TABLE OF CONTENTS (Not Final) 1.0 1.1 1.2 1.3 2.0 2.1 2.1.1 2.1.2 2.1.3 2.1.4 2.1.5 2.1.6 2.1.7.1 2.2 2.2.1 2.2.2 2.2.2.1 2.2.3 2.2.4 2.2.5 2.2.6 2.2.7 2.2.8 2.2.8.1 2.3 2.3.1 2.3.1.1 2.3.2 2.3.2.1 2.4 2.4.1 2.4.1.1 2.4.1.2 2.4.1.3 2.4.1.4 2.4.1.5 2.4.1.6 2.4.1.7 2.4.2 2.4.3 2.4.4 2.4.5 2.5 2.5.1 2.5.2 2.5.3 3.0 3.1 3.1.1 3.1.1.1 3.1.1.2 3.1.1.3 3.1.1.4 3.1.2 3.1.2.1 3.1.2.2 3.1.2.3 3.1.2.4 Introduction 20 Executive Summary 21 Objectives of This Report 23 Key Questions Answered in This Report 23 Prenatal Pregnancy Complications: An Overview 25 Advanced Maternal Age (AMA) 25 Risk for Down syndrome with Increased AMA 25 Risk of Miscarriage with Increased AMA 26 Risk of Cesarean Section with Increasing Maternal Age 27 Risk of Gestational Diabetes with Advanced Maternal Age 28 Risk for Pregnancy-Induced Hypertension with Advanced Maternal Age 29 Risk of Placenta Previa with Advanced Maternal Age 29 First Birth Rates for 35-39 Aged Women by Race in the U.S. 31 Pre-Existing Maternal Medical Conditions 32 Pregnancy Outcome in Women with Renal Disease 33 Pregnancy Outcome in Diabetic Women 34 Pregnancy Outcome in Women with Pre-Existing Thyroid Disease 34 Pregnancy Outcome in Obese Women 34 Pregnancy Outcome in Asthmatic Women 35 Pregnancy Outcome in Women with Epilepsy 36 Pregnancy Outcome in Women with Autoimmune Disease 36 Pregnancy Outcome in Women with Hemoglobinopathies 37 Pre-Existing Chronic Diseases among Women of Reproductive Ages in the U.S. 38 Chronic Disease Risk Behaviors and Risk Factors among Women of Reproductive Agein the U.S. Medical Conditions Occurring during Pregnancy 40 Preeclampsia (Toxemia) 40 Prevalence of Preeclampsia in the U.S. 40 Gestational Diabetes 42 Prevalence of Gestational Diabetes (GDM) in the U.S. 42 Pregnancy-Related Issues 44 Premature labor 44 Common Medical Complications in Pre-Mature Babies 45 Global Prevalence of Preterm Births 45 Prevalence of Preterm Births in the U.S. by Stage 46 Prevalence of Preterm Births in the U.S. by Race/Ethnicity 46 Prevalence of Preterm Births in the U.S. by Plurality of Birth 47 Prevalence of Preterm Births in the U.S. by Maternal Age 48 Multiple Births in the U.S. 49 Placenta Previa 50 Breech Presentation 50 Meconium Stained Liquor 50 Oligohydramnios and Polyhydramnios 51 Fetal Problems 52 Fetal Growth Restriction 52 Imperforate Anus 52 Congenital Heart Disease 53 Types of Genetic Diseases in Fetuses: An overview 54 Single Gene Disorders 54 Autosomal Dominant Genetic Disorders 54 Huntington Disease (HD) 55 Familial hypercholesterolaemia (FH) 56 Marfan syndrome 56 Myotonic dystrophy 57 Autosomal Recessive Genetic Disorders 58 Cystic Fibrosis (CF) 59 Canavan Disease 62 Neutropenia 63 Ellis-van Creveld Syndrome (EVC) 63 3.1.2.5 3.1.2.6 3.1.2.7 3.1.2.8 3.1.2.9 3.1.2.10 3.1.2.11 3.1.2.12 3.1.2.13 3.1.2.14 3.1.2.15 3.1.3 3.1.3.1 3.1.3.2 3.1.3.3 3.1.3.4 3.1.3.5 3.1.4 3.1.4.1 3.1.4.2 3.1.4.3 3.1.4.4 3.1.4.5 3.1.4.6 3.1.4.7 3.1.4.8 3.1.4.9 3.2 3.2.1 3.2.1.1 3.2.2 3.2.2.1 3.2.3 3.2.3.1 3.2.4 3.2.4.1 3.2.5 3.2.5.1 3.2.5.2 3.2.5.3 3.2.6 3.2.6.1 3.2.6.2 3.2.7 3.2.7.1 3.2.8 3.2.8.1 3.2.8.2 3.2.9 3.2.9.1 3.2.10 3.2.11 3.2.12 3.2.13 3.3 3.3.1 3.3.1.1 3.3.1.2 3.3.1.3 3.3.2 Familial Mediterranean fever (FMF) 64 Fanconi Anemia (FA) 64 Gaucher Disease 64 Mucopolysaccharidosis (MPSs) 65 Phenylketonuria (PKU) 66 Sickle Cell Disease 66 Beta Thalassaemia 67 Inheritance Pattern of Autosomal Recessive Genetic Disorders 68 Chances of Inheriting a Single Gene Disorder 70 Common Recessive Disease Traits in Selected Ethnic Groups 71 Comprehensive List of Common Single Gene Disorders 71 X-Linked Dominant Genetic Disorders 73 Hypophosphotemic Rickets 73 Incontinentia Pigmenti 74 Focal Dermal Hypoplasia 74 Orofaciodigital Syndrome 74 Inheritance of Sex-Linked Dominant Disorders 75 X-Linked Recessive Disorders 76 Lesch-Nyhan Syndrome 76 Menkes Disease (Kinky hair syndrome) 77 Hemophilia A and B 77 Fabry’s Disease 78 Wiskott-Aldrich Syndrome (WAS) 79 Bruton’s Aggamaglobulinemia 79 Color Blindness 80 Complete Androgen Insensitivity Syndrome 80 Inheritance of X-Linked Recessive Traits 80 Chromosomal Disorders 82 47, XXY (Klinefelter Syndrome) 83 Prenatal Diagnosis of Klinefelter Syndrome 83 47, XYY Syndrome 84 Diagnosis of 47, XYY Syndrome 84 45, X Syndrome (Turner Syndrome) 84 Prenatal Diagnosis of Turner Syndrome 85 47, XXX (Triple X Syndrome) 85 Tests and Diagnosis for Triple X Syndrome 86 Trisomy 21 86 Tests and Diagnosis of Trisomy 21 86 Incidence of Down Syndrome by Maternal Age 87 Developmental Delay in Down syndrome Children 88 Trisomy 18 (Edward’s Syndrome) 89 Prenatal Diagnosis of Trisomy 18 89 Clinical Manifestations of Edward’s Syndrome 89 Trisomy 13 (Patau Syndrome) 90 Prenatal Diagnosis of Trisomy 13 91 Triploid Syndrome 91 Congenital Anomalies Associated with Triploidy 92 Prenatal Diagnosis of Triploidy 93 Prevalence of Trisomies in the U.S. 93 Trisomies and Abortions 93 Maternal Age-Related Frequencies of Aneuploid Fetuses 94 Clinical Features of Common Autosomal or Sex Chromosome Aneuploidy 95 Maternal Age and Aneuploidy 95 Sensitivity and Specificity of Maternal Serum and Ultrasound Tests for Aneuploids Structural Chromosomal Abnormalities 97 Autosomal Deletions 97 Wolf-Hirschhorn Syndrome (WHS) 97 Cri du chat Syndrome 98 Langer-Giedion Syndrome 98 Common Autosomal Microdeletion Syndromes 99 96 3.3.2.1 Williams syndrome 100 3.3.2.2 WAGR Syndrome 101 3.3.2.3 Prader-Willi Syndrome (PWS) 101 3.3.2.4 Angelman Syndrome 103 3.3.2.5 Miller-Dicker Syndrome 103 3.3.2.6 Smith-Magenis Syndrome (SMS) 104 3.3.2.7 Alagille Syndrome (ALGS) 105 3.3.2.8 CATCH 22 Syndrome 105 3.3.2.9 DiGeorge Syndrome 106 3.3.3 Autosomal Duplication Syndromes 107 3.3.3.1 Beckwith-Wiedemann Syndrome (BWS) 107 3.3.3.2 Charcot-Marie-Tooth Disease Type 1A (CMTI) 109 3.3.3.3 Cat-Eye Syndrome 109 3.3.3.4 Appropriate Technologies for the Detection of Microdeletions, Duplication, Copy Number Variation and Translocation110 4.0 Reproductive Genetic Counseling: An Overview 111 4.1 Impact of Recent Advances in Clinical Genomics on Genetic Counseling 112 5.0 Prenatal Screening for Genetic Diseases: An Overview 113 5.1 Routine Prenatal Screening Tests 113 5.2 Less-Routine Prenatal Screening Tests 113 5.3 Beta Human Chorionic Gonadotropin (β-hCG) Screening Test 114 5.3.1 hCG Kits and Manufacturers 115 5.4 First Trimester Pregnancy-Associated Plasma Protein-A (PAPP-A) Screening Test 115 5.5 Maternal Serum Alpha-Fetoprotein (MSAFP) Screening Test 116 5.6 Second Trimester Serum β-hCG Screening Test 116 5.7 Second Trimester Unconjugated Estriol (uE3) Screening Test 116 5.8 Second Trimester Inhibin-A Screening Test 117 5.9 Second Trimester Maternal Hexosaminidase Screening Test 117 5.10 Second Trimester Triple-Screen and Quad Screen Tests 117 5.11 Second Trimester Screening of Cell-Free Fetal DNA (cffDNA) 118 5.11.1 Sensitivity and Specificity of NIPT 118 5.11.2 Diagnostic Applications of cffDNA 119 5.11.3 Time of Availability of cffDNA in Maternal Blood 119 5.11.4 The Cost of NIPT Testing 120 5.11.5 Cost of NIPTs by Product 120 5.11.6 History of Aneuploidy Testing from 1970s to 2011 Culminating in NIPTs 121 5.11.7 NIPT Methods of Detecting Aneuploidy 121 5.11.7.1 Shotgun Method 121 5.11.7.2 Targeted Massively Parallel Sequencing (t-MPS) 121 5.11.7.3 Single-Nucleotide Polymorphisms (SNPs) 121 5.11.8 Comparison of Amniocentesis and NIPTs 122 5.11.9 Advantages of NIPTs 122 5.11.10 Disadvantages of NIPTs 123 5.11.11 Comparison of Some Performance Criteria for the commonly used Prenatal Tests 123 5.11.12 Comparison of NIPT Detection Rate with Traditional Screening Tests 124 5.11.13 False Positive Rates of NIPTs Compared with those of Conventional Screening Tests 124 5.11.14 Fetal Genetic Disorders Detectable by NIPTs and Other Screening Tests 124 5.12 First Trimester Ultrasound Screening Test 125 5.12.1 Nuchal Translucency (NT) Screening Test 125 5.12.2 Reliability of NT Test 126 5.13 Magnetic Resonance Imaging (MRI) in Prenatal Screening 127 5.14 Prenatal Diagnosis of Genetic Disorders 127 5.14.1 Amniocentesis (AC) 128 5.14.1.1 Reliability of Amniocentesis 128 5.14.2 Chorionic Villus Sampling (CVS) Diagnostic Test 128 5.14.2.1 Reliability of CVS Test 129 5.14.3 Cordocentesis or Percutaneous Umbilical Blood Sampling (PUBS) 130 5.15 Advantages and Disadvantages of Prenatal Diagnostic Tests 130 5.16 Future of Invasive Prenatal Tests 131 5.16.1 Indispensability of Invasive Tests 132 5.17 5.17.1 5.18 6.0 6.1 6.2 6.3 6.4 6.4.1 6.4.1.1 6.4.2 6.4.2.1 6.4.2.2 6.4.2.3 6.4.3 6.4.3.1 6.4.3.2 6.4.3.3 6.4.4 6.4.4.1 6.4.4.2 6.4.5 6.4.5.1 6.4.5.2 6.4.6 6.4.6.1 6.4.6.2 6.4.6.3 6.4.7 6.4.7.1 6.4.7.2 6.4.7.3 6.4.8 6.4.8.1 6.4.8.2 7.0 7.1 7.1.1 7.1.2 7.1.3 7.1.4 7.1.5 7.1.6 7.2 7.3 7.4 7.5 8.0 8.1 8.1.1 8.1.2 8.1.3 8.2 8.2.1 8.3 8.3.1 8.4 8.4.1 8.5 8.5.1 Intact Circulating Fetal Cells for Noninvasive Prenatal Tests 132 Scheme for Isolating Intact Fetal Cells for Prenatal Diagnosis 133 Trophoblast Retrieval and Isolation from Cervix (TRIC) 134 Newborn Genetic Screening 135 Status of Newborn Screening in Developed and Developing Countries 136 Status in Middle East and North Africa (MENA) 136 Screening Tests Recommended for All Newborns in the U.S. 137 The Most Common Newborn Genetic Disorders 139 Phenylketonuria (PKU) 139 Screening Techniques used for Diagnosis of PKU 140 Congenital Hypothyroidism (CHT) 140 Inheritance of CHT 140 Signs and Symptoms of CHT 140 Diagnosis of CHT 140 Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) 141 Inheritance of 21-OHD CAH 141 Symptoms of 21-OHD CAH 141 Diagnosis of 21-OHD CAH 141 Galactosemia 141 Signs and Symptoms of Galactosemia 142 Diagnosis of Galactosemia 142 Sickle Cell Anemia (SCD) 142 Symptoms of SCD 142 Tests and Diagnosis of SCD 142 Biotidinase Deficiency 143 Inheritance of Biotidinase Deficiency 143 Signs and Symptoms of Biotidinase Deficiency 143 Diagnosis of Biotidinase Deficiency 143 Hypocystinuria 144 Inheritance of Hypocystinuria 144 Signs and Symptoms of Hypocystinuria 144 Diagnosis of Hypocystinuria 144 Maple Syrup Urine Disease (MSUD) 144 Inheritance of MSUD 145 Diagnosis of MSUD 145 Preimplantation Genetic Screening and Preimplantsion Genetic Diagnosis (PGS/PGD) PGS/PGD Technologies 146 Fluorescent in situ Hybridization (FISH) 146 Array Comparative Genome Hybridization (aCGH) 147 Single Nucleotide Polymorphism (SNP) Microarray 147 Oligonucleotide Genome Sequencing (OGS) 147 Express Genome Screening (EGS) 147 Next-Generation Sequencing (NGS) 147 Strengths and Weaknesses of Currently Available PGS/PGD Technologies 147 Genetic Diseases Detected during PGD 148 PGS/PDD Testing Products in the Market 153 Cost of PGD 154 Pregnancy, Prenatal, Newborn and PGD-Related Testing Technologies: An overview Beta human chorionic gonadotropin (β-hCG) Test 156 Set-Up of the Test Strip (hCG) 156 Test Procedure (hCG) 157 Interpretation of the Result (hCG) 157 Pregnancy Associated Plasma Protein-A (PAPP-A) Test 158 Principle of PAPP-A Test 158 Maternal Serum Alpha Fetoprotein (MSAFP) Test 158 Principle of the Test (MSAFP) 158 Unconjugated Estriol (uE3) Test 159 Principle of the Assay (uE3) 159 Inhibin A Test 159 Principle of the Test (Inhibin A) 159 146 156 8.6 8.7 8.8 8.8.1 8.8.2 8.8.2.1 8.8.3 8.8.3.1 8.8.3.2 8.8.3.3 8.8.3.4 8.8.4 8.9 8.9.1 8.9.1.1 8.9.1.2 8.9.1.3 8.9.1.4 8.9.1.5 8.9.1.6 8.9.1.7 8.9.1.8 8.9.1.9 8.9.1.10 8.9.2 8.9.3 8.9.4 8.9.5 8.9.6 8.9.7 8.9.8 8.9.9 8.9.10 8.9.10.1 8.10 8.11 8.11.1 8.11.2 8.11.3 8.11.3.1 8.11.3.2 8.11.3.3 8.11.3.4 8.11.4 8.11.4.1 8.11.4.2 8.11.4.3 8.11.4.4 8.11.5 8.11.5.1 8.11.5.2 8.11.5.3 8.11.5.4 8.11.6 8.11.6.1 8.11.6.2 8.11.6.3 8.11.6.4 8.11.7 8.11.7.1 Fetal Karyotyping 160 Extended Banding Chromosome Studies 160 Innovation in Invasive Testing: Rapid Aneuploidy Detection Method 160 Microarrays: An Alternative for Karyotyping 161 Rapid Aneuploid Detection by QF-PCR 161 Principles of QF-PCR 161 Fluorescence in situ Hybridization (FISH) 162 The Format of FISH Test Result 163 Commonly Used FISH-Based Tests 164 Microdeletions/Microduplications Detectable by FISH 165 Types of FISH Probes and their Functions 165 Microarray-Based Comparative Genomic Hybridization (array-CGH) 166 Advances in Prenatal Testing: The Power to Know Sooner 167 Noninvasive Prenatal Tests (NIPTs): An overview of Tests and Technologies 168 Harmony Test 168 InformaSeq 170 Panorama Test 170 Prena Test 171 NIFTY Test 172 IONA Test 172 Verifi Test 174 MaterniT GENOME Test 175 MaterniT21 PLUS Test 176 HerediT UNIVERSAL Carrier Screen 177 Comparison of MaterniT21 PLUS, Verifi, Harmony and Panorama Tests 177 U.S. Patents for NIPTs by Company in the U.S. 178 Selected Issued Patents of NIPTs 178 Assignees of Major U.S. Patents and their Current Licensees 179 Global Availability of NIPTs 180 Cost Effectiveness of NIPTs 181 Strategies to be adopted for Clinical Implementation of NIPT for all Pregnancies Integration of NIPT into Healthcare System: Patient-Directed Model 182 Controversial Advertisements of NIPT 183 FDA Regulatory Loophole 184 Tandem Mass Spectrometry (MS/MS) in Newborn Screening 184 Fetal Ultrasound in Prenatal Screening 185 Types of Fetal Ultrasound Exams 185 Best Obstetric and Gynecological Ultrasounds in the Market 185 Best Premium Fetal Ultrasound Machines 186 Philips Epiq 7 186 GE Voluson E8 187 GE Voluson E10 187 Samsung UGEO WS80A 188 High-End Systems 188 Philips Epiq 5 188 Philips Affinity 70 189 GE Voluson E6 189 GE Voluson S8 190 Midrange Systems 190 Philips Affinity 50 190 GE Voluson S6 191 Samsung AccuVix A30 191 Philips ClearVue 650 191 Economy Systems 192 Philips ClearVue 550 192 GE Logiq P5 192 Samsung H60 193 Alpinion Ecube 7 193 Portable Systems 193 GE Voluson i 194 182 8.11.7.2 9.0 9.1 9.1.1 9.2 9.3 9.4 9.4.1 9.5 9.6 9.7 10.0 10.1 10.2 10.3 10.4 11.0 11.5.1 11.5.2 11.5.2.1 11.5.2.2 11.5.2.3 11.5.2.4 11.5.2.5 11.5.3 11.5.4 11.5.5 11.6 11.6.1 11.6.2 11.6.3 11.6.4 11.7 11.8 11.8.1 11.8.2 11.9 10.11 12.0 12.1 12.2 12.2.1 12.3 12.3.1 12.3.2 12.4 12.4.1 12.5 12.6 12.6.1 12.7 12.7.1 12.7.2 12.7.3 12.7.3.1 12.7.3.2 12.7.3.3 12.7.3.4 12.8 12.8.1 Samsung UGEO HM70A 194 Prenatal Screening and Diagnosis: Market Overview 195 Global Market for Fetal Ultrasound 195 Market Leaders in Fetal Ultrasound 196 Global Market for Prenatal MRI Screening 197 Global Market for Maternal Serum Screening Tests 199 Global Market for Non-Invasive Prenatal Tests (NIPT) using cffDNA 200 Global Market for NIPTs by Product 202 Global Market for Prenatal Diagnostic Tests 203 Global Market for Newborn Screening for Genetic Diseases 204 Global Market for Pre-implantation Genetic Screening/Diagnosis (PGS/PGD) Other Genetic Testing-Related Markets: A Brief Overview 207 Emerging Trends in Molecular Diagnostics Market 207 Emerging Trends in Liquid Biopsy Market 208 Emerging Trends in Personalized Medicine Diagnostics Market 209 Emerging Trends in in vitro Diagnostics (IVD) Market 210 Market SWOT and Strategy Analysis 212 Strategies of Major Players in Prenatal Screening Industry 212 Acquisition Activities in Prenatal Screening Industr5y 212 Acquisition of BlueGenome by Illumina 212 Illumina’s Acquisition of Verinata Health 212 Eurofin’s Joint Venture with Emory Genetics Laboratory 212 Roche’s Acquisition of Ariosa Diagnostics 212 Cooper Surgical’s Acquisition of Reprogenetics 212 Market Drivers of Prenatal Screening 213 Market Restraints 213 Future of Prenatal Screening 213 Legislation Mandating Newborn Screening by Geography 213 Newborn Screening Programs in Americas 214 Newborn Screening Programs in Asia/Pacific 214 Newborn Screening Programs in Europe 214 Newborn Screening Programs in Middle East and Northern Africa (MENA) Ethical Voices against Problematic Applications of NIPT and NIPD 215 Clinical Implementation of NIPTs 216 Implementation of NIPT in Developed Countries 216 Implementation of NIPTs in Developing and Under-Developed Countries Adoption Rates for Different Prenatal Testing in the U.S. 217 Reimbursement for NIPTs 217 Company Profiles 218 23andMe Inc. 218 Abbott Laboratories 219 ARCHITECT AFP Assay 219 Abbott Molecular Inc. 219 AneuVysion 219 Cystic Fibrosis Genotyping Assay 220 Abcam plc 220 hCG Human ELISA Kit 220 AB Sciex LLC 220 Adaltis S.r.l 221 CLIAgen Free Beta-hCG Kit 221 Adaptive Biotechnologies Corp. 221 ImmunoSEQ Platform 221 ClonoSEQ 222 Pipeline 222 Quantifying Tumor Infiltration Lymphocytes in Solid Tumors 222 Measuring Immune Reconstitution Post Transplant 222 Diagnosing Cutaneous T-Cell Lymphoma (CTCL) 222 Therapeutics 222 Affymetrix Inc. 223 Microarray Solutions 223 205 215 216 12.9 Agena Biosciences Inc. 224 12.9.1 MassARRAY System 224 12.10 Agilent Technologies Inc. 225 12.10.1 SureScan Microarray Scanner 225 12.10.2 OneSeq 225 12.11 Ambry Genetics Corp. 225 12.11.1 Clinical Diagnostic Tests 225 12.12 Analogic Corp. 227 12.12.1 Flex Focus 500 227 12.12.1 SonixTouchQ+ 227 12.12.3 SonixSP Q+ 227 12.13 Ariosa Diagnostics Inc. 228 12.13.1 Harmony Test 228 12.14 Ansh Labs 228 12.14.1 picoPAPP-A ELISA Kit 228 12.14.2 Inhibin A ELISA Kit 228 12.15 Appistry Inc. 229 12.15.1 GenomePilot 229 12.15.3 Variant Annotation and Analysis Suite 229 12.15.4 CloudDx Translational 229 12.15.5 CloudDx Clinical 229 12.16 ARUP Laboratories 230 12.16.1 Prenatal Screening and Diagnosis 230 12.16.2 Next-Generation Sequencing (NGS) 230 12.16.3 Noninvasive Prenatal Test for Aneuploids 230 12.17 AssureRx Health Inc. 231 12.17.1 GeneSight Psychotropic 231 12.17.2 GeneSight Analgesic 231 12.17.3 GeneSight ADHD 231 12.17.4 GeneSight MTHFR 231 12.18 Asuragen Inc. 232 12.18.1 AmplideX FMR1 PCR 232 12.18.2 AmplideX FMR1 mPCR 232 12.18.3 AmplideX Controls 232 12.18.4 Quantidex Pan Cancer Kit 232 12.18.5 Quantidex BCR/ABL1 Quant Kit 232 12.18.6 Quantidex DNA Assay 233 12.18.7 Signature Technology 233 12.18.8 Signature KRAS Mutations 233 12.18.9 Signature BRAF Mutations 233 12.18.10 Signature LTx v2.0 233 12.18.11 Signature NPM1 Mutations 233 12.19 Ariosa Diagnostics Inc. 234 12.19.1 Harmony Test 234 12.20 Athena Diagnostics Inc. 234 12.21 AutoGenomics Inc. 235 12.21.1 INFINITI System 235 12.22 Base4 Innovation Ltd. 235 12.22.1 Microdroplet Sequencing 236 12.23 Beckman Coulter Inc. 236 12.23.1 SPRIworks System I for Illumina Genome Analyzer 236 12.23.2 SPRIworks HT for Illumina NGS Platform 236 12.23.3 SPRIselect Reagent Kit 236 12.23.4 Automated Sample Preparation 237 12.23.5 Genomic Services 237 12.23.6 Access Total Beta-hCG Reagent 237 12.23.7 Access Inhibin A Assay 237 12.24 Berry Genomics Co., Ltd. 237 12.24.1 Bambni Test 238 12.25 Bina Technologies Inc. 238 12.25.1 12.25.2 12.26 12.27 12.28 12.28.1 12.29 12.29.1 12.29.2 12.30 12.30.1 12.30.2 12.31 12.31.1 12.31.2 12.32 12.32.1 12.32.2 12.32.3 12.33 12.34 12.35 12.35.1 12.36 12.37 12.37.1 12.38 12.38.1 12.38.2 12.39 12.39.1 12.39.2 12.40 12.40.1 12.41 12.42 12.42.1 12.42.2 12.42.3 12.43 12.44 12.44.1 12.44.2 12.44.3 12.45 12.45.1 12.45.2 12.46 12.47 12.47.1 12.48 12.48.1 12.49 12.49.1 12.50 12.50.1 12.50.2 12.50.3 12.51 12.52 Bina RAVE 238 Bina AAiM 238 Bio-Rad (Israel) Laboratories Inc. 239 BGI 239 Blueprint Genetics Oy 240 Services 240 Boreal Genomics Inc. 240 OnTarget Mutation Detection System 241 Aurora Platform 241 Cambridge Epigenetix Ltd. 241 TrueMethyl Seq Kit 241 TrueMethyl Array 242 Caris Lifesciences 242 ADAPT Biotargeting System 242 Caris Molecular Intelligence 242 CeGaT GmbH 243 NGS Service 243 ADME Research Panel 243 Forschungsexom 243 Centogene AG 244 Chromsystems Instruments & Chemicals GmbH Chronix Biomedical Inc. 245 Technology 245 Claritas Genomics Inc. 245 CLC bio A/S 248 Products 248 Combimatrix Corp. 249 CombiSNP Array for Prenatal Diagnosis 249 CombiPGS 249 Contec Medical Systems Co., Ltd. 255 CMS600P B-Ultrasound Diagnostic System 255 CMS600B3 B-Ultrasound Diagnostic System Coriell Life Sciences Inc. 255 GeneDose 255 Correlagen Diagnostics Inc. 256 Counsyl Inc. 258 Family Prep Screen 258 Informed Pregnancy Screen 258 Inherited Cancer Screen 258 Courtagen Life Sciences Inc. 259 Creative Diagnostics 259 Alpha-Fetoprotein, AFP ELISA Kit 259 hCG ELISA Kit 260 Human Free Estriol ELISA Kit 260 Cynvenio Biosystems Inc. 260 LiquidBiopsy 260 ClearID 260 Diagnostic Automation/Cortez Diagnostics Inc. Demeditec Diagnostics GmbH 261 Estriol, Free/Uncojugated ELISA 261 DRG International Inc. 262 DRG PAPP-A ELISA 262 DNA Electronics Ltd. 262 Genalysis 262 DNA Link Inc. 263 Services 263 DNAGPS 264 AccuID 264 DNAnexus Inc. 264 Eagle Biosciences Inc. 265 244 255 261 12.52.1 12.52.2 12.53 12.53.1 12.53.2 12.54 12.54.1 12.54.2 12.55 12.55.1 12.55.2 12.55.3 12.55.4 12.55.5 12.56 12.56.1 12.57 12.57.1 12.58 12.58.1 12.58.2 12.58.3 12.58.4 12.59 12.59.1 12.60 12.60.1 12.60.2 12.60.3 12.60.4 12.60.5 12.60.6 12.60.7 12.60.8 12.61 12.61.1 12.62 12.63 12.64 12.64.1 12.64.2 12.64.3 12.65 12.65.1 12.66 12.66.1 12.66.2 12.66.3 12.67 12.67.1 12.67.2 12.67.3 12.67.4 12.68 12.69 12.69.1 12.70 12.70.1 12.70.2 12.71 Alport Syndrome Kit 265 Free Beta-hCG ELISA 265 Eagle Genomics Ltd. 265 EagleCore 266 EagleNsembl 266 Enzymatics Inc. 266 Reagents 266 SPARK DNA Sample Preparation Kit 266 Esoate SpA 267 MyLabGamma 267 MyLab GOLD Platform 267 MyLab 50 267 MyLab 40 267 MyLab 25Gold 267 Eurofins MWG Operon Inc. 268 Products and Services 268 Exiqon A/S 269 Products and Services 269 Fakuda Denshi Co., Ltd. 270 UF-400AX 270 UF-550XTD 270 UF-760AG 271 UF-870AG 271 GATC Biotech AG 272 Sanger Sequencing 272 GE Healthcare Ltd. 272 VScan 273 VScan with Dual Probe 273 Logiq P5 273 Logiq P6 273 GE Venue 50 273 GE Venue 40 273 Logiq S8 273 Logiq E9 274 GenapSys Inc. 274 GENIUS 274 Gene by Gene Ltd. 274 Genection Inc. 275 GeneDx Inc. 276 Cytogenetics and Biochemical Tests 276 Deletion/Duplication Analysis 276 Carrier Mutation-Specific Testing 277 GenePeeks Inc. 277 Matchright Technology 277 Genesis Genetics 278 GeniSeq24 278 UltraPGD 278 ArrayCGH 278 Genetadi Biotech S.L. 279 AMNIOCHIP 279 FERTICHIP 279 PRENATAL GENE 279 NEONATAL-ONE 280 Genoma Group Srl 280 Genomed AG 280 Aneufast 281 GenPath Diagnostics 281 InheriGen, InheriGen Plus and InheriGen Tx Prenatal Tests 281 Genway Biotech Inc. 282 281 12.72 Good Start Genetics Inc. 282 12.72.1 EmbryVu 282 12.73 Hitachi Medical Systems America Inc. 282 12.73.1 Arietta 70 283 12.73.2 ProSound Alpha 7 283 12.73.3 Noblus 283 12.73.4 ProSound F37 283 12.74 Hologic Inc. 283 12.74.1 InPlex CF Molecular Test 283 12.74.2 Rapid fFN Test 284 12.75 Illumina Inc. 284 12.75.1 The Verifi Prenatal Test 284 12.76 INEX Innovations Exchange Pte Ltd. 285 12.76.1 iGene 285 12.76.2 FlashFISH 285 12.77 Invitae Corp. 286 12.78 Laboratory Corporation of America Inc. 286 12.78.1 Services 286 12.79 LifeCodexx AG 287 12.79.1 Prena Test 287 12.80 Monobind Inc. 287 12.80.1 Fertility VAST Panel: HCG, FSH, LH, SPRL 12.80.2 PAPP-A Test 288 12.81 Multiplicom NV 288 12.81.1 Clarigo 288 12.82 Myriad Genetics 288 12.83 Natera Inc. 289 12.83.1 Panorama Prenatal Screen 289 12.83.1.1 Accuracy of Panorama Test 289 12.83.1.2 Minimal False Negatives in Panorama 12.83.2 Horizon Carrier Screening 290 12.83.3 Spectrum Preimplantation Test 291 12.83.4 Natera’s 24-chromosome PGS 292 12.83.5 Anora Miscarriage Test 292 12.83.6 Prenatal Paternity Test 292 12.84 Natus Medical Inc. 292 12.84.1 ABaer 293 12.84.2 Algo 5 293 12.84.3 Algo 3i 293 12.84.4 AuDX 293 12.84.5 Echo-Screen III 293 12.85 NewGene Ltd. 294 12.85.1 Hereditary Disorders 294 12.85.2 Alport Syndrome 294 12.85.3 Aortopathy Panel 294 12.85.4 RASopathy Gene Panel 295 12.85.5 Familial Hypercholesterolaemia 295 12.86 NIPD Genetics Ltd. 295 12.86.1 VERACITY Test (NIPT) 295 12.87 Oxford Gene Technology (OGT) 296 12.87.1 SureSeq NGS Library Preparation Kit 296 12.87.2 CytoSure Embryo Screen Array 296 12.87.3 Cytocell FISH Probes 296 12.87.4 CytoSure Embryo Screen Array 296 12.87.5 CytoSure Aneuploidy Array 296 12.87.6 CytoSure Chromosome X Arrays 297 12.88 Parabase Genomics Inc. 297 12.88.1 NewbornDx Test 297 12.89 Pathway Genomics Corp. 298 12.89.1 Carrier Screening 298 288 290 12.90 PerkinElmer Life and Analytical Sciences Inc. 298 12.90.1 DELFIA Xpress PIGF Assay 298 12.90.2 DELFIA Xpress PAPP-A Kit 298 12.90.3 AutoDELFIA PAPP-A Kit 299 12.90.4 StepOne Newborn Screens 299 12.91 Premaitha Health PLC 299 12.91.1 IONA Test 299 12.92 Progenity Inc. 300 12.92.1 nxtPanel Test 300 12.92.2 Verifi Test 300 12.93 Qiagen N.V. 301 12.93.1 Next-Generation Sequencing (NGS) 301 12.93.2 Target Enrichment Solutions 301 12.93.3 Library Construction 302 12.94 Quest Diagnostics Inc. 302 12.94.1 QNatal Advanced 302 12.94.2 Inhibin A 302 12.95 Ravgen Inc. 303 12.95.1 Prenatal Downs Syndrome Testing 303 12.95.2 Single Gene Disorder Testing 303 12.96 Recombine Inc. 303 12.96.1 CarrierMap 303 12.97 Reproductive Genetics Institute Inc. 304 12.98 Reprogenetics Laboratories 304 12.98.1 Array CGH (aCGH) 304 12.98.2 Single Gene Disorder Testing 304 12.99 Sebia Inc. 305 12.100 Sequenom Inc. 305 12.100.1 MaterniT GENOME Test 305 12.100.1.1 Sensitivity and Specificity of MaterniT GENOME Test 12.100.2 MaterniT21 PLUS 307 12.100.2.1 Sensitivity and Specificity of MaterniT21 PLUS 307 12.100.3 HerediT UNIVERSAL Carrier Screen 307 12.100.4 VisibiliT Prenatal Test 308 12.100.5 HerediT Cystic Fibrosis Carrier Screen 308 12.100.5.1 Clinical Data for HerediT 308 12.100.6 SensiGene Fetal RHD Genotyping 309 12.100.7 NextView Prenatal Diagnostic Tests 309 12.101 SeraCare Life Sciences Inc. 310 12.101.1 Seraseq Trisomy 21 Aneuploidy Reference Material 310 12.102 Siemens Healthcare 311 12.102.1 Acuson S2000 311 12.102.2 Acuson X700 311 11.102.3 Acuson X600 311 12.102.4 Acuson X300 PE 311 12.102.5 Acuson X150 312 12.102.6 Acuson Antares 312 12.102.7 Acuson P300 312 12.103 Sophia Genetics SA 312 12.103.1 Clinical Genomic Modules 312 12.104 SpOtOn Clinical Diagnostics Ltd. 313 12.104.1 Newborn Screening 313 12.104.2 Ante-Natal Testing 313 12.105 Stra Biotech GmbH 313 12.106 Sygnis AG 314 12.106.1 TruePrime Single Cell WGA Kit 314 12.106.2 TruePrime WGA Kit 314 12.106.3 TruePrime RCA Kit 314 12.106.4 SunScript Reverse Transcriptase RNaseH+ and RNaseH- Kits 314 12.106.5 SensiPhi/QualiPhi 314 306 12.107 SynapDx Corporation 315 12.107.1 ASD Diagnosis 315 12.108 Thermo Fisher Scientific Inc. 315 12.108.1 Thermo Fisher’s Brands 315 12.109 Transgenomic Inc. 316 12.109.1 Technology Suite 316 12.109.2 MX-ICP Technology 317 12.109.3 ICEme Kit 317 12.109.4 Other Products 317 12.110 Trivitron Healthcare Private Ltd. 317 12.111 Trovagene Inc. 318 12.111.1 PCM BRAF V600E Mutation Detection Test 318 12.111.2 PCM KRAS Mutation Detection Test 318 12.111.3 PCR EGFR Mutation Detection Test 319 12.111.4 HPV HR Detection Test 319 12.112 Tute Genomics Inc. 319 12.112.1 Tute Platform 320 12.113 Warp Drive Bio LLC 320 12.113.1 Wrap’s New Approach 320 12.113.2 Chemomemes 320 12.113.3 Genomic Search Engine 320 12.114 ZS Genetics Inc. 321 12.114.1 3G Sequencing 321 12.115 Zymo Research Corporation 321 12.115.1 DNA Methylation Products 321 12.115.1.1 Bisulfite Conversion 321 12.115.1.2 Methylated DNA Standards 322 12.115.1.3 DNA Methyltransferases 322 12.115.1.4 5-mC ELISA 322 12.115.1.5 5-mC Antibodies and Immunoprecipitation 322 11.115.1.6 Region-Specific DNA Methylation Analysis 322 12.115.1.7 Global 5-mC Quantification 322 12.115.1.8 Genome-wide 5-mC Analysis 323 12.115.2 DNA Purification Products 323 12.115.2.1 DNA Clean-up 323 12.115.2.2 Plasmid DNA Purification 323 12.115.2.3 Genomic DNA 323 12.115.3 Microbial and Environmental DNA Isolation324 12.115.4 DNA/RNA Co-Purification 324 12.115.5 Sample Collection and Stabilization 324 12.115.6 DNA Ladders 324 12.115.7 Enzymes 324 12.115.8 High-Throughput/Automated Isolation 325 12.115.9 DNA Analysis Kits 325 12.115.10 Other Products 325 INDEX OF FIGURES Figure 1.1: Summary of Prenatal Screening, Prenatal Diagnosis, Newborn Screening and PGS/PGD Markets, Through 2021 22 Figure 2.1: Risk of Down syndrome and All Chromosomal Abnormalities Due to Maternal Age 26 Figure 2.2: Risk of Miscarriage with Increasing Maternal Age 27 Figure 2.3 Increased Rate of Cesarean Section with Increasing Maternal Age 28 Figure 2.4: Risk of Gestational Diabetes with Advanced Maternal Age 29 Figure 2.5: Risk of Placenta Previa with Advanced Maternal Age 30 Figure 2.6: Increasing Rates for First Births to Older Women in the U.S. 31 Figure 2.7: First Birth Rates for 35-39 Aged Women by Race in the U.S. 32 Figure 2.8: Pre-Existing Chronic Diseases among Women of Reproductive Ages in the U.S. 39 Figure 2.9: Chronic Disease Risk Behaviors and Risk Factors among Women of Reproductive Age in the U.S. 39 Figure 2.10: Prevalence of Preeclampsia during Pregnancy by Race/Ethnicity in the U.S. 41 Figure 2.11: Prevalence of Preeclampsia during Pregnancy by Maternal Age in the U.S. 41 Figure 2.12: Prevalence of Gestational Diabetes by Maternal Age in the U.S. 43 Figure 2.13: Prevalence of Gestational Diabetes by Maternal Race/Ethnicity in the U.S. 43 Figure 2.14: Causes of Preterm Labor 44 Figure 2.15: Prevalence of Preterm Births in the U.S. by Stage 46 Figure 2.16: Prevalence of Preterm Births in the U.S. by Race/Ethnicity, 2013 47 Figure 2.17: Prevalence of Preterm Births in the U.S. by Plurality of Birth, 2013 48 Figure 2.18: Prevalence of Preterm Births in the U.S. by Maternal Age, 2013 49 Figure 2.19: Prevalence of Multiple Births in the U.S. 49 Figure 3.1: Autosomal Dominant Faulty Gene Inheritance When One Parent is a Carrier 57 Figure 3.2: Autosomal Dominant Faulty Gene Inheritance When Both the Parents are Carriers 58 Figure 3.3: Percent of Patients with Sweat Chloride Test Reported in the U.S. Registry, 1988-2013 59 Figure 3.4: Age at CF Diagnosis for All People Reported in the U.S. Registry, 2013 60 Figure 3.5: Distribution of Race/Ethnicity among People with CF in the U.S. 60 Figure 3.6: Percent of New CF Diagnosis in Newborn Screening in the U.S., 1990-2013 61 Figure 3.7: Autosomal Recessive Inheritance with Both the Parents being Carriers 68 Figure 3.8: Autosomal Recessive Inheritance with Carrier Mother and Non-Carrier Father 69 Figure 3.9: Autosomal Recessive Inheritance from Homozygous Recessive Mother and Carrier Father 69 Figure 3.10: Autosomal Recessive Inheritance from Both the Parents being Affected 70 Figure 3.11: Inheritance Pattern of Sex-Linked Dominant Disorder with Mother being affected and Father being a Non-Carrier 75 Figure 3.12: X-Linked Recessive Inheritance with a Carrier Mother and Non-Carrier Father 81 Figure 3.13: X-Linked Recessive Inheritance with Normal Mother and Affected Father 81 Figure 3.14: Prevalence of Down syndrome by Mother’s Age in the U.S. 88 Figure 3.15: Prevalence of Trisomies in the U.S. 93 Figure 3.16: Relative Frequencies of Different Abnormalities in Chromosomally Abnormal Spontaneous Abortions 94 Figure 3.17: Maternal Age and Chromosomal Abnormalities Detected at Amniocentesis 96 Figure 5.1: Genetic Disorders (%) Detectable by Prenatal Testing Methods 125 Figure 5.2: Nuchal Translucency as Seen in an Ultrasound Scan 126 Figure 5.3: The Amniocentesis Procedure 128 Figure 5.4: Transabdominal CVS Test 129 Figure 5.5: Transvaginal CVS Test 129 Figure 5.6: Scheme for Isolating Fetal Cells to be used for Noninvasive Prenatal Genetic Diagnosis 134 Figure 7.1: Indications for PGD 146 Figure 8.1: Markings on a hCG Test Strip 156 Figure 8.2: Procedure of the Test (hCG) 157 Figure 8.3: Interpretation of hCG Result 157 Figure 8.4: The Fetal Karyotype Showing Down Syndrome 160 Figure 8.5: Peak Heights Indicating Aneuploidy in QF-PCR Study 162 Figure 8.6: Diagrammatic Representation of Steps Involved in FISH Test 163 Figure 8.7: FISH Test Showing Chromosomal Deletion 163 Figure 8.8: Steps involved in array-CGH 166 Figure 8.9: History of Innovation in NIPTs from 2011 to 2015 168 Figure 8.10: Detection Rate of Harmony Test Compared with Traditional Maternal Serum Tests 169 Figure 8.11: Global Availability of NIPTs 180 Figure 8.24: Patient-Directed Model of Integrating NIPTs into Healthcare Setting 183 Figure 9.1: Global Market for Prenatal Screening by Ultrasound, Through 2021 195 Figure 9.2: Global Market for Fetal Ultrasound Screening by Geography, Through 2021 196 Figure 9.3: Global Fetal Ultrasound Market Share by Company, 2014 197 Figure 9.4: Global Market for Prenatal Screening by MRI, Through 2021 198 Figure 9.5: Global Market for MRI Prenatal Screening by Geography, Through 2021 198 Figure 9.6: Global Market for Maternal Serum Screening Tests by Geography, Through 2021 200 Figure 9.7: Global Market for NIPT, Through 2021 201 Figure 9.8: Global Market for NIPT by Geography, Through 2021 201 Figure 9.9: Global Market for NIPTs by Product 202 Figure 9.10: Global Market for Prenatal Diagnostic Tests, Through 2021 203 Figure 9.11: Global Market for Newborn Screening for Genetic Diseases, Through 2021 204 Figure 9.12: Global Market for Newborn Screening by Technology, Through 2021 205 Figure 9.13: Global Market for Pre-implantation Genetic Diagnosis (PGD), Through 2021 Figure 9.14: Global Market for Pre-implantation Genetic Diagnosis (PGD), Through 2021 Figure 10.1: Global Market for Molecular Diagnostics, Through 2021 208 Figure 10.2: Global Liquid Biopsy Market, Through 2021 209 Figure 10.3: Global Personalized Medicine Diagnostics Market, Through 2021 210 Figure 10.4: Global Market for IVD, Through 2021 211 Figure 12.1: Comparison of False Negative Rates 290 Figure 12.2: Sensitivity and Specificity of MaterniT GENOME Test 306 206 206 INDEX OF TABLES Table 1.1: Summary of Prenatal Screening, Prenatal Diagnosis, Newborn Screening and PGS/PGD Markets, Through 2021 22 Table 2.1: Risk of Down syndrome and Chromosomal Abnormalities Due to Maternal Age 26 Table 2.2: Maternal Age and Pregnancy Loss Rate 27 Table 2.3: Risk of Cesarean Section with Increasing Maternal Age 28 Table 2.4: Risk of Gestational Diabetes with Advanced Maternal Age 28 Table 2.5: Risk of Placenta Previa with Advanced Maternal Age 29 Table 2.6: Increasing Rates (per Thousand Women) for First Births to Older Women in the U.S. 30 Table 2.7: First Birth Rates for 35-39 Aged Women by Race in the U.S. 31 Table 2.8: Maternal and Fetal Concerns Due to Pre-Existing Medical Issues 33 Table 2.9: Pregnancy Outcome in Women with Pre-Existing Renal Problems 33 Table 2.10: Hypothyroidism-Related Adverse Effects During Pregnancy 34 Table 2.11: Risks Associated with Pregnancy in Obese Women 35 Table 2.12: Pregnancy Complications in Asthmatic Women 35 Table 2.13: Pregnancy-Related Complications and Neonatal Outcomes in Women with Epilepsy 36 Table 2.14: Maternal and Fetal Complications in Women with Autoimmune Diseases 37 Table 2.15: Complications Due to Hemoglobinopathies in Pregnancy 38 Table 2.16: Prevalence of Gestational Diabetes in the U.S. 42 Table 2.17: Countries with Higher and Lower Rates of Preterm Births 45 Table 2.18: Prevalence of Preterm Births in the U.S. by Stage 46 Table 2.19: Prevalence of Preterm Births in the U.S. by Race/Ethnicity 47 Table 2.20: Prevalence of Preterm Births in the U.S. by Plurality of Birth, 2013 48 Table 2.21: Prevalence of Preterm Births in the U.S. by Maternal Age 48 Table 2.22: Related Complications of Placenta Previa 50 Table 2.23: Mode of Delivery for Beech Presentation 50 Table 2.24: Perinatal Outcome due to Meconium Stained Liqor 51 Table 2.25: Pregnancy Outcome due to Polyhydramnios 51 Table 2.26: Causes of Fetal Growth Restrictions 52 Table 2.27: Prevalence of Congenital Cardiovascular Defects in Fetuses in the U.S. 53 Table 3.1: Worldwide Prevalence of Huntington Disease by Selected Country 55 Table 3.2: Prevalence of 25 Most Common CFTR Mutations in the U.S.,2013 62 Table 3.3: Molecular Genetic Testing Used in Canavan Disease 63 Table 3.4: Incidence of SCD in the U.S. 66 Table 3.5: Red Blood Cell Indices in Beta-Thalassemia 67 Table 3.6: Molecular Genetic Testing Used in Beta-Thalassemia 68 Table 3.7: Chances of Inheriting a Single Gene Disorder 70 Table 3.8: More Common Recessive Disease Traits in Selected Ethnic Groups 71 Table 3.9: A Comprehensive List of Genetic Disorders 71 Table 3.10: Turnaround Time and Average Cost for Hemophilia Genetic Testing 78 Table 3.11: Incidence of Chromosomal Abnormalities 83 Table 3.12: Karyotypes Commonly Associated with Klinefelter Syndrome 84 Table 3.13: Features of Turner Syndrome in Different Age Groups 85 Table 3.14: Some Complications of Down syndrome 86 Table 3.15: Incidence of Down syndrome by Maternal Age 88 Table 3.16: Developmental Delay in Down syndrome Children 89 Table 3.17: Frequently Observed Anomalies in Babies with Edward’s Syndrome 90 Table 3.18: Common Clinical Features of Trisomy 13 91 Table 3.19: Congenital Anomalies Associated with Triploidy 92 Table 3.20: Relative Frequencies of Different Abnormalities in Chromosomally Abnormal Spontaneous Abortions 94 Table 3.21: Maternal Age-Related Frequency of Aneuploid Fetuses Detected Prenatally 94 Table 3.22: Clinical Features of Babies with Common Autosomal or Sex Chromosome Aneuploidy 95 Table 3.23: Maternal Age and Chromosomal Abnormalities Detected at Amniocentesis 95 Table 3.24: Sensitivity and Specificity of Maternal Serum and Ultrasound Tests 96 Table 3.25: Common Autosomal Deletions, Resulting Syndromes and Clinical Features 97 Table 3.26: Common Autosomal Microdeletion Syndromes 100 Table 3.27: Commonly Encountered Problems in Prader-Willi Syndrome 102 Table 3.28: Testings Used in Prader-Willi Syndrome 102 Table 3.29: Molecular Genetic Testing Used in the 22q 11.2 Deletion Syndrome 106 Table 3.30: Autosomal Duplication Syndromes 107 Table 3.31: Molecular Genetic Testing Used in Beckwith-Wiedemann Syndrome 108 Table 3.32: Molecular Genetic Testing Used in Charcot-Marie-Tooth Neuropathy Type 1 (CMT1) 109 Table 5.1: Major Prenatal Screening Tests during the First and Second Trimesters 113 Table 5.2: Other Routine and Non-Routine Prenatal Screening Tests 114 Table 5.3: hCG Levels from Date of Conception to 40th Week 114 Table 5.4: Selected β-hCG Kits and Manufacturers 115 Table 5.5: Selected PAPP-A Kits and Manufacturers 115 Table 5.6: Selected MSAFP Test Kits and Manufacturers 116 Table 5.7: Selected uE3 Test Kits 116 Table 5.8: Selected Inhibin-A Test Kits 117 Table 5.9: Selected Hexosaminidase Test Kits 117 Table 5.10: Comparison of the Four Maternal Serum Screening Analyte Patterns 118 Table 5.11: The Five Popular Commercially Available NIPTs 118 Table 5.12: Sensitivity and Specificity of NIPT 119 Table 5.13: Prenatal Screening/Diagnostic Applications of cffDNA 119 Table 5.14: Time of Availability of cffDNA in Maternal Plasma 119 Table 5.15: The Cost of NIPT Testing by Country/Region 120 Table 5.16: Cost of NIPTs by Product 120 Table 5.17: History of Aneuploid Screening 121 Table 5.18: NIPT Methods for Detecting Aneuploidy 122 Table 5.19: Comparison of Amniocentesis and NIPTs 122 Table 5.20: Advantages and Disadvantages of NIPTs 123 Table 5.21: Comparison of Some Performance Criteria for the commonly used Prenatal Tests 123 Table 5.22: Comparison of NIPT Detection Rate with Traditional Screening Tests 124 Table 5.23: False Positive Rates (FPR) of NIPTs Compared with Traditional Screening Tests 124 Table 5.24: Different Applications of Ultrasound in Different Trimesters 126 Table 5.25: MRI Indications for Prenatal Screening when the Ultrasound Screen is Inadequate 127 Table 5.26: Prenatal Diagnostic Tests by Pregnancy Stage 127 Table 5.27: Comparison of CVS and Amniocentesis 130 Table 5.28: Advantages and Disadvantages of Prenatal Diagnostic Tests 131 Table 5.29: Comparison of Noninvasive Prenatal Diagnosis Using Fetal DNA and Intact Fetal Cells Isolated from Maternal Blood 133 Table 6.1: Thirty One Core Conditions Detected During Newborn Screening 135 Table 6.2: The Combined Incidence of Amino Acidemias, Organic Acidemias and Fatty Acid Oxidation Defects in Selected Countries 136 Table 6.3: Catyegories of Newborn Genetic Disorders 137 Table 6.4: Genetic or Metabolic Disorders Detectable by MS/MS and their Scores 138 Table 6.5: Incidence of PKU by Region 139 Table 6.6: Molecular Genetic Testing Used in Biotinidase Deficiency 143 Table 7.1: Advantages and Disadvantages of Available PGS/PGD Technologies 148 Table 7.2: Genetic Diseases Detected during PGD 148 Table 7.3: Currently Available Products for PGD Testing 153 Table 7.4: Average Cost of in vitro Fertilization and Related Procedures 154 Table 8.1: Karyotyping vs. Microarray Analysis 161 Table 8.2: The Format of FISH Test Results 164 Table 8.3: Some commonly used FISH-Based Tests 164 Table 8.4: Microdeletions/Microduplications Detectable by FISH 165 Table 8.5: FISH Probes and Functions 166 Table 8.6: Presentation Format of array-CGH Test Report 167 Table 8.7: Harmony vs. Traditional Down Syndrome Tests 168 Table 8.8: Predictive Value, Sensitivity and Specificity of InformaSeq Test 170 Table 8.9: Detection Rates of Panorama Test 171 Table 8.10: NIFTY Test Options 172 Table 8.11: Clinical Data for Iona Test 173 Table 8.12: Sensitivity and Specificity of Verfy Test 174 Table 8.13: Sensitivity and Specificity of Verify for Microdeletion Syndromes 175 Table 8.14: Comparison of Karyotyping and MaterniT GENOME Test 175 Table 8.15: Sensitivity and Specificity of MaterniT GENOME Test 176 Table 8.16: MaterniT21 PLUS Test’s Independent Validation 176 Table 8.17: The Three Panels Offered by HerediT UNIVERSAL Carrier Screen 177 Table 8.18: Comparison of MaterniT21 PLUS, Verifi, Harmony and Panorama Tests 177 Table 8.19: U.S. Patents for NIPTs by Company 178 Table 8.20: Selected Issued Patents of NIPTs 179 Table 8.21: Major U.S. Patents and Applications of Current and Emerging Prenatal Aneuploidy Tests Table 8.22: Detection, False Positive, Uptake and Failure Rates for Prenatal Screening Types 181 Table 8.23: Cost of Different Prenatal Screens 181 Table 9.1: Global Market for Fetal Ultrasound Screening by Geography, Through 2021 196 Table 9.2: Global Fetal Ultrasound Market Share by Company, 2014 197 Table 9.3: Global Market for MRI Prenatal Screening by Geography, Through 2021 198 Table 9.4: Global Market for Maternal Serum Screening Tests by Geography, Through 2021 199 Table 9.5: Global Market for NIPT by Geography, Through 2021 201 Table 9.6: Global Market for NIPTs by Product 202 Table 9.7: Global Market for Prenatal Diagnostic Tests, Through 2021 203 Table 9.8: Global Market for Newborn Screening by Technology, Through 2021 205 Table 9.9: Global Market for Pre-implantation Genetic Diagnosis (PGD), Through 2021 206 Table 11.1: Adoption Rates for Prenatal Screening in the U.S. 217 Table 12.1: Comparison of Harmony and Other Traditional Tests 234 Table 12.2: CombiSNP Prenatal Targeted Array Disorder List 249 Table 12.3: Genetic Tests Offered by Correlagen by Gene and Disease 256 Table 12.4: GeneDx’s Cytogenetics and Biochemical Tests 276 Table 12.5: Performance of Verifi Test 284 Table 12.6: Verifi Prenatal Test Lab Partners in the U.S. 285 Table 12.7: Comparison of Prenatal Test Performance 289 Table 12.8: Comparison of False Negative Rates 290 Table 12.9: A Small Sample of Diseases Screened by Horizon Test 291 Table 12.10: Clinical Data for IONA Test 299 Table 12.11: Sensitivity and Specificity of MaterniT GENOME Test 306 Table 12.12: Sensitivity and Specificity of MaterniT21 PLUS Test 307 Table 12.13: Three Options Offered by HeridiT UNIVERSAL Carrier Screen 308 Table 12.14: Clinical Evaluation Performance of VisibiliT Prenatal Test 308 Table 12.15: CF Detection Rates for Standard and Expanded Panels 309 Table 12.16: Accuracy, Sensitivity and Specificity of SensiGene Fetal RHD 309 Table 12.17: NextView Diagnostic Test Platforms 310 180