Keeling's Fetal and Neonatal Pathology

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