Keeling's Fetal and Neonatal Pathology

Description

This sixth edition provides an overview of fetal and neonatal pathology through a system-based approach. This book contains new chapters on immunology, with a continued focus on molecular aspects of pathology in the perinatal setting. The general principles of perinatal pathology and their clinical situations are also discussed, along with specific pathological entities and their organ systems. Keeling’s Fetal and Neonatal Pathology, sixth edition aims to help the reader treat common problems through anatomical pathology findings and is relevant to practicing and trainee pathologists, obstetricians, maternal and fetal medicine specialists, neonatologists, and pediatricians. Preface Acknowledgments Contents Contributors 1: Perinatal Pathology 1.1 Global Burden of Disease 1.2 Perinatal Pathology 1.2.1 The Perinatal Pathologist as a Treating Physician 1.2.2 The Perinatal Pathologist as a Diagnostic Clinician 1.2.3 The Perinatal Pathologist as a Clinical Manager 1.3 Water-Shed References 2: The Perinatal Autopsy 2.1 Reasons for Performing a Perinatal Autopsy 2.2 The Perinatal Autopsy 2.2.1 An Evolving Practice 2.2.2 Location of Service 2.2.3 Equipment 2.2.3.1 Measuring 2.2.3.2 Dissection Instruments 2.2.4 Preliminary Formalities 2.2.4.1 Consent 2.2.4.2 Adequate Clinical Information 2.2.4.3 Place of Structured Request Forms in Perinatal Pathology 2.2.5 Prior Discussions 2.3 Autopsy Method 2.3.1 Measurement 2.3.2 Assessment of Size and Growth 2.3.3 Postmortem Imaging 2.3.4 Photography 2.3.5 External Examination 2.3.6 Examination of Body Cavities 2.3.7 Evisceration 2.3.7.1 Abdominal Vessels and Genitourinary System 2.3.7.2 Thoracic and Upper Abdominal Viscera 2.3.7.3 Examination of the Heart 2.3.7.4 Head and Cranial Contents 2.3.7.5 Spinal Cord 2.3.7.6 Skeleton 2.3.8 Histological Examination 2.3.9 Microbiological Examination 2.3.10 Genetics 2.3.11 Sampling for Biochemical Investigations 2.4 Examination of the Placenta 2.4.1 Macroscopic Examination 2.4.2 Membranes 2.4.3 Umbilical Cord 2.4.4 Placental Surface 2.4.5 Slicing the Placenta 2.5 The Postmortem Examination Report References 3: Genetic and Epigenetic Basis of Development and Disease 3.1 Genetic Structures 3.2 Nomenclature 3.3 Inheritance 3.4 Epigenetics 3.4.1 Genomic Imprinting 3.4.2 Nucleosome Position 3.4.3 Histone Modification 3.4.4 CpG Methylation 3.4.5 Non-Coding RNA 3.5 Somatic Variation 3.6 Genetic Testing 3.6.1 Sampling 3.6.2 Complementarity: The Basis of Genetic Testing 3.6.3 Cytogenetics 3.6.4 Fluorescent In Situ Hybridisation 3.6.5 Automated DNA Sequencing 3.6.6 Restriction Fragment Analysis 3.6.7 Linkage Analysis 3.6.8 Southern, Northern & Western Blots 3.6.9 Polymerase Chain Reaction (PCR) 3.6.9.1 Gap PCR 3.6.9.2 Long Range PCR (L-PCR) 3.6.9.3 Multiplex Ligation-Dependent Probe Amplification (MLPA) 3.6.10 Matrix-assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) Mass Spectrometry 3.6.11 Mini/Micro Satellite Repeats 3.6.12 CpG Methylation 3.6.13 Cytogenetic Microarray (CGH & SNP Array) 3.6.14 Next-Generation Sequencing (NGS) 3.6.15 Non-Invasive Prenatal Screening (NIPS) 3.7 Bioinformatics 3.8 Future of Genetic Testing References 4: The Placenta 4.1 Development of the Placenta 4.1.1 Early Development 4.1.2 Development of the Definitive Form 4.1.3 Mature Placenta 4.1.4 Villous Structure: Vasculature and Histology 4.1.4.1 Electron Microscopy 4.1.4.2 Morphometry 4.1.5 Development of the Membranes 4.1.6 Development of the Umbilical Cord 4.1.7 Development of the Uteroplacental Circulation 4.2 Abnormalities in Development and Placentation 4.3 Umbilical Cord Pathology 4.3.1 Cord Dimensions 4.3.2 Single Umbilical Artery 4.3.3 Umbilical Cord Insertion 4.3.4 Cord Knots and Entanglements 4.3.5 Cord Coiling, Torsion, and Constriction 4.3.6 Localized Cord Swelling 4.3.7 Abnormalities of Umbilical Cord Vessels 4.4 Amniochorial Membranes Pathology 4.4.1 Amnion Nodosum and Squamous Metaplasia 4.4.2 Amniotic Bands 4.4.3 Meconium Staining 4.4.4 Inflammation and Decidual Vasculopathy 4.4.5 Myometrial Fibers 4.5 Placental Parenchyma Pathology 4.5.1 Uteroplacental Circulation 4.5.1.1 Pathological Basis of Maternal Vascular Malperfusion 4.5.1.2 Pathological Effects: Gross and Microscopic Infarction Retroplacental Hemorrhage Laminar Necrosis 4.5.1.3 Adaptive Changes Chorangiosis Villous Maturation Increased Intervillous Fibrin and Villous Agglutination Nucleated Red Blood Cells 4.5.2 Intervillous Circulation 4.5.2.1 Intervillous Thrombosis 4.5.2.2 Perivillous Fibrin Deposition and Maternal Floor Infarction 4.5.3 Fetal Circulation 4.5.3.1 Pathological Basis of Fetal Vascular Malperfusion 4.5.3.2 Pathological Effects 4.5.3.3 Chorangiosis, Chorangioma 4.5.4 Villous Maturation Irregularities 4.5.4.1 Delayed Villous Maturity 4.5.4.2 Accelerated Villous Maturation 4.5.4.3 Placental Edema 4.6 Inflammation 4.6.1 Acute Inflammation 4.6.1.1 Acute Chorioamnionitis 4.6.1.2 Acute Villitis 4.6.2 Chronic Inflammation 4.6.2.1 Villitis of Unknown Etiology 4.6.2.2 Chronic Villitis, Infectious 4.6.2.3 Chronic Deciduitis 4.6.2.4 Chronic Chorioamnionitis 4.6.2.5 Chronic Intervillositis 4.6.2.6 Eosinophil T-Cell Chorionic Vasculitis 4.7 Other Miscellaneous Lesions 4.7.1 Placental Mesenchymal Dysplasia 4.7.2 Other 4.8 Clinico-Pathologic Correlation 4.8.1 Maternal Disorders 4.8.1.1 Maternal Hypertension 4.8.1.2 Diabetes Mellitus 4.8.1.3 Maternal Obesity 4.8.1.4 Intrahepatic Cholestasis of Pregnancy 4.8.1.5 Collagen Vascular Disease 4.8.1.6 Sickle Cell Disease and Other Hematological Disorders 4.8.1.7 Cigarette Smoking 4.8.1.8 Maternal Malignant Disease 4.8.2 Intrauterine Fetal Death 4.8.3 Fetal Abnormalities 4.8.3.1 Chromosomal Abnormalities 4.8.3.2 Inborn Errors of Metabolism 4.8.3.3 Fetal Hydrops and Non-immune Hydrops 4.8.3.4 Fetal Growth Restriction 4.8.3.5 Fetal Hypoxia 4.8.3.6 Fetal Tumors References 5: Perinatal Imaging 5.1 PM Imaging Modalities 5.1.1 Perinatal PM Radiography (PMXR) 5.1.2 Fetal PM Ultrasound 5.1.3 Fetal PMCT 5.1.4 Fetal PMMR 5.1.5 Fetal PM Micro CT 5.2 PM Imaging Across Different Clinical Settings 5.3 What Is the Value of a Normal PM Imaging Investigation? 5.4 Minimally Invasive Autopsy Sampling 5.5 Towards an Integrated “Examination After Death” 5.6 Conclusion References 6: Epidemiology of Fetal and Neonatal Death 6.1 Definitions 6.2 Principles of Epidemiology 6.3 Perinatal Data Quality 6.4 Challenges in Assessing Perinatal Mortality 6.5 Numbers, Rates and Trends 6.5.1 Are Stillbirth and Neonatal Death Rates Improving? 6.6 Classification and Causes of Stillbirth and Neonatal Death 6.6.1 Important Features of a Classification System 6.6.2 Causes of Stillbirth and Neonatal Death 6.6.2.1 Causes of Stillbirth Causes and Classification of Stillbirth in Regions with High Stillbirth Rates Causes and Classification of Stillbirth in Regions with Low Stillbirth Rates 6.6.2.2 Causes Of Neonatal Death 6.7 Contributing Factors to Causes of Perinatal Mortality 6.7.1 Gestational Age 6.7.2 Disparity 6.7.3 Maternal Demographic Factors 6.7.4 Maternal Weight and Nutrition 6.7.5 Smoking 6.7.6 Alcohol and Illicit Drug Use 6.7.7 Birthweight And Preterm Birth 6.7.8 Previous Obstetric History 6.7.9 Maternal Medical Conditions and Pregnancy Complications 6.7.10 Substandard Care 6.7.11 Other Factors 6.8 Conclusions References 7: Pathology of Early Pregnancy Loss 7.1 Spontaneous Abortion 7.1.1 Etiology 7.1.1.1 Parental Factors 7.1.1.2 Chromosomal Abnormalities 7.1.1.3 Congenital Anatomical Abnormalities 7.1.1.4 Infection 7.1.1.5 Maternal Medical Conditions 7.1.1.6 Occupational and Environmental 7.2 Pathology of Miscarriage 7.2.1 Classification 7.2.2 Pathology 7.2.3 Pathogenesis of Miscarriage 7.2.3.1 Placentation and Immunology 7.2.3.2 Mosaicism, Uniparental Disomy and Genomic Imprinting 7.3 Ectopic Pregnancy 7.3.1 Tubal Ectopic Pregnancy 7.3.2 Non-tubal Ectopic Pregnancy 7.3.3 Heterotopic Pregnancy 7.4 Gestational Trophoblastic Disease 7.4.1 Hydatidiform Mole 7.4.1.1 Clinical Presentation 7.4.1.2 Genetics and Pathology 7.4.1.3 Practical Consideration: Partial Versus Complete Mole 7.4.1.4 Practical Consideration: Molar Versus Non-Molar Villi 7.4.1.5 Prognosis 7.4.2 Gestational Trophoblastic Neoplasia References 8: Congenital Abnormalities: Prenatal Diagnosis and Screening 8.1 Definitions [1] 8.2 Causes of Congenital Malformations 8.2.1 Single-Gene Disorders 8.2.1.1 Autosomal Dominant Inheritance 8.2.1.2 Autosomal Recessive 8.2.1.3 X-Linked Dominant 8.2.1.4 X-Linked Recessive 8.2.2 Chromosome Abnormalities 8.2.2.1 Triploidy 8.2.2.2 Autosomal Trisomy 8.2.3 Structural Chromosome Abnormality 8.2.4 Sex Chromosome Abnormality 8.2.5 Multifactorial Disorders 8.2.6 Environmental Teratogens 8.2.7 Maternal Disorders 8.2.8 Drugs 8.2.8.1 Prescribed Medication 8.2.8.2 Recreational Drugs, Alcohol, and Tobacco 8.2.9 Infection 8.2.10 Physical Agents 8.2.10.1 Heat 8.2.10.2 Radiation 8.2.10.3 Ultrasound 8.2.10.4 Pregnancy Reduction 8.2.10.5 Amniotic Bands 8.3 Prenatal Diagnosis 8.3.1 Ultrasound Examination 8.3.1.1 First Trimester 8.3.1.2 Second Trimester 8.3.2 Invasive Tests 8.3.2.1 Chorionic Villus Sampling Indications for Chorionic Villus Sampling Complications of Chorionic Villus Sampling 8.3.2.2 Amniocentesis Indications for Amniocentesis Complications of Amniocentesis 8.3.2.3 Fetal Blood Sampling 8.3.2.4 Other Invasive Tests/Fetal Surgery 8.3.3 Non-invasive Prenatal Testing 8.3.4 Prenatal Diagnosis and DNA Analysis 8.3.5 Prenatal Diagnosis and Cystic Fibrosis 8.3.6 Whole Exome Sequencing in Pregnancy 8.3.7 Prenatal Maternal Serum Screening for Neural Tube Defects 8.3.7.1 Antenatal Screening for Down Syndrome 8.3.8 Future Developments in Prenatal Diagnosis 8.3.8.1 Earlier Diagnosis 8.3.8.2 Novel Imaging Techniques 8.3.9 Fetal and Placental Examination 8.3.9.1 Value of Fetal Examination 8.4 Specific Fetal Anomalies 8.4.1 Hydrocephalus 8.4.2 Encephalocele 8.4.3 Anencephaly 8.4.4 Posterior Nuchal Fluid Accumulation/Translucency 8.4.5 Abdominal Wall Defects 8.4.6 Cystic Kidneys 8.4.7 Chromosome Anomalies 8.4.8 Early Amnion Rupture Sequence (EARS)/Amniotic Band Sequence (ABS) References 9: Infection of Mother and Baby 9.1 Infectious Presentations of Mother and Baby 9.1.1 Antenatal 9.1.1.1 Urinary Tract Infection Background Epidemiology Microbiology Pathogenesis Clinical Features Diagnosis Treatment Prevention Public Health Issues 9.1.1.2 Pneumonia Background Epidemiology Microbiology Clinical Features Pathogenesis Testing and Diagnosis Treatment Prevention Public Health Issues 9.1.1.3 Bacterial Vaginosis Background Microbiology Epidemiology Pathogenesis Clinical Features Diagnosis Treatment Prevention Public Health Issues 9.1.1.4 Vulvovaginal Candidiasis Background Epidemiology Microbiology Pathogenesis Clinical Features Diagnosis Treatment Prevention Public Health Issues 9.1.1.5 Chorioamnionitis Background Microbiology Epidemiology Pathogenesis Clinical Features Diagnosis Treatment Prevention Public Health Issues 9.1.1.6 Hydrops Fetalis Background Epidemiology Microbiology Pathogenesis Testing and Diagnosis Treatment Prevention Public Health Issues 9.1.1.7 Intrauterine Death Background Epidemiology Pathogenesis Microbiology Testing and Diagnosis Treatment Prevention Public Health Issues 9.1.2 Postpartum 9.1.2.1 Postpartum Endometritis Background Epidemiology Pathogenesis Microbiology Clinical Features Testing and Diagnosis Treatment Prevention Public Health Issues 9.1.2.2 Mastitis Background Microbiology Pathogenesis Clinical Features Testing and Diagnosis Treatment Prevention Public Health Issues 9.1.2.3 Neonatal Sepsis Background Microbiology Pathogenesis Clinical Features Testing and Diagnosis Treatment Prevention Public Health Issues 9.1.2.4 Neonatal Eye Infection Background Microbiology Pathogenesis Clinical Features Testing and Diagnosis Treatment Prevention Public Health Issues 9.1.2.5 Neonatal Microcephaly Background Microbiology Pathogenesis Clinical Features Testing and Diagnosis Treatment Prevention 9.2 Organism-Specific Presentations in Mother and Baby 9.2.1 Bacterial 9.2.1.1 Chlamydia (Chlamydia trachomatis) Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Issues 9.2.1.2 Gonorrhoea (Neisseria gonorrhoeae) Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Issues 9.2.1.3 Tuberculosis (Mycobacterium Tuberculosis) Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Issues 9.2.1.4 Group A Streptococcal Infection (Streptococcus pyogenes) Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Issues 9.2.1.5 Group B Streptococcal Infection (Streptococcus Agalactiae) Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Issues 9.2.1.6 Syphilis (Treponema pallidum) Background Epidemiology Pathogenesis Presentation Treatment Prevention Public Health Issues 9.2.1.7 Listeriosis (Listeria Monocytogenes) Background Epidemiology Presentation Treatment Prevention Public Health Issues 9.2.2 Parasitic 9.2.2.1 Toxoplasmosis (Toxoplasma gondii) Background Epidemiology Presentation Treatment Prevention Public Health Issues 9.2.2.2 Trichomaniasis (Trichomonas vaginalis) Background Epidemiology Clinical Features Treatment Prevention Public Health Issues 9.2.2.3 Malaria (Plasmodium spp) Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Issues 9.2.3 Viral 9.2.3.1 Human Herpes Simplex Viruses 1 and 2 Background Epidemiology Pathogenesis Clinical Features Genital Herpes Neonatal Herpes Treatment Prevention Public Health Issues 9.2.3.2 Varicella Zoster Virus Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Issues 9.2.3.3 Cytomegalovirus Background Epidemiology Pathogenesis Presentation Treatment Prevention Public Health Issues 9.2.3.4 Parvovirus B19 Background Epidemiology Presentation Treatment Prevention Public Health Issues 9.2.3.5 Rubella Background Epidemiology Pathogenesis Clinical Features Postnatal Infection (Adults and Children) Antenatal Infection Treatment Prevention Public Health Issues 9.2.3.6 Human Immunodeficiency Virus Background Epidemiology Pathogenesis Clinical Features Treatment Prevention Public Health Strategies References 10: Perinatal Hematology 10.1 Maternal and Fetal Bleeding 10.2 Fetal Blood Loss 10.2.1 Fetomaternal 10.2.2 Twin-to-Twin Transfusion Syndrome 10.2.3 Intrapartum Blood Loss 10.3 Neonatal Blood Loss 10.4 Maternal Factors 10.4.1 Fetal Growth Restriction 10.4.1.1 Hematological Abnormalities in the Growth-Restricted Infant 10.4.2 Infection 10.4.3 Immune 10.4.3.1 Hemolytic Disease of the Newborn 10.4.3.2 Neonatal Alloimmune Thrombocytopenia 10.4.4 Maternal Idiopathic Thrombocytopenic Purpura 10.4.5 Deficiencies, Drugs and Toxins 10.4.5.1 Deficiencies 10.4.5.2 Drugs 10.4.5.3 Toxins 10.5 Fetal and Neonatal Factors 10.5.1 Fetal and Neonatal Coagulopathy 10.5.1.1 Investigation 10.5.2 Acquired Defects 10.5.3 Thrombocytopenia 10.5.4 Thrombosis 10.5.5 Congenital Defects 10.5.6 Purpura Fulminans 10.6 Congenital/Inherited Cytopenia 10.6.1 Anemia 10.6.2 Hydrops Fetalis 10.6.3 Neutropenia 10.6.4 Thrombocytopenia 10.6.5 Myelodysplastic Syndrome 10.7 Leukocytosis 10.7.1 Leukemoid Reaction 10.7.2 Acute Leukemia 10.7.3 Transient Abnormal Myelopoiesis (TAM) References 11: Genetic Metabolic Disease 11.1 Historical Perspective 11.2 When to Think of an IEM 11.3 Laboratory Methods of Diagnosing Inborn Errors of Metabolism 11.3.1 Routine Biochemistry Tests 11.3.1.1 Plasma Ammonium 11.3.2 Specialist Biochemical Genetics Tests 11.3.2.1 Organic Acids 11.3.2.2 Amino Acid Analysis 11.3.2.3 Glycosaminoglycan Screening 11.3.2.4 Acylcarnitine Profile 11.3.2.5 Other GC-MS Methods 11.3.2.6 Expanded Newborn Screening 11.3.2.7 Genetic Testing 11.4 Clinical Presentations of IEM 11.4.1 Acute Metabolic Encephalopathy 11.4.1.1 Amino Acidopathies 11.4.1.2 Organic Acidopathies 11.4.1.3 Urea Cycle Disorders 11.4.1.4 Disorders of Fat Catabolism 11.4.1.5 Disorders of Carbohydrate Utilization 11.4.1.6 Neonatal Lactic Acidosis 11.4.2 Approach to Testing Neonatal Metabolic Encephalopathy 11.4.3 Treatment of Neonatal Metabolic Encephalopathy 11.4.4 Neonatal Epileptic Encephalopathy (NEE) 11.4.5 Neonatal Hepatic Disease and Nonimmune Jaundice 11.4.5.1 Hepatic Intoxication 11.4.5.2 Neonatal Cholestasis 11.4.6 IEM Causing Hydrops Fetalis 11.4.7 IEM Causing Cardiomyopathy 11.4.8 IEM with Dysmorphic Features 11.4.8.1 Peroxisomal Disorders 11.4.8.2 Disorders of Cholesterol Biosynthesis 11.4.8.3 Congenital Disorders of Glycosylation 11.4.8.4 Lysosomal Storage Disorders 11.4.8.5 Maternal Phenylketonuria 11.4.8.6 Mitochondrial Respiratory Chain Disorders 11.5 Investigation of the Patient in the Perimortem Period References 12: Immunology in the Fetus and Neonate 12.1 Introduction 12.2 Development of the Immune System 12.2.1 The Innate Immune System 12.2.1.1 Cells 12.2.1.2 Complement and Other Serum Proteins 12.2.2 The Adaptive Immune System 12.2.2.1 T Cells 12.2.2.2 B Cells 12.2.2.3 Immunoglobulins 12.3 Diseases Resulting from Primary Immune Deficiency 12.3.1 Disease with Abnormal Organ Development 12.3.1.1 Asplenia 12.3.1.2 Absent Tonsils 12.3.1.3 Athymia/Small Thymus Di George Syndrome CHARGE Syndrome Severe Combined Immune Deficiency (SCID) 12.3.2 Disease with Abnormal Cell Function 12.3.2.1 Familial HLH 12.3.2.2 IPEX 12.3.2.3 Wiskott Aldrich Syndrome 12.3.3 Disease with Abnormal Skeletal Development 12.3.3.1 Cartilage Hair Hypoplasia 12.3.3.2 Hyper IgE Syndrome 12.4 Diseases Resulting from Secondary Immune Deficiency 12.4.1 Diseases Resulting from Maternal Autoimmune Disease 12.5 Diagnosis of Primary Immunodeficiency In Utero, at Birth and Post-mortem 12.5.1 Fetal Blood Testing 12.5.2 New-Born Screening 12.5.3 Immunophenotyping 12.5.4 Serum Protein Analysis 12.5.4.1 Immunoglobulins 12.5.4.2 Complement 12.5.4.3 Other Serum Proteins 12.5.5 Genetic Analysis 12.6 Summary References 13: Fetal Hydrops 13.1 Introduction 13.2 Global Patterns and Incidence 13.3 Morbidity and Mortality 13.4 Clinical Presentation 13.5 Fetal Fluid Dynamics 13.5.1 Amniotic Fluid 13.6 Causes and Mechanisms of Fetal Hydrops 13.6.1 Cardiovascular Disease 13.6.2 Chromosomal and Genetic Abnormality 13.6.3 Anemia 13.6.4 Intrauterine Infection 13.6.5 Other Organ Systems 13.6.6 Placenta, Multiple Pregnancies, Maternal Disease 13.7 Investigation of Fetal Hydrops 13.7.1 Pathological Findings 13.7.1.1 External 13.7.1.2 Internal 13.7.2 Histology 13.7.3 Placenta 13.8 Prenatal Therapy for Fetal Hydrops References 14: Pathology of Twinning 14.1 Introduction 14.2 Vanishing Twin 14.3 Monochorionic Twin Placentas 14.4 Acardiac Twin, Twin-Reversed Arterial Perfusion (TRAP sequence) 14.5 Acute TTTS 14.6 Chronic TTTS 14.7 Twin Anemia Polycythemia Sequence (TAPS) 14.8 Acute Perimortem TTTS 14.9 Vascular Anatomy of Monochorionic Placentas and Correlation with Clinical Outcome References 15: Macerated Stillbirth 15.1 Definitions, Demographics, and Risk Factors 15.2 Approach to the Autopsy 15.2.1 Changes Associated with Maceration 15.2.2 Limitations of Examination in Macerated Babies 15.2.3 Maceration and Associated Artefacts 15.2.4 Mimics of Maceration 15.3 Additional Investigations 15.3.1 Clinical History 15.3.2 Histological Examination 15.3.3 Bacteriology 15.3.4 Virology 15.3.5 Genetic Analysis 15.3.6 Radiography 15.4 Pathological Findings in Stillbirth 15.4.1 Mode of Death 15.4.2 Placental Disease 15.4.3 Asphyxiation 15.4.4 Central Nervous System Pathology 15.4.5 Malformations 15.4.6 Maternal Disorders Associated with Stillbirth 15.4.7 Stillbirth, Multiple Gestation, and Assisted Reproductive Technologies References 16: Intrapartum Problems 16.1 Intrapartum Asphyxia 16.2 Incidence of Intrapartum Asphyxia 16.3 Pathophysiology of Intrapartum Asphyxia 16.4 Effects of Intrapartum Asphyxia 16.4.1 Effects on the Fetal Circulation 16.4.2 Effects on Fetal Breathing 16.4.3 Effects on the Fetal Brain 16.4.4 Other Effects of Intrapartum Asphyxia 16.5 Causes of Intrapartum Asphyxia 16.5.1 Maternal Disorders 16.5.2 Placenta 16.5.3 Umbilical Cord 16.5.4 Fetal Conditions 16.6 Pathological Findings 16.6.1 Early Deaths 16.6.2 Late Deaths 16.6.3 Birth Trauma 16.6.4 Placenta 16.6.5 The Post Mortem Examination References 17: Complications of Prematurity 17.1 Pulmonary System 17.1.1 Hyaline Membrane Disease 17.1.2 Bronchopulmonary Dysplasia (BPD) 17.1.3 Pulmonary Interstitial Emphysema (PIE) 17.1.4 Pulmonary Arterial Hypertension (PAH) 17.1.5 Pulmonary Hemorrhage 17.1.6 Tracheal Granuloma 17.2 Central Nervous System 17.2.1 Intraventricular Hemorrhage (IVH)/Germinal Matrix Hemorrhage 17.2.2 Cerebellar Hemorrhage 17.2.3 Periventricular Leukomalacia (PVL) 17.2.4 Pontosubicular Necrosis 17.2.5 Kernicterus 17.2.6 Final Comments on Etiology 17.2.7 Retinopathy of Prematurity (ROP) 17.3 Intestinal System 17.3.1 Necrotizing Enterocolitis (NEC) 17.3.2 Spontaneous Intestinal Perforation (SIP) 17.4 Liver 17.4.1 TPN Hepatopathy 17.4.2 Spontaneous Hepatic Hemorrhage 17.5 Bone 17.5.1 Metabolic Bone Disease 17.6 Vascular System 17.6.1 General Types of Fluids 17.6.2 Locations of Effusions 17.7 Infection 17.7.1 Sepsis 17.7.2 Neonatal Pneumonia 17.7.3 Neonatal Meningitis 17.7.4 Candida spp. Infection 17.8 Placenta 17.8.1 Acute Chorioamnionitis, Funisitis, and Chorionic Plate Vasculitis 17.8.2 Maternal Vascular Malperfusion References 18: Iatrogenic Disease 18.1 Iatrogenic Lesions in the Prenatal Period 18.1.1 Ultrasonography 18.1.2 Magnetic Resonance Imaging 18.1.3 Amniocentesis 18.1.4 Chorionic Villus Sampling 18.1.5 Cordocentesis 18.1.6 Fetoscopy and Fetal Surgery 18.1.6.1 Obstetric Endoscopy 18.1.6.2 Closed Fetal Surgery 18.1.6.3 Open Fetal Surgery 18.2 Maternal Medication during Pregnancy 18.2.1 Over-the-Counter Medicines (OTCs) 18.2.2 Teratogenic Drugs 18.2.3 Non-Teratogenic Drug Effects 18.2.4 Drugs in Labor and Effects on the Fetus 18.3 Complications of the Intrapartum Period 18.3.1 Extracranial Hemorrhage 18.3.2 Skull Fractures 18.3.3 Occipital Osteodiastasis 18.3.4 Subdural Hemorrhage 18.3.5 Extracranial Injuries 18.3.5.1 Fractures 18.3.5.2 Visceral Injuries 18.3.5.3 Injuries to the Spinal Cord 18.3.5.4 Peripheral Nerve Injuries 18.3.6 Complications Related to Cesarean Section Delivery 18.4 Complications of Neonatal Therapy 18.4.1 Respiratory System 18.4.1.1 Injuries Caused by Endotracheal Intubation 18.4.1.2 Patent Ductus Arteriosus 18.4.1.3 Complications of Assisted Ventilation 18.4.1.4 Respiratory Distress Syndrome and Chronic Lung Disease 18.4.1.5 Oxygen Toxicity 18.4.1.6 Positive Pressure Ventilation 18.4.1.7 Pulmonary Air Leak 18.4.1.8 Pneumothorax 18.4.1.9 Pulmonary Interstitial Emphysema 18.4.1.10 Extrapulmonary Air Leakage 18.4.1.11 Pulmonary Gas Embolism 18.4.1.12 Other Ventilator Injury 18.4.1.13 Special Techniques Extra Corporeal Membrane Oxygenation (ECMO) Nitric Oxide Liquid Ventilation 18.4.1.14 Complications of Pharmacological Interventions in Neonatal Lung Disease Surfactant Therapy Indomethacin Anti-Oxidant Therapy 18.4.1.15 Complications of Chest Drains 18.4.2 Infection 18.5 Complications Related to Monitoring, Vascular Cannulation and Blood Sampling 18.5.1 Arteries 18.5.2 Veins 18.6 Other Causes of Complications 18.6.1 Burns 18.6.2 Topical Preparations 18.6.2.1 Hexachlorophene 18.6.2.2 Alcohol Based Cleansing Solutions 18.6.3 Systemic Treatments 18.6.3.1 Antibiotics 18.6.3.2 Diuretics 18.6.3.3 Steroids 18.6.3.4 Tolazaline 18.6.3.5 Prostaglandin E1 18.6.3.6 Total Parenteral Nutrition 18.6.3.7 Blood Transfusion Infection Graft-Versus-Host Disease 18.6.4 Skeletal Abnormalities References 19: Congenital Tumors 19.1 Incidence 19.2 Etiology 19.3 Inherited Tumors 19.4 Malformation Syndromes and Tumors 19.5 Malformations and Tumors 19.6 Prenatal Exposure to Environmental Agents, Maternal Medical Therapies and Tumors 19.7 Oncogenesis 19.8 Investigation of Congenital Tumors 19.9 Teratomas 19.9.1 Sacrococcygeal Teratomas 19.9.2 Teratomas and Germ Cell Tumors at Other Sites 19.10 Congenital Neuroblastoma 19.11 Small Round Blue Cell Tumors 19.12 Hematological Tumors 19.12.1 Congenital Leukemia 19.12.2 Lymphoma 19.12.3 Histiocytic Disorders 19.12.4 Langerhans’ Cell Histiocytosis 19.12.5 Hemophagocytic Lymphohistiocytosis 19.12.6 Juvenile Xanthogranuloma 19.13 Congenital Soft Tissue Tumors 19.13.1 Mesenchymal Tumors 19.13.2 Vascular Tumors 19.13.3 Fibromatoses 19.13.4 Congenital Myofibromatosis (Solitary and Multicentric) 19.13.5 Infantile Desmoid-type Fibromatosis 19.13.6 Fibromatosis Colli 19.13.7 Infantile Digital Fibromatosis 19.13.8 Cranial Fasciitis 19.13.9 Inflammatory Myofibroblastic Tumor 19.13.10 Giant Cell Fibroblastoma/Dermatofibrosarcoma Protruberans (DFSP) 19.13.11 Congenital (Infantile) Fibrosarcoma 19.13.12 Fibrous Hamartoma of Infancy 19.13.13 Hyalinosis and Juvenile Hyaline Fibromatosis 19.13.14 Others 19.14 Extrarenal Rhabdoid Tumor 19.15 Rhabdomyosarcoma 19.16 Neural Tumors 19.17 Melanotic Neuroectodermal Tumor of Infancy (Retinal Anlage Tumor) 19.18 Adipose Tumors 19.19 Chest Wall Hamartoma 19.20 Renal Tumors 19.20.1 Congenital Mesoblastic Nephroma 19.20.2 Metanephric Tumors 19.20.3 Nephroblastoma (Wilms Tumor) 19.20.4 Nephroblastomatosis and Nephrogenic Rests 19.20.5 Cystic Nephroma and Anaplastic Sarcoma of the Kidney 19.20.6 Rhabdoid Tumor of Kidney 19.20.7 Ossifying Renal Tumor of Infancy 19.20.8 Other Renal Tumors 19.21 Liver Tumors 19.21.1 Hepatic Vascular Tumors 19.21.2 Mesenchymal Hamartoma 19.21.3 Hepatoblastoma 19.22 Tumors of the Central Nervous System 19.23 Gonadal Tumors 19.24 Skin Tumors 19.25 Lung Lesions 19.26 Cardiac Lesions 19.27 Tumors of the Cord and Placenta 19.28 Maternal Malignant Disease in Pregnancy References 20: Cardiovascular System 20.1 Development of the Heart 20.1.1 The Heart Fields 20.2 The Heart Tube and Looping 20.3 Development of the Chambers and Septation 20.4 The Fetal Circulation and Changes at Birth 20.4.1 The Venous Duct and Oval Foramen 20.4.2 Arterial Duct, Lungs and Systemic Circulation 20.4.3 Postnatal Adaptation 20.5 Examination of the Normal and Malformed Heart 20.5.1 Normal Anatomy 20.5.1.1 The Right and Left Atrium 20.5.1.2 The Ventricles 20.5.2 The Abnormal Heart 20.5.3 Examination of the Heart 20.5.4 Simulated Echocardiographic Views 20.5.5 Histology 20.5.6 Weights and Measures 20.6 Structural Congenital Heart Disease 20.6.1 Ventricular Septal Defect (VSD) 20.6.2 Atrioventricular Septal Defect (AVSD) 20.6.3 Atrial Septal Defect (ASD) 20.6.4 Abnormalities of the Arterial Duct (Ductus Arteriosus) 20.6.4.1 Absence of the Arterial Duct and Bilateral Ducts 20.6.4.2 Normal Closure 20.6.4.3 Premature Closure In Utero 20.6.4.4 Persistent Patency of the Duct 20.6.4.5 Aneurysm of the Duct 20.6.5 Coarctation of the Aorta 20.6.6 Pulmonary Atresia and Stenosis Including Tetralogy of Fallot 20.6.6.1 Pulmonary Atresia with Intact Interventricular Septum 20.6.6.2 Pulmonary Stenosis with Intact Interventricular Septum 20.6.6.3 Pulmonary Stenosis with VSD Including Tetralogy of Fallot 20.6.6.4 Pulmonary Atresia with Ventricular Septal Defect 20.6.6.5 Absence of the Pulmonary Valve 20.6.7 Aortic Stenosis 20.6.7.1 Valvar Stenosis 20.6.7.2 Subvalvar Stenosis 20.6.7.3 Supravalvar Stenosis 20.6.8 Hypoplastic Left Heart 20.6.9 Transposition of the Great Arteries 20.6.10 Common Arterial Trunk (Truncus Arteriosus) 20.6.11 Double Inlet Ventricle 20.6.11.1 Double Inlet Left Ventricle 20.6.11.2 Double Inlet Right Ventricle 20.6.12 Double Outlet Ventricle 20.6.12.1 Double Outlet Right Ventricle 20.6.13 Abnormaliies of the Pulmonary Veins 20.6.13.1 Anomalous Pulmonary Venous Connection 20.6.13.2 Pulmonary Vein Stenosis 20.6.14 Ebstein’s Malformation 20.6.15 Tricuspid Atresia 20.6.16 Uhl’s Anomaly 20.6.17 Atrial Isomerism 20.6.17.1 Right Atrial Isomerism 20.6.17.2 Left Atrial Isomerism 20.6.17.3 Juxtaposition of the Atrial Appendages 20.6.18 Structural Abnormalities of the Coronary Arteries 20.6.18.1 Anomalous Origin of the Coronary Arteries from the Aorta 20.6.18.2 Anomalous Origin of the Coronary Arteries from the Pulmonary Trunk 20.6.19 Other Abnormalities 20.6.19.1 Persistent Left Superior Vena Cava 20.6.19.2 Ectopia Cordis 20.7 Structural Heart Disease in the Fetus 20.8 Inflammation 20.8.1 Infectious Endocarditis 20.8.2 Myocarditis 20.8.3 Pericarditis 20.9 Myocardial Ischemia and Infarction 20.10 Cardiomyopathy 20.10.1 Hypertrophic Cardiomyopathy 20.10.2 Dilated Cardiomyopathy 20.10.3 Restrictive Cardiomyopathy 20.10.4 Arrhythmogenic Right Ventricular Cardiomyopathy 20.10.5 Non-Compaction of the Ventricular Myocardium 20.10.6 Histiocytoid Cardiomyopathy 20.10.7 Mitochondrial Cardiomyopathy 20.10.8 Metabolic Cardiomyopathy 20.11 Tumors 20.11.1 Rhabdomyoma 20.11.2 Fibroma 20.11.3 Teratoma 20.11.4 Other Tumors 20.12 Vascular System 20.12.1 Iatrogenic Disease 20.12.2 Marfan Syndrome 20.12.3 Fibromuscular Dysplasia 20.12.4 Idiopathic Arterial Calcification 20.12.5 The Coronary Arteries 20.13 The Cardiac Conduction System 20.13.1 Normal Anatomy 20.13.2 Histological Sampling 20.13.3 Neonatal Lupus 20.13.4 Arrhythmia in the Absence of Structural Heart Disease References 21: The Respiratory System 21.1 Normal Development 21.1.1 Upper Respiratory Tract 21.1.2 Lower Respiratory Tract 21.1.3 Lung Development: Control 21.1.4 Biochemical and Physiological Maturation 21.1.4.1 Surfactant 21.1.4.2 Lung Liquid Secretion 21.1.4.3 Antioxidant Enzymes 21.1.5 Pulmonary Vascular Changes at Birth 21.2 Post-Mortem Examination of the Respiratory System 21.3 Developmental Anomalies 21.3.1 Anterior and Posterior Nares 21.3.2 Lips and Palate 21.3.3 Larynx 21.3.3.1 Laryngeal Atresia 21.3.3.2 Laryngeal Stenosis 21.3.3.3 Laryngeal Clefts 21.3.3.4 Laryngeal Cysts 21.3.3.5 Laryngomalacia 21.3.4 Trachea 21.3.4.1 Tracheal Agenesis 21.3.4.2 Tracheal Stenosis 21.3.4.3 Tracheo-esophageal Fistula 21.3.4.4 Tracheomalacia and Bronchomalacia 21.3.5 Lungs 21.3.5.1 Bronchial Abnormalities 21.3.5.2 Pulmonary Agenesis 21.3.5.3 Other Pulmonary Lobar Anomalies 21.3.5.4 Pulmonary Cystic Disease Bronchogenic Cysts Congenital Lobar Emphysema Congenital Pulmonary Airway Malformation (CPAM) Pulmonary Sequestration 21.3.5.5 Other Pulmonary Lesions: Heterotopias/Hamartomas 21.3.5.6 Alveolar Capillary Dysplasia 21.3.5.7 Congenital Alveolar Dysplasia 21.3.5.8 Lymphangiectasia 21.3.5.9 Lung Hypoplasia Mechanisms and Causes of Lung Hypoplasia 21.3.5.10 Congenital Diaphragmatic Hernia 21.4 Respiratory Distress 21.4.1 Respiratory Distress Syndrome/Hyaline Membrane Disease 21.4.2 Transient Tachypnea of Newborn 21.4.3 Pulmonary Hemorrhage 21.4.4 Meconium Aspiration Syndrome 21.4.5 Persistent Pulmonary Hypertension 21.4.6 Air Leaks 21.4.7 Surfactant Protein Deficiency 21.5 Chronic Lung Disease 21.5.1 Bronchopulmonary Dysplasia 21.5.1.1 Airway 21.5.1.2 Parenchyma 21.5.1.3 Vascular Disease 21.6 Infection 21.6.1 Ascending Infection 21.6.1.1 Miscarriage and Stillbirths 21.6.1.2 Neonatal Infection 21.6.1.3 Fungal Infection 21.6.1.4 Viral Infection References 22: The Alimentary Tract and Exocrine Pancreas 22.1 Development 22.1.1 Foregut 22.1.2 Midgut 22.1.3 Hindgut 22.1.4 Epithelium 22.1.5 Smooth Muscle 22.2 Oral Cavity 22.2.1 Cleft Lip and Palate 22.2.2 Tongue 22.2.3 Cysts and Tumors 22.3 Esophagus 22.3.1 Esophageal Atresia and Tracheoesophageal Fistula 22.3.2 Mucosal Anomalies 22.3.3 Esophageal Stenosis and Esophageal Duplication 22.4 Stomach 22.4.1 Microgastria 22.4.2 Infantile Hypertrophic Pyloric Stenosis 22.4.3 Spontaneous Gastric Perforation 22.4.4 Gastric Erosions and Ulcers 22.4.5 Pyloric Atresia 22.5 Small Intestine 22.5.1 Enteric Duplication Cysts 22.5.2 Vitellointestinal Duct Remnants 22.5.3 Abnormalities of Intestinal Rotation and Fixation 22.5.4 Short Bowel Syndrome 22.6 Intestinal Atresia and Stenosis 22.6.1 Duodenal Atresia 22.6.2 Jejunoileal Atresia 22.6.3 Colonic Atresia 22.6.4 Multiple Atresias 22.7 Meconium Abnormalities 22.7.1 Meconium Ileus 22.7.2 Meconium Plug Syndrome 22.7.3 Meconium Peritonitis 22.8 Necrotizing Enterocolitis 22.9 Spontaneous Intestinal Perforation 22.10 Bowel Ischemia Associated with Thromboembolic Disease 22.11 Colon and Rectum 22.11.1 Hirschsprung Disease (HD) 22.11.1.1 Epidemiology 22.11.1.2 Pathogenesis 22.11.1.3 Clinical Presentation 22.11.1.4 Genetics 22.11.1.5 Diagnostic Histopathology 22.11.1.6 Diagnostic Rectal Biopsies 22.11.1.7 Histologic Assessment of Rectal Biopsies 22.11.1.8 Ganglion Cells 22.11.1.9 Hypertrophic Nerves 22.11.1.10 AChE Histochemical Staining 22.11.1.11 Calretinin Staining 22.11.1.12 Choline Transporter Staining 22.11.1.13 Management 22.11.2 Hirschsprung-Associated Enterocolitis 22.11.3 Intestinal Neuronal Dysplasia 22.11.4 Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome 22.12 Malformations 22.12.1 Anorectal Malformations 22.12.2 Abdominal Wall Defects and Hernias 22.12.2.1 Exomphalos 22.12.2.2 Gastroschisis 22.12.2.3 Other Abdominal Wall Defects 22.12.3 Diaphragmatic Hernia 22.13 Exocrine Pancreas 22.13.1 Development 22.13.2 Pancreatic Aplasia and Hypoplasia 22.13.3 Pancreas Divisum 22.13.4 Annular Pancreas 22.13.5 Ectopic Pancreatic Tissue 22.13.6 Pancreatic Lesions in Trisomy 13 and 18 22.13.7 Cystic Fibrosis 22.13.8 The Pancreas in Systemic Disease 22.13.9 Pancreatic Cysts References 23: Liver and Gallbladder 23.1 Normal Development 23.1.1 Vasculature 23.1.2 Biliary System 23.1.2.1 Canaliculi 23.1.2.2 Intrahepatic Ducts 23.1.2.3 Extrahepatic Bile Ducts and Gallbladder 23.2 Functional Development of the Liver and Physiological Adaptations at Birth 23.2.1 Synthetic Function 23.2.2 Metabolic and Detoxifying Function 23.2.3 Hemopoiesis 23.3 Abnormalities of Development 23.3.1 Hepatic Anatomy 23.3.2 Vasculature 23.3.3 Biliary Abnormalities Including Polycystic Syndromes 23.3.4 Cysts 23.4 The Jaundiced Neonate 23.4.1 Biliary Atresia 23.4.1.1 Etiology/Pathogenesis 23.4.1.2 Histological Findings 23.4.1.3 Treatment/Prognosis 23.4.2 Alpha 1 Antitrypsin Deficiency 23.4.2.1 Etiology/Pathogenesis 23.4.2.2 Histological Findings 23.4.2.3 Treatment/Prognosis 23.4.3 Neonatal Hepatitis 23.4.3.1 Etiology/Pathogenesis 23.4.3.2 Histological Findings 23.4.3.3 Clues to a Metabolic Etiology 23.4.3.4 Clues to a Viral Etiology 23.4.3.5 Treatment/Prognosis 23.4.4 Paucity of Intrahepatic Bile Ducts 23.4.4.1 Etiology/Pathogenesis 23.4.4.2 Histological Findings 23.4.4.3 Treatment/Prognosis 23.4.5 Rare Causes of Neonatal Jaundice 23.5 The Neonate with Liver Failure 23.5.1 Metabolic Causes of Liver Failure 23.5.1.1 Galactosemia 23.5.1.2 Mitochondrial Hepatopathy/Respiratory Chain Disorders 23.5.1.3 Tyrosinemia 23.5.1.4 Niemann Pick C and Other Storage Disorders 23.5.1.5 Fatty Acid Oxidation Disorders 23.5.1.6 Urea Cycle Defects 23.5.1.7 Miscellaneous Metabolic Conditions 23.5.2 Neonatal Hemochromatosis 23.5.2.1 Etiology/Pathogenesis 23.5.2.2 Histological Findings 23.5.2.3 Treatment/Prognosis 23.5.3 Infectious Causes of Liver Failure 23.5.3.1 Viruses Enteroviruses Herpes Viruses Adenovirus Parvovirus B19 Hepatotropic Viruses 23.5.3.2 Non Viral Infections 23.6 Trauma and Iatrogenic Conditions Including Parenteral Nutrition 23.6.1 Trauma 23.6.2 Biopsy 23.6.3 Drugs 23.6.4 Parenteral Nutrition/Intestinal Failure Associated Liver Disease (IFALD) 23.6.4.1 Etiology/Pathogenesis 23.6.4.2 Histology 23.6.4.3 Treatment/Prognosis 23.7 Tumors 23.7.1 Hepatic Vascular Lesions 23.7.2 Mesenchymal Hamartoma 23.7.3 Hepatoblastoma 23.8 Gallbladder 23.9 Miscellaneous Conditions 23.9.1 Infants Born to Diabetic Mothers 23.9.2 Down Syndrome References 24: The Urinary System 24.1 Embryo-Histogenesis 24.1.1 Signaling 24.2 Congenital Anomalies of Kidney and Urinary Tract 24.2.1 Obstructive Uropathies 24.2.2 Anomalies of Number, Size and Position of the Kidneys 24.2.2.1 Renal Agenesis 24.2.2.2 Renal Hypoplasia 24.2.2.3 Hypoplasia with Dysplasia (Hypodysplasia) 24.2.2.4 Renal Hyperplasia 24.2.2.5 Supernumerary Kidney/Pyelon, Ectopic Kidney, and Horseshoe Kidney 24.2.2.6 Reno-Urinary Malformations in Syndromic Associations 24.3 Polycystic Kidney Diseases 24.3.1 Autosomal Recessive Polycystic Kidney Disease 24.3.1.1 Macroscopy 24.3.1.2 Microscopy 24.3.1.3 Clinical Features 24.3.1.4 Genetics 24.3.2 Autosomal Dominant Polycystic Kidney Disease 24.3.2.1 Macroscopy 24.3.2.2 Microscopy 24.3.2.3 Genetics 24.3.3 Cystic Kidneys in Malformation Syndromes 24.3.3.1 Meckel Syndrome Pathology Genetics 24.3.3.2 Bardet-Biedl Syndrome (BBS) Pathology Genetics 24.3.3.3 Reno-Hepato-Pancreatic Dysplasia (RHPD) 24.3.3.4 Asphyxiating Thoracic Dysplasia (Jeune Syndrome) Genetics 24.3.3.5 Tuberous Sclerosis 24.3.4 Apparently Isolated Cystic Renal Lesions 24.3.4.1 Infantile Nephronophthisis 24.4 Prenatal Expression of Hereditary Nephropathies 24.4.1 The Congenital Nephrotic Syndromes 24.4.2 Bartter Syndrome 24.4.3 Renal Tubular Dysgenesis (RTD) 24.5 Acquired Diseases of Immature Kidneys 24.5.1 Drugs and Anomalies of Renal Development 24.5.1.1 Inhibitors of Angiotensin-Converting Enzyme/Inhibitors of Angiotensin II type 1 Receptor 24.5.1.2 Prostaglandin Inhibitors 24.5.2 Renal Infection 24.5.3 Renal Glomerular Lesions in Cyanotic Congenital Heart Disease 24.6 Congenital Abnormalities of the Renal Pelvis and Ureter 24.6.1 Duplication 24.6.2 Vesicoureteric Reflux 24.6.3 Ureteric Ectopia 24.6.4 Ureterocele 24.6.5 Retrocaval Ureter 24.6.6 Congenital Hydrocalycosis 24.6.7 Congenital Hydronephrosis 24.6.8 Ureteral Dilatation 24.7 Congenital Abnormalities of the Bladder 24.7.1 Bladder Exstrophy 24.8 Congenital Abnormalities of the Urethra 24.8.1 Urethral Valves and Strictures 24.8.2 Prune Belly Syndrome 24.8.3 Megacystis/Megaureter Syndrome 24.8.4 Urethral Atresia 24.8.5 Urethral Duplication 24.8.6 Prostatic Utricle (Müllerian Duct) Cyst 24.8.7 Polyp of the Verumontanum 24.8.8 Megalourethra and Urethral Diverticulum 24.8.9 Hypospadias 24.9 Conclusion References 25: The Reproductive System 25.1 Development of the Reproductive System 25.1.1 Morphologically Indifferent Stage: Up to Six Weeks of Development 25.1.1.1 Relevant Structures Before the Sixth Week of Development Primordial Germ Cells: Specification, Determination, Migration Formation of Mesonephric Ducts and Genital Ridges 25.1.1.2 Relevant Structures That Develop During the Sixth Week of Development Fusion of Urorectal Septum with Cloacal Membrane: The Primitive Urogenital Sinus Paramesonephric Ducts 25.1.2 Reproductive System Development Beyond Six Weeks 25.1.2.1 SRY and Male Development 25.1.2.2 Female Development 25.1.3 External Genitalia from Six to Nine Weeks 25.1.4 External Genitalia from Nine to Fourteen Weeks 25.1.4.1 Male External Genitalia 25.1.4.2 Female External Genitalia 25.1.4.3 Ambiguous Genitalia and Examination 25.1.5 Descent of the Gonads 25.1.6 Derivative and Remnant Structures 25.1.7 Expression of Immature Germ Cell Markers Until the Early Post-natal Period 25.2 Disorders of Sex Development 25.2.1 Genetics of DSD: General Remarks 25.2.2 DSD Terminology 25.2.2.1 Complete Gonadal Dysgenesis 46,XY Complete Gonadal Dysgenesis 46,XX Complete Gonadal Dysgenesis 25.2.2.2 Partial Gonadal Dysgenesis 25.2.2.3 Mixed Gonadal Dysgenesis (MGD) 25.2.2.4 Ovotestis 25.2.3 DSD Categories 25.2.3.1 Sex Chromosome DSD Turner Syndrome Klinefelter Syndrome 45,X/46,XY and 45,X/47XYY Mixed Gonadal Dysgenesis 46,XX/46,XY or 46,XX/47,XXY Chimeric or Mosaic Ovotesticular DSD 25.2.3.2 46,XY DSD 46,XY DSD with Disordered Gonadal Development (Isolated or Syndromic) 46,XY DSD with Gonadal Dysgenesis 25.2.3.3 46,XY DSD, Ovotesticular 46,XY DSD with Disordered Androgen Synthesis or Action (Isolated or Syndromic) Luteinizing Hormone Receptor Defects/Leydig Cell Hypoplasia Androgen Biosynthesis Defects Androgen Action Defects 46,XY DSD with Defects in Anti-Müllerian Hormone or Receptors: The Persistent Müllerian Duct Syndrome Unclassified 46,XY DSD and Other Reproductive System Anomalies 25.2.3.4 46,XX DSD 46,XX DSD with Disordered Gonadal Development (Isolated or Syndromic) 46,XX DSD with Gonadal Dysgenesis 46,XX DSD, Testicular 46,XX DSD, Ovotesticular 46,XX DSD with Androgen Excess Unclassified 46,XX DSD and Other Reproductive System Anomalies 25.2.4 Genetic Evaluation 25.2.5 Germ Cell Neoplasia in DSD 25.3 Other Fetal and Neonatal Disorders of the Reproductive System References 26: The Endocrine System 26.1 Introduction 26.1.1 Fetal Hormones and Fetal Growth 26.1.2 Fetal Hormones and the Placenta 26.2 Hypothalamic-Pituitary Axis 26.2.1 Development 26.2.2 Hormone Production and Regulation 26.2.3 Pathology 26.2.3.1 Developmental Abnormalities 26.2.4 Anencephaly 26.2.5 Idiopathic Pituitary Insufficiency 26.3 Adrenal Glands 26.3.1 Development 26.3.2 Hormone Production and Regulation of the Adrenal Cortex 26.3.3 Pathology: Developmental Anomalies 26.3.3.1 Adrenal Agenesis 26.3.3.2 Ectopic Adrenal Tissue 26.3.3.3 Secondary Adrenal Hypoplasia 26.3.3.4 Idiopathic Adrenal Hypoplasia 26.3.3.5 Partial Adrenal Hypoplasia 26.3.3.6 Fusion 26.3.4 Pathology: Acquired Pathology 26.3.5 Fatty Adrenals 26.3.6 Microscopic Pathology 26.3.6.1 Neuroblastoma In Situ 26.3.6.2 Hemopoietic Activity 26.3.6.3 Adrenal Cytomegaly 26.3.6.4 Pseudocysts and Pseudofollicular Changes 26.3.6.5 Other Changes 26.3.7 Functional Pathology 26.3.7.1 Congenital Adrenal Hyperplasia (Adrenogenital Syndrome) 26.3.7.2 Lipoid CAH 26.3.8 Infections 26.3.9 Tumors of the Adrenal Gland 26.3.9.1 Congenital Neuroblastoma 26.3.9.2 Adrenocortical Tumors 26.4 Thyroid Gland 26.4.1 Development 26.4.2 Developmental Abnormalities 26.4.3 Fetal Goiter 26.4.4 Congenital Hypothyroidism 26.4.5 Congenital Hyperthyroidism 26.4.6 Tumors of the Thyroid 26.5 Parathyroid Glands 26.5.1 Development 26.5.2 Developmental Abnormalities 26.5.3 Congenital Hypoparathyroidism and Hypocalcemia 26.5.4 Hyperparathyroidism/Hypercalcemia 26.6 Endocrine Pancreas 26.6.1 Development 26.6.2 Specific Histological Features and Normal Variation 26.6.3 Physiology of Fetal Glucose Homeostasis 26.6.4 Insulin Secretion 26.6.5 Developmental Abnormalities 26.6.6 Neonatal Hypoglycemia/Hyperinsulinemia 26.6.7 Infants of Diabetic Mothers 26.6.7.1 Histology 26.6.8 Complications During Pregnancy and Delivery, Perinatal Morbidity (IDM) 26.6.9 Congenital Hyperinsulinism 26.6.9.1 Histology (Fig. 26.37) 26.6.10 Beckwith–Wiedemann Syndrome 26.6.11 Liver Disease 26.6.12 Neonatal Diabetes Mellitus 26.6.13 Infection References 27: The Reticuloendothelial System 27.1 Spleen 27.1.1 Normal Development 27.1.2 Developmental Anomalies 27.1.2.1 Asplenia, Polysplenia 27.1.2.2 Ectopic Spleen 27.1.2.3 Splenogonadal Fusion 27.1.2.4 Splenopancreatic Fusion 27.1.3 Splenomegaly 27.1.4 Neoplasms 27.2 Thymus 27.2.1 Normal Development 27.2.2 Developmental Anomalies 27.2.2.1 Ectopic Thymus 27.2.2.2 Thymic Aplasia 27.2.3 Pathological Thymic Involution 27.2.4 Thymic Enlargement References 28: Brain Malformations 28.1 Epidemiology: Classification 28.2 Neural Tube Defects: Dysraphism 28.2.1 Craniorachischisis 28.2.2 NTDS Affecting the Anterior Part of the Neural Tube 28.2.2.1 Anencephaly 28.2.2.2 Exencephaly 28.2.2.3 Cranial Meningocele and Meningo-Encephalocele 28.2.3 NTDS Affecting the Posterior Part of the Neural Tube: Spina Bifida or Rachischisis 28.2.3.1 Iniencephaly 28.2.3.2 Myelomeningocele and Myelocele 28.2.3.3 Arnold-Chiari Type II Malformation 28.2.3.4 Spina Bifida Occulta 28.3 Disorders of Prosencephalon Patterning: Holoprosencephaly Spectrum 28.3.1 Aprosencephaly/Atelencephaly 28.3.2 “Classic Holoprosencephaly” 28.3.3 Middle Interhemispheric Fusion 28.3.4 “Microform Holoprosencephaly” 28.3.5 Holoprosencephaly 28.4 Midline Defects: Corpus Callosum and Septum Pellucidum Anomalies 28.4.1 Callosal Anomalies: Morphological Aspects 28.4.1.1 Agenesis of Corpus Callosum (ACC) 28.4.1.2 Callosal Hypoplasia 28.4.1.3 Dysmorphic Corpus Callosum 28.4.2 Pathogenic Mechanisms Of Callosal Anomalies 28.4.3 Etiology of Callosal Anomalies 28.4.4 Anomalies of the Septum Pellucidum 28.4.4.1 Septal Agenesis 28.4.4.2 Septo-Optic Dysplasia (SOD) or De Morsier Syndrome 28.5 Malformations of Cortical Development (MCds) Neuronal Migration Defects (NMDS) 28.5.1 Lissencephalies 28.5.1.1 “Classic” Lissencephaly 28.5.1.2 Subcortical Band Heterotopia 28.5.1.3 Variant lissencephalies 28.5.2 “Cobblestone” Dysplasia 28.5.2.1 Cobblestone Lissencephaly 28.5.3 Heterotopia 28.5.4 Polymicrogyria 28.5.5 Schizencephaly 28.5.6 Tubulinopathies 28.6 Disorders of Brain Growth 28.6.1 Microcephaly: Micrencephaly 28.6.2 Primary Hereditary Microcephaly (MCPH) 28.6.3 Microlissencephaly 28.6.4 Macrocephaly: Megalencephaly—mTORopathies 28.6.4.1 Primary Megalencephaly 28.6.4.2 Secondary Megalencephaly 28.6.4.3 Hemimegalencephaly 28.7 Cerebellum and Brainstem Malformations 28.7.1 Cellular and Molecular Events that Form the Brainstem And Cerebellum 28.7.2 Brainstem Malformations 28.7.3 Cerebellar Malformations 28.7.4 Midline Defects: Vermian Anomalies 28.8 Congenital Ventriculomegaly-Hydrocephalus 28.8.1 Etiology 28.9 Ciliopathies 28.10 Blood Vessel Malformations 28.10.1 Aneurysm of Vein of Galen 28.10.2 Fowler Syndrome References 29: Degenerative and Metabolic Brain Diseases 29.1 General Pathophysiological Principles 29.1.1 Classification Systems 29.1.2 Making a Diagnosis: A Collaborative Effort 29.1.3 Practical Guidelines for Post-Mortem Examination of the Brain 29.1.3.1 Clinicopathological Correlation 29.1.3.2 Brain Weight and Maturation of the Brain 29.1.3.3 Cutting, Sampling and Storing Tissues 29.1.3.4 Other Organs 29.2 Diseases Primarily Affecting the Gray Matter 29.2.1 GM2 Gangliosidosis (Tay-Sachs Disease) 29.2.2 Congenital Neuronal Ceroid Lipofuscinosis 29.2.3 Niemann-Pick Disease 29.2.4 Gaucher Disease 29.2.5 Alpers-Huttenlocher Syndrome 29.2.6 Menkes Disease 29.3 Diseases Primarily Affecting the White Matter 29.3.1 Canavan Disease 29.3.2 Alexander Disease 29.3.3 Krabbe Disease 29.3.4 Pelizaeus-Merzbacher Disease 29.4 Diseases Affecting Gray and White Matter 29.4.1 Leigh Syndrome 29.4.2 Congenital Disorders of Glycosylation 29.5 Other Neurometabolic Disorders 29.5.1 Hyperbilirubinemia and Kernicterus 29.5.2 Disorders of Amino Acid Metabolism 29.5.3 Glycogenoses References 30: Acquired Diseases of the Nervous System 30.1 Pathological Reactions in the Human Perinatal and Fetal Brain 30.1.1 Edema 30.1.2 Cell Death 30.1.3 Microgliosis 30.1.4 Capillary Proliferation 30.1.5 Mineralisation 30.1.6 Astrocytosis 30.2 Patterns of Injury 30.3 Trauma 30.3.1 Skull Fracture 30.3.2 Extradural and Subdural Hemorrhage 30.3.2.1 Extradural Hemorrhage 30.3.2.2 Subdural Hemorrhage 30.3.3 Spinal Cord Injury 30.4 Brain Damage Due to Hypoxia and Ischemia 30.4.1 Timing of Parenchymal Damage 30.4.2 The Encephalopathy of Prematurity 30.4.3 Periventricular Leukomalacia (PVL) 30.4.3.1 Focal PVL 30.4.3.2 Diffuse PVL 30.4.3.3 Grey Matter Injury 30.4.4 Other Patterns of Ischemic Injury 30.4.4.1 Thalamus and Basal Ganglia 30.4.4.2 Cerebral Cortex 30.4.4.3 Brainstem 30.4.4.4 Pontosubicular Necrosis 30.4.4.5 Cerebellum 30.4.4.6 Spinal Cord 30.4.4.7 Porencephaly and Schizencephaly 30.4.4.8 Hydranencephaly 30.4.5 Perinatal Stroke 30.4.5.1 Perinatal Arterial Ischemic Stroke 30.4.5.2 Venous Infarction and Cerebral Venous Sinus Thrombosis 30.5 Hemorrhage 30.5.1 Subarachnoid Hemorrhage 30.5.2 Subpial Hemorrhage 30.5.3 Subependymal Germinal Matrix and Intraventricular Hemorrhage 30.5.4 Parenchymal Hemorrhagic Infarction 30.5.5 Sequelae of Subependymal Germinal Matrix and Intraventricular Hemorrhage 30.5.6 Choroid Plexus Hemorrhage 30.5.7 Intracerebellar Hemorrhages 30.6 Infections of the Nervous System 30.6.1 Viral Infections 30.6.1.1 Cytomegalovirus (CMV) 30.6.1.2 Herpes Simplex Virus (HSV) 30.6.1.3 Human Immunodeficiency Virus (HIV) 30.6.1.4 Zika Virus (ZikV) 30.6.2 Protozoal Infections 30.6.2.1 Toxoplasmosis 30.6.3 Bacterial Infections 30.6.3.1 Listeria Meningitis 30.6.4 Fungal Infections 30.6.4.1 Candidiasis 30.7 Metabolic and Toxic Disorders 30.7.1 Kernicterus 30.7.2 Hypoglycemia 30.7.3 Fetal Alcohol Syndrome and Other Recreational Drugs 30.8 Cardiac Surgery References 31: Skeletal Muscle and Peripheral Nerves 31.1 Development of Skeletal Muscle 31.2 Neuromuscular Disorders Affecting the Fetus and Neonate 31.2.1 The Phenotype: Arthrogryposis, Fetal Akinesia Deformation Sequence, and the Pena-Shokeir Syndrome 31.2.1.1 Amyoplasia 31.2.1.2 Other Central Nervous System Disorders 31.2.1.3 The Multiple Pterygium Syndromes 31.2.1.4 The Distal Arthrogryposes 31.2.2 Conditions Resulting in Intrauterine Constraint 31.2.3 Restrictive Dermopathy 31.2.4 Congenital Inflammatory Myopathies 31.2.5 Primary Fetal Neuromuscular Disorders 31.2.5.1 Spinal Muscular Atrophy 31.2.5.2 Congenital Myotonic Dystrophy 31.2.5.3 Congenital Myopathies General Features of the Congenital Myopathies Nemaline Myopathy Centronuclear/Myotubular Myopathy Congenital Fiber-Type Disproportion The Core Myopathies 31.2.5.4 Congenital Muscular Dystrophies Congenital Muscular Dystrophy with Laminin-α2 Deficiency (Merosin-Deficient CMD, MDC1A) α-Dystroglycanopathies (Including Fukuyama Muscular Dystrophy, Muscle-Eye-Brain Disease, Walker-Warburg Syndrome, and MDC1C) Collagen VI-Related Congenital Muscular Dystrophies Other Congenital Muscular Dystrophies 31.2.5.5 Neuromuscular Transmission Disorders Transient Neonatal Myasthenia Congenital Myasthenic Syndromes 31.2.5.6 The Metabolic Myopathies Myopathic Glycogenoses Disorders of Fatty Acid Oxidation Mitochondrial Myopathies Cytochrome c Oxidase Deficiency 31.2.6 Peripheral Neuropathies 31.2.6.1 Hereditary Motor and Sensory Neuropathy 31.2.6.2 Hereditary Sensory and Autonomic Neuropathy 31.2.6.3 Other Inherited Peripheral Neuropathies 31.3 Prenatal Diagnosis of Neuromuscular Disease 31.3.1 Fetal Ultrasound and MRI Examination 31.3.2 Prenatal Genetic Testing 31.4 Investigation of Fetal and Neonatal Neuromuscular Disease 31.5 The Autopsy Approach 31.5.1 Prior to the Autopsy Dissection 31.5.2 The Autopsy Dissection References 32: The Skeletal System 32.1 Osteochondrodysplasias 32.1.1 FGFR3 Chondrodysplasia Group (Group 1) 32.1.1.1 Thanatophoric Dysplasia with Bowed Femora With or Without Cloverleaf Skull (Type I) 32.1.1.2 Thanatophoric Dysplasia with a Straight Femur With or Without a Cloverleaf Skull (Type II) 32.1.2 Osteogenesis Imperfecta and Decreased Bone Density Group (Group 25) 32.1.3 Type 2 Collagen Group and Related Disorders (Group 2) 32.1.3.1 Achondrogenesis Type 2 (Langer–Saldino Dysplasia) 32.1.3.2 Torrance Dysplasia, Hypochondrogenesis and Spondyloepiphyseal Dysplasia Congenita (SEDC) 32.1.4 Sulfation Disorders Group (Group 4) 32.1.5 Ciliopathies with Major Skeletal Involvement (Group 9) 32.1.5.1 SRPS Type 1/3 (Saldino-Noonan/Verma-Naumoff) 32.1.5.2 SRPS Type 2 (Majewski) 32.1.5.3 SRPS Type 4 (Beemer) 32.1.6 Other Generalized Skeletal Abnormalities Recognizable at Birth 32.1.6.1 Chondrodysplasia Punctata (Group 21) 32.1.6.2 Fibrochondrogenesis (Group 3) 32.1.6.3 Campomelic Dysplasia (Group 18) 32.1.6.4 Homozygous Achondroplasia (Group 1) 32.1.6.5 Metatropic Dysplasia (Group 8) 32.1.6.6 Boomerang Dysplasia (Group 7) 32.1.6.7 Schneckenbecken Dysplasia (Group 14) 32.2 Fractures 32.3 Osteomyelitis References 33: The Skin 33.1 Development of the Skin 33.1.1 Periderm 33.1.2 Keratinocyte 33.1.3 Melanocytes 33.1.4 Langerhans’ Cells 33.1.5 Dermis and Dermo-Epidermal Junction 33.1.6 Skin Function 33.2 Disorders of Development 33.2.1 Amniotic Constriction Bands 33.2.2 Dermoid Cysts 33.2.3 Accessory Auricle, Preauricular Pit and Sinus 33.2.4 Congenital Cysts and Sinuses 33.2.5 Aplasia Cutis Congenita 33.3 Pigment Abnormalities in the Newborn and Infant 33.3.1 Albinism 33.3.2 Piebaldism 33.3.3 Waardenburg Syndrome 33.3.4 Tuberous Sclerosis Complex 33.3.5 Nevus Depigmentosus and Pigment Mosaicism 33.3.6 Nevus Anemicus 33.4 Common Neonatal Skin Conditions 33.4.1 Erythema Toxicum Neonatorum 33.4.2 Diaper Dermatitis 33.4.3 Milia 33.4.4 Neonatal Acne 33.4.5 Miliaria 33.4.6 Infantile Seborrheic Dermatitis 33.4.7 Subcutaneous Fat Necrosis 33.4.8 Sclerema Neonatorum 33.5 Birthmarks 33.5.1 Pigmented Birthmarks 33.5.1.1 Mongolian Spot 33.5.1.2 Café au Lait Spots 33.5.1.3 Lentigines 33.5.1.4 Melanocytic Nevi and Malignant Melanoma 33.5.1.5 Other Melanocytic Birthmarks 33.5.2 Vascular Anomalies 33.5.2.1 Congenital Hemangiomas 33.5.2.2 Kaposiform Hemangioendothelioma/Tufted Angioma/Kasabach-Merritt Syndrome 33.5.2.3 Port Wine Stain/Capillary Malformations 33.5.2.4 Angiokeratoma 33.5.3 Lymphatic and Venous Malformations 33.5.4 Other Birthmarks 33.5.4.1 Epidermal Nevi and Organoid Nevi 33.6 Congenital Infections with Skin Manifestations 33.6.1 Viral Infections 33.6.1.1 Cytomegalovirus, Rubella 33.6.1.2 Herpes Viruses 33.6.2 Bacterial Infections 33.6.2.1 Staphylococcus aureus 33.6.2.2 Staphylococcal Scalded Skin Syndrome 33.6.2.3 Group A β-hemolytic Streptococcus 33.6.2.4 Congenital Syphilis 33.7 Congenital Genetically Determined Diseases 33.7.1 Ectodermal Dysplasia 33.7.2 Disorders of Keratinization 33.7.2.1 Congenital Ichthyosis 33.7.2.2 X-Linked Ichthyosis 33.7.2.3 Syndromic Ichthyoses 33.7.2.4 Keratinopathic Ichthyosis (KI) 33.7.2.5 Palmoplantar Keratodermas 33.8 Blistering Disorders 33.8.1 Epidermolysis Bullosa Simplex (EBS) 33.8.2 Junctional Epidermolysis Bullosa (JEB) 33.8.3 Dystrophic Epidermolysis Bullosa (DEB) 33.8.4 Kindler Syndrome 33.9 Other Genetic Diseases 33.9.1 Incontinentia Pigmenti 33.9.2 Lipoid Proteinosis (Hyalinosis Cutis et Mucosae) 33.10 Dermal Developmental Disorders 33.10.1 Ehlers–Danlos Syndrome 33.10.2 Cutis Laxa 33.10.3 Focal Dermal Hypoplasia (Goltz’s Syndrome) 33.11 Skin Disorders with Disordered Immune Responses 33.11.1 Neonatal Lupus Erythematosus 33.11.2 Graft Versus Host Disease 33.12 Skin Infiltrations and Tumor-Like Lesions 33.12.1 Cutaneous Mastocytosis 33.12.2 Langerhans’ Cell Histiocytosis 33.12.3 Juvenile Xanthogranuloma References 34: The Special Senses 34.1 The Eye 34.1.1 Embryology 34.1.1.1 The Lens 34.1.1.2 The Retina 34.1.1.3 The Choroid, Sclera, Ciliary Body, Iris, Cornea, and Anterior and Posterior Chambers 34.1.1.4 The Vitreous Body 34.1.1.5 The Hyaloid Vessels 34.1.1.6 The Extraocular Muscles 34.1.1.7 The Eyelids 34.1.1.8 The Accessory Ocular Glands 34.1.1.9 Genetic Regulation of Ocular Development 34.1.1.10 Postnatal Development of the Eye 34.1.1.11 Abnormalities of Periocular Tissues 34.1.1.12 Developmental Abnormalities of Oculogenesis 34.1.2 Abnormalities of the Globe 34.1.2.1 Anophthalmia/Microphthalmia 34.1.2.2 Nanophthalmia/Nanophthalmos 34.1.2.3 Cyclopia/Synophthalmia 34.1.2.4 Cryptophthalmos 34.1.2.5 Globe Enlargement 34.1.2.6 Coloboma 34.1.3 Developmental Abnormalities of the Cornea 34.1.4 Anterior Segment Dysgenesis 34.1.5 Developmental Abnormalities of the Lens 34.1.6 Persistent Fetal Vasculature (PFV) 34.1.7 Developmental Abnormalities of the Retina 34.1.8 Vitreoretinal Disorders 34.1.8.1 X-linked Retinoschisis (Congenital Vascular Veils in the Vitreous) 34.1.8.2 Familial Exudative Vitreoretinopathy 34.1.9 Disorders of Ocular Pigmentation 34.1.9.1 Congenital Ocular Melanosis 34.1.9.2 Reduced Ocular Pigmentation 34.1.10 Disorders of Optic Nerve Development 34.1.10.1 Optic Nerve Aplasia 34.1.10.2 Optic Nerve Hypoplasia (ONH) 34.1.10.3 Optic Nerve Coloboma 34.1.11 Retinopathy of Prematurity 34.1.12 Infection and the Eye 34.1.12.1 Intrauterine Infection 34.1.12.2 Neonatal Infection 34.1.13 Neonatal and Perinatal Ocular and Periocular Neoplasms 34.1.13.1 Retinoblastoma 34.1.14 Trauma 34.2 The Ear 34.2.1 Embryology 34.2.1.1 The External Ear 34.2.1.2 The Inner Ear 34.2.1.3 The Middle Ear 34.2.2 Developmental Abnormalities of the Ear 34.2.2.1 The External Ear 34.2.2.2 The Middle and Inner Ear 34.2.2.3 Hearing Loss 34.2.3 Syndromes Affecting Oculogenesis and Otogenesis 34.3 Olfaction 34.3.1 Embryology 34.3.2 Congenital Disorders of Olfaction 34.3.2.1 Examination of the Nose 34.3.3 Nasal Tumors 34.3.3.1 Nasal Glioma 34.3.3.2 Nasal Dermoid 34.4 Taste References 35: Forensic Aspects of Perinatal Pathology 35.1 Definitions 35.2 Neonaticide 35.2.1 Incidence 35.2.2 Perpetrators 35.2.3 Delivery 35.2.4 Motive 35.2.5 Means 35.2.6 Disposal 35.3 Investigation 35.3.1 Personnel and Division of Responsibilities 35.3.2 Circumstances/Scene 35.3.3 Post Mortem Radiology 35.3.4 Autopsy 35.3.4.1 Estimation of Gestational Age 35.3.4.2 Was the Baby Born Alive? 35.3.4.3 Injuries Toxicology 35.3.4.4 DNA Sampling Placenta 35.3.5 Umbilical Cord 35.4 Cause of Death 35.5 Summary References Index