Table Of ContentChristina Vogt Isaksen
PRENATAL ULTRASOUND AND
POSTMORTEM FINDINGS
A ten year correlative study of fetuses and infants
with developmental anomalies
NTNU Trondheim
Norwegian University of Science and Technology
1!1 Faculty of Medicine
Christina Vogt Isaksen
PRENATAL ULTRASOUND AND POSTMORTEM FINDINGS
A ten year correlative study off etuses and infants with developmental anomalies
Christina Vogt Isaksen
PRENATAL ULTRASOUND AND
POSTMORTEM FINDINGS
A ten year correlative study of fetuses and infants with
developmental anomalies
I dedicate this thesis to
my three children who
were given the gift of life
Publication from the Norwegian University
of Science and Technology
National Center for Fetal Medicine
Depmtment of Gynecology and Obstetlics
Department of Pathology
Department of Laboratory Medicine
Trondheim University Hospital
N-7005 Trondheim, Norway
© Christina Vogt Isaksen
ISSN 0805-7680
Printed by TAPIR trykkeri
Januar 2000
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CONTENTS
ACKNOWLEDGMENTS .............................................................................................. 7
ABBREVIATIONS ........................................................................................................ lO
LIST OF PAPERS ......................................................................................................... ll
SUMMAR¥. ................................................................................................................... 12
INTRODUCTION ......................................................................................................... 14
General Background ..................................................................................................... 14
Historical Background .................................................................................................. 16
Congenital anomalies .......................................................................................... 16
Ultrasound examination ...................................................................................... 17
Perinatal pathology ............................................................................................. 18
Fluorescence in situ hybridization (FISH) .......................................................... 21
General Considerations ................................................................................................ 22
Terminology and definitions ............................................................................... 22
Etiology ............................................................................................................... 23
Chromosome aberrations ......................................................................... 23
Inherited genetic diseases ........................................................................ 24
Non-genetic causes .................................................................................. 25
Survey of Anomalies ..................................................................................................... 30
Central nervous system anomalies (CNS) ........................................................... 30
Congenital heatt defects (CHD) .......................................................................... 35
Urinary system anomalies ................................................................................... 37
Body wall defects ............................................................................................... 40
Fetal hydrops ...................................................................................................... 41
Cystic hygroma .................................................................................................. .42
Nuchal edema ..................................................................................................... .42
Chromosome aberrations ................................................................................... .43
AIM OF THE STUD¥. ................................................................................................ 48
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MATERIAL AND METHODS .................................................................................. .49
Study population ................................................................................................ .49
Ultrasound examination ..................................................................................... .49
Autopsy ............................................................................................................... 50
Fluorescence in situ hybridization (FISH) .......................................................... 51
RESULTS ..................................................................................................................... 52
GENERAL DISCUSSION ........................................................................................... 61
Introduction ........................................................................................................ 61
Value of perinatal autopsy .................................................................................. 62
Perinatal mortality and incidences of congenital anomalies ............................... 63
Comparison of prenatal ultrasound and postmortem findings ............................ 63
Comparison of the different organ systems ....................................................... 65
Comparison of detection rate between CNS anomalies, CHD, and
urinary system anomalies ................................................................................... 67
Detection of anomalies over time ....................................................................... 69
Markers of chromosome aberrations ................................................................. 69
Fluorescence in situ hybridization (FISH) ......................................................... 70
Quality assurance ............................................................................................... 70
CONCLUSIONS .......................................................................................................... 73
REFERENCES ............................................................................................................ 74
PAPERS I-V ................................................................................................................. 90
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ACKNOWLEDGMENTS
This work is the result of a joint study between the Department of Pathology and the National
Center for Fetal Medicine (NCFM), Department of Obstetrics and Gynecology, University
Hospital ofTrondheim. For all those who have supported me in my work, I am greatly
indebted.
Without the National Center for Fetal Medicine this work would not have been possible. The
center has provided the background and the material for the present study. It is therefore
natural to commence by expressing sincere gratitude to my tutor, Professor Sturla Hall Eik-
Nes, who has guided me through these exciting years of gathering knowledge about
congenital anomalies. His dedicated work for the center has laid the foundation for collecting
the material. His clear thinking, enthusiasm and interest have encouraged and inspired me. He
set forth to stagger my impatience and teach me the impmiance of meticulous and detailed
research. I am very grateful for his always constructive advice, positive attitude and
friendship.
My colleague, Sverre Helge Torp, M.D. Ph.D. has been my co-tutor and co-author at the
Department of Pathology. He has given me valuable advice and help in systematizing and
organizing my thoughts and ideas. His constant support and encouragement have helped me
through feelings of despair and lack of confidence. I want to express my sincere gratefulness
for his friendship, for his positive and constructive criticism and for being easily accessible.
The former head of the Department of Pathology, Professor Olav A. Haugen, provided the
facilities and support necessary to accomplish the project, for which I am very grateful. The
present head of the department Tore B. Halvorsen, M.D. Ph.D. has continued this benevolence
and encouraged me through the final preparations. Professor Kare Moine, head of the
Department of Gynecology has inspired me through his positive attitude.
My co-author Harm-Gerd Blaas, M.D. Ph.D. has contributed to this work in introducing me
into the world of fetal development and congenital anomalies. His extensive knowledge in this
field has been of great help and immense inspiration. His appreciation of my work, his
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encouragement and enthusiasm have greatly enhanced my dedication to fetal and perinatal
pathology.
My co-authors not already mentioned deserve special thanks. My office-neighbor S0lvi
Skarsvag M.Sc. Ph.D. has stimulated me with challenging discussions in addition to
encouraging me through these years. I have great respect for her knowledge of molecular
biology. The perseverance ofBorgny Ytterhus B.Sc. made possible the use ofFISH
technology and C.N.M. Eva Tegnander's knowledge of congenital heart defects has inspired
me to further learning.
Financial support for the project has been furnished by the county of S0r-Trondelag. I feel
very privileged to have been given the opportunity to become absorbed in this comparative
study of ultrasound and pathology. I therefore want to direct my thanks to this financial source
and to the persons involved, in particular Professor Helge L. Waldum who through these years
has given me valuable advice and encouragement.
I owe special thanks to all my collaborators/co-workers in the two departments and to mention
some would mean to leave out others. A few persons do deserve special attention though: at
the NCFM I want to thank Gunn Barreth for her never ending cheerful obligingness, Kristin
T. Gnesli for enthusiastic help with data collection and figures, and Richard Holm, M.Sc.,
also for help with figures. At the Department of Pathology I want to thank Sigrun 0rnsj0 for
always being helpful with typing lists of literature and advice on word processing and Gunnar
Kopstad, M.Sc. Ph.D, for computer assistance. I also want to thank the technicians at the
autopsy lab: Thorbjorn Aass, Oddgeir Jakobsen and Bj0rn Reinsborg, for their always
constructive help and support in the practical pati of this work. Finally, without the help of my
colleague Anne-Grete Bolz, M.D., performing the autopsies in my absence and always willing
to help, this work would have been difficult to fulfill.
Nancy Lea Eik-Nes deserves a special word of gratitude. Her dedicated revision of the
manuscripts and this thesis has been of invaluable help. My confidence in her understanding
of medical writing is infinite.
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My warm thoughts go to all the parents and siblings of these fetuses and infants who were not
destined to live. No word of condolence can ever ease their pain. It is my hope that increased
knowledge of congenital anomalies will teach us more about the mechanisms and etiologies
of these conditions enabling us to prevent at least some of them.
Last, but not the least, I want to thank my family and my friends who supported and
encouraged me. I sincerely appreciate my husband Lennart's kind patience and understanding
when I had no time for him. A never ending source of inspiration has been my beloved three
children Lena, Daniel and Joachim who helped me by taking responsibility and being present
and accessible whenever I had a little spare time.
Trondheim, June 1999
Christina Vogt Isaksen
