Genetic Disorders and the Fetus

1 Genetic Counseling: Prelude to Prenatal Diagnosis.- 1. Introductory Perspectives.- 2. Prerequisites for Genetic Counseling.- 2.1. Introduction.- 2.2. Prerequisites for Genetic Counseling.- 3. Guiding Principles in Genetic Counseling.- 3.1. Accurate Diagnosis.- 3.2. Nondirective Counseling.- 3.3. Concern for the Individual.- 3.4. Truth in Counseling.- 3.5. Confidentiality and Trust.- 3.6. Timing of Genetic Counseling.- 3.7. Parental Counseling.- 3.8. Education.- 4. Genetic Counseling As a Prelude to Prenatal Diagnosis.- 4.1. Informed Consent.- 4.2. Carrier Detection.- 4.3. Special Cases.- 4.4. Special Considerations.- 5. Counseling for "Environmental" Exposures or Maternal Illness.- 6. Psychological Aspects of Genetic Counseling.- 7. Efficacy of Genetic Counseling.- 8. References.- 2 Amniocentesis.- 1. Introduction.- 2. Prerequisites.- 3. Technique of Amniocentesis.- 3.1. Timing.- 3.2. Surgical Aspects.- 3.3. Ultrasound prior to Amniocentesis.- 3.4. Ultrasound Concurrent with Amniocentesis.- 3.5. Multiple Gestations.- 3.6. Selective Feticide.- 3.7. Rh Isoimmunization in Amniocentesis.- 3.8. Discolored Amniotic Fluid.- 4. Safety of Genetic Amniocentesis.- 4.1. Maternal Risks.- 4.2. Fetal Risks.- 4.3. Conclusions Regarding Risks.- 5. References.- 3 Amniotic Fluid.- 1. Introduction.- 2. Amniotic Fluid Dynamics.- 2.1. Formation and Circulation.- 2.2. Volume.- 2.3. Origin.- 3. Biochemical and Other Characteristics of Amniotic Fluid.- 3.1. Proteins.- 3.2. Lipids.- 3.3. Enzymes.- 3.4. Amino Acids.- 4. The Disaccharidases.- 4.1. Introduction.- 4.2. Origin of Amniotic Fluid Disaccharidases.- 4.3. Development of Amniotic Fluid Disaccharidases.- 4.4. Clinical Use of Amniotic Fluid Disaccharidases.- 5. Miscellaneous Biochemical Constituents and Other Characteristics of Amniotic Fluid.- 5.1. Trace Elements.- 5.2. Creatinine.- 5.3. Blood Group Substances.- 5.4. Immunoglobulins.- 6. Antibacterial Activity of Amniotic Fluid.- 6.1. Bacteriostatic Effect.- 6.2. Isolation of Infectious Agents.- 7. Hormones.- 8. References.- 4 Amniotic Fluid Cell Culture.- 1. Introduction.- 2. Amniotic Fluid Cell Types.- 2.1. Cellular Contents of Native Fluids.- 2.2. Colony-Forming Cells: Morphology and Nomenclature.- 2.3. Biochemical Characterization.- 2.4. Intermediate Filament System.- 3. Origin of Colony-Forming Cell Types.- 4. Culture Technique.- 5. Enhancement of Amniotic Fluid Cell Growth.- 5.1. Enrichment Techniques.- 5.2. Growth on Extracellular Matrix Surface.- 5.3. Reduction of Oxygen Supply.- 5.4. Serum Testing.- 5.5. Defined Growth Factor Supplements.- 6. Culture Hazards.- 6.1. Syringe Toxicity.- 6.2. Contamination.- 6.3. Mycoplasma.- 6.4. Plasticware and Media Storage.- 6.5. Incubator Failure.- 7. Perspective.- 8. References.- 5 Prenatal Diagnosis of Chromosome Abnormalities.- 1. Introduction.- 2. Incidence of Chromosome Abnormalities.- 2.1. Data from Live Births.- 2.2. Midtrimester Amniocentesis Data.- 2.3. Data on Spontaneous Abortuses.- 2.4. Data on Induced Abortuses.- 2.5. Data on Stillbirths and Neonatal Deaths.- 3. Indications.- 3.1. Advanced Maternal Age.- 3.2. Advanced Paternal Age (A Disputable Indication).- 3.3. Carrier of a Balanced Structural Rearrangement.- 3.4. Previous Child with Chromosome Abnormalities.- 3.5. Antenatal Sex Determination for Prenatally Undiagnosable X-Linked Disorders.- 3.6. Other Indications.- 4. Technical Considerations for Prenatal Cytogenetic Diagnosis.- 5. Problems and Pitfalls.- 5.1. Chromosome Mosaicism.- 5.2. Maternal Cell Contamination.- 5.3. Chromosome Polymorphisms.- 5.4. De Novo Structural Rearrangement.- 5.5. Supernumerary Marker Chromosomes.- 5.6. Tetraploidy.- 5.7. Problems in Cell Cultures.- 5.8. Twin Pregnancy.- 5.9. Errors in Prenatal Cytogenetic Diagnosis.- 6. Genetic Counseling in Prenatal Cytogenetic Diagnosis.- 7. Concluding Remarks.- 8. References.- 6 The Prenatal Diagnosis of the Fragile X Syndrome.- 1. Introduction.- 1.1. First Reports of the Marker or Fragile X Chromosome.- 1.2. Characterization of the Fragile X Induction System.- 1.3. The Estimated Incidence/Prevalence of the Fragile X Syndrome.- 1.4. The Fragile X Phenotype.- 1.5. Female Carriers.- 1.6. Male Carriers.- 1.7. Histiotypic Distribution of Fragile X.- 2. Worldwide Experience in Fragile X Prenatal Testing.- 2.1. Tissues Used to Detect Positive Cases.- 2.2. Fragile X Induction Systems.- 3. The 5-Fluorodeoxyuridine Fragile X Induction System and Its Effect on Fragile X Frequency and Mitotic Index.- 3.1. Introduction.- 3.2. Temporal and Cell Density Effects on the 5-Fluorodeoxyuridine Fragile X Induction System.- 4. False-Negative and False-Positive Prenatal Fragile X Diagnoses.- 5. The Future.- 5.1. General.- 5.2. DNA Restriction Fragment Length Polymorphisms Can Complement Cytogenetic Fragile X Pre- and Postnatal Diagnoses.- 6. Conclusion.- 7. References.- 7 Disorders of Lipid Metabolism.- 1. Introduction.- 2. GM1 Gangliosidoses.- 3. GM2 Gangliosidoses.- 4. Fabry Disease (Angiokeratoma Corporis Diffusum).- 5. Gaucher Disease.- 6. Metachromatic Leukodystrophy and Multiple Sulfatase Deficiency.- 7. Krabbe Disease (Globoid Cell Leukodystrophy).- 8. Niemann-Pick Disease.- 9. Farber Disease (Acid Ceramidase Deficiency).- 10. Wolman Disease and Cholesterol Ester Storage Disease.- 11. Adrenoleukodystrophy.- 12. Refsum Disease (Phytanic Acid Storage Disease).- 13. Neuronal Ceroid-lipofuscinosis (Batten Disease).- 14. Lipoprotein-Associated Disorders.- 15. References.- 8 Disorders of Mucopolysaccharide Metabolism.- 1. Hurler Syndrome (?-L-Iduronidase Deficiency: Mucopolysaccharidosis IH).- 2. Scheie Syndrome (?-L-Iduronidase Deficiency: Mucopolysaccharidosis IS).- 3. Hurler-Scheie Compound Disease (?-L-Iduronidase Deficiency: Mucopolysaccharidosis IH/S).- 4. Hunter Syndrome (Iduronate Sulfatase Deficiency: Mucopolysaccharidosis II).- 5. Sanfillipo Syndrome (Mucopolysaccharidosis III).- 6. Morquio Syndrome (Mucopolysaccharidosis IV).- 7. Maroteaux-Lamy Syndrome (Mucopolysaccharidosis VI).- 8. ?-Glucuronidase Deficiency (Mucopolysaccharidosis VII).- 9. References.- 9 Disorders of the Metabolism of Amino Acids and Related Compounds.- 1. Introduction.- 2. Urea Cycle Disorders.- 2.1. N-Acetylglutamate Synthetase Deficiency.- 2.2. Carbamylphosphate Synthetase Deficiency.- 2.3. Ornithine Carbamyltransferase Deficiency.- 2.4. Argininosuccinate Synthetase Deficiency (Citrullinemia).- 2.5. Argininosuccinate Lyase Deficiency (Argininosuccinic Aciduria).- 2.6. Arginase Deficiency (Hyperargininemia).- 2.7. Therapy for Urea Cycle Disorders.- 3 Disorders of Ornithine Metabolism.- 3.1. Hyperornithemia, Hyperammonemia, and Homocitrullinuria (HHH Syndrome).- 3.2. Ornithine Aminotransferase Deficiency Associated with Gyrate Atrophy of the Choroid and Retina.- 4 Disorders of Lysine Metabolism.- 4.1. Periodic Hyperlysinemia with Hyperammonemia.- 4.2. Familial Hyperlysinemia.- 4.3. Saccharopinuria.- 5 Disorders of Sulfur Amino Acid Metabolism.- 5.1. Hypermethioninemia.- 5.2. Homocystinuria Due to Cystathionine ?-Synthase Deficiency.- 5.3. ?-Cystathionase Deficiency.- 5.4. Sulfite Oxidase Deficiency.- 5.5. Combined Sulfite Oxidase Deficiency and Xanthine Oxidase Deficiency (A Defect in Molybdenum Metabolism).- 6 Disorders of Phenylalanine Metabolism.- 6.1. Phenylketonuria.- 6.2. Hyperphenylalaninemia Due to Tetrahydrobiopterin Deficiency.- 7 Disorders of Tyrosine Metabolism.- 7.1. Hereditary Tyrosinemia Type I (Hepatorenal Type).- 7.2. Other Types of Tyrosinemia.- 8 Nonketotic Hyperglycinemia.- 9 Disorders of Branched-Chain Amino Acid Metabolism.- 9.1. Hypervalinemia.- 9.2. Hyperleucine-isoleucinemia.- 9.3. Maple Syrup Urine Disease.- 10 Disorders of Organic Acids.- 10.1. Introduction.- 10.2. The ?-Ketothiolase Deficiencies.- 10.3. Propionic Acidemia.- 10.4. Methylmalonic Acidemia.- 10.5. Isovaleric Acidemia.- 10.6. Biotin-Resistant ?-Methylcrotonylglycinuria.- 10.7. 3-Methylglutaconic and 3-Methylglutaric Aciduria.- 10.8. 3-Hydroxy-3-methylglutaryl-CoA Lyase Deficiency.- 10.9. 3-Hydroxyisobutyl-CoA Deacylase Deficiency.- 10.10. Glutaric Acidemia Type I.- 10.11. Multiple Acyl-CoA Dehydrogenation Disorders (Glutaric Aciduria Type II, Ethylmalonic-adipic Aciduria, Dicarboxylic Aciduria).- 10.12. 4-Hydroxybutyric Aciduria.- 10.13. Mevalonic Aciduria.- 11. Disorders of the Peroxisomes.- 12. Miscellaneous Disorders of Amino Acid Metabolism.- 12.1. Prolidase Deficiency.- 12.2. Disorders of Proline Metabolism.- 12.3. Histidinemia.- 12.4. Disorders of Renal Amino Acid Transport.- 13. References.- 10 Prenatal Diagnosis of Disorders of Carbohydrate Metabolism.- 1. Introduction.- 2. Observations and Comments on 39 Metabolic Disorders.- 3. Conclusion.- 4. References.- 11 X-Linked Diseases and Disorders of the Sex Chromosomes.- 1. Introduction.- 2. Clinical Significance of X-Chromosome Inactivation.- 3. Chromosome-Related Problems.- 3.1. XXY and Related Syndromes.- 3.2. The XYY Individual.- 3.3. XX Males and True Hermaphrodites.- 3.4. Miscellaneous Structural Disorders of the Y Chromosome.- 3.5. Turner Syndrome.- 3.6. The 47, XXX Female.- 3.7. Miscellaneous Structural Disorders of the X Chromosome.- 3.8. XY Gonadal Dysgenesis and Agenesis.- 3.9. Translocations Involving Sex Chromosomes.- 3.10. Fragile X Syndrome.- 4. Prenatal Diagnosis.- 4.1. Fetal Sex Determination.- 4.2. Determination of the Sex Chromatin (Barr Body).- 4.3. Y-Chromosome Fluorescence.- 4.4. Complete Chromosome Analysis.- 4.5. Amniotic Fluid Hormone Levels.- 4.6. Molecular Techniques.- 4.7. Ultrasonography.- 4.8. Preconception Sex Selection.- 4.9. Prenatal Diagnosis from Fetal Blood or Tissue.- 4.10. Biochemical Assays.- 4.11. Fetal Imaging.- 4.12. DNA-Related Tests: Direct Identification of Mutant Genes.- 4.13. Diagnosis when the Disease Locus Is Not Known.- 5. References.- 12 Prenatal Detection of Congenital Adrenal Hyperplasia.- 1. Introduction.- 2. 21-Hydroxylase Deficiency.- 2.1. Background.- 2.2. Prenatal Diagnosis of 21-Hydroxylase Deficiency.- 2.3. Prenatal Treatment of Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.- 3. 11?-Hydroxylase Deficiency.- 3.1. Background.- 3.2. Prenatal Diagnosis of Congenital Adrenal Hyperplasia Due to 11?-Hydroxylase Deficiency.- 4. Conclusion.- 5. References.- 13 Prenatal Diagnosis of Cystic Fibrosis.- 1. Introduction.- 2. Prevalence and Genetics.- 3. Early Attempts at Prenatal Diagnosis of Cystic Fibrosis.- 3.1. Alkaline Phosphatase Inducibility.- 3.2. 4-Methylumbelliferylguanidinobenzoate Protease Titration.- 3.3. Immunoreactive Trypsin.- 4. Micro villar Enzymes and the Prenatal Diagnosis of Cystic Fibrosis.- 4.1. Confirmation of Diagnosis.- 4.2. Pregnancies Suitable for Prenatal Diagnosis.- 4.3. Current Status of Microvillar Enzyme Testing.- 5. Molecular Biology and Prenatal Diagnosis.- 6. Conclusions.- 7. References.- 14 Prenatal Diagnosis of Miscellaneous Biochemical Disorders.- Inborn Errors of Folate and Cobalamin Metabolism.- 1. Inborn Errors of Folate Metabolism.- 1.1. Congenital Folate Malabsorption.- 1.2. Formiminotransferase Deficiency.- 1.3. Methylenetetrahydrofolate Reductase Deficiency.- 2. Inborn Errors of Cobalamin Metabolism.- 2.1. Transcobalamin II Deficiency.- 2.2. Disorders of Vitamin B12 Utilization.- 3. References.- Prenatal Diagnosis of Adenosine Deaminase Deficiency, Purine Nucleoside Phosphorylase Deficiency, and Severe Combined Immunodeficiency of Unknown Etiology.- 1. Introduction.- 2. Prenatal Diagnosis of Adenosine Deaminase Deficiency.- 3. Prenatal Diagnosis of Purine Nucleoside Phosphorylase Deficiency.- 4. Prenatal Diagnosis of Severe Combined Immunodeficiency of Unkown Etiology.- 5. Prenatal Diagnosis of Other Immunodeficiency Disorders.- 6. References.- Prenatal Diagnosis of Cytinosis.- 1. Cystinosis.- 2. Nephropathic Cystinosis.- 3. Benign Cystinosis.- 4. Late Onset Cystinosis (Intermediate or Adolescent Cystinosis).- 5. Prenatal Diagnosis.- 6. Therapy.- 7. References.- Prenatal Diagnosis of Miscellaneous Genetic Disorders.- References.- 15 Biochemical and Biologic Problems and Pitfalls in the Prenatal Diagnosis of Inborn Errors of Metabolism.- 1. Introduction.- 2. Cell-Free Amniotic Fluid.- 3. Noncultivated Amniotic Fluid Cells.- 4. Cultured Amniotic Fluid Cells.- 4.1. Biologic Problems in Amniotic Fluid Cell Culture.- 4.2. Biochemical Pitfalls in the Use of Cultivated Amniotic Fluid Cells for the Diagnosis of Inborn Errors of Metabolism.- 5. References.- 16 The Prenatal Diagnosis of Neural Tube and Other Congenital Defects.- 1. Introduction.- 2. Etiology.- 3. Biology of ?-Fetoprotein.- 4. Amniotic Fluid ?-Fetoprotein.- 4.1. Experience with Amniotic Fluid ?-Fetoprotein Assays.- 4.2. False-Positive and False-Negative Rates.- 4.3. Twin Pregnancy.- 4.4. Causes of Elevated Amniotic Fluid ?-Fetoprotein in the Absence of Neural Tube Defects.- 4.5. Problems and Pitfalls.- 5. Amniotic Fluid Acetylcholinesterase.- 5.1. Experience.- 5.2. Advantages and Disadvantages of the Acetylcholinesterase Assay.- 5.3. Recommendations for Prenatal Diagnosis of Neural Tube Defects Using Amniotic Fluid ?-Fetoprotein and Acetylcholinesterase Assays.- 6. Other Techniques to Detect Neural Tube Defects.- 7. Maternal Serum ?-Fetoprotein Screening.- 7.1. Experience with Maternal Serum ?-Fetoprotein Screening.- 7.2. ?-Fetoprotein Assay Considerations.- 7.3. Maternal Serum ?-Fetoprotein Screening and Diabetes Mellitus.- 7.4. Maternal Serum ?-Fetoprotein As a Predictor of Adverse Pregnancy Outcome.- 7.5. Other Causes of Elevated Serum ?-Fetoprotein Levels.- 7.6. Maternal Serum ?-Fetoprotein Screening or Ultrasound for Neural Tube Defects.- 7.7. Maternal Serum ?-Fetoprotein Screening for Down Syndrome.- 8. Primary Prevention of Neural Tube Defects.- 8.1. Genetic Counseling.- 8.2. Nutritional Supplementation.- 9. Patient and Family Considerations.- 10. Maternal Serum ?-Fetoprotein Screening and Cost-Benefit Analysis.- 11. Maternal Serum ?-Fetoprotein Screening: Policy Guidelines.- 12. The Impact of Maternal Serum ?-Fetoprotein Screening.- 13. First Trimester Maternal Serum ?-Fetoprotein Screening.- 14. References.- 17 Diagnosis of Fetal Abnormalities by Ultrasound.- 1. Introduction.- 2. Ultrasound Imaging Techniques.- 3. Safety of Ultrasound.- 4. Diagnosis of Fetal Malformations.- 4.1. Craniospinal Defects.- 4.2. Gastrointestinal Tract Defects.- 4.3. Urinary Tract Anomalies.- 4.4. Congenital Heart Disease.- 4.5. Skeletal Dysplasias.- 4.6. Abnormalities of the Amniotic Fluid Volume.- 4.7. Hydrops Fetalis.- 4.8. Cystic Hygromas.- 5. Routine Ultrasound Examination.- 5.1. Gestational Age.- 5.2. Multiple Pregnancy.- 5.3. Fetal Abnormalities.- 6. Ultrasound As a Guide to Invasive Techniques for Prenatal Diagnosis.- 6.1. Amniocentesis.- 6.2. Fetal Blood Sampling.- 6.3. Fetal Tissue Biopsy.- 6.4. Chorionic Villus Sampling.- 7. References.- 18 Fetal Blood Sampling and Fetoscopy.- 1. Fetoscopy.- 1.1. History.- 1.2. Instrumentation.- 1.3. Fetoscopy Room.- 1.4. The Fetoscopist.- 1.5. Timing of the Procedure.- 1.6. Procedure.- 1.7. Risks of Fetoscopy.- 1.8. Indications for Fetoscopy.- 2. Placental Aspiration.- 3. Percutaneous Umbilical Cord Blood Sampling.- 4. Uses of Fetoscopically Obtained Material for Prenatal Diagnosis.- 4.1. Congenital Immunodeficiency.- 4.2. Overview of the Cell Components of the Immune System.- 4.3. Severe Combined Immunodeficiency Syndrome.- 4.4. Chronic Granulomatous Disease.- 5. Blood Sampling in the Assessment of Fetal Infection.- 5.1. Toxoplasmosis.- 5.2. Rubella.- 5.3. Cytomegalovirus.- 6. Cytogenetic Diagnosis Using Midtrimester Fetal Blood Samples.- 7. Prenatal Diagnosis of Coagulopathies.- 7.1. Disorders of Factor VIII: Hemophilia A and von Willebrand Disease.- 7.2. Prenatal Diagnosis of Hemophilia B.- 7.3. Prenatal Diagnosis of the Thrombocytopenias.- 8. Prenatal Diagnosis of the Hemoglobinopathies.- 9. Prenatal Diagnosis of Skin Disorders.- 10. Fetal Liver Biopsy.- 11. Selective Feticide.- 12. References.- 19 Prenatal Diagnosis of the Hemoglobinopathies.- 1. Introduction.- 2. Clinical Types.- 2.1. ?-Thalassemia.- 2.2. ?-Thalassemia.- 2.3. Hemoglobin E Thalassemia.- 2.4. Sickle Cell Thalassemia.- 2.5. Sickle Cell Anemia.- 3. Carrier Detection.- 4. Prenatal Diagnosis Using Fetal Blood.- 4.1. Fetal Blood Sampling.- 4.2. Methods of Analysis.- 4.3. Limitations.- 5. Prenatal Diagnosis Using Fetal DNA.- 5.1. Amniotic Fluid DNA.- 5.2. Chorionic Villus DNA.- 5.3. Methods of Analysis: DNA Hybridization.- 5.4. Methods of Analysis: Restriction Enzyme Mapping.- 5.5. Limitations of DNA Methods.- 6. Future Prospects.- 7. References.- 20 Chorionic Villus Sampling.- 1. Introduction.- 2. Anatomy of Early Human Gestation.- 3. History of Chorionic Villus Sampling.- 4. Currently Used Techniques of Chorionic Villus Sampling.- 4.1. Catheter Aspiration under Sonographic Guidance.- 4.2. Sonographically Guided Biopsy Forceps.- 4.3. Endoscopically Directed Biopsy Forceps.- 4.4. Transabdominal Needle Biopsy under Sonographic Guidance.- 4.5. Relative and Absolute Contraindications to Chorionic Villus Sampling.- 4.6. Chorionic Villus Sampling in Twin Gestation.- 5. Laboratory Analyses Using Chorionic Villi.- 5.1. Cytogenetic Analyses.- 5.2. Enzymatic Analyses.- 5.3. DNA Analyses.- 6. Questions to Be Answered about Chorionic Villus Sampling.- 7. References.- 21 Molecular Genetic Techniques for Prenatal Diagnosis.- 1. Introduction.- 2. Background: DNA and Gene Structure.- 2.1. DNA Structure.- 2.2. Gene Structure.- 3. Molecular Genetic Techniques Used in Prenatal Diagnosis.- 3.1. Restriction Endonuclease Analysis and Southern Blots.- 3.2. Mutation-Specific Oligonucleotide Probes: ?1-Antitrypsin Deficiency.- 4. Applications of Molecular Genetic Techniques to Prenatal Diagnosis.- 4.1. Chromosome-Specific Probes.- 4.2. Gene-Specific Probes.- 4.3. Genetic Disorders of Unknown Biochemical Basis.- 5. Problems and Pitfalls.- 5.1. Sampling Techniques.- 5.2. Sources of Error.- 5.3. Time Required for Sample Analysis.- 6. Future Directions.- 6.1. Additional Disease-Specific Probes.- 6.2. Construction of a Human Linkage Map.- 6.3. Technical Improvements.- 7. Conclusion.- 8. References.- 22 Fetal Diagnosis by X Ray.- 1. Radiation Hazards.- 2. Plain Roentgenograms.- 3. Other Techniques.- 4. Uses and Possible Uses.- 5. References.- 23 Prenatal Detection of Connective Tissue Disorders.- 1. Introduction.- 2. Heritable Disorders of Connective Tissue.- 2.1. Ehlers-Danlos Syndrome.- 2.2. Marfan Syndrome.- 2.3. Cutis Laxa.- 2.4. Homocystinuria.- 2.5. Osteogenesis Imperfecta.- 2.6. Arthrogryposis.- 2.7. Chondrodystrophies.- 2.8. Mucopolysaccharidoses.- 2.9. Genetically Inherited Skin Diseases.- 3. Other Conditions with Skin or Connective Tissue Involvement As a Secondary Effect.- 3.1. Myotonic Dystrophy.- 3.2. Systemic Lupus Erythematosus.- 3.3. Myasthenia Gravis.- 3.4. Conditions Associated with Teratogens.- 4. References.- 24 Elective Abortion: Techniques, Risks, and Complications.- 1. Introduction.- 2. Timing of Abortions.- 3. Techniques.- 3.1. Surgical Evacuation.- 3.2. Induction of Uterine Contractions.- 3.3. Cervical Dilatation.- 4. Conclusions.- 5. References.- 25 Human Metaphase Chromosomes: Analysis and Sorting by Flow Cytometry.- 1. Introduction to Flow Cytometry and Human Chromosomes.- 2. Preparation Methods.- 3. The Technique of Flow Cytometry.- 4. Fluorescence Distribution of Human Chromosomes.- 5. Fluorescence Profiles of Human Chromosomes.- 6. Chromosome Sorting.- 7. Concluding Comments.- 8. References.- 26 Diagnosis, Treatment, and Prevention of Isoimmune Hemolytic Disease of the Newborn.- 1. Introduction.- 2. Counseling the Sensitized Patient.- 3. Management.- 3.1. Intrauterine Transfusion.- 3.2. Alternative and Experimental Management Regimens.- 4. References.- 27 Prenatal Diagnosis and Management of Congenital Malformations in the Third Trimester of Pregnancy.- 1. Introduction.- 2. Diagnostic Methods.- 2.1. Ultrasound.- 2.2. Amniocentesis.- 2.3. Fetal Blood Sampling in the Third Trimester.- 2.4. Urine Sampling.- 2.5. X-Ray Examination and Amniography.- 3. Screening.- 3.1. Routine Screening with Ultrasound.- 3.2. Biochemical Screening.- 4. Indications for Third Trimester Prenatal Diagnosis.- 4.1. Complaints by the Pregnant Woman.- 4.2. Obstetrician's Findings.- 4.3. Intrauterine Growth Disturbance.- 4.4. Abnormal Amounts of Amniotic or Fetal Fluid.- 5. Some Parental Diseases Associated with Fetal Congenital Malformations.- 5.1. Diabetes.- 5.2. Cystic Fibrosis.- 5.3. Hyperthyroidism.- 5.4. Connective Tissue Disease.- 6. Some Genetic Structural Abnormalities in the Fetus.- 6.1. Urinary System Malformations.- 6.2. Gastrointestinal Abnormalities.- 6.3. Abdominal Wall Defects.- 6.4. Congenital Heart Disease.- 6.5. Nervous System Malformations.- 6.6. Skeletal Abnormalities.- 6.7. Myotonic Dystrophy.- 7. Treatment and Ethical Problems.- 8. Problems and Possibilities of Third Trimester Prenatal Diagnosis.- 9. Advantages of Third Trimester Prenatal Diagnosis.- 10. References.- 28 Medicolegal Aspects of Prenatal Diagnosis.- 1. Introduction.- 2. General Concepts of Medical Malpractice.- 3. The Constitutional Right of Privacy in Reproductive Decisions.- 4. The Doctrine of Informed Consent.- 5. The Development of Prenatal Law and Preconception Tort Law.- 6. Wrongful Birth and Wrongful Life Suits.- 6.1. Some Definitions.- 6.2. The Evolution of Wrongful Birth Suits Brought by Parents.- 6.3. Recent Trends in Wrongful Life Suits Brought by Children.- 6.4. Analysis of Alleged Negligent Acts and Outcomes in Wrongful Birth and Wrongful Life Suits in Cases Resulting in the Birth of an Abnormal Child.- 7. Final Comments from the Vantage Point of the Child.- 8. Appendix: Summaries of Cases Listed in Table II.- 9. References.- 29 Moral Problems and Ethical Guidance in Prenatal Diagnosis: Past, Present, and Future.- 1. Introduction.- 1.1. The Purposes and Tasks of Ethics.- 1.2. Descriptive Ethics and Metaethics (Nonnormative Ethics).- 1.3. General Normative Ethics and Applied Normative Ethics.- 2. Problems of Moral Choice in Prenatal Diagnosis.- 2.1. Abortion Choices.- 2.2. Controversial Indications for Prenatal Diagnosis.- 2.3. Problems in Disclosure of Findings.- 2.4. Risks, Benefits, and Research in Prenatal Diagnosis.- 2.5. Problems in Access to and Distribution of Service.- 3. Is There a Dominant Body of Ethical Guidance for Prenatal Diagnosis?.- 3.1. Hypothesis A: A Dominant Moral Approach Has Evolved.- 3.2. Ethical Guidance for Prenatal Diagnosis.- 3.3. Consequences of Existing Ethical Guidance.- 4. The Future: Ethics and Trends in Prenatal Diagnosis.- 4.1. Coevolution of Technical, Legal, and Ethical Issues.- 4.2. Hypothesis B: Technical Trends Will Introduce New Ethical Choices in Prenatal Diagnosis That Will Increasingly Involve Society's Interests.- 5. Conclusion: Is There a Need for Consensus on Ethical Guidance in Prenatal Diagnosis?.- 6. References.- 30 Prenatal Diagnosis and Public Policy.- 1. Introduction.- 2. Government Support of Research, Development, and Assessment of New Technologies.- 3. Patient Care and Population Screening.- 4. Government Regulation of Products and Tests.- 5. Insurance Coverage/Payment for Genetic Services.- 6. A Framework for Decision-Making: Tools for Public Policy Analysis.- 7. Public Education, Public Attitudes, Access to Information from Screening.- 8. References.