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Placental Pathology and Implications for Fetal Medicine

Key Points Pathological examination of the placenta may provide useful information regarding the underlying mechanisms of a range of pregnancy complications that may guide future management and improve understanding of disease pathophysiology. Placentas should be submitted for examination by specialist pathologists in all complicated pregnancies according to national and local guidelines. Interpretation of the clinical significance of many placental histologic changes remains difficult, and novel approaches…

Placental Function in Maternofetal Exchange

Key Points Maternofetal exchange across the placenta provides the solutes and water needed for fetal development and growth and enables the waste products of fetal metabolism to be transferred to the maternal circulation. The placental exchange barrier consists of the syncytiotrophoblast epithelial cell layer, basement membrane and connective tissue, and the fetal capillary endothelium. All contribute to the barrier, but the syncytiotrophoblast is probably the most…

Development of the Placenta and Its Circulation

Key Points The development and structure of the human haemochorial placenta The development of the uteroplacental and fetoplacental circulations Introduction This chapter highlights areas in which developmental placental biology directly impinges on clinical practice. Pregnancies complicated by the pathologies of stillbirth, severe preeclampsia and intrauterine growth restriction (IUGR), especially those that deliver before 34 weeks, are associated with significant gross and microscopic placental pathology (covered in…

The Immunology of Implantation

Key Points The extravillous pathway of trophoblast differentiation is essential for the development of the fetoplacental blood supply. As they invade into the maternal decidua, extravillous trophoblast cells express a unique array of human leukocyte antigen (HLA) class I molecules, HLA-G, HLA-E and HLA-C. The main population of maternal immune cells in the decidua during placentation are uterine natural killer (uNK) cells. Interaction between polymorphic killer…

Early Pregnancy Failure

Key Points Miscarriage and ectopic pregnancy are the commonest early pregnancy complications. The diagnosis of early pregnancy failure should be made on transvaginal ultrasound scan given its high diagnostic sensitivity and specificity. Sporadic chromosomal abnormalities are the overriding cause of miscarriage. Early pregnancy failure should be managed in a dedicated early pregnancy unit. Management of early pregnancy failure can be expectant, medical or surgical depending on…

Teratology

Key Points At baseline, each pregnancy has a 2% to 4% risk for a congenital anomaly diagnosed at birth. The adverse effects of exposures on embryo-fetal development depend on the agent, dose, and timing of exposure. Resources are available for up-to-date information on specific exposures during pregnancy. Introduction A teratogenic exposure is one that has the ability to interfere with normal development of the fetus. Some…

Staging Embryos in Development and the Embryonic Body Plan

Key Points This chapter presents the concepts and timing of embryonic development. The problems of using staging systems to describe a continuous process are discussed. The method behind staging of animal development is presented. A revision of the timing of early human development is presented. Embryonic and obstetric stages of development are presented. The embryonic body plan, main embryological stages and their approximate times are presented.…

Cellular Mechanisms and Embryonic Tissues

Key Points This chapter describes the tissue types present in early embryos and the interactions between these tissues. The membrane systems and cytoskeletal elements within a typical cell are reviewed. Early embryos contain only epithelial and mesenchymal populations. Each tissue type produces specialised extracellular matrix molecules and proteins which permit and encourage tissue interactions. Specific interactions between developing epithelia and mesenchyme are presented, and the common…

Early Concepts and Terminology

Key Points This chapter considers the language used within embryological research and how it is evolving. The terms used to describe embryos, cells and tissues derive from the social constructs of science during the time they were created. Newer terms have been added as scientific methods have increased, although there may not be a consensus on the definition of some terms. The application of computer sciences…

Genetic Variants and Neonatal Disease

Introduction Infants with complex phenotypes and infants born at early gestational age are two of the most challenging groups of patients cared for in neonatal intensive care units (NICUs). Since the initial reports of the sequence of the human genome, , clinicians have hoped that the “genomic revolution” would lead to increasing likelihood of diagnoses for infants with complex phenotypes and identification of common variants associated…

Pathophysiology of Genetic Neonatal Disease

Introduction Genetic diseases are a leading cause of neonatal morbidity and mortality. Estimates of the incidence of genetic disease in neonates admitted to intensive care units have historically been based on targeted genetic testing of cohorts selected to have a high pretest probability, such as those with multiple congenital anomalies. However, the neonatal presentation of many thousands of genetic diseases overlaps with common, typically nongenetic conditions…

Pathophysiology of Chorioamnionitis: Host Immunity and Microbial Virulence

Introduction Approximately 1% to 10% of all births in the United States are complicated by chorioamnionitis, but the incidence varies significantly by study population, gestational age at presentation, and diagnostic criteria. Histologic chorioamnionitis is a pathologic term that refers to an influx of maternal inflammatory cells (neutrophils, macrophages, and T cells) into the placental membranes. The term clinical chorioamnionitis is used when overt signs of intraamniotic…

Pathophysiology of Preterm Birth

Introduction Although clinically managed as if it were a single disease, preterm birth is increasingly recognized as a syndrome secondary to multiple causative mechanisms and etiologies. In this chapter, we discuss the epidemiology of preterm birth, the endocrinology and physiology of parturition, and current practice in prediction and prevention of preterm labor (PTL). Epidemiology of Preterm Birth PTL is defined as the onset of labor before…

Pathophysiology of Preeclampsia

Introduction Preeclampsia is a multiorgan disease specific to pregnancy most often characterized by hypertension and proteinuria occurring after 20 weeks gestation. It is among the most common medical complication of pregnancy and is a leading cause of maternal/fetal morbidity and mortality highest in the developing nations. Although the eclamptic convulsion may have been recognized 4000 years ago and the term “eclampo” signifying “lightning” used to describe…

Pathophysiology of NeuralTube Defects

Acknowledgments The authors’ research on neurulation and NTDs is supported by grants from the Medical Research Council, Wellcome, NC3Rs, Sparks, Newlife, Action Medical Research, the Bo Hjelt Spina Bifida Foundation, Great Ormond Street Hospital Children’s Charity, and the National Institute for Health Research, Biomedical Research Centre, at Great Ormond Street Hospital for Children, NHS Foundation Trust, and University College London. Introduction Neural tube defects (NTDs) are…

Pathophysiology of Neonatal Acute Bacterial Meningitis

Bacterial Meningitis Meningitis is a life-threatening infection of the central nervous system (CNS) that affects the pia mater, the arachnoid, and the subarachnoid space. The microorganisms can activate the host immune response, and both inflammatory mediators and microorganisms can break down the blood-brain barrier, allowing the influx of fluid and solutes into the brain, triggering the brain edema. This infection is a significant cause of morbidity…

Pathophysiology of Neonatal Hypoxic-Ischemic Brain Injury

Acknowledgment This work was partially supported by NIH grants NS 100850, NS 099109, NS 088197. Introduction The pathophysiology of neonatal hypoxic-ischemic (HI) brain injury or hypoxic-ischemic encephalopathy (HIE) defines the response of central nervous system (CNS) to ischemia and reperfusion. Neonatal HI brain injury usually occurs due to a collapse of systemic circulation at or near birth or during the neonatal period. If not interrupted, HI…

Pathophysiology of Retinopathy of Prematurity

Acknowledgments The authors thank Maria Isabel Gomez for her expert help in organization and formatting the manuscript. Introduction Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide and is increasing in emerging countries able to save premature infants but without resources to provide optimal care. , ROP, first identified as retrolental fibroplasia (RLF) in the United States, was reported by Terry as…

Pathophysiology of Edema

Acknowledgment The editors thank David P. Carlton for his excellent work on this chapter in the fifth edition. It has been republished here essentially unchanged. General Considerations Edema is the clinical term used to describe excessive fluid accumulation in the adventitial tissue spaces of the body. Excess fluid accumulates when the net rate of transvascular fluid filtration from the microcirculation is exceeded by the rate of…

Pathophysiology of Neonatal AcuteKidney Injury

Introduction In recent years, there has been an exponential expansion of our understanding of the epidemiology and adverse outcomes associated with neonatal acute kidney injury (AKI). From a multitude of single-center studies and in the recent multicenter Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, AKI is now known to be associated with several adverse outcomes (increased length of stay, length of mechanical…