BENIRSCHKE'S PATHOLOGY OF THE HUMAN PLACENTA

Preface
Acknowledgments
Contents
Contributors
1: Examination of the Placenta
	Storage
	Photography
	Examination
	Placentas of Multiple Births
	Sections
	mRNA and Microarray Analyses
	Special Procedures
	References
2: Macroscopic Features of the Delivered Placenta
	Fetal Surface
	Maternal Surface
	The Terms “Fetal Placenta” and “Maternal Placenta”
	References
3: Microscopic Survey
	Typical Histological Features of the First Trimester Placenta
	Typical Histological Features of the Third Trimester Placenta
4: Placental Types
	Histotrophic Versus Hemotrophic Nutrition
	Choriovitelline Versus Chorioallantoic Placentas
	Placental Shapes
	Types of Maternal-Fetal Interdigitation
	Maternal-Fetal Interface
	Maternal-Fetal Blood Flow Interrelations
	Placental Types and Phylogeny
	Genomic Imprinting
	Human Placenta
	Animal Models
	References
5: Early Development of the Human Placenta
	The Origin of Trophoblast
	Implantation and the Prelacunar Stage (Carnegie Stage 5a)
	Lacunar Stage (Carnegie Stages 5b and 5c)
	Early Villous Stages
	The Role of Histotrophic Nutrition
	Villus Regression and Formation of the Definitive Placenta
	Growth of the Definitive Placenta
	Trophoblast Stem Cells
	Formation of the Amnion
	The Yolk Sac
	References
6: Basic Structure of a Placental Villus
	Syncytiotrophoblast
		Microvillous Surface
		Extracellular Vesicles
		Basal Surface
		Organelles
		Nuclei
		Cytoskeleton
		Enzymes
		Glycogen
		Specialized Regions of the Villous Surface
		Syncytial Sprouts and Knots
		Intervillous Bridges
		Transtrophoblastic Channels
	Villous Cytotrophoblast (Langhans’ Cells)
		Villous Cytotrophoblast Cell Types
		Cytotrophoblast Fusion
		Junctional Proteins
		Endogenous Retroviral Glycoproteins
		Externalization of Phosphatidylserine
		Reorganization of the Cytoskeleton and Organelles
		Reorganization of the Plasma Membranes
		Overview of Trophoblast Fusion
	Syncytiotrophoblast Regeneration and Repair
	Trophoblast Senescence and Apoptosis
		Trophoblast Apoptosis
	Trophoblastic Basement Membrane
	The Villous Stromal Core
		Connective Tissue
		Matrix Components of the Villous Stroma
	Villous Macrophages (Hofbauer Cells)
		Origin and Distribution
		Functions
	Fetal Vasculature
		Stem Villous Arteries
		Fetal Capillaries
		Vasomotor Control
	Lymphatics
	Fibrinoid of the Villous Trees
		Perivillous Fibrinoid
		Intravillous Fibrinoid
	References
7: Architecture of the Villous Trees
	Classification of Villous Types
		Stem Villi
		Cytotrophoblast Cell Columns
		Immature Intermediate Villi
		Mature Intermediate Villi
		Terminal Villi
		Mesenchymal Villi
		Cell Islands
	Differentiation and Growth of Villous Types
		Formation of Mesenchymal Villi
		Differentiation of Mesenchymal Villi
		Development of the Terminal Villi
	The Lobular Architecture of the Villous Trees
		The Intervillous Clefts
	Characterization of the Developmental Stages
		Third Month P.M. 9–12th Weeks P.M.; Days 43–70 P.c
		Fourth Month P.M. 13–16th Weeks P.M.; 11–14th Weeks P.c
		Fifth Month P.M. 17–20th Weeks P.M.; 15–18th Weeks P.c
		Sixth Month P.M. 21–24th Weeks P.M.; 19–22nd Weeks P.c
		Seventh Month P.M. 25–28th Weeks P.M.; 23–26th Weeks P.c
		Eighth Month P.M. 29–32nd Weeks P.M.; 27–30th Weeks P.c
		Ninth Month P.M. 33–36th Weeks P.M.; 31–34th Weeks P.c
		Tenth Month P.M. 37–40th Weeks P.M.; 35–38th Weeks P.c
	Villous Maldevelopment
		Histopathological Significance of Inhomogeneity of Villous Trees
		Three-Dimensional Interpretation of Two-Dimensional Sections
		Classification of Villous Maldevelopment
	References
8: The Placental Bed
	Decidua
		Composition of Decidua
		Endometrial Stromal Cells and Decidual Cells
		Endocrine and Paracrine Aspects of Decidua
		Uterine Natural Killer Cells (uNK Cells)
		Macrophages
		Dendritic Cells
		B Cells and T Cells
		Regulatory T Cells
	Endometrial Glands
	Decidual Extracellular Matrix
	Extravillous Trophoblast
		Origins of Extravillous Trophoblast and Cell Columns
		Regulation of Extravillous Trophoblast Differentiation
		Cytotrophoblastic Shell
		Invasive Interstitial Extravillous Trophoblast Cells
		Multinucleated Placental Bed Giant Cells
		Endovascular Trophoblast
		Endoglandular Trophoblast
		Proteinases, Activators, and Inhibitors Involved in Trophoblast Invasion
		Cytokines, Growth Factors, and Other Factors Influencing Invasion of Extravillous Trophoblast
		Oxygen as a Modulator of the Invasive Pathway
		Failure of Extravillous Trophoblast Invasion in Pathological Pregnancies
	References
9: The Placental Circulations
	Angioarchitecture of the Placental Villi
		Larger Vessels of Stem Villi
		Paravascular Capillary Net of Stem Villi
		Arrangement of Vessels in Mature Intermediate and Terminal Villi
		Sinusoids of Terminal Villi
	General Aspects of Placental Vasculogenesis and Angiogenesis
		Vasculogenesis (Day 15–32)
		Angiogenesis and Vascular Remodeling (Day 32 to Week 40)
		Relationship to the Development of the Fetal Heart
	Molecular Regulation of Placental Vasculogenesis and Angiogenesis
		Vascular Endothelial Growth Factor
		Placental Growth Factor
		Angiopoietins
		Fibroblast Growth Factor
		Homeobox Genes
	Oxygen and Oxygen-Controlled Growth Factors as Regulators of Villous and Vascular Development
		Evidence for Oxygen-Controlled Fetal-Placental Angiogenesis
	The Anatomy of the Uteroplacental Vasculature
		Establishment of the Maternal Arterial Circulation
		Number and Position of the Uteroplacental Vessels
		Importance of Physiological Changes of Uteroplacental Arteries
		Stages of Physiological Changes in Uteroplacental Arteries
		Structure of Uteroplacental Veins
	Maternal-Fetal Flow Interrelations
		The Lobule as an Individual Maternal-Fetal Exchange Unit
	References
10: The Chorionic and Basal Plates
	The Chorionic Plate
		Development
		Structure at Term
		Amnion
		Spongy Layer
		Chorionic Mesoderm
		Cytotrophoblast Cells
		Langhans’ Fibrinoid Layer
		Attachment of the Umbilical Cord
	Marginal Zone
		Subchorial Closing Ring
		Marginal Lake
	Basal Plate
		Development of the Basal Plate
		Layers of the Basal Plate at Term
		Septa
		Calcification
	The Placental Membranes
	Fibrinoid
		Fibrin-Type Fibrinoid
		Matrix-Type Fibrinoid
		Localization of Fibrinoid Subtypes
		Functions of Fibrinoid
	References
11: Approach to Histologic Examination of the Placenta
	Approach to Microscopic Slide Examination
	Umbilical Cord
	Fetal Membranes
		Chorionic Plate
		Chorionic Villi
		Decidua Basalis
	References
12: Abortion and Chromosomal Anomalies
	Rates of Fetal Loss
		First- and Early Second-Trimester Loss
	Clinical Workup
		Placental Examination for Genetic Changes and After Spontaneous Abortion
	Non-Genetic Placental Causes of Abortion
		The Progression of Fetal Loss
		Risk Factors
		Anatomical Findings of the Embryo and First-Trimester Fetus
		Placental Examination in Spontaneous Abortions
	Molar Pregnancy
	Aneuploid Placentas
		Polyploidies
			Triploidy
			Tetraploidy
			Monosomy X
	Other Genetic Changes
	Induced Abortion
		Incomplete Abortion
	Genetic Testing of the Conceptus
		Chemical Markers and Trisomy
	Genetic Tests
		Noninvasive Genetic Testing
		Other Causes of Spontaneous Miscarriage
		Recurrent or Habitual Abortion (Recurrent Pregnancy Loss)
		Immune System and the Paradox of Pregnancy
	Thrombophilias and Pregnancy Loss
		Breus’ Mole (Massive Subchorionic (Thrombo-)Hematoma)
	References
13: Extrauterine Implantation and Involution of Implantation Site
	Introduction
	Fallopian Tube Pregnancy
	Cervical and Ovarian Pregnancy
	Abdominal Pregnancy
	Heterotopic Pregnancy
	Involution of the Placental Site
	Subinvolution of Placental Site
	Placental “Polyps”
	Placental Site Nodule
	References
14: The Placenta Accreta Spectrum
	Pathology of PAS
		Occult Placenta Accreta
		Classification and Reporting Guidelines
	References
15: Anatomy and Pathology of the Placental Membranes
	Overview
		Composition of the Fetal Membranes
		Development
		Amnion
	Amnionic Epithelium: Different Cell Types and Cell Degeneration
	Cytological and Functional Aspects of the Amnionic Epithelium
		Amnionic Fluid
		Chromosomal Determinations
	Glycogen and Cellular Changes in the Amnion
		Glycogen
		Cellular Changes in the Amnion
			Squamous Metaplasia
	Amnionic Mesoderm
		Other Issues Related to the Amnion
		Clinical and Research Applications
	Chorion Laeve
	Intermediate (Spongy) Layer
	Chorionic Mesoderm
	Trophoblast Layer
	Decidua
	Tensile Properties of the Membranes
	Pathology of the Membranes
		Preterm Rupture of the Membranes
		Cysts and Hemorrhage
		Amnionic Fluid Embolism
			Vernix Dissection
		Meconium
		Gastroschisis and Amniotic Membranes
		Epidermolysis Bullosa and Amniotic Epithelium
		Amnion Nodosum
		Amnionic Bands and Limb-Body Wall Complex
		Extramembranous Pregnancy
	Circumvallate Placenta (Extrachorial, Circummarginate Placentas)
	References
16: Anatomy and Pathology of the Umbilical Cord
	Development
	Amnionic Epithelium
	Wharton’s Jelly
	Structure of Umbilical Vessels
		Innervation
		Contractility of Umbilical Vessels
		Hyrtl Anastomosis, False Knots, and Hoboken Nodes
		Allantois
		Omphalomesenteric Duct
	Spiral Turns of the Cord (“Twist”)
	Length of the Cord
		Abnormal Length and Nuchal Cord
		Site of Cord Insertion
		Furcate Cord Insertion
		Velamentous Cord Insertion
	Cysts and Edema
	Single Umbilical Artery
	Placental Transfusion
	Knots
	False Knots
	Strictures
	Rupture
	Hematoma
	Varices/Aneurysms
	Myonecrosis of the Umbilical Blood Vessels
	Thrombosis of the Umbilical Vessels
	Tumors of the Umbilical Cord
	References
17: Placental Shape Aberrations
	Abnormal Shapes (“Errors in Outline”)
	Bilobate and Succenturiate Placenta
	Placenta Fenestrata
	Placenta Membranacea
	Placenta Previa
	References
18: Multiple Pregnancies
	Zygosity
	Causes of Multiple Births and Incidence
	Third Type of Twin
	Twinning Incidence
	Superfetation and Superfecundation
		The Placenta in Zygosity
	Vascular Anatomy of Twin Placentas
	Twin-Twin Transfusion Syndrome
		Twin-Twin Transfusion Syndrome
	Twin Anemia Polycythemia Sequence
	Monoamniotic Monochorionic Twin Placenta
	Diamniotic-Monochorionic Twin Placenta
	Diamniotic, Dichorionic Twin Placenta
	Fetus Papyraceus and Vanishing Twin Phenomenon
	Acardiac Twins
	Conjoined Twins
	Sacrococcygeal Teratoma and Epignathus
	Cytogenetics and “Heterokaryotypic MZ Twins”
		Chimerism and Mosaicism
	Whole-Body Chimerism
	Triplets and Higher Multiple Births
	Twins in Abortion and Ectopic Pregnancy
	Morbidity and Mortality
	Hormones in Twin Pregnancy
	References
19: Maternal Vascular Malperfusion and Associated Maternal Diseases
	Maternal Vascular Malperfusion
		Grading and Patterns of Maternal Vascular Malperfusion
		Clinical Consequences of Maternal Vascular Malperfusion
		Normal Uterine Circulation and Gestational Adaptations
		Pathophysiology of Maternal Vascular Malperfusion
		Spiral Artery Remodeling and Updates in Other Processes Enabling Placental Development
	Placental Manifestations of Maternal Vascular Malperfusion
		Placenta Hypoplasia
		Placental Infarction
		Retroplacental Hemorrhage/Hematoma, Placental Abruption, and Marginal Abruption
			Retroplacental Hemorrhage
			Marginal Hematoma/Abruption
		Villous Maturation Disorders
			Distal Villous Hypoplasia
			Accelerated Villous Maturation and Syncytial Knots (Tenney-Parker Change)
		Decidual Arteriopathy
			Features of Decidual Arteriopathy
		Other Findings
	Hypertensive Disorders in Pregnancy Including Preeclampsia and HELLP Syndrome Spectrum
	Lupus Erythematosus and Lupus Anticoagulant/Antiphospholipid Syndrome
		Systemic Lupus Erythematosus
		Antiphospholipid Syndrome/Lupus Anticoagulant Syndrome
	Conclusions
	References
20: Maternal Diabetes and Obesity
	Diabetes Mellitus and Obesity During Pregnancy
		Definitions
		Consequences of Diabetes Mellitus and Obesity on Maternal and Fetal Health
		Pathophysiology of Diabetes and Obesity in Pregnancy
	Diabetes, Obesity, and Placental Pathology
		Placental Development
		Placental Pathology: Overview of Current Strengths and Limitations in Knowledge
		First Trimester in Diabetes and Obesity
		Late Second and Third Trimester Macroscopic Features of the Placenta Exposed to Diabetes Mellitus and Obesity
		Late Second and Third Trimester Histological Features of the Placenta Exposed to Diabetes Mellitus and Obesity
		Immunohistochemistry of the Placenta Exposed to Diabetes Mellitus
		Ultrastructural Features of the Third Trimester Placenta Exposed to Diabetes Mellitus
	References
21: Other Maternal Disorders Complicating Pregnancy
	Introduction
	Autoimmune and Connective Tissue Diseases
		Scleroderma
		Dermatomyositis and Polymyositis
		Ehlers–Danlos Syndrome
		Rheumatoid Arthritis
	Vasculitis
	Renal, Liver, and Heart Disease
		Renal Disease
		Liver Disease
		Heart Disease
	Hematological Disorders Including Inherited Thrombophilia
		Sickle Cell Disease
		ß-Thalassemias
		Idiopathic Thrombocytopenia and Evans Syndrome
		Thrombotic Thrombocytopenic Purpura
		Neonatal Thrombocytopenia
		Von Willebrand Disease and Factor VII Deficiency
		Hereditary Hemorrhagic Telangiectasia
		Hereditary Thrombophilia
		Folate Deficiency
		Anemia and High Altitude
	Endocrine Disorders
		Thyroid Diseases
		Cushing’s Disease
		Diabetes Insipidus
		Other Endocrine Disorders
	Maternal Neoplasms
		Non-hematological Neoplasms
			Malignant Melanoma
			Fetal Giant Pigmented Nevi
			Breast Cancer
			Other Non-hematological Malignancy
		Hematological Malignancies
		Sarcoidosis
	Dermatoses of Pregnancy
	Other Maternal Diseases in Pregnancy
	Drug Use: Illicit and Therapeutic
		Alcohol (Ethanol)
		Illicit Drugs
		Therapeutic Drugs in Pregnancy
	Cigarette Smoking and Wildfire (Bushfire) Smoke
	Irradiation
	References
22: Fetal Vascular Malperfusion
	Introduction
	Terminology
	Placental Surface Vessels
		Thrombosis of the Placental Vascular Tree
	Etiology
		Maternal Conditions Predisposing to FMV
		Fetal Conditions Predisposing to FVM
		Umbilical Cord Mechanical Flow Restrictions
		Placental Conditions with Increased Risk of Fetal Vascular Malperfusion
	Gross Examination
	FVM Histology
		Patterns of FVM
		Grading
		Characteristics of the Individual Components of FVM
		Differential Diagnosis
	Clinical Complications of FVM
	Recurrence Risk
	References
23: Erythroblastosis Fetalis, Hydrops Fetalis, and Transplacental Hemorrhage
	Hydrops Fetalis
	Hydrops Due to Fetal Anemia
		Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn)
			Evaluation, Monitoring, and Treatment of HDFN
			Placental Pathology of HDFN
			Fetal Pathology of HDFN (Erythroblastosis Fetalis)
		Nonimmune Causes of Fetal Hemolytic Anemia Which May Result in Hydrops Fetalis
		Anemia Due to Diminished Erythropoiesis
			α-Thalassemia and Hemoglobin Bart’s Hydrops Fetalis Syndrome
			α-Thalassemia Hemoglobin H Disease and Other Hemoglobinopathies
			Other Causes of Ineffective Hematopoiesis and Hydrops Fetalis
		Anemia Due to Fetal Hemorrhage, Including Fetal-Maternal Hemorrhage
			Diagnosis of Chronic Fetal-Maternal Hemorrhage
			Placental and Fetal Pathology of Fetal-Maternal Hemorrhage
		Infection and Hydrops, with and Without Anemia
	Chromosomal Abnormalities and Fetal Hydrops
	Hydrops Due to Congenital Heart Disease
	Hydrops Due to Cardiac Arrhythmias
	Hydrops Due to Nephrotic Syndrome
	Congenital Malformations Associated with Hydrops Fetalis
	Hydrops Due to Chorangioma and Fetal Neoplasms
		Fetal Solid Tumors Associated with Hydrops Fetalis
		Fetal Circulating Tumors with Hydrops
	Fetal Myeloid Proliferations and Histiocytoses with Hydrops
	Gestational Alloimmune Liver Disease and Hydrops
	Metabolic Disease and Fetal Hydrops
	Unexplained Fetal Hydrops and Whole Exome Sequencing
	Clinical Algorithm for the Investigation of Nonimmune Hydrops Fetalis
	Maternal Changes in Fetal Hydrops
	References
24: Fetal Storage Disorders
	Inborn Errors of Metabolism and Placental Studies
	Closing Comment
	References
25: Infectious Diseases
	Chorioamnionitis
		Macroscopic Appearance
		Microscopic Appearance and Biochemical Features
		Necrotizing Funisitis
	Specific Microorganisms
		Bacterial
			Neisseria gonorrhoeae
			Group B Streptococci
			Group A β-Hemolytic Streptococci
			Streptococcus pneumoniae
			Haemophilus influenzae
			E. coli and Other Gram-Negative Bacilli
			Salmonella typhi
			Shigella sonnei
			Clostridium perfringens
			Diphtheroids
			Fusobacterium
			Bacteroides fragilis
			Campylobacter (Vibrio) fetus
			Streptobacillus moniliformis
			Gardnerella (Haemophilus, Corynebacterium) vaginalis
			Francisella tularensis
			Brucella
			Listeriosis
			Actinomyces
			Mycoplasma hominis and Ureaplasma urealyticum
			Chlamydia trachomatis and C. psittaci
			Bacterial Vaginosis
			Burkholderia pseudomallei
	Mycobacterial Infections
		Leprosy
		Tuberculosis
	Viral Infections
		Cytomegalovirus Infection
		Herpes Simplex Virus Infection
		Varicella (Chickenpox)
		Epstein-Barr Virus
		Smallpox, Vaccinia, and Alastrim (Variola Minor)
		Parvovirus B19
		Enteroviruses
		Influenza, Mumps, and Rabies
		Hepatitis
		Rubella (German Measles) and Other Viral Infections
		Rubeola: Measles
		Human Immunodeficiency Virus (HIV) Infection
		Dengue, Ebola, West Nile Virus, and Lymphocytic Choriomeningitis Virus
		Zika Virus
		Novel Coronavirus (2019-nCoV)
	Spirochetes
		Syphilis
		Other Spirochetal Diseases
	Fungal Infections
		Candida
		Coccidioides
		Cryptococcosis and Blastomycosis
	Parasitic Infections
		Toxoplasmosis
		Kala-Azar
		Chagas Disease
		Babesiosis, Trichomoniasis, Rickettsia, and Ehrlichia
		Malaria
		Other Parasitic Infections
	References
26: Placental Disorders of Uncertain Etiology
	Chronic Inflammatory Lesions of the Placenta
		Overview
		Chronic Villitis (Including CVUE and Basal CV)
		Chronic Intervillositis (CIV)
		Chronic Chorioamnionitis (CC)
		Chronic Deciduitis (CD)
		Eosinophilic/T-Cell Chorionic Vasculitis (ETCV)
		Chorionic Histiocytic Hyperplasia (CHH)
	Perivillous Fibrinoid Deposition (PVFD)
		Overview
		Maternal Floor Infarction (MFI)
		Massive (or Transmural) Perivillous Fibrinoid Deposition (MPFD)
		Other Patterns of Perivillous Fibrinoid Deposition
	Placental Thrombi
		Intervillous, Subchorionic, and Intramembranous Thrombi
			Intervillous Thrombus with Hematoma
			Intervillous Thrombus with Adjacent Infarction
			Intramembranous Thrombus with Hemosiderin Deposition
	Chorionic Cysts
		Overview
			Chorionic Septum (Skeleton of Placenta)
			Extravillous Trophoblast
		Cysts in Fetal Surface, Septum, and Membranes
	Laminar Necrosis of the Membranes (LMN)
	References
27: Placental Mesenchymal Dysplasia
	Introduction and Historical Context
	Macroscopic Findings
	Histopathologic Features
	Clinical Associations
	Differential Diagnosis
		Partial Hydatidiform Mole (PMH)
		Complete Hydatidiform Mole
		Multiple Subchorionic Cystic Thrombohematomas
	Molecular Pathology and Pathogenesis
		Androgenetic-Biparental Mosaicism/Chimerism (ABM/C)
		Isolated Alterations of the 11p15.5 BWS Chromosomal Locus
		Mosaic Disruption of the Maternal GRB10 Allele
		Miscellaneous Genetic Findings
	Molecular Diagnosis
	References
28: Molar Pregnancies
	Introduction
	Epidemiology of Hydatidiform Moles
	Genetics of Moles
	Recurrent Hydatidiform Moles
	Complete Hydatidiform Moles
	Partial Hydatidiform Mole
	Early Hydatidiform Moles
	P57 Immunohistochemistry
	Short Tandem Repeat Genotyping and Other Molecular Tests
	Histopathology Associated with Moles
	Deportation
	Invasive Mole
	Therapy
	Ectopic Moles
	Hydatidiform Mole and Coexistent Fetus
	Hydatidiform Mole with Twin Gestation
	Mimics of Mole
	References
29: Gestational Trophoblastic Neoplasms
	Introduction
	Gestational Choriocarcinoma
		Epidemiology and Risk Factors
		Pathogenesis
		Clinical Presentation
		Macroscopic Pathology
		Microscopic Pathology
		Ancillary Studies
		Early Forms of Gestational Choriocarcinoma
		Differential Diagnosis
		Clinicopathological Correlations
	Placental Site Trophoblastic Tumor
		Epidemiology and Risk Factors
		Clinical Presentation
		Pathogenesis
		Macroscopic Pathology
		Microscopic Pathology
		Ancillary Studies
		Differential Diagnosis
		Clinicopathology Correlation
	Epithelioid Trophoblastic Tumor
		Epidemiology and Risk Factors
		Clinical Presentation
		Pathogenesis
		Macroscopic Pathology
		Microscopic Pathology
		Ancillary Studies
		Differential Diagnosis
		Clinicopathology Correlations
	Mixed Trophoblastic Tumors
	Exaggerated Placental Site (EPS) Reaction
	Placental Site Nodule (PSN) and Atypical Placental Site Nodule (APSN)
	References
30: Chorangiotic Lesions, Benign Tumors, and Heterotopias
	Chorangiomas: Pathogenesis
	Chorangioma: Gross and Microscopic Pathology
	Chorangioma: Clinical Features
	Chorangioma: Prognosis
	Chorangioma Variants
		Chorangiomatosis
		Chorangiosis
		“Heterotopias,” Nodules, and Other Benign Tumors
	References
31: Innovations in Placental Pathology
	Introduction
	Molecular Characterization of the Human Placenta During Normal Development and Disease
		Genome-Wide RNA Profiling of Placental Cells and Tissues in Normal Development
		Genome-Wide RNA Profiling of Placental Tissues in the Setting of Complicated Pregnancies
		Cell Type–Specific Methods of Placental Profiling
		Other Methods of Profiling, Limitations, and Future Directions
	Circulating Markers of Placental Development and Function
		Utility of Molecular “Clocks” in the Management of Pregnancy
			Prediction of Timing of Parturition
			Determination of Gestational Age
			The Performance of Pregnancy Biomarkers Is Dependent on Gestational Age
		Circulating Biomarkers
			Steroid Hormones
			Proteins
				Circulating Protein Biomarkers in Clinical Use
				Exploratory Protein Biomarkers
			Cell-Free DNA
			mRNAs
			miRNAs
		Placental Extracellular Vesicles (EVs)
			Placental Extracellular Vesicle Cargo
				Proteins
				Lipids
				Nucleic Acids
			Placental EV Functions
			Limitations and Future Directions
	Modeling the Human Placenta In Vitro
		2D Models for Study of Human Trophoblast Differentiation
			Pluripotent Stem Cell-Based Models
			Expanded Potential Stem Cells
			Human Trophoblast Stem Cells
		3D Models of the Human Placenta
			Placental Organoids
			Placenta-on-a-Chip
			STEMbryo Models
		Conclusion and Future Directions
	Emerging Technologies/Techniques for Placental Evaluation During and After Pregnancy
		Macroscopic Imaging
		Microscopic Imaging
			Immunohistochemistry and In Situ Hybridization
			Digital Spatial Profiling
			3D Microscopic Imaging
	References
32: Imaging of Placental Pathology
	Introduction to Placental Imaging
		History
		Ultrasound
			2D Technique for Placental Anatomy
			Doppler Imaging for Blood Flow Evaluation
			3D and 4D Ultrasound for Volumetric Evaluation
		Safety of Ultrasound
		MRI
		Safety of the MRI in Pregnancy
	Physiology Assessed by Ultrasound Examination
		Normal Development
	(Common) Placental Lesions
		Gestational Trophoblastic Disease (Chap. 28)
		MVM (Chap. 13)
		Parenchymal Infarction
		Retro Placental Hemorrhage/Abruption
		Intervillous Thrombus/Placental Lake
		Subchorionic Thrombohematoma (Breus’ Mole)
		Small Placenta (Placenta Hypoplasia)
		Circumvallata
		Other Placental Parenchymal Abnormalities (Chaps. 16 and 29)
			Placenta Mesenchymal Dysplasia (PMD)
			Chorangioma
	Twin Pregnancies: Twin-to-Twin Transfusion Syndrome (TTS)/Twin Anemia Polycythemia Syndrome (TAPS) (Chap. 18)
		Placentas in Selective Fetal Growth Restriction (sFGR)
	Placenta Accreta Spectrum (Chap. 14)
		Ultrasound
		MRI
		Placenta Previa, Membranous Vessels, Vasa Previa (Chap. 17)
			Ultrasound
			MRI
		Umbilical Cord
			Umbilical Cord Development and Sonography
	Pathology of the Umbilical Cord (Chap. 27)
		Abnormality in Number of Vessels
		Persistent Right Umbilical Vein
		Umbilical Vein Varix
		Cord Insertion Abnormalities
		Cord Coiling Abnormalities (Both Hyper- and Hypo-Coiling)
		Cord Tumors
	Novel and Potential Future Placental Imaging Modalities
		MicroCT
			Photoacoustic Imaging
	References
33: Assisted Reproductive Technologies
	Introduction
	Placental Implantation Disorders
		Placenta Previa
		Placenta Accreta
	Umbilical Cord Insertion
	Placental Weight
	Placental Vascularization
		Villous Vasculature
		Maternal Vascular Malperfusion
		Fetal Vascular Malperfusion and Distal Villous Immaturity
		3D Vascular Placental Modeling
	Placental Angiogenic Markers
	Placental Metabolism
	Placental Biomarkers
	Cell-Free Fetal DNA
	Genetic Aneuploidies
	Placenta Immunology
	Conclusion
	References
34: Legal Considerations
	Acute Intrapartum Processes
	Inflammation
	Meconium
	Fetal Vascular Malperfusion
	Maternal Vascular Malperfusion
	Other Pathology
	References
Appendix
	Normative Values and Tables
References
Index