Table Of ContentJ.
H. W. Sutherland· M. Stowers
D. W. M. Pearson (Eds.)
Carbohydrate Metabolism
in Pregnancy
and the Newborn ·IV
With 60 Figures
Springer-Verlag
london Berlin Heidelberg New York
Paris Tokyo
H. W. Sutherland, MBChB, FRCOG
Clinical Reader in Obstetrics and Gynaecology, Aberdeen Maternity Hospital,
Foresterhill, Cornhill Road, Aberdeen, AB9 2ZA, UK
J. M. Stowers, MA, MBChB, MD, FRCP, FRCOG
Emeritus Professor of Dietetics and Endocrinology, University of Aberdeen,
13 Westerton Road, Cults, Aberdeen, ABI 9MR, UK
D. W. M. Pearson, MBChB, MRCP
Consultant Physician, Diabetic Clinic, Woolman Hill, Aberdeen Royal Infirmary,
Aberdeen AB9 2ZB, UK
ISBN-13: 978-1-4471-1682-0 e-ISBN-13: 978-1-4471-1680-6
DOl: 10.1007/978-1-4471-1680-6
British Library Cataloguing in Publication Data
Carbohydrate metabolism in pregnancy and the newborn IV
1. Newborn babies & pregnant women. Carbohydrates. Metabolism I. Sutherland,
Hamish W. (Hamish Watson), 1933- II. Stower, John M. (John Marcus), 1919-
III. Pearson, D.W.M. (Donald W.M.), 1950- 612'.396
Library of Congress Cataloging-in-Publication Data
Carbohydrate metabolism in pregnancy and the newborn IVIH.W. Sutherland, J.M.
Stowers, D.W.M. Pearson (editors). p. cm.
Based on the Fourth International Colloquium on Carbohydrate Metabolism in
Pregnancy and the Newborn held at the University of Aberdeen, Scotland in 1988.
Includes bibliographies and index.
1. Diabetes in pregnancy-Congresses. 2. Infants (Newborn)-Health and
hygiene--Congresses. 3. Carbohydrates-Metabolism-Disorders
Congresses. I. Sutherland, Hamish W. II. Stowers, John M. III. Pearson, D.
W. M. (Donald W. M.), 1950-- IV. International Colloquium on
Carbohydrate Metabolism in Pregnancy and the Newborn (4th: 1988: University of
Aberdeen [DNLM: 1. Abnormalities--etiology--congresses. 2. Carbohydrates
metabolism--congresses. 3. Pregnancy in Diabetes--complications-
congresses. 4. Pregnancy in Diabetes-metabolism--congresses. WQ 248 C2643
1988] RG580.D5C36 1989 618.3-dcI9 DNLMlDLC for Library of
Congress 89-4291 CIP
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Foreword
Traditions are dangerous; doubly so in science. Traditions are
unchanging; science is about change. This was the 4th International
Colloquium on Carbohydrate Metabolism in Pregnancy and the
Newborn to be held in Aberdeen, and by now the form is set. How
much its content has changed is a matter of nice judgement and not
under the control of the organizers. It is not within their power to bring
news of revolution, if there has been no revolution. Certainly many of
the speakers had kent faces from previous Aberdeen meetings, but so
they would be at any meeting on diabetes anywhere in the world.
The written proceedings of scientific conferences have purposes
other than to record changes: sometimes they need to state a
consensus. The 3rd Colloquium came to an agreement about the
importance of prepregnancy recognition and control of abnormalities
of carbohydrate metabolism. The 4th set out to examine what results it
had achieved. Much of this book is taken up with follow-up studies of
the applications of similar regimes in different parts of the world.
Since the first Aberdeen meeting in 1973, progress in the manage
ment of diabetic pregnancy has been slow and steady, but the change
in the city and the society where the meetings took place has been fast.
The foreword to the record of the 2nd Colloquium spoke of the lovely
crown tower of the University that has brooded over the six centuries
of academic comings and goings. The 3rd had no such tranquillity. It
spoke instead of the economic blight that had wilted conferences but
stated confidently that the University had survived many crises in its
long history and would emerge from this one a bit battered and a good
deal slimmer. In the short term, that confidence has been justified.
This book proves that we met again, on schedule, 5 years later. If our
masters in London mean what they say, the next one is in doubt.
It takes a lot of people to organize a conference and edit a book. It is
invidious to select one person and say: "He did it". There may not be
another opportunity to record one salient fact about all four of the
Aberdeen Colloquia on Carbohydrate Metabolism in Pregnancy and
the Newborn. Hamish Sutherland did it.
Aberdeen Arnold Klopper
November 1988
Preface
This book is based on the concepts discussed, clinical practice
described and ideas developed by the experts assembled at the Fourth
Quinquennial International Colloquium on Carbohydrate Metabo
lism in Pregnancy and the Newborn held in the University of
Aberdeen, Scotland, in 1988. The programme for the colloquium was
planned to cover all aspects of clinical care for women with established
diabetes and gestational diabetes mellitus. The aim of providing an
up-to-date, comprehensive manual for use in clinical practice
prompted the editors to include an additional chapter on obstetric
aspects of diabetic pregnancy. We trust that the expertise of all
authors will be appreciated by a wide clinical and scientific readership
in addition to those physicians, obstetricians and paediatricians
directly involved in metabolic and perinatal medicine. The over-riding
theme is the importance of integrated care in the management of
women with diabetes mellitus and this theme is paralleled by the
interdisciplinary research approach. The editors are most grateful to
the zeal and scholarship of the contributors and the expedition with
which they produced their manuscripts.
Grateful acknowledgement is made to Novo Industries and Nordisk
for sponsoring our Scandinavian colleagues and to Eli Lilly for
sponsoring our American colleagues. The following companies were
also generous to our travel fund: Boehringer, Bayer, Upjohn,
Hypoguard, Syntex Pharmaceuticals Limited, Becton Dickinson,
Boots & Company PLC, Clydesdale Bank, Rocket of London,
Scientific Medical Systems Limited, Picker, R. L. Dolby & Co.,
Schering, Amex and Vickers Medical. Lipha Pharmaceuticals contri
buted generously to the preparation of the colour illustrations.
Regrettably, the stimulating discussion following the papers and
posters at the colloquium is not included in this volume as we and the
publishers were anxious to achieve an early date for publication.
We wish to record our thanks to Michael Jackson of Springer
Verlag for his help and understanding in bringing this to fruition.
Lastly, we owe a great debt to the careful work of Mrs. Elaine Stirton
and Mrs. Sheila Mearns in the University Department of Obstetrics
and Gynaecology who have been tireless in their efforts to translate
viii Preface
our concept to the Fourth Colloquium and now to this publication
respectively and to Professor Templeton, Regius Professor of Obste
trics and Gynaecology for his enthusiastic support.
Aberdeen Hamish W. Sutherland
November 1988 John M. Stowers
Donald W. M. Pearson
Contents
1 The Development of Diabetes and its Relation to
Pregnancy: The Long-Term and Short-Term Historical
Viewpoint 1
D. R. Hadden, The Royal Victoria Hospital and
The Royal Maternity Hospital, Belfast, UK
Insulin-Dependent Diabetes 4
Non-Insulin-Dependent Diabetes 5
Gestational Diabetes, or the Onset of Hyperglycaemia
in Pregnancy 6
2 Polyendocrinopathy 9
R. L. Himsworth, Department of Medicine,
University of Aberdeen, Aberdeen, UK
3 Obesity and Fat Distribution 15
M. E. J. Lean, Diabetic Clinic, Aberdeen Royal
Infirmary, Aberdeen, UK; H. W. Sutherland, Aberdeen
Maternity Hospital, Aberdeen, UK; P. Garthwaite,
Department of Statistics, University of Aberdeen,
Aberdeen, UK
Introduction 15
Metabolic Aspects of Obesity 15
Genetics 15
Metabolic Factors Causing Obesity 16
Biochemical Effects of Obesity on Carbohydrate
Tolerance 17
Effect of Pregnancy on Obesity and Body Fat Content 19
Metabolic Association of Body Fat Distribution 19
Effect of Obesity and Fat Distribution on Carbohydrate
Tolerance in Pregnancy and Effects on the Newborn 20
Conclusions 23
x Contents
4 Nutrition in Pregnancy 25
W. T. James and Ann Ralph, Rowett Research Institute,
Bucksburn, Aberdeen, UK
Introduction 25
Protein Requirements in Pregnancy 26
Direct Assessment of Nutritional Status 28
Iron Requirements in Pregnancy 29
Plasma Vitamin Concentrations 30
Placental Transfer of Water-Soluble Vitamins 31
Dietary Fibre 33
Trace Elements 34
Calcium 35
Conclusions 35
5 The Metabolic Basis for Birth Defects in Pregnancies
Complicated by Diabetes Mellitus 39
N. Freinkel, Center for Endocrinology, Metabolism and
Nutrition, Northwestern University Medical School,
Chicago, IL 60611, USA
Studies with Rat Embryo Culture 40
Clinical Extrapolation 42
The "Honeybee Syndrome" and Implications for
Periconceptional Management of Diabetes 43
General Summary 46
6 Diabetes in Pregnancy: Genetic and Temporal
Relationships of Maldevelopment in the Offspring of
Diabetic Rats 51
U. J. Eriksson, J. Styrud and R. S. M. Eriksson,
Department of Medical Cell Biology, University of
Uppsala, Sweden
Introduction 51
Genetic Predisposition 52
Teratogenic Period 55
Organ Maldevelopment 58
Methods 58
Results and Discussion 58
Conclusions 61
7 Diabetes Mellitus and Infertility 65
J. M. Randall, A. Hesham and A. A. Templeton,
Department of Obstetrics and Gynaecology, University of
Aberdeen, Aberdeen, UK
Introduction 65
Endocrine Abnormalities and Defects of Ovulation 65
Problems of Oocyte Pick-up 66
Unexplained Infertility 67
Secondary Infertility 67
Contents xi
Survey of Diabetic Women 68
Male Infertility 69
Impotence 70
Retrograde Ejaculation 70
8 Epidemiology of Spontaneous Abortion in Insulin-
Dependent Diabetic Women 75
N. C. Smith, Aberdeen Maternity Hospital, Aberdeen,
UK
Introduction 75
Pathogenesis of Spontaneous Abortion in Insulin-
Dependent Diabetic Women 76
Problems of Data Collection and Analysis 77
Definition 77
Methods of Detection 77
Characteristics of the Study Population 78
The Frequency of Spontaneous Abortion 78
Conclusions 80
9 Ultrasound Studies on Fetal Growth 83
J. Fog-Pedersen, L. MfjJlsted-Pedersen and S. MfjJller,
University of Copenhagen, Copenhagen, Denmark
Early Growth Delay 83
Summary and Conclusions on Early Growth Delay 86
Fetal Growth in the Second and Third Trimesters 86
Growth of Head and Trunk 86
The Population Growth Curve 89
Detection of Manifest Macrosomia 90
Detection of Developing Macrosomia 91
10 Magnetic Resonance Imaging of the Feto-placental Unit 95
F. W. Smith, Department of Nuclear Medicine, Aberdeen
Royal Infirmary, Aberdeen, UK
Introduction 95
Physical Principles 96
Patients and Methods 98
Observations 98
Discussion 104
11 The Placenta in Diabetes Mellitus 109
H. Fox, Department of Pathology, University of
Manchester, Stopford Building, Oxford Road,
Manchester, UK
Introduction 109
Morphology of the Placenta in Diabetes Mellitus 109
Macroscopic Appearances 109
Histological Findings 110
Ultrastructural Changes 110
xii Contents
Morphometric Studies 111
Immunopathology of the Placenta in Diabetes Mellitus 112
Relationship Between Placental Abnormalities, Severity
of the Diabetic State and Degree of Diabetic
Control 112
Pathogenesis of Placental Abnormalities in Diabetes
Mellitus 113
Functional Significance of Placental Changes in Diabetes
Mellitus 115
Conclusions 115
12 Amniotic Fluid Levels of Insulin and C-Peptide in
Pregnancies Complicated by Diabetes Mellitus 119
B. Persson, H. Pschera, U. Hanson, N. O. Lunell,
Department of Paediatrics, KS/St Goran's Hospital,
Department of Obstetrics and Gynaecology, KS and
Huddinge Hospitals, Karolinska Institute, Stockholm,
Sweden
Levels of Insulin and C-Peptide in Amniotic Fluid 119
Amniotic Fluid C-Peptide/Insulin and Substrate Levels 123
Amniotic Fluid C-Peptide/lnsulin and Fetal Size 124
Amniotic Fluid C-Peptide and other Hormones in
Amniotic Fluid 125
Amniotic Fluid C-Peptide/Insulin and Perinatal Outcome 126
13 Prepregnancy Preparation 129
Judith M. Steel, Diabetic Department, Edinburgh Royal
Infirmary, Edinburgh, UK; F. D. Johnstone, Department
of Obstetrics and Gynaecology, University of Edinburgh,
Edinburgh, UK; A. F. Smith, Department of Clinical
Chemistry, Edinburgh Royal Infirmary, Edinburgh, UK
Congenital Abnormalities 129
Relevance of Hyperglycaemia 129
Possible Relevance of Hypoglycaemia 132
Complications of Diabetes 134
Retinopathy 134
Nephropathy 135
Attendance at Prepregnancy Clinic 136
Infertility 137
Conclusion 138
14 Management of the Insulin-Dependent Diabetic Woman:
Problems with Pregnancy 141
D. W. M. Pearson, Diabetic Clinic, Aberdeen Royal
Infirmary, Aberdeen, UK; H. W. Sutherland, Aberdeen
Maternity Hospital, Aberdeen, UK
