332
Vitamin A----:---- Page # 1332
Vitamin D----:---- Page # 1332
Vitamin E----:---- Page # 1332
Vitamin K----:---- Page # 1332
Options for Enteral Nutrition----:---- Page # 1332
Human Milk----:---- Page # 1333
Maternal Milk----:---- Page # 1333
Human Milk Nutrient Content----:---- Page # 1333
Protein----:---- Page # 1333
Fat----:---- Page # 1334
Carbohydrate----:---- Page # 1334
Essential Fatty Acids----:---- Page # 1334
Carnitine----:---- Page # 1334
Human Milk Enzymes----:---- Page # 1334
Vitamins and Minerals----:---- Page # 1334
Donor Human Milk----:---- Page # 1334
Differences Between Maternal and Donor Human Milk----:----
Page # 1336
Initiation, Mode, and Advancement of Enteral Feedings----:---- Page #
1336
Tube Feeding----:---- Page # 1336
Human Milk Fortification----:---- Page # 1337
Standard Fortification----:---- Page # 1337
Adjustable Fortification----:---- Page # 1338
Target (or Individualized) Fortification----:---- Page #
1338
Infant Nutrition and Growth----:---- Page # 1338
Assessing Growth and Body Composition in Infants----:---- Page # 1339
Growth and Developmental Outcomes in Preterm Infants----:---- Page #
1339
Postdischarge Nutrition for the Premature Infant----:---- Page # 1340
69 Parenteral Nutrition for the High-Risk Neonate----:---- Page # closed----:----
Page # 1346
69 Parenteral Nutrition for the High-Risk Neonate----:---- Page # 1346
Components of Parenteral Nutrition----:---- Page # 1346
Protein----:---- Page # 1346
Energy----:---- Page # 1348
Glucose----:---- Page # 1348
Lipids----:---- Page # 1349
Electrolytes, Minerals, Trace Elements, and Vitamins----:----
Page # 1350
Complications of Parenteral Nutrition----:---- Page # 1351
Use of Parenteral Nutrition in the Neonatal Intensive Care Unit\: A
Practical Approach----:---- Page # 1352
70 Gastrointestinal Tract Development----:---- Page # closed----:---- Page # 1357
XIV Gastrointestinal System----:---- Page # 1357
70 Gastrointestinal Tract Development----:---- Page # 1357
Structural and Functional Development----:---- Page # 1357
Foregut----:---- Page # 1357
Esophagus----:---- Page # 1357
Stomach----:---- Page # 1357
Liver and Pancreas----:---- Page # 1358
Midgut and Hindgut----:---- Page # 1359
Small Intestine----:---- Page # 1359
Colon----:---- Page # 1360
Mucosal Immune System Development----:---- Page # 1361
Gastrointestinal Microbiota----:---- Page # 1361
Digestive Physiology----:---- Page # 1362
Carbohydrate Digestion----:---- Page # 1362
Protein Digestion----:---- Page # 1362
Fat Digestion----:---- Page # 1362
71 Structural Anomalies of the Gastrointestinal Tract----:---- Page #
closed----:---- Page # 1365
71 Structural Anomalies of the Gastrointestinal Tract----:---- Page # 1365
Disorders of the Oral Cavity----:---- Page # 1365
Mouth----:---- Page # 1365
Tongue----:---- Page # 1366
Salivary Glands----:---- Page # 1366
Disorders of the Neck----:---- Page # 1366
Branchial Anomalies----:---- Page # 1367
Thyroid----:---- Page # 1367
Other Neck Masses----:---- Page # 1367
Disorders of the Esophagus----:---- Page # 1368
Esophageal Atresia----:---- Page # 1368
Etiology and Associated Anomalies----:---- Page # 1368
Classification----:---- Page # 1368
Preoperative Management----:---- Page # 1369
Operation----:---- Page # 1369
Postoperative Management----:---- Page # 1370
Laryngotracheoesophageal Cleft----:---- Page # 1370
Congenital Esophageal Stenosis----:---- Page # 1371
Esophageal Duplication Cyst----:---- Page # 1371
Esophageal Perforation----:---- Page # 1371
Disorders of the Stomach----:---- Page # 1372
Pyloric Atresia----:---- Page # 1372
Gastric Duplication----:---- Page # 1373
Pyloric Stenosis----:---- Page # 1373
Gastric Perforation----:---- Page # 1373
Disorders of the Intestine----:---- Page # 1374
Malrotation and Volvulus----:---- Page # 1374
Intestinal Atresia----:---- Page # 1375
Duodenal Atresia----:---- Page # 1375
Jejunoileal and Colon Atresia----:---- Page # 1376
Meconium Ileus----:---- Page # 1376
Enteric Duplication Cysts----:---- Page # 1377
Intussusception----:---- Page # 1377
Disorders of the Colon----:---- Page # 1377
Neonatal Appendicitis----:---- Page # 1377
Hirschsprung Disease----:---- Page # 1377
Meconium Plug----:---- Page # 1378
Anorectal Disorders----:---- Page # 1378
72 Innate and Mucosal Immunity in the Developing Gastrointestinal Tract----:----
Page # closed----:---- Page # 1383
72 Innate and Mucosal Immunity in the Developing Gastrointestinal
Tract----:---- Page # 1383
Development of the Gastrointestinal Tract----:---- Page # 1383
Fetal Development----:---- Page # 1383
Role of Amniotic Fluid in Early Gastrointestinal
Mucosal Immunity in the Developing Gastrointestinal Tract----:---- Page
# 1385
Physical and Chemical Barriers----:---- Page # 1386
Epithelial Cell Layer and Tight Junctions----:---- Page # 1387
Specialized Epithelial Immune Cells----:---- Page # 1388
Monocytes, Macrophages, Dendritic Cells, and Mast
Cells----:---- Page # 1388
Gut-Associated Lymphoid Tissue and Adaptive Immunity----:----
Page # 1389
Antigen Sampling and Presentation----:---- Page # 1389
Microfold Cell and Dendritic Cell Pathway----:---- Page #
1389
Receptor-Mediated Endocytosis and Processing\: Toll-Like
and Nucleotide-Binding Oligomerization Domain Receptors----:---- Page # 1389
T-Helper 1/T-Helper 2 Polarization----:---- Page # 1390
Exogenous Exposures and Their Impact on Innate Intestinal Immune
Defenses----:---- Page # 1390
Bacterial Colonization----:---- Page # 1390
Mode of Delivery----:---- Page # 1391
Diet----:---- Page # 1391
Environment----:---- Page # 1392
Antibiotic Use----:---- Page # 1392
The Intestinal Microbiota, Gut Immunity, and
Inflammation----:---- Page # 1392
Diet\: Human Milk and Infant Formula----:---- Page # 1392
Impact of Altered Mucosal Immunity on Early and Later Disease----:----
Page # 1393
Prematurity and Necrotizing Enterocolitis----:---- Page # 1393
Inadequate Physical and Chemical Barriers----:---- Page #
1393
Abnormal Colonization of the Preterm Gut----:---- Page #
1393
Atopic Diseases----:---- Page # 1394
Inflammatory Bowel Disease, Celiac Disease, and Type 1
Diabetes----:---- Page # 1395
Obesity----:---- Page # 1396
Acknowledgements----:---- Page # 1396
73 Abdominal Wall Defects----:---- Page # closed----:---- Page # 1402
73 Abdominal Wall Defects----:---- Page # 1402
Umbilical Cord Abnormalities----:---- Page # 1402
Noncoiled Umbilical Cord----:---- Page # 1402
Single Umbilical Artery----:---- Page # 1402
Umbilical Vessel Dilatations----:---- Page # 1402
Umbilical Cord Cysts----:---- Page # 1403
Umbilical Cord Hematomas----:---- Page # 1403
Umbilical Abnormalities----:---- Page # 1403
Delayed Separation of the Umbilical Cord----:---- Page # 1403
Umbilical and Periumbilical Infections----:---- Page # 1403
Umbilical Granulomas----:---- Page # 1403
Persistent Remnants of Urachus and Omphalomesenteric
Duct----:---- Page # 1403
Abdominal Wall Defects----:---- Page # 1404
Gastroschisis----:---- Page # 1405
Omphalocele----:---- Page # 1408
Other Abdominal Wall Defects----:---- Page # 1409
Body Stalk Anomaly----:---- Page # 1409
Bladder Exstrophy----:---- Page # 1410
Cloacal Exstrophy----:---- Page # 1410
Prune Belly Syndrome----:---- Page # 1410
Abdominal Wall Hernias----:---- Page # 1410
Diastasis Recti----:---- Page # 1410
Epigastric Hernia----:---- Page # 1410
Umbilical Hernia----:---- Page # 1410
Inguinal Hernia and Hydrocele----:---- Page # 1411
74 Neonatal Gastroesophageal Reflux----:---- Page # closed----:---- Page # 1416
74 Neonatal Gastroesophageal Reflux----:---- Page # 1416
Normal Anatomy and Physiology----:---- Page # 1416
Abnormal Physiology\: Gastroesophageal Reflux Disease----:---- Page #
1416
Objective Measures----:---- Page # 1417
24-Hour pH Monitoring----:---- Page # 1417
24-Hour Combined pH and Multichannel Intraluminal
Impedance----:---- Page # 1417
Manometry----:---- Page # 1417
Gastric Scintigraphy----:---- Page # 1417
Upper Gastrointestinal Series----:---- Page # 1417
Indications for Medical and Surgical Management of Gastroesophageal
Reflux Disease----:---- Page # 1418
Options for Interventions----:---- Page # 1418
Pharmacologic Agents----:---- Page # 1418
Surgical Intervention----:---- Page # 1419
75 The Intestinal Microbiome----:---- Page # closed----:---- Page # 1421
75 The Intestinal Microbiome----:---- Page # 1421
Historical Perspectives----:---- Page # 1421
Beyond Culture----:---- Page # 1421
Technologies----:---- Page # 1421
Other “Omics”----:---- Page # 1422
Actions of the Intestinal Microbiome----:---- Page # 1423
Intestinal Inflammation and Immune Function----:---- Page # 1423
The Bioreactor Function----:---- Page # 1423
Development of the Intestinal Microbiome----:---- Page # 1424
The Nonsterile Fetal Environment----:---- Page # 1424
Maternal Intestinal Host–Microbial Interactions----:---- Page #
1425
The Fetal–Maternal Microbiome Source----:---- Page # 1425
The Infant Microbiome----:---- Page # 1426
Mode of Delivery----:---- Page # 1426
Intestine-Derived Inflammation----:---- Page # 1426
Total Parenteral Nutrition----:---- Page # 1426
Effect of Diet----:---- Page # 1426
Effects of Antibiotics on Intestinal Microbiota----:---- Page #
1426
Effects of H2 Blockers----:---- Page # 1426
Summary----:---- Page # 1426
76 Necrotizing Enterocolitis and Short Bowel Syndrome----:---- Page #
closed----:---- Page # 1431
76 Necrotizing Enterocolitis and Short Bowel Syndrome----:---- Page # 1431
Prematurity and Low Birth Weight----:---- Page # 1431
Formula Feeding----:---- Page # 1432
Blood Transfusions----:---- Page # 1432
Infectious Agents----:---- Page # 1432
Bowel Ischemia----:---- Page # 1432
Abnormal Bacterial Colonization----:---- Page # 1432
Impaired Gut Barrier Function and Proinflammatory
Response----:---- Page # 1432
Medical Management----:---- Page # 1435
Surgical Management----:---- Page # 1435
Laparotomy Versus Peritoneal Drain Placement----:---- Page # 1435
Surgical Options----:---- Page # 1436
Exclusive Use of Human Milk----:---- Page # 1436
Probiotics----:---- Page # 1437
Short Bowel Syndrome----:---- Page # 1437
77 Disorders of the Liver----:---- Page # closed----:---- Page # 1441
77 Disorders of the Liver----:---- Page # 1441
Introduction to Neonatal Liver Disease----:---- Page # 1441
Cholestatic Liver Disease----:---- Page # 1442
Biliary Atresia----:---- Page # 1443
Alagille Syndrome (Arteriohepatic Dysplasia)----:---- Page # 1444
α-1 Antitrypsin Deficiency----:---- Page # 1445
Cystic Fibrosis Liver Disease----:---- Page # 1446
Disorders of Bile Acid Synthesis----:---- Page # 1446
Progressive Familial Intrahepatic Cholestasis----:---- Page #
1446
Congenital Hepatic Fibrosis----:---- Page # 1447
Infections----:---- Page # 1447
Parenteral Nutrition–Associated Liver Disease----:---- Page #
1447
Metabolic Liver Disease----:---- Page # 1447
Disorders of Carbohydrate Metabolism----:---- Page # 1447
Hereditary Fructose Intolerance----:---- Page # 1448
Disorders of Amino Acid Metabolism----:---- Page # 1449
Tyrosinemia Type 1----:---- Page # 1449
Disorders of Organic Acid Metabolism----:---- Page # 1450
Fatty Acid Oxidation Defects----:---- Page # 1450
Urea Cycle Defects----:---- Page # 1450
Mitochondrial Hepatopathies----:---- Page # 1450
Gestational Alloimmune Liver Disease----:---- Page # 1451
Vascular Malformations----:---- Page # 1451
Arteriovenous Malformations----:---- Page # 1452
Congenital Portosystemic Shunts----:---- Page # 1452
Hereditary Hemorrhagic Telangiectasia----:---- Page # 1452
Infantile Hepatic Hemangiomas----:---- Page # 1454
Liver Masses----:---- Page # 1455
Hepatoblastoma----:---- Page # 1455
Congenital Hepatic Cysts----:---- Page # 1455
78 Developmental Hematology----:---- Page # closed----:---- Page # 1458
XV Hematologic System and Disorders of Bilirubin Metabolism----:---- Page #
1458
78 Developmental Hematology----:---- Page # 1458
Introduction to Embryonic Hematopoiesis----:---- Page # 1458
Stem Cell Biology----:---- Page # 1458
Developmental Aspects of Erythropoiesis----:---- Page # 1459
Primitive and Definitive Erythropoiesis----:---- Page #
1459
Switch of the Primary Site of Erythropoiesis----:---- Page
# 1460
Yolk Sac----:---- Page # 1460
Aortogonadomesonephron----:---- Page # 1461
Liver----:---- Page # 1461
Bone Marrow----:---- Page # 1461
Factors Influencing the Sites of Erythropoiesis----:----
Page # 1461
Extramedullary Hematopoiesis----:---- Page # 1461
Ontogeny of Erythrocytes----:---- Page # 1461
Developmental Changes in the Regulation of
Erythropoiesis----:---- Page # 1462
Ontogeny, Organization, and Structure of
Hemoglobins----:---- Page # 1462
Changes in Hemoglobin Synthesis With
Red Blood Cell Transfusion----:---- Page # 1462
Bilirubin Metabolism----:---- Page # 1463
Developmental Aspects of Megakaryocytopoiesis----:---- Page #
1463
Sites of Megakaryocyte Production----:---- Page # 1463
Megakaryocyte Precursors----:---- Page # 1464
Control of Megakaryocytopoiesis----:---- Page # 1464
Thrombopoietin----:---- Page # 1464
Developmental Changes in Platelet Count----:---- Page # 1464
Platelet Transfusions----:---- Page # 1464
Developmental Aspects of Granulocytopoiesis----:---- Page # 1465
Overview of Hematopoietic Cytokines----:---- Page # 1465
79 Neonatal Bleeding and Thrombotic Disorders----:---- Page # closed----:---- Page
# 1469
79 Neonatal Bleeding and Thrombotic Disorders----:---- Page # 1469
The Neonatal Hemostatic System----:---- Page # 1469
Developmental Hemostasis----:---- Page # 1469
Bleeding Disorders in the Neonate----:---- Page # 1470
Laboratory Investigation----:---- Page # 1471
Hemophilia----:---- Page # 1471
von Willebrand Disease----:---- Page # 1472
Other Rare Inherited Coagulation Disorders----:---- Page # 1472
Acquired Coagulation Disorders----:---- Page # 1473
Vitamin K Deficiency----:---- Page # 1473
Disseminated Intravascular Coagulation----:---- Page # 1473
Liver Disease----:---- Page # 1474
Neonatal Thrombosis----:---- Page # 1474
Risk Factors for Neonatal Thromboembolism----:---- Page # 1474
Prothrombotic Disorders\: Pathophysiology and Their Role in
Neonatal Thromboembolism----:---- Page # 1474
Locations of Neonatal Thromboses, Imaging Modalities to Diagnose
Them, and Management Guidelines for Specific Thromboses----:---- Page # 1475
Arterial Thromboses----:---- Page # 1475
Perinatal Arterial Ischemic Stroke----:---- Page # 1475
Iatrogenic/Spontaneous Arterial Thromboses----:---- Page #
1477
Venous Thrombosis----:---- Page # 1478
Catheter-Related Thrombosis (Umbilical Venous Catheters and
Peripherally Inserted Central Venous Catheters)----:---- Page # 1478
Intracardiac Thromboses and Thromboses in Infants With
Complex Congenital Heart Disease----:---- Page # 1480
Renal Vein Thrombosis----:---- Page # 1481
Portal Vein Thrombosis----:---- Page # 1481
Cerebral Sinovenous Thrombosis----:---- Page # 1481
Prothrombotic Laboratory Evaluation for Clinically Symptomatic
Neonatal Thromboses----:---- Page # 1482
Management of Thrombosis----:---- Page # 1483
Unfractionated Heparin----:---- Page # 1484
Low-Molecular-Weight Heparin----:---- Page # 1485
Recombinant Tissue Type Plasminogen Activator----:---- Page #
1485
Surgery----:---- Page # 1486
New Anticoagulants----:---- Page # 1486
80 Neonatal Platelet Disorders----:---- Page # closed----:---- Page # 1491
80 Neonatal Platelet Disorders----:---- Page # 1491
Fetal and Neonatal Platelet Production----:---- Page # 1491
Platelet Counts During Development and Reference Ranges----:---- Page #
1491
Platelet Function and Primary Hemostasis----:---- Page # 1491
Thrombocytosis in the Neonate----:---- Page # 1493
Thrombocytopenia in the Neonate----:---- Page # 1493
Approach to the Thrombocytopenic Neonate—Evaluation and
Classification----:---- Page # 1493
Early-Onset Thrombocytopenia (Fig. 80.2, Box 80.1)----:---- Page
# 1493
Late-Onset Thrombocytopenia (Fig. 80.3, Box 80.1)----:---- Page #
1495
Immune Thrombocytopenia----:---- Page # 1496
Neonatal Alloimmune Thrombocytopenia----:---- Page # 1496
Laboratory Investigation----:---- Page # 1496
Management of the Neonate With Suspected Neonatal
Alloimmune Thrombocytopenia (Pregnancy Unknown to the Mother)----:---- Page # 1496
Management of the Neonate With Known Neonatal
Alloimmune Thrombocytopenia----:---- Page # 1497
Management of Pregnant Women With Previous History of
Autoimmune Thrombocytopenia----:---- Page # 1497
Maternal Management----:---- Page # 1498
Congenital Thrombocytopenias----:---- Page # 1498
Management of Neonatal Thrombocytopenia----:---- Page # 1499
Platelet Transfusions in the Neonatal Intensive Care
Unit----:---- Page # 1499
Alternative Tests to Guide Platelet Transfusions----:----
Page # 1501
Nontransfusional Therapies----:---- Page # 1501
Platelet Function Disorders----:---- Page # 1501
Etiology/Pathophysiology----:---- Page # 1501
81 Neonatal Erythrocyte Disorders----:---- Page # closed----:---- Page # 1507
81 Neonatal Erythrocyte Disorders----:---- Page # 1507
Reference Intervals----:---- Page # 1507
Neonatal Anemia----:---- Page # 1513
Anemia Caused by Failure of Erythrocyte Production----:---- Page
# 1514
Anemia of Prematurity----:---- Page # 1514
The “Late” Anemia of Rhesus Hemolytic Disease----:---- Page
# 1515
Neonatal Iron Deficiency----:---- Page # 1515
Diamond–Blackfan Anemia and Somewhat Related
Conditions----:---- Page # 1516
Neonatal Anemia Caused by Hemorrhage----:---- Page # 1516
Prenatal Hemorrhage----:---- Page # 1516
Perinatal Hemorrhage----:---- Page # 1518
Postnatal Hemorrhage----:---- Page # 1519
Anemia Caused by Hemolysis----:---- Page # 1520
Immune-Mediated Hemolytic Disease of the Neonate----:----
Page # 1520
Rhesus----:---- Page # 1520
ABO----:---- Page # 1523
Kell----:---- Page # 1524
Kidd----:---- Page # 1524
Duffy----:---- Page # 1524
MNS----:---- Page # 1524
Maternal Disease----:---- Page # 1524
Nonimmune-Mediated, Acquired Hemolytic Disease of the
Neonate----:---- Page # 1524
Hereditary Hemolytic Anemias Caused by Red Blood Cell
Cytoskeletal Mutations----:---- Page # 1524
Hereditary Spherocytosis----:---- Page # 1524
Hereditary Elliptocytosis----:---- Page # 1528
Hereditary Pyropoikilocytosis----:---- Page # 1528
Hereditary Hemolytic Anemias Caused by Red Blood Cell Enzyme
Abnormalities----:---- Page # 1528
Glucose 6-Phosphate Dehydrogenase Deficiency----:---- Page
# 1529
Pyruvate Kinase Deficiency----:---- Page # 1529
Neonatal Hemolysis Associated With Unstable
Hemoglobins----:---- Page # 1529
Neonatal Hemolysis Associated With Alpha or Gamma
Thalassemia----:---- Page # 1529
Alpha Thalassemia----:---- Page # 1530
Gamma Thalassemia----:---- Page # 1530
Neonatal Polycythemia/Hyperviscosity and Methemoglobinemia----:----
Page # 1530
Polycythemia/Hyperviscosity----:---- Page # 1530
Methemoglobinemia----:---- Page # 1531
Treatment Considerations----:---- Page # 1532
Treatment of Anemia----:---- Page # 1532
Treatment of Hyperviscosity----:---- Page # 1534
82 Neonatal Transfusion----:---- Page # closed----:---- Page # 1539
82 Neonatal Transfusion----:---- Page # 1539
Red Blood Cell Transfusion----:---- Page # 1539
Component----:---- Page # 1539
Preparation----:---- Page # 1539
Risks of Red Blood Cell Transfusion----:---- Page # 1541
Immunologic Complications----:---- Page # 1541
Transfusion-Related Acute Lung Injury----:---- Page #
1542
Nonimmunologic Complications----:---- Page # 1542
Transfusion-Associated Circulatory Overload----:----
Page # 1542
Metabolite Derangements----:---- Page # 1542
Fatal Transfusion Reactions----:---- Page # 1542
Platelet Transfusion----:---- Page # 1543
Component----:---- Page # 1543
Risks----:---- Page # 1543
Plasma and Cryoprecipitate Transfusion----:---- Page # 1543
Components----:---- Page # 1543
Risks----:---- Page # 1544
Special Circumstances----:---- Page # 1544
Massive Transfusion----:---- Page # 1544
Exchange Transfusion----:---- Page # 1544
Intravenous Immune Globulin----:---- Page # 1544
Decreasing the Need for Red Blood Cell Transfusion----:---- Page
# 1545
83 Neonatal Leukocyte Physiology and Disorders----:---- Page # closed----:---- Page
# 1549
83 Neonatal Leukocyte Physiology and Disorders----:---- Page # 1549
Neutrophil Physiology and Function----:---- Page # 1549
Ontogeny----:---- Page # 1549
Circulating and Marginated Blood Neutrophil Pools----:---- Page #
1549
Neutrophil Heterogeneity----:---- Page # 1549
Neonatal Neutropenia----:---- Page # 1550
Sepsis-Induced Neutropenia----:---- Page # 1550
Alloimmune Neonatal Neutropenia----:---- Page # 1551
Maternal Hypertension–Associated Neutropenia----:---- Page
# 1551
Treatment of Neonatal Neutropenia----:---- Page # 1551
Monocyte Physiology and Dysfunction----:---- Page # 1552
Circulating Monocytes----:---- Page # 1552
Monocyte Subsets----:---- Page # 1553
Function----:---- Page # 1553
Developmental Defects in the Phagocytic Immune System in
Neonates----:---- Page # 1554
Leukocytes Contributing to Acquired Immunity----:---- Page # 1554
T-Lymphocyte Physiology and Function----:---- Page # 1554
T-Cell Receptor Repertoire----:---- Page # 1555
T-Cell Subtypes----:---- Page # 1555
T-Helper Cells----:---- Page # 1555
Regulatory T Cells----:---- Page # 1555
Cytotoxic T Lymphocytes----:---- Page # 1555
γδ T Cells----:---- Page # 1555
Natural Killer T Cells----:---- Page # 1555
Circulating T Cells----:---- Page # 1555
Neonatal T-Lymphocyte Function----:---- Page # 1556
B-Lymphocyte Physiology and Function----:---- Page # 1556
B-Cell Subtypes----:---- Page # 1556
Circulating B Cells----:---- Page # 1556
Neonatal B-Lymphocyte Function----:---- Page # 1556
Immunoglobulin Production----:---- Page # 1556
Immunoglobulin Repertoire----:---- Page # 1556
Serum Immunoglobulin Levels----:---- Page # 1557
Dendritic Cell Physiology and Function----:---- Page # 1557
Dendritic Cell Subtypes----:---- Page # 1557
Morphology----:---- Page # 1557
Innate Lymphoid Cell Physiology and Function----:---- Page # 1558
Natural Killer Cell Physiology and Function----:---- Page # 1558
Natural Killer Cell Subtypes----:---- Page # 1558
Noncytotoxic Innate Lymphoid Cell Physiology and
Innate Lymphoid Cell Subtypes----:---- Page # 1558
Summary----:---- Page # 1559
84 Neonatal Indirect Hyperbilirubinemia and Kernicterus----:---- Page #
closed----:---- Page # 1564
84 Neonatal Indirect Hyperbilirubinemia and Kernicterus----:---- Page # 1564
Hemolytic Disease—Increased Hepatic Bilirubin Load----:---- Page # 1564
Red Cell Membrane Defects----:---- Page # 1565
Red Cell Enzyme Deficiencies----:---- Page # 1566
Glucose-6-Phosphate Dehydrogenase Deficiency----:---- Page
# 1566
Heritable Causes of Hemolysis— Hemoglobinopathies----:---- Page #
1567
Acquired Causes of Hemolysis----:---- Page # 1567
Immune-Mediated Hemolytic Disease----:---- Page # 1567
Non-ABO Alloantibodies----:---- Page # 1567
ABO Hemolytic Disease----:---- Page # 1568
Decreased Hepatic Bilirubin Clearance----:---- Page # 1569
Hepatic Bilirubin Uptake----:---- Page # 1569
Hepatic Bilirubin Conjugation----:---- Page # 1569
Gilbert Syndrome----:---- Page # 1569
Enhanced Enterohepatic Circulation----:---- Page # 1570
Other Clinically Relevant Icterogenic Conditions----:---- Page # 1570
Late-Preterm Gestation----:---- Page # 1571
Exclusive Breast-Milk Feeding----:---- Page # 1571
East Asian Ethnicity----:---- Page # 1572
Jaundice Observed in the First 24 Hours of Life----:---- Page #
1572
Cephalohematoma or Significant Bruising----:---- Page # 1572
Previous Sibling Treated With Phototherapy----:---- Page # 1573
African-American Ethnicity----:---- Page # 1573
Combining Clinical Risk Factor Assessment With Predischarge
Bilirubin Measurement----:---- Page # 1573
Clinical Evaluation of Jaundice----:---- Page # 1574
Kernicterus—Chronic Bilirubin Encephalopathy----:---- Page # 1574
Molecular Pathogenesis----:---- Page # 1575
Preterm Neonates and Low-Bilirubin Kernicterus----:---- Page #
1577
Clinical Efforts at Kernicterus Prevention----:---- Page # 1577
Treatment Considerations----:---- Page # 1578
Phototherapy----:---- Page # 1579
Exchange Transfusion----:---- Page # 1582
Intravenous Immunoglobulin----:---- Page # 1583
85 Congenital Malignant Disorders----:---- Page # closed----:---- Page # 1590
XVI Neoplasia----:---- Page # 1590
85 Congenital Malignant Disorders----:---- Page # 1590
Epidemiology, Etiology, and Diagnosis of Neonatal
Malignancy----:---- Page # 1590
Epidemiology\: Incidence and Mortality----:---- Page # 1590
Genetic Predisposition Syndromes and Congenital
Defects----:---- Page # 1590
Transplacental Tumor Passage----:---- Page # 1593
Twin-to-Twin Transmission----:---- Page # 1593
Diagnosis and Evaluation----:---- Page # 1593
Specific Neoplasms----:---- Page # 1593
Neuroblastoma----:---- Page # 1593
Presentation----:---- Page # 1594
Unusual Presentations----:---- Page # 1595
Catecholamine Secretion----:---- Page # 1596
Pathologic Classification----:---- Page # 1596
Genetic Prognostic Factors\: Tumor Biology----:----
Page # 1596
Staging----:---- Page # 1597
Newborn Screening----:---- Page # 1598
Congenital Leukemia----:---- Page # 1598
Laboratory Manifestations----:---- Page # 1598
Cellular Morphology and Immunophenotype----:---- Page
# 1599
Genetics----:---- Page # 1599
Transient Myeloproliferative Disorders and Leukemia
in Patients With Down Syndrome----:---- Page # 1600
Transient Myeloproliferative Disorder----:---- Page #
1600
Germ Cell Tumors----:---- Page # 1601
Pathology----:---- Page # 1601
Evaluation----:---- Page # 1601
Sacrococcygeal Teratomas----:---- Page # 1601
Renal Neoplasms----:---- Page # 1602
Congenital Mesoblastic Nephroma----:---- Page # 1602
Wilms Tumor----:---- Page # 1602
Hereditary Associations and Congenital
Anomalies----:---- Page # 1602
Prognostic Factors----:---- Page # 1603
Evaluation and Staging----:---- Page # 1603
Rhabdoid Tumor of the Kidney----:---- Page # 1603
Persistent Nephrogenic Rests and
Nephroblastomatosis----:---- Page # 1603
Retinoblastoma----:---- Page # 1603
Genetics----:---- Page # 1603
Central Nervous System Tumors----:---- Page # 1604
Incidence and Epidemiology----:---- Page # 1604
Sarcomas----:---- Page # 1605
Histiocytosis----:---- Page # 1605
Hepatoblastoma----:---- Page # 1606
Hepatic Hemangioendothelioma----:---- Page # 1607
Treatment Considerations in Infants----:---- Page # 1607
Chemotherapy Dosing----:---- Page # 1607
Radiation Effects----:---- Page # 1607
Pain Management----:---- Page # 1607
Intravenous Access----:---- Page # 1608
Transfusions----:---- Page # 1608
Immunizations----:---- Page # 1608
Psychosocial Considerations----:---- Page # 1608
Late Effects----:---- Page # 1608
86 Renal Development----:---- Page # closed----:---- Page # 1612
XVII Renal and Genitourinary Systems----:---- Page # 1612
86 Renal Development----:---- Page # 1612
Factors Influencing Organogenesis----:---- Page # 1612
Development of the Renal Vascular Bed----:---- Page # 1613
Renal Morphogenesis----:---- Page # 1613
Glomerular Development----:---- Page # 1617
Ureteral Growth and Development----:---- Page # 1619
Renin–Angiotensin System Interaction for Programing Fetal
Fetal Programing of Renal Function and Perinatal Environmental
Factors Influence Development of Renal Function and Adult Renal Disease----:----
Page # 1621
87 Developmental Abnormalities of the Kidneys----:---- Page # closed----:---- Page
# 1624
87 Developmental Abnormalities of the Kidneys----:---- Page # 1624
Abnormalities of Kidney Number----:---- Page # 1624
Unilateral Renal Agenesis----:---- Page # 1624
Bilateral Renal Agenesis----:---- Page # 1625
Abnormalities of Renal Position----:---- Page # 1625
Ectopic Kidney----:---- Page # 1625
Horseshoe Kidney----:---- Page # 1626
Abnormalities of Renal Organization----:---- Page # 1626
Multicystic Dysplastic Kidney----:---- Page # 1626
Isolated Renal Dysplasia----:---- Page # 1627
Renal Coloboma Syndrome----:---- Page # 1627
Brachio–Oto–Renal Syndrome----:---- Page # 1627
Hypothyroidism–Deafness–Renal Dysplasia Syndrome----:---- Page #
1627
VACTERL----:---- Page # 1627
Eagle–Barrett Syndrome----:---- Page # 1627
Abnormalities With Renal Overgrowth----:---- Page # 1629
Abnormalities Predominated by Renal Cysts----:---- Page # 1629
Ciliopathies----:---- Page # 1629
Autosomal Recessive Polycystic Kidney Disease----:---- Page #
1629
Autosomal Dominant Polycystic Kidney Disease----:---- Page # 1630
Tuberous Sclerosis Complex----:---- Page # 1630
Bardet–Biedl Syndrome----:---- Page # 1631
Jeune Syndrome----:---- Page # 1631
Nephronophthisis----:---- Page # 1631
Meckel–Gruber Syndrome----:---- Page # 1631
Joubert Syndrome and Joubert-Related Disorders----:---- Page #
1631
Orofaciodigital Syndrome----:---- Page # 1632
Cranioectodermal Dysplasia----:---- Page # 1632
Renal–Hepatic–Pancreatic Dysplasia----:---- Page # 1632
Glomerulocystic Kidney Disease----:---- Page # 1632
Renal Tubular Dysgenesis----:---- Page # 1632
Renal Teratogens----:---- Page # 1632
Multiple Acyl-CoA Dehydrogenase Deficiency----:---- Page # 1633
Smith–Lemli–Opitz Syndrome----:---- Page # 1633
Zellweger Syndrome----:---- Page # 1633
Congenital Disorders of Glycosylation----:---- Page # 1633
88 Developmental Abnormalities of the Genitourinary System----:---- Page #
closed----:---- Page # 1636
88 Developmental Abnormalities of the Genitourinary System----:---- Page #
1636
Early Kidney and Urinary Tract Embryologic Development----:---- Page #
1636
Anomalies of the Kidney----:---- Page # 1637
Renal Agenesis----:---- Page # 1637
Renal Ectopia and Fusion----:---- Page # 1638
Supernumerary Kidney----:---- Page # 1638
Cystic Disease of the Kidney----:---- Page # 1638
Renal Tumors----:---- Page # 1639
Adrenal Hemorrhage----:---- Page # 1640
Anomalies of the Ureters----:---- Page # 1640
Duplication of the Ureters----:---- Page # 1640
Ureteral Ectopia----:---- Page # 1640
Ureterocele----:---- Page # 1640
Ureteropelvic Junction Obstruction----:---- Page # 1641
Ureterovesical Obstruction----:---- Page # 1642
Vesicoureteral Reflux----:---- Page # 1642
Anomalies of the Bladder----:---- Page # 1642
Bladder Exstrophy----:---- Page # 1642
Cloacal Exstrophy----:---- Page # 1643
Patent Urachus----:---- Page # 1643
Posterior Urethral Valves----:---- Page # 1644
Genital Abnormalities in Males----:---- Page # 1644
Cryptorchidism----:---- Page # 1644
Hypospadias and Chordee----:---- Page # 1645
Other Penile Anomalies----:---- Page # 1645
Webbed Penis----:---- Page # 1645
Buried Penis----:---- Page # 1645
Micropenis----:---- Page # 1645
Aphallia----:---- Page # 1646
Epispadias----:---- Page # 1646
Urethral Duplication----:---- Page # 1646
Differences in Sex Development----:---- Page # 1646
Phimosis----:---- Page # 1646
Testicular Tumors----:---- Page # 1646
Testicular Torsion----:---- Page # 1647
Urinary Tract Infections----:---- Page # 1647
Myelodysplasia----:---- Page # 1647
Prune-Belly Syndrome----:---- Page # 1647
Anorectal Malformation----:---- Page # 1647
Female Genital Anomalies----:---- Page # 1647
Female Genital Tract Development----:---- Page # 1647
Hydrocolpos and Hydrometrocolpos----:---- Page # 1648
Vaginal Agenesis----:---- Page # 1648
Cloacal Anomalies and Urogenital Sinus----:---- Page # 1649
Müllerian Duplication Anomalies----:---- Page # 1649
Introital Masses in Children----:---- Page # 1649
89 Clinical Evaluation of Renal and Urinary Tract Disease----:---- Page #
closed----:---- Page # 1654
89 Clinical Evaluation of Renal and Urinary Tract Disease----:---- Page #
1654
Prenatal Evaluation of Renal and Urinary Tract Disease----:---- Page #
1654
Prenatal Renal Ultrasound----:---- Page # 1654
Fetal Magnetic Resonance Imaging----:---- Page # 1655
Amniotic Fluid and Chorionic Villus Sampling----:---- Page # 1655
Prenatal Management of Renal and Urinary Tract Disease----:---- Page #
1656
Goals of Management and Prognostic Factors----:---- Page # 1656
Interventions----:---- Page # 1656
Postnatal Evaluation of Renal and Urinary Tract Disease----:---- Page #
1656
Prenatal and Perinatal History----:---- Page # 1656
Family History----:---- Page # 1656
Hypertension----:---- Page # 1656
Micturition----:---- Page # 1657
Abdominal Masses----:---- Page # 1657
Edema----:---- Page # 1657
Ascites----:---- Page # 1657
Laboratory Tests----:---- Page # 1657
Serum Estimates of Glomerular Filtration Rate----:---- Page
# 1657
Other Serum Chemistries----:---- Page # 1657
Urine----:---- Page # 1658
Concentrating/Diluting----:---- Page # 1658
Proteinuria----:---- Page # 1658
Other Urinary Findings (Hematuria, Hemoglobinuria,
Myoglobinuria, Uricosuria)----:---- Page # 1658
Imaging----:---- Page # 1658
Renal Ultrasound----:---- Page # 1658
Computed Tomography Scan----:---- Page # 1659
Voiding Cystourethrography----:---- Page # 1659
Nuclear Medicine----:---- Page # 1659
90 Acute Kidney Injury and Chronic Kidney Disease----:---- Page # closed----:----
Page # 1662
90 Acute Kidney Injury and Chronic Kidney Disease----:---- Page # 1662
Acute Kidney Injury----:---- Page # 1662
Infants With Perinatal Asphyxia----:---- Page # 1664
Infants Undergoing Cardiac Pulmonary Bypass
Surgery----:---- Page # 1665
Infants Requiring Extracorporeal Membrane
Oxygenation----:---- Page # 1665
Very Low Birth Weight and Extremely Low Birth Weight
Neonates----:---- Page # 1665
Pathophysiology of Neonatal Acute Kidney Injury----:---- Page #
1665
Prerenal----:---- Page # 1665
Intrinsic Acute Kidney Injury----:---- Page # 1666
Ischemic Acute Kidney Injury----:---- Page # 1666
Nephrotoxic Acute Kidney Injury----:---- Page # 1667
Postrenal Acute Kidney Injury----:---- Page # 1668
Evaluation and Management of Neonatal Acute Kidney
Injury----:---- Page # 1668
Step 1\: Understand the Cause of Acute Kidney
Injury----:---- Page # 1668
Step 2\: Intervene to Preserve or Prevent Further Acute
Kidney Injury----:---- Page # 1669
Step 3\: Provide Renal Support----:---- Page # 1670
Renal Support Therapy With Dialysis----:---- Page # 1671
Indications for Dialysis Initiation----:---- Page # 1671
Access----:---- Page # 1671
Peritoneal Dialysis----:---- Page # 1672
Hemodialysis----:---- Page # 1672
Acute Kidney Injury as a Cause of Long-Term Chronic Kidney
Disease----:---- Page # 1672
Renal Vascular Disease in the Newborn----:---- Page # 1673
Renal Arterial Thrombus----:---- Page # 1673
Renal Cortical and Medullary Necrosis----:---- Page # 1675
Management and Prognosis----:---- Page # 1675
Chronic Kidney Disease----:---- Page # 1675
Clinical Sequelae----:---- Page # 1676
Pathophysiology of Anemia----:---- Page # 1676
Management of Anemia----:---- Page # 1676
Growth and Development----:---- Page # 1677
Nutritional Assessment----:---- Page # 1677
Nutritional Management----:---- Page # 1678
Acid–Base and Electrolytes----:---- Page # 1678
Renal Osteodystrophy----:---- Page # 1680
Renal Replacement Therapy----:---- Page # 1680
Peritoneal Dialysis----:---- Page # 1680
Hemodialysis----:---- Page # 1680
Transplantation----:---- Page # 1680
Hospitalization----:---- Page # 1680
Survival----:---- Page # 1681
Ethics of Initiating or Withdrawing Renal Replacement
Therapy----:---- Page # 1682
91 Glomerulonephropathies and Disorders of Tubular Function----:---- Page #
closed----:---- Page # 1688
91 Glomerulonephropathies and Disorders of Tubular Function----:---- Page #
1688
Glomerulonephropathies----:---- Page # 1688
Congenital Nephrotic Syndrome----:---- Page # 1688
Primary Congenital Nephrotic Syndromes----:---- Page # 1688
Finnish-Type Congenital Nephrotic Syndrome (MIM \#
256300)----:---- Page # 1688
Congenital Nephrotic Syndrome Type 2 (MIM \
#600995)----:---- Page # 1689
Wilms Tumor Suppressor Gene Mutation Syndromes (MIM \
#194072, 136680, 194080)----:---- Page # 1689
Pierson Syndrome (MIM \#609049)----:---- Page # 1689
Other Primary Causes of Congenital Nephrotic Syndrome
(MIM \#251300, 161200)----:---- Page # 1689
Management of Primary Congenital Nephrotic
Syndromes----:---- Page # 1690
Secondary Causes of Congenital Nephrotic Syndrome----:----
Page # 1691
Other Glomerular Diseases----:---- Page # 1691
Renal Tubular Disorders----:---- Page # 1691
Renal Tubular Acidosis----:---- Page # 1691
Fanconi Syndrome----:---- Page # 1691
Nephropathic Cystinosis (MIM \#219800)----:---- Page # 1692
Other Causes of Fanconi Sydrome----:---- Page # 1692
Isolated Proximal Renal Tubular Acidosis (Type 2
RTA)----:---- Page # 1692
Distal Renal Tubular Acidosis (Type 1 RTA)----:---- Page #
1692
Hyperkalemic Tubulopathies (Type 4 RTA)----:---- Page #
1692
Hypoaldosteronism----:---- Page # 1692
Pseudohypoaldosteronism Type 1----:---- Page # 1692
Gordon Syndrome (Pseudohypoaldosteronism Type
2)----:---- Page # 1693
Hypokalemic Tubulopathies----:---- Page # 1693
Bartter Syndrome (MIM \#601678, 241200, 607364, 613090,
602522, 601198)----:---- Page # 1693
Gitelman Syndrome (MIM \#263800)----:---- Page # 1693
Liddle Syndrome (MIM \#177200)----:---- Page # 1693
Other Tubulopathies----:---- Page # 1693
Nephrogenic Diabetes Insipidus (MIM \# 304800,
125800)----:---- Page # 1693
92 Urinary Tract Infections and Vesicoureteral Reflux----:---- Page #
closed----:---- Page # 1697
92 Urinary Tract Infections and Vesicoureteral Reflux----:---- Page # 1697
Bacteriology----:---- Page # 1698
Urine Sample----:---- Page # 1699
Imaging----:---- Page # 1700
Treatment of Urinary Tract Infection----:---- Page # 1700
Antibiotic Resistance----:---- Page # 1701
Treatment of Vesicoureteral Reflux----:---- Page # 1701
Continuous Antibiotic Prophylaxis----:---- Page # 1701
93 Neonatal Hypertension----:---- Page # closed----:---- Page # 1705
93 Neonatal Hypertension----:---- Page # 1705
Factors That Influence Neonatal Blood Pressure----:---- Page # 1705
Definition of Hypertension----:---- Page # 1705
Incidence of Hypertension----:---- Page # 1706
Etiology and Pathophysiology----:---- Page # 1706
Renovascular Causes----:---- Page # 1707
Congenital and Acquired Renal Disease----:---- Page # 1709
Genetic Causes----:---- Page # 1710
Miscellaneous Causes----:---- Page # 1710
Diagnostic Evaluation----:---- Page # 1711
Blood Pressure Measurement----:---- Page # 1711
History and Physical Examination----:---- Page # 1711
Diagnostic Testing----:---- Page # 1711
94 Developmental Endocrinology----:---- Page # closed----:---- Page # 1717
XVIII Endocrine Disorders----:---- Page # 1717
94 Developmental Endocrinology----:---- Page # 1717
Endocrine Systems----:---- Page # 1717
Endocrine Organ Development and Perinatal Transition----:----
Page # 1718
The Maternal–Placental–Fetal Unit----:---- Page # 1718
Hypothalamic and Pituitary Development----:---- Page # 1719
Diseases of Hypothalamic or Pituitary Maldevelopment----:----
Page # 1721
Adrenal Gland Development----:---- Page # 1721
Thyroid Gland Development----:---- Page # 1722
Reproductive Axis Development----:---- Page # 1722
Development of the Endocrine Pancreas----:---- Page # 1723
Development of the Parathyroid Glands and Fetal Mineral
Homeostasis----:---- Page # 1723
Hormonal Regulation of Fetal Growth----:---- Page # 1724
Insulin----:---- Page # 1724
Insulin-Like Growth Factor 1----:---- Page # 1724
Insulin-Like Growth Factor 2----:---- Page # 1724
Epidermal Growth Factor–Transforming Growth Factor
System----:---- Page # 1724
Placental Factors----:---- Page # 1724
Developmental Origin of Health and Disease----:---- Page # 1724
95 Disorders of Calcium and Phosphorus Metabolism----:---- Page # closed----:----
Page # 1727
95 Disorders of Calcium and Phosphorus Metabolism----:---- Page # 1727
Homeostatic Control of Calcium and Magnesium----:---- Page # 1727
Homeostatic Control of Phosphorus----:---- Page # 1728
Parathyroid–Renal Hormonal Axis----:---- Page # 1728
Parathyroid Hormones----:---- Page # 1728
Vitamin D----:---- Page # 1729
Calcitonin----:---- Page # 1730
Perinatal Mineral Metabolism----:---- Page # 1730
Pregnancy----:---- Page # 1731
The Neonate----:---- Page # 1731
Neonatal Hypocalcemia----:---- Page # 1731
Early Neonatal Hypocalcemia----:---- Page # 1732
Late Neonatal Hypocalcemia----:---- Page # 1733
Hypocalcemia Caused by Hypoparathyroid
Syndromes----:---- Page # 1733
Neonatal Hypocalcemia Associated With Maternal
Hyperparathyroidism----:---- Page # 1735
Neonatal Hypocalcemia Associated With Hypomagnesemia
or Renal Tubular Acidosis----:---- Page # 1735
Hypocalcemia Resulting From Vitamin D
Disorders----:---- Page # 1735
Phosphate-Induced Hypocalcemia----:---- Page # 1736
Other Causes of Neonatal Hypocalcemia----:---- Page #
1736
Hypocalcemic Crisis.----:---- Page # 1737
Nonemergency Treatment.----:---- Page # 1737
Magnesium Administration.----:---- Page # 1737
Vitamin D Treatment.----:---- Page # 1737
Recombinant Parathyroid Hormone
Analogue.----:---- Page # 1737
Neonatal Hypercalcemia----:---- Page # 1737
Neonatal Hyperparathyroid Syndromes Associated With
CaSR Mutations----:---- Page # 1738
Neonatal Hyperparathyroidism Not Associated With CASR
mutations----:---- Page # 1739
Williams Syndrome and Idiopathic Infantile
Hypercalcemia----:---- Page # 1739
Neonatal Hypercalcemia Associated With Subcutaneous
Fat Necrosis----:---- Page # 1739
Hypercalcemia Due to Iatrogenic Causes----:---- Page
# 1740
Other Causes of Neonatal Hypercalcemia----:---- Page
# 1740
Neonatal Disorders of Serum Magnesium----:---- Page # 1740
Metabolic Bone Disease in Newborns and Infants----:---- Page # 1741
Metabolic Bone Disease of Prematurity----:---- Page # 1741
Clinical Findings of Metabolic Bone Disease of
Prematurity----:---- Page # 1742
Mineral Deficiency in Metabolic Bone Disease----:---- Page # 1742
Imaging for Metabolic Bone Disease----:---- Page # 1742
Vitamin D–Deficiency Rickets----:---- Page # 1743
Renal Osteodystrophy----:---- Page # 1743
Inherited Metabolic Bone Disease in Infancy----:---- Page # 1744
96 Disorders of the Adrenal Gland----:---- Page # closed----:---- Page # 1749
96 Disorders of the Adrenal Gland----:---- Page # 1749
The Adrenal Gland----:---- Page # 1749
Embryology----:---- Page # 1749
Morphology----:---- Page # 1749
Fetal and Adult Adrenal Functions----:---- Page # 1749
Control of Glucocorticoid and Mineralocorticoid
Production----:---- Page # 1752
Molecular Basis of Adrenal Development----:---- Page # 1752
Assessing Adrenal Function in the Newborn----:---- Page # 1753
Primary Adrenal Disorders----:---- Page # 1753
Steroidogenic Defects Caused by Adrenal Enzyme
Deficiency----:---- Page # 1753
Disorders That Lead to Virilization in Females----:----
Page # 1753
21-Hydroxylase Deficiency----:---- Page # 1753
Pathophysiology.----:---- Page # 1753
Clinical Signs and Symptoms.----:---- Page #
1754
Epidemiology.----:---- Page # 1754
Molecular Genetics.----:---- Page # 1754
Management Issues.----:---- Page # 1754
11β-Hydroxylase Deficiency----:---- Page # 1755
1755
Disorders That Lead to Males With
Undervirilization----:---- Page # 1755
17α-Hydroxylase/17,20-Lyase Deficiency----:---- Page
# 1755
Clinical Features.----:---- Page # 1755
3β-Hydroxysteroid Dehydrogenase Type 2
Deficiency----:---- Page # 1756
1756
Lipoid Congenital Adrenal Hyperplasia----:---- Page #
1756
Rare Form of Congenital Adrenal Hyperplasia With
Variable Phenotypes----:---- Page # 1757
Familial Glucocorticoid Deficiency----:---- Page # 1757
Triple A Syndrome----:---- Page # 1757
Neonatal Adrenoleukodystrophy----:---- Page # 1757
Defective Cholesterol Metabolism\: Smith–Lemli–Opitz
Adrenal Insufficiency Associated With Other Syndromic
Disorders----:---- Page # 1758
Mitochondrial Disorders----:---- Page # 1758
Intrauterine Growth Retardation, Metaphyseal Dysplasia,
Adrenal Hypoplasia Congenita, and Genital Anomalies----:---- Page # 1758
Adrenal Hypoplasia Congenita----:---- Page # 1758
Adrenal Hypoplasia as Part of Contiguous Gene Deletion
Abnormalities of Development\: DAX-1 and Steroidogenic
Factor-1 Deficiency----:---- Page # 1759
Secondary and Tertiary Adrenal Insufficiency----:---- Page # 1759
Iatrogenic Adrenal Insufficiency----:---- Page # 1759
Developmental Adrenal Insufficiency----:---- Page # 1759
Initial Management----:---- Page # 1760
Maintenance Therapy----:---- Page # 1760
Stress Replacement----:---- Page # 1760
Secondary or Tertiary Adrenal Insufficiency----:---- Page # 1762
97 Disorders of Sexual Differentiation----:---- Page # closed----:---- Page # 1768
97 Disorders of Sexual Differentiation----:---- Page # 1768
General Considerations in the Approach to the Newborn With Ambiguous
Genitalia----:---- Page # 1768
Embryology of Sex Determination and Differentiation----:---- Page #
1768
Clinical Assessment of Differences of Sex Development----:---- Page #
1772
History----:---- Page # 1772
Clitoris----:---- Page # 1772
Penis (Phallus)----:---- Page # 1772
Labioscrotal Folds----:---- Page # 1772
Gonads----:---- Page # 1772
Hypospadias, Perineum----:---- Page # 1772
Radiologic Investigations----:---- Page # 1775
Pelvic Ultrasonography----:---- Page # 1775
Genitourethrogram----:---- Page # 1775
Laboratory Investigations----:---- Page # 1776
46,XX Differences in Sex Development----:---- Page # 1777
Virilization of the Female----:---- Page # 1777
Prenatal Diagnosis and Treatment----:---- Page # 1780
Increased Levels of Maternal Androgens and
Progestins----:---- Page # 1781
Placental Aromatase Deficiency----:---- Page # 1781
46,XY Differences in Sex Development----:---- Page # 1781
Androgen Receptor Defects (Androgen Insensitivity)----:---- Page
# 1781
Complete Androgen Insensitivity----:---- Page # 1781
Partial Androgen Insensitivity----:---- Page # 1782
5α-Reductase Type 2 Deficiency----:---- Page # 1783
Testosterone Biosynthetic Defects----:---- Page # 1783
17β-Hydroxysteroid Dehydrogenase Type 3 Deficiency (17-
Ketosteroid Reductase Deficiency)----:---- Page # 1784
Congenital Lipoid Adrenal Hyperplasia----:---- Page # 1784
3β-Hydroxysteroid Dehydrogenase Deficiency 2----:---- Page
# 1785
17α-Hydroxylase/17,20-Lyase Deficiency----:---- Page # 1785
Leydig Cell Hypoplasia----:---- Page # 1785
Persistent Müllerian Duct Syndrome----:---- Page # 1785
Gonadal Differentiation and Chromosomal Disorders----:---- Page # 1785
46,XY Complete Gonadal Dysgenesis----:---- Page # 1785
46,XY Partial Gonadal Dysgenesis----:---- Page # 1785
Mixed Gonadal Dysgenesis----:---- Page # 1786
Testicular Regression Syndrome----:---- Page # 1786
Ovotesticular Disorder of Sex Differentiation----:---- Page #
1787
Syndromes Associated With Ambiguous Genitalia----:---- Page # 1787
Other Disorders of Genital Differentiation----:---- Page # 1788
Overview of the Surgical Management of Disorders of Sexual
Differentiation----:---- Page # 1788
Feminizing Genitoplasty----:---- Page # 1788
Clitoral Reduction----:---- Page # 1788
Vaginoplasty----:---- Page # 1788
Flap Vaginoplasty----:---- Page # 1788
Total Urethral Mobilization----:---- Page # 1789
Pull-Through Vaginoplasty----:---- Page # 1789
Vaginal Agenesis----:---- Page # 1789
Undervirilized Males----:---- Page # 1789
Gonadectomy----:---- Page # 1789
Removal of Müllerian Remnants----:---- Page # 1789
98 Disorders of the Thyroid Gland----:---- Page # closed----:---- Page # 1795
98 Disorders of the Thyroid Gland----:---- Page # 1795
Regulation of Thyroid Function----:---- Page # 1795
Thyroid Hormone Synthesis----:---- Page # 1795
Serum Protein Binding and Transport----:---- Page # 1795
Embryogenesis of Hypothalamic– Pituitary–Thyroid Axis----:---- Page #
1796
Fetal–Placental–Maternal Thyroid Interaction----:---- Page # 1796
Thyroid System Maturation----:---- Page # 1797
Fetal Thyroid Hormone Metabolism----:---- Page # 1798
Extrauterine Thyroid Adaptation----:---- Page # 1798
Congenital Hypothyroidism----:---- Page # 1798
Neonatal Screening for Hypothyroidism----:---- Page # 1801
Thyroid Function Tests----:---- Page # 1801
Interpreting Thyroid Function Tests----:---- Page # 1801
Thyroid Dysgenesis----:---- Page # 1803
Thyroid Dyshormonogenesis----:---- Page # 1803
Central Hypothyroidism----:---- Page # 1804
Down Syndrome and the Thyroid----:---- Page # 1804
Consumptive Hypothyroidism----:---- Page # 1805
Transient Primary Hypothyroidism----:---- Page # 1805
Euthyroid Sick Syndrome----:---- Page # 1805
Transient Hypothyroxinemia of Prematurity----:---- Page # 1806
Low Triiodothyronine Syndrome in Premature Infants----:---- Page # 1806
Iodine Deficiency----:---- Page # 1806
Disorders of Thyroid Hormone Carrier Protein----:---- Page # 1807
Thyroxine-Binding Globulin Deficiency----:---- Page # 1807
Thyroxine-Binding Globulin Excess----:---- Page # 1807
Familial Dysalbuminemic Hyperthyroxinemia----:---- Page # 1807
Treatment of Hypothyroidism----:---- Page # 1807
Hyperthyroidism----:---- Page # 1808
99 Disorders of Carbohydrate Metabolism----:---- Page # closed----:---- Page # 1812
99 Disorders of Carbohydrate Metabolism----:---- Page # 1812
Fetal to Neonatal Transition and Energy Metabolism----:---- Page # 1812
Transitional Neonatal Hypoglycemia----:---- Page # 1813
Signs and Symptoms of Hypoglycemia----:---- Page # 1814
Monitoring of Blood Glucose----:---- Page # 1814
Normoinsulinemic Hypoglycemia----:---- Page # 1815
Hypoglycemia in Premature and Small for Gestational Age
Infants----:---- Page # 1815
Counterregulatory Hormone Deficiency----:---- Page # 1815
Hypopituitarism----:---- Page # 1815
Isolated Adrenocorticotropic Hormone Deficiency----:----
Page # 1816
Primary Adrenal Insufficiency----:---- Page # 1816
X-Linked Adrenal Hypoplasia Congenita----:---- Page #
1816
IMAGe Syndrome----:---- Page # 1816
Adrenocorticotropic Hormone Resistance----:---- Page
# 1817
Defects of Fatty Acid Catabolism and Ketogenesis----:----
Page # 1817
Hereditary Fructose Intolerance----:---- Page # 1817
Hyperinsulinemic Hypoglycemia----:---- Page # 1817
Mechanism of Insulin Secretion----:---- Page # 1817
Diagnosis of Hyperinsulinism----:---- Page # 1819
Hypoglycemia in Infants of Diabetic Mothers----:---- Page # 1820
Perinatal Stress and Transient Hyperinsulinism----:---- Page #
1820
Mutations in the ATP-Sensitive Potassium Channel Genes KCNJ11 and
ABCC8----:---- Page # 1820
Activating Mutation of the GLUD1 Gene\: Hyperinsulinemia–
Hyperammonemia Syndrome----:---- Page # 1820
HADH Mutation----:---- Page # 1820
GCK Mutations----:---- Page # 1820
HNF4A and HNF1A Mutations----:---- Page # 1821
Other Genetic Causes of Hyperinsulinism----:---- Page # 1821
Beckwith–Wiedemann Syndrome----:---- Page # 1821
After Fundoplication----:---- Page # 1821
Differentiation Between Focal Adenomatous and Diffuse Pancreatic
Hyperplasia----:---- Page # 1821
Management of Hyperinsulinemic Hypoglycemia----:---- Page # 1821
Hyperglycemia in the Neonate----:---- Page # 1823
Transient Stress-Related Hyperglycemia----:---- Page # 1823
Genetic Causes of Neonatal Diabetes----:---- Page # 1823
Transient Neonatal Diabetes Mellitus Due to Chromosome Band
6q24 Anomalies----:---- Page # 1823
Transient Neonatal Diabetes Mellitus Due to ATP-Sensitive
Potassium Channel Gene Mutations----:---- Page # 1823
Additional Genetic Causes of Transient Neonatal Diabetes
Mellitus----:---- Page # 1824
Nonsyndromic Causes of Permanent Neonatal Diabetes
Mellitus----:---- Page # 1824
Syndromic Causes of Neonatal Diabetes Mellitus----:----
Page # 1824
Treatment of Neonatal Hyperglycemia----:---- Page # 1824
100 Craniofacial Malformations----:---- Page # closed----:---- Page # 1829
XIX Craniofacial and Orthopedic Conditions----:---- Page # 1829
100 Craniofacial Malformations----:---- Page # 1829
Micrognathia/Robin Sequence----:---- Page # 1829
Phenotype----:---- Page # 1829
Intensive Care Unit Concerns----:---- Page # 1829
Stickler Syndrome----:---- Page # 1833
Orofacial Clefting----:---- Page # 1833
Anatomy----:---- Page # 1834
ICU Concerns----:---- Page # 1835
Syndromes Associated With Cleft Lip and/or Palate----:----
Page # 1835
22q11.2 Deletion Syndrome----:---- Page # 1836
Epidemiology and Genetics----:---- Page # 1836
Evaluation and Management----:---- Page # 1836
Craniosynostosis----:---- Page # 1836
Definitions/Epidemiology----:---- Page # 1836
Single Suture Synostosis----:---- Page # 1837
Multiple Suture Synostosis----:---- Page # 1838
ICU Concerns----:---- Page # 1840
Evaluation----:---- Page # 1841
Disorders of the First and Second Branchial Arches----:---- Page
# 1842
Craniofacial Microsomia----:---- Page # 1842
Other Branchial Arch Malformations----:---- Page # 1843
Moebius Syndrome----:---- Page # 1843
Treacher Collins Syndrome----:---- Page # 1843
CHARGE Syndrome----:---- Page # 1845
Macroglossia/Beckwith– Wiedemann Syndrome----:---- Page # 1846
Frontonasal Dysplasia, Hypertelorism, Encephalocele----:---- Page
# 1847
Embryology----:---- Page # 1847
Phenotype and Genetics----:---- Page # 1847
Prenatal Screening for Fetal Face Anomalies----:---- Page # 1848
101 Common Neonatal Orthopedic Conditions----:---- Page # closed----:---- Page #
1852
101 Common Neonatal Orthopedic Conditions----:---- Page # 1852
Developmental Dysplasia of the Hip----:---- Page # 1852
Torticollis----:---- Page # 1854
Foot Deformities----:---- Page # 1856
Torsional and Angular Deformities of the Lower Extremities----:----
Page # 1858
Congenital Vertebral Malformations----:---- Page # 1860
Obstetric Trauma----:---- Page # 1861
Neonatal Osteomyelitis and Septic Arthritis----:---- Page # 1862
102 Skeletal Dysplasias and Heritable Connective Tissue Disorders----:---- Page #
closed----:---- Page # 1867
102 Skeletal Dysplasias and Heritable Connective Tissue Disorders----:----
Page # 1867
Clinical Spectra of Disorders With Common Molecular Bases----:---- Page
# 1867
Approach to Diagnosis----:---- Page # 1867
Clinical and Molecular Evaluation----:---- Page # 1869
Disorders of Bone Fragility----:---- Page # 1871
Osteogenesis Imperfecta Types II and III----:---- Page # 1871
Radiographic Features----:---- Page # 1871
Inheritance----:---- Page # 1872
Handling an Infant With Osteogenesis Imperfecta----:----
Page # 1873
Perinatal Hypophosphatasia----:---- Page # 1873
FGFR3 Spectrum----:---- Page # 1873
Achondroplasia----:---- Page # 1873
Thanatophoric Dysplasia----:---- Page # 1875
COL2A1 Spectrum----:---- Page # 1876
Spondyloepiphyseal Dysplasia Congenita----:---- Page # 1876
Achondrogenesis Type II–Hypochondrogenesis----:---- Page # 1877
SLC26A2 Spectrum----:---- Page # 1877
Diastrophic Dysplasia----:---- Page # 1877
Achondrogenesis Type IB----:---- Page # 1878
Other Skeletal Dysplasias----:---- Page # 1879
Campomelic Dysplasia----:---- Page # 1879
Heritable Connective Tissue Disorders----:---- Page # 1880
Early-Onset /Rapidly Progressive (Congenital\----:---- Page #
Neonatal, Infantile) Marfan Syndrome----:---- Page # 1880
Congenital Contractural Arachnodactyly (Beals Syndrome\----:----
Page # Distal Arthrogryposis Type 9)----:---- Page # 1882
Ehlers–Danlos Syndromes----:---- Page # 1882
Cutis Laxa----:---- Page # 1883
Menkes Syndrome----:---- Page # 1883
Family Support and Education----:---- Page # 1884
103 Newborn Skin Development - Structure and Function----:---- Page #
closed----:---- Page # 1887
XX Dermatologic Conditions----:---- Page # 1887
103 Newborn Skin Development----:---- Page # 1887
Epidermis----:---- Page # 1887
Dermoepidermal Junction----:---- Page # 1887
Dermis and Subcutis----:---- Page # 1888
Appendages----:---- Page # 1888
Specialized Skin Cells----:---- Page # 1888
Epidermal Stem Cells----:---- Page # 1889
Impact of Prematurity----:---- Page # 1889
Care of Newborn Skin----:---- Page # 1889
Morphologic Approach to Skin Pathology----:---- Page # 1890
Collodion Membrane----:---- Page # 1890
Vesicopustular and Bullous Eruptions----:---- Page # 1891
Blueberry Muffin Baby----:---- Page # 1891
Erythroderma----:---- Page # 1892
Birthmarks With Neurologic Implications----:---- Page # 1892
104 Congenital and Hereditary Disorders of the Skin----:---- Page # closed----:----
Page # 1895
104 Congenital and Hereditary Disorders of the Skin----:---- Page # 1895
Ichthyoses----:---- Page # 1895
Collodion Baby----:---- Page # 1895
Autosomal Recessive Congenital Ichthyosis\: Harlequin Ichthyosis,
Lamellar Ichthyosis, and Nonbullous Congenital Ichthyosiform Erythroderma----:----
Page # 1896
Epidermolytic Ichthyosis----:---- Page # 1901
Diagnosis of Ichthyoses----:---- Page # 1901
Prognosis and Treatment of Ichthyoses----:---- Page # 1902
Epidermolysis Bullosa----:---- Page # 1902
Classification of Epidermolysis Bullosa----:---- Page # 1902
Epidermolysis Bullosa Simplex----:---- Page # 1902
Junctional Epidermolysis Bullosa----:---- Page # 1902
Dystrophic Epidermolysis Bullosa----:---- Page # 1903
Diagnosis of Epidermolysis Bullosa----:---- Page # 1905
Management of Epidermolysis Bullosa----:---- Page # 1905
Incontinentia Pigmenti----:---- Page # 1906
Cutaneous Findings----:---- Page # 1906
Extracutaneous Findings----:---- Page # 1906
Prognosis and Treatment----:---- Page # 1907
Focal Dermal Hypoplasia (Goltz Syndrome)----:---- Page # 1907
Ehlers–Danlos Syndrome----:---- Page # 1907
Cutis Laxa----:---- Page # 1908
Ectodermal Dysplasias----:---- Page # 1908
Hypohidrotic Ectodermal Dysplasia----:---- Page # 1908
Management of Ectodermal Dysplasias----:---- Page # 1909
Disorders With Generalized Hypopigmentation----:---- Page # 1910
Diagnosis of Oculocutaneous Albinism----:---- Page # 1910
Treatment of Oculocutaneous Albinism----:---- Page # 1910
Disorders With Localized Hypopigmentation----:---- Page # 1911
Piebaldism----:---- Page # 1911
Porphyrias----:---- Page # 1912
Congenital Erythropoietic Porphyria----:---- Page # 1912
Erythropoietic Protoporphyria and X-Linked Erythropoietic
Protoporphyria----:---- Page # 1913
Hepatoerythropoietic Porphyria----:---- Page # 1914
105 Infections of the Skin----:---- Page # closed----:---- Page # 1916
105 Infections of the Skin----:---- Page # 1916
Staphylococcus aureus Infections----:---- Page # 1916
Impetigo----:---- Page # 1916
Staphylococcal Scalded Skin Syndrome----:---- Page # 1917
Streptococcus Species Infections----:---- Page # 1918
Omphalitis----:---- Page # 1918
Candida Species Infections----:---- Page # 1919
Localized Candida Infection (Primary Cutaneous)----:---- Page #
1919
Oral Candidiasis (Thrush)----:---- Page # 1919
Candida Diaper Dermatitis----:---- Page # 1919
Diagnosis of Localized Cutaneous Candida Infection----:----
Page # 1919
Congenital (Intrauterine) Candidiasis----:---- Page # 1919
Disseminated/Invasive Candidiasis----:---- Page # 1920
Prognosis and Treatment----:---- Page # 1921
Primary Cutaneous Aspergillosis----:---- Page # 1921
Diagnosis and Treatment----:---- Page # 1921
Tinea Capitis and Tinea Corporis----:---- Page # 1921
Diagnosis and Treatment----:---- Page # 1921
Herpes Simplex Virus Infection----:---- Page # 1922
106 Common Newborn Dermatoses----:---- Page # closed----:---- Page # 1926
106 Common Newborn Dermatoses----:---- Page # 1926
Erythema Toxicum Neonatorum----:---- Page # 1926
Transient Neonatal Pustular Melanosis----:---- Page # 1926
Eosinophilic Pustular Folliculitis----:---- Page # 1927
Acropustulosis of Infancy----:---- Page # 1927
Milia----:---- Page # 1928
Miliaria----:---- Page # 1928
Epstein Pearls and Bohn Nodules----:---- Page # 1928
Sebaceous Hyperplasia----:---- Page # 1929
Neonatal Cephalic Pustulosis (Neonatal Acne)----:---- Page # 1929
Seborrheic Dermatitis----:---- Page # 1930
Atopic Dermatitis----:---- Page # 1930
Diaper Dermatitis----:---- Page # 1931
Harlequin Color Change----:---- Page # 1931
Subcutaneous Fat Necrosis----:---- Page # 1932
Cutis Marmorata----:---- Page # 1932
Dermal Melanocytosis----:---- Page # 1932
Aplasia Cutis Congenita----:---- Page # 1933
107 Cutaneous Congenital Defects----:---- Page # closed----:---- Page # 1935
107 Cutaneous Congenital Defects----:---- Page # 1935
Vascular Anomalies----:---- Page # 1935
Vascular Tumors----:---- Page # 1935
Infantile Hemangiomas----:---- Page # 1935
Local Complications----:---- Page # 1940
Ulceration.----:---- Page # 1940
Disfigurement.----:---- Page # 1941
Functional Complications----:---- Page # 1942
Periocular Hemangiomas.----:---- Page #
1942
Auricular Hemangiomas.----:---- Page #
1942
Potential Life-Threatening
Airway Hemangiomas.----:---- Page # 1942
Hepatic Hemangiomas.----:---- Page # 1942
Parotid Hemangiomas.----:---- Page # 1942
Active Nonintervention.----:---- Page # 1942
Topical Therapies.----:---- Page # 1943
Systemic Therapies----:---- Page # 1943
Propranolol.----:---- Page # 1943
Corticosteroids.----:---- Page # 1943
Other Therapies.----:---- Page # 1943
Surgical Therapies----:---- Page # 1943
Laser Therapy.----:---- Page # 1943
Surgical Excision.----:---- Page # 1943
Wound Care.----:---- Page # 1943
Work-Up and Associations.----:---- Page # 1944
Visceral Involvement/Hepatic
Hemangiomas.----:---- Page # 1944
Segmental Hemangiomas----:---- Page #
1944
PHACE Syndrome.----:---- Page #
1944
LUMBAR/SACRAL/PELVIS
Syndrome.----:---- Page # 1945
Congenital Hemangiomas.----:---- Page #
1945
Rapidly Involuting Congenital
Noninvoluting Congenital
Partially Involuting Congenital
Kaposiform Hemangioendotheliomas and
Tufted Angiomas.----:---- Page # 1945
Pyogenic Granulomas.----:---- Page # 1946
Vascular Malformations----:---- Page # 1946
Nevus Simplex----:---- Page # 1946
Capillary Malformation (Port-Wine Stain)----:----
Page # 1947
Venous Malformations----:---- Page # 1948
Lymphatic Malformations----:---- Page # 1948
Arteriovenous Malformations----:---- Page # 1948
Lymphedema----:---- Page # 1949
Disorders of Pigmentation----:---- Page # 1949
Hypopigmented Lesions----:---- Page # 1949
Nevus Depigmentosus (Nevus Achromicus)----:---- Page # 1949
Pigmentary Mosaicism----:---- Page # 1950
Ash Leaf Macules----:---- Page # 1950
Hyperpigmented Lesions----:---- Page # 1950
Café au Lait Macules----:---- Page # 1950
Lentigines----:---- Page # 1951
Congenital Dermal Melanocytosis (Mongolian Spots)----:----
Page # 1951
Nevus of Ota/Ito----:---- Page # 1951
Melanocytic Nevi----:---- Page # 1951
Congenital Melanocytic Nevi----:---- Page # 1952
Nevus Spilus----:---- Page # 1953
Congenital Tumors of Epithelial Origin----:---- Page # 1953
Epidermal Nevus----:---- Page # 1953
Nevus Sebaceous----:---- Page # 1953
Epidermal (Linear Sebaceous) Nevus Syndrome----:---- Page #
1954
Congenital Tumors of Dermal and Subcutaneous Origin----:---- Page #
1954
Juvenile Xanthogranuloma----:---- Page # 1954
Mastocytosis----:---- Page # 1955
Connective Tissue Nevus (Connective Tissue Hamartoma)----:----
Page # 1956
Neurofibroma----:---- Page # 1956
Developmental Anomalies of the Skin----:---- Page # 1956
Midline Anomalies----:---- Page # 1956
Preauricular Pits and Sinuses----:---- Page # 1957
Accessory Tragus----:---- Page # 1957
Congenital Cartilaginous Rests of the Neck (Cervical Tabs,
Wattles)----:---- Page # 1958
Supernumerary Digits (Rudimentary Polydactyly)----:---- Page #
1958
Supernumerary Nipples (Polythelia, Accessory Nipples)----:----
Page # 1958
Median Raphe Cysts (Congenital Sinus and Cysts of Genitoperineal
Raphe, Mucous Cysts of the Penile Skin, Parameatal Cysts)----:---- Page # 1958
108 Eye and Vision Disorders----:---- Page # closed----:---- Page # 1964
XXI Eyes and Ears----:---- Page # 1964
108 Eye and Vision Disorders----:---- Page # 1964
General Examination Techniques----:---- Page # 1964
The Newborn Eye Examination\: Approach and
Equipment----:---- Page # 1964
Inspection (the I in I-ARM)----:---- Page # 1966
Acuity and Visual Development (the A in I-ARM)----:----
Page # 1967
Pupillary Response and the Red Reflex (the R in I-
ARM)----:---- Page # 1968
Motility and Alignment (the M in I-ARM)----:---- Page #
1968
Common Diagnostic Problems----:---- Page # 1970
Leukocoria and Abnormal Red Reflex----:---- Page # 1970
Cataract----:---- Page # 1970
Retinoblastoma----:---- Page # 1971
Persistent Hyperplastic Primary Vitreous (Persistent Fetal
Vasculature)----:---- Page # 1971
Coloboma----:---- Page # 1972
Corneal Clouding----:---- Page # 1972
Red Eye/Eye Discharge----:---- Page # 1973
Motility Abnormalities and Nystagmus----:---- Page # 1974
Ptosis and Other Eyelid and Lacrimal Abnormalities----:----
Page # 1975
Ocular Trauma in the Neonatal Period----:---- Page # 1976
Retinal Hemorrhages and Abusive Head Injury----:---- Page #
1977
Retinopathy of Prematurity----:---- Page # 1978
Classification of Retinopathy of Prematurity----:----
Page # 1979
Prevalence and Incidence of Retinopathy of
Prematurity----:---- Page # 1980
Pathogenesis of Retinopathy of Prematurity----:----
Page # 1980
Prediction of Retinopathy of Prematurity----:----
Page # 1980
Prevention of Retinopathy of Prematurity----:----
Page # 1980
Detection of Serious Disease----:---- Page # 1981
Telemedicine and Retinopathy of Prematurity----:----
Page # 1981
Treatment of Retinopathy of Prematurity----:---- Page
# 1982
Common Ophthalmic Manifestations of Systemic Diseases----:----
Page # 1982
Role of the Neonatal Healthcare Provider----:---- Page # 1982
109 Ear and Hearing Disorders----:---- Page # closed----:---- Page # 1990
109 Ear and Hearing Disorders----:---- Page # 1990
Normal Hearing----:---- Page # 1990
Permanent Hearing Loss—The Challenge----:---- Page # 1990
Hearing Disorders----:---- Page # 1990
Methods for Newborn Hearing Screening----:---- Page # 1991
Risk Factors for Permanent Hearing Loss in Infants and Children (Table
109.4)----:---- Page # 1992
Family Factors----:---- Page # 1993
Risk Factor 1----:---- Page # 1993
Neonatal----:---- Page # 1993
Stigmata, Syndromes, and Neurodegenerative Disorders----:----
Page # 1993
Risk Factors 5 and 6----:---- Page # 1993
Neonatal or Postneonatal----:---- Page # 1994
Risk Factors 9, 10, and 11----:---- Page # 1994
After Newborn Hearing Screening\: Audiology Diagnostic
Protocols----:---- Page # 1994
Medical Workup for Hearing Loss----:---- Page # 1994
Multidisciplinary Team----:---- Page # 1994
Communication Options----:---- Page # 1995
Amplification----:---- Page # 1995
Hearing Aids----:---- Page # 1995
Frequency-Modulated Systems----:---- Page # 1995
Cochlear Implants----:---- Page # 1995
Comprehensive Early Intervention----:---- Page # 1995
Neonatal Intensive Care Unit Infants and Hearing Loss----:---- Page #
1996
The Brain, Language Outcomes, and Access to Language----:---- Page #
1997

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Avery's Diseases of the Newborn 10th Edition----:---- Page # 1

Front Matter----:---- Page # closed----:---- Page # 52

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