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The Utility of Embryofeto-Pathology Following Surgical Terminations of Pregnancy

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The Utility of Embryofeto-Pathology Following Surgical Terminations of Pregnancy THE UTILITY OF EMBRYOFETO-PATHOLOGY FOLLOWING SURGICAL TERMINATIONS OF PREGNANCY by ROBERT TOD LENARD MACPHERSON B.Sc., The University of British Columbia, 1992 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Medical Genetics Graduate Programme, Department of Medical Genetics) We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA December 1997 ® Robert Tod Lenard MacPherson, 1997 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department The University of British Columbia Vancouver, Canada DE-6 (2/88) Abstract Embryofeto-pathology examination findings for 521 consecutive pregnancy terminations for fetal abnormalities were compared on the basis of method of termination, results of prenatal cytogenetic investigations, and gestational age at termination. Comparisons were undertaken to ascertain if, as generally assumed, the amenability of the products of conception to embryofeto-pathological examination is less following pregnancy termination by surgical means than following termination by induction. Embryofeto-pathological examination provided a diagnosis that could be used for genetic counseling 42.2 (95% C.I. = 5.45 - 327.04) times more often following termination by induction, as compared to termination by surgical procedures. Pregnancy termination was performed by surgical procedure 2.17 (95% C.I. = 1.39- 3.39; P = 0.0006) times more often when the fetus was identified prenatally to be karyotypically abnormal and 0.72 (95% C.I. = 0.66 - 0.78; P < 0.0001) times less often with each one week increase in the estimated gestational age at termination between 10 and 24 weeks. Among terminated pregnancies with specific ultrasound diagnosed fetal abnormalities, the ability to evaluate ultrasound-identified fetal abdominal wall defects was 30.60 (95% C.I. = 1.63 - 575.84; P = 0.00107) and cystic hygroma was 146.18 (95% C.I. = 7.97 - 2680.93; P < 0.00001) times less likely at autopsy following surgical termination procedures as compared to terminations by induction. The ability to evaluate ultrasound identified fetal anencephaly 8.91 (95% C.I. = 0.39 - 202.07; P = 0.15), cystic kidney disease (odds ratio N/A, P = N/A), diaphragm defects 19.00 (95% C.I. = 0.83 - 434.47; P = 0.03), fetal hydrops 9.00 (95% C.I. = 0.45 - 178.12; P = 0.13), and structural heart defects 21.00 (95% C.I. = 1.08 - 409.15; P=0.01) times less likely following surgical termination procedures as compared to terminations by induction. As multiple tests were performed on the data, a critical P value of 0.00385 was used to test for significance. The trend in each case was for surgical termination to be informative less frequently than medical termination. Among pregnancies terminated with any prenatally diagnosed fetal abnormality, the ability to evaluate the CNS tissue was 36.20 (95% C.I. = 21.77 - 60.19; p<0.00001), heart was 16.76 (95% C.I. = 5.18 - 54.24; pO.OOOOl) and kidneys was 5.04 (95% C.I. = 1.74 - 14.61; p=0.0005) times less likely at autopsy following surgical pregnancy termination procedures, as compared to termination by induction. The ability to evaluate the CNS tissue, heart and kidneys at autopsy following surgical termination procedures were found to be 1.26 (95% C.I. = 1.1 - 1.44; P = 0.0008), 1.19 (95% C.I. = 1.07 - 1.32; P = 0.0012) and 1.35 (95% C.I. = 1.15 - 1. 58; P = 0.0001) times, respectively, more likely for each one week increase in the estimated gestational age at termination. The results of these comparisons confirm that the amenability of the products of conception to embryofeto-pathological examination is reduced following surgical termination procedures, as compared to medical termination procedures. This may have important clinical implications for women considering pregnancy termination following ultrasound diagnosis of fetal abnormalities. V Table of Contents Page Abstract ii Table of Contents v List of Tables x List of Figures xi Acknowledgments xii Chapter 1 Introduction 1 1.1 Overview of Prenatal Diagnosis 1 1.1.1 Accuracy Measures of Prenatal Diagnosis 2 1.2 Maternal Serum Triple Screening 2 1.3 Cytogenetic Investigations 4 1.3.1 Chorionic Villus Sampling 5 1.3.2 Amniocentesis 6 1.3.3 Cordocentesis 8 1.4 Overview of Ultrasonography 9 1.4.1 Accuracy of Ultrasonography 13 1.4.2 Ultrasound Markers of Aneuploidy 15 1.4.3 Ultrasound Detection of Anencephaly 18 1.4.4 Ultrasound Detection of Abdominal Wall Defects 18 1.4.5 Ultrasound Detection of Congenital Heart Defects 20 1.4.6 Ultrasound Detection of Cystic Hygroma 21 1.4.7 Ultrasound Detection of Cystic Kidneys 22 vi 1.4.8 Ultrasound Detection of Diaphragmatic Defects 23 1.4.9 Ultrasound Detection of Fetal Hydrops 24 1.5 Overview of Pregnancy Termination 25 1.5.1 Overview of Medical Termination Procedures 26 1.5.1.1 Advantages and Disadvantages of Medical Terminations 26 1.5.2 Overview of Surgical Termination Procedures 27 1.5.2.1 Dilatation of the Cervix 27 1.5.2.2 Disruption of the Fetus 29 1.5.2.3 Advantages and Disadvantages of Surgical Terminations 29 1.6 Overview of Fetal Pathology 30 1.6.1 Overview of the Autopsy Examination 30 1.6.2 Overview of Congenital Abnormalities 31 1.6.2.1 Classification of Fetal Abnormalities 31 1.6.3 Etiology of Fetal Abnormalities 32 1.7 Overview of Genetic Counseling 33 1.7.1 Recurrence Risks 34 1.8 Aims of the Study 3 5 Chapter 2 Methods and Subjects 38 2.1 Ascertainment of Subjects 38 2.2 Sources of Data 39 2.2.1 Maternal Information 39 vii 2.2.2 Ultrasound Information 39 2.2.3 Autopsy Information 40 2.2.4 Cytogenetics Information 40 2.3 Database Construction 41 2.4 Data Coding 41 2.5 Analysis 42 2.5.1 Ability to Make a Final Diagnosis at Autopsy 42 2.5.2 Method of Pregnancy Termination 43 2.5.3 Tissues Examined at Autopsy 44 2.5.4 CNS, Heart and Kidneys Evaluated at Autopsy 47 2.6 Statistical Analysis 48 2.6.1 Chi Square Test 48 2.6.2 Fisher's Exact Test 50 2.6.3 Multiple Logistic Regression 51 2.6.3.1 Evaluation of Multiple Logistic Regression 54 2.6.4 Odds Ratios 56 2.6.5 Significance Levels 57 2.7 Ethical Review 58 Chapter 3 Results 60 3.1 Sample Analyzed 60 3.2 Sample for Method of Termination Analysis 60 3.3 Diagnosis Based on Autopsy Analysis 62 viii 3.4 Specific Tissue Examined At Autopsy Analysis 63 3.5 Evaluation of CNS, Heart, Kidney at Autopsy Analysis 68 3.6 Results of the Strength of Relationships Analysis 71 Chapter 4 Discussion 77 4.1 Population of Cases 77 4.2 Diagnosis Based on Autopsy Findings 79 4.3 Method of Termination 82 4.4 Specific Fetal Tissues Evaluated at Autopsy 87 4.5 CNS, Heart, and Kidneys Evaluated at Autopsy 94 Chapter 5 Conclusion 99 Reference 102 Appendix I 111 Appendix II 112 Appendix III 147 Appendix IV 196 Appendix V 204 Appendix VI 205 ix List of Tables From Chapter 1 - Introduction Table 1.1 Ultrasound Markers of Trisomy 21 17 Table 1.2 Ultrasound Markers of Trisomy 13 17 Table 1.3 Ultrasound Markers of Trisomy 18 17 Table 1.4 Markers of Chromosomal Aneuploidy 17 Table 1.5 Disorders Associated With Nonimmune Hydrops Fetalis 24 Table 1.6 Recommendations For Cervical Dilatation 28 From Chapter 2 - Methods and Subjects Table 2.1 Case Subgroups Used in Analysis 45 Table 2.2 Sample 2X2 Contingency Table 48 Table 2.3 Response Variables Used in Logistic Regression 53 From Chapter 3 - Results Table 3.1 Results of Cytogenetic Investigations 61 Table 3.2 Distribution of Method of Termination By Prenatal Cytogenetic Results 62 ' Table 3.3 Distribution of Cases With Diagnosis Based on Autopsy Findings 63 Table 3.4 Distribution of the Cases Terminated with Specific Ultrasound-Identified or -Suspected Fetal Abnormalities 65 Table 3.5 Distribution of Surgically Terminated Cases with Specific Ultrasound-Identified or -Suspected Fetal Abnormalities By The Results of Prenatal Cytogenetic Investigations 67 X Table 3.6 Distribution of Surgically Terminated Cases with Specific Ultrasound-Identified or -Suspected Fetal Abnormalities By The Estimated Gestational Age at Termination 68 Table 3.7 Distribution of Cases with CNS Tissue, Heart, and Kidney Exam At Autopsy By The Method of Termination 70 Table 3.8 Distribution of Surgically Terminated Cases with CNS Tissue, Heart, or Kidney Exam at Autopsy By The Prenatal Cytogenetic Results 71 Table 3.9 Results of Multiple Logistic Regression Analysis - Part A 73 Table 3.10 Results of Multiple Logistic Regression Analysis - Part B 76 List of Figures Figure 2.1 Relationships Analyzed in Logistic Regression 53 Figure 3.1 Distribution of Method of Termination By Estimated Gestational Age at Termination 62 Figure 3.2 Distribution of Surgically Terminated Cases Against the Estimated Gestational Age at Termination 72 Acknowledgments I would like to thank my supervisor, Dr. B. McGillivray, without whose guidance and continuous encouragement this project would not have been possible.
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