Table Of ContentPathology of
Multiple Pregnancy
Virginia J. Baldwin
Pathology of
Multiple Pregnancy
With 199 Illustrations in 316 Parts
Springer-Verlag
New York Berlin Heidelberg London Paris
Tokyo Hong Kong Barcelona Budapest
Virginia J. Baldwin, M.D.
British Columbia's Children's Hospital
Department of Pathology
4480 Oak Street
Vancouver, B.C. V6H 3V4 Canada
Library of Congress Cataloging-in-Publication Data
Baldwin, Virginia J.
Pathology of multiple pregnancy / Virginia J. Baldwin.
p. cm.
Includes bibliographical references and index.
ISBN-13:978-1-4613-9516-4
I. Multiple pregnancy-Complications. I. Title.
[DNLM: I. Diseases in Twins. 2. Pregnancy Complications.
3. Pregnancy, Multiple. 4. Twins, Monozygotic. WQ 235 BI82p 1993]
RG567.B35 1993
618.2'5-dc20
DNLMlDLC
for Library of Congress 92-48343
Printed on acid-free paper.
© 1994 Springer-Verlag New York Inc.
Softcover reprint of the hardcover I st edition 1994
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ISBN-13:978-1-4613-9516-4 e-ISBN-13:978-1-4613-9514-0
DOl: 10.1007/978-1-4613-9514-0
This text is dedicated to the multiplets-the twins and
supertwins. I hope that what we have learned from you
will help those yet to come.
Foreword
It is almost exactly twenty years since Virginia J. Baldwin, M.D., first became
part of my laboratory at the Chicago Lying-In Hospital as a special trainee in
placentology. She demonstrated quickly the capacity for close attention to detail so
evident in the pages that follow of this important compilation on twinning. She was
able to spend this time with my late colleague, Prof. John R. Esterly and myself,
and later, with Drs. William Blanc and Kurt Benirschke, because of the supportive
environment created in Vancouver by the then chairman of pathology, Prof. David
F. Hardwick. She was thus in an institution with a large obstetrical service and
active interests in reproductive pathology with the intellectual climate so vital to
thoughtful work. This wonderful book is the logical product of that skill given the
opportunity to exercise it. Such circumstances are all too rare these days; my own
career goes back to the time when it was the norm to give a scholar or researcher the
time to work at length on a matter of importance, undistracted by grant deadlines
or the necessity for competition for resources that is occasionally destructive of
creative insight. This may be an unrecognized benefit ofthe Canadian health care
system, which, while less dedicated to research in general, is large enough for
universities with medical institutions to be able to provide the occasional niche for
genuine scholarly endeavor. In my own more recent career, I have tried to find that
in the American system; my current post in Memphis is perhaps the best that can be
obtained on our side of the border.
It was through this environment that Dr. Baldwin became aware of the embryo
collection so well managed by Dr. Betty Poland. That function made great use of
photodocumentation. The benefit of an expert photographic unit is generously
evidenced in this book, a treasure of mostly original photographs illustrating very
broad experience.
You, the reader, have before you a carefully crafted work, one very well
illustrated and drawing from the richness of twin literature. Twins do continue to
fascinate and the reader benefits from Dr. Baldwin's evident fascination. She
gives us a synopsis of the history of twinning, the early concepts, and then goes
into an exposition on mechanisms. I was personally gratified to see her treatment
of the less well known phenomenon of dispermic monovular twinning, and in
particular the discussion of the seeming paradox of paternal factors.
Over thirty years ago I became the father of twins in a family with two other sets
of twins close by entirely on my side of the family with their paternal grandmother
as the link. To be more precise, I have twin daughters, twin grandnephews (via my
Vll
viii Foreword
sister and her elder daughter), and a pair of male-female twin great uncles and
aunts (siblings of my maternal grandmother). This may be of interest because
examination of the placenta of my twins, and later, at age 12, of their blood groups
(ABO, Rh, MNS) and fingerprints, strongly indicated dispermic monovular
twinning. Now, by the much more comprehensive techniques so well summarized
by Dr. Baldwin in Chapter 2, similar cases would have a larger data matrix of
proof, especially DNA studies. As she well emphasizes, the likelihood is that this
"third" type of twinning is more common than is generally considered. Neverthe
less, as she is at pains to emphasize, there is a lot that remains unknown about the
mysteries of twinning.
Dr. Baldwin provides food for thought for the speculative mind as well in her
discussion of the relationship of children derived from monofollicular in vitro
polyfertilization and other marvels of the age. This is one of the compelling
features of a work rich with detail. The pathologist can be left behind so quickly as
interventionist medicine expands and becomes complexly interrelated. Even a
researcher so well versed in these matters (witness her familiarity with the
homeobox genes) may not have it all in hand, or more likely in these kinds of
projects, on the desk or floor nearby. Invasive intrauterine diagnostic probes have
been shown to contribute to the confusion of membrane interpretation.
In a study by Megory et al., 1 a disruption of the common membrane between the
twin sacs, found at 39 weeks, was attributed to funipuncture at 24 weeks but not to
earlier amniocenteses at 17 and 21 weeks. The extent of entanglement illustrated
by these authors is impressive. Their study indicated the placental membranes
were dichorionic-diamniotic on fused dichorionic placental disks. Thus the title of
the article is somewhat misleading; it should have been something like "Postcor
docentesis Fenestration of Common Dichorionic Twin Membranes." A datum
missing from the account is the location of the twins with respect to the sacs at the
time of delivery. The possible role of earlier punctures is not explored. Neverthe
less, such cases deserve wide publicity so that accumulative experience will be
availabl~ by which to assess both the clinical impact of such procedures on the
fetuses and newborns and the effect on the placental specimen. Certainly the
entanglement of the umbilical cords from fused dichorionic placentas is something
outside of the expected natural experience.
The method used by Dr. Baldwin in examining placentas is very well described.
The suggestion that the interested pathologist keep an independent record of
especially interesting cases is a good one, particularly when one has teaching
duties. For continuing research, however, more detailed access to computerized
data or summaries is required.
The value of this book to clinicians is contained in Chapter 4. The citation to
Abn and Phelan2 as authority that 20% to 40% of twins may remain undiagnosed
until onset of labor, or even until delivery, comports with the teaching of the 1940s
and 1950s, but is no longer acceptable in the United States, even just 5 years later.
In fact, modem obstetricians who fail to determine the number and relative
location of multiple fetuses by ultrasound are close to res ipsa loquitur malpractice
and would certainly receive a summons should anything go wrong! This chapter
also contains useful information on the various other clinical factors that may have
an impact on fetal development, with emphasis on possible discordancy between
twins. This chapter is an artful weaving of the literature and the immediate
Vancouver experience. The scope and richness of detail exists nowhere else, not in
her other papers, nor in any of the contributions of Perrin, Benirschke, Blanc,
Foreword ix
Naeye, or myself. This obstetrical snapshot of twins is matched by instant
photography of the newborn and the effect of twinning on various postnatal
disorders and subsequent development. Any such compilation must be viewed (a)
as the limited field of the source material (we are all slaves to our data source), and
(b) as a very firm foundation on which to build future observations.
Here Dr. Baldwin reaches the high plane of pathologist as natural historian, not
only in the immediate descriptive sense, but in the older nineteenth century
meaning as one whose field of study is all of nature and the interrelationship of the
living world upon the evolving rocks of time. She prepared us to make use of this
perspective by the background of basic human biology in Chapters 1 through 3.
Chapter 5 carries this sense to its fruition, the mortality of twins. This is a meaty
chapter, worthy of a major review article or brief monograph when combined with
Chapter 6, on the morbidity of twins. I suppose this shows the bias of the
pathologist, to put the chapter for mortality ahead of the chapter for morbidity;
perhaps I merely expose my clinical side from years ago, to raise such a question!
When Chapters 5,6, and 7 (anomalous development) are taken together, one has
the essence of the overall twin problem. It is most seemly, and very good, that Dr.
Baldwin has eschewed the use of statistical methods. She occasionally gives us the
relative frequency between two aspects or categories, but makes no effort to divine
statistical significance. This is good because in the first place embryonic develop
ment and lesion formation is not a statistical field as presently understood, and in
the second place these details might well require a file of all the twins born in North
America over an equivalent period of time, if one could write the comparative
matrix table for analysis. True to her calling as natural historian, she is content to
show general relationships, many time-or stage-dependent, confident that future
work is likely to show whether variations are significantly different in a causal
way.
Beginning with Chapter 8 we find three exquisite sections on the very special
problems of monozygous twinning, including much original work on the vascular
anastomoses of such placentas and the twin transfusion syndrome. Chapter 10
considers the problem that physicians most often encounter in patient counseling,
explanation of why some so-called identical twins are not in fact identical, and
why they sometimes show discordant or very different anomalies or other
diseases. While I endorse her conclusion that the age-old question of teratoma
versus amorphous fetus remains open, it does no harm to wonder whether a rule of
thumb acturu.ly might exist, theoretically. Clearly, the suggestion that DNA typing
be done, or chromosome counts be determined, would be of assistance. So far, the
consequences of in vitro fertilization have not shed light on this subject.
In Chapter 10, on anomalies of monozygous duplication, we have a compilation
that appears nowhere else in the literature, comparing a set of specific references,
by which to obtain a common vocabulary and more precise definitions. This
section is a worthy advance in the field, and I hope that the system of analysis
provided here will be adopted by others. The addition of her own material gives
cohesion to a fragmented, sometimes occult, subject. This section has much to
recommend it.
The fin<;ll chapter, Chapter 11, which discusses triplets and higher combina
tions, also contains much new information. The section reminds me of that old
aphorism, turned upside down, that prematures are not simply small children, they
are not even just small newborns; this implies they are a different form of human
existence. Likewise, triplet and quadruplet sets, while often containing twins, are
x Foreword
not simply "larger" twinnings. They represent another order of human develop
ment. Perhaps in the future someone will have collected an experience in these
higher orders of fetal life equivalent to Dr. Baldwin's collection of twins. The true
sequel of this book can then be written. For the present, this most valuable book
should spur additional efforts on the pathology oftwinning, and in particular, the
pathology of twin placentas.
In conclusion, there is treasure trove in this tome, much to recommend it to
many kinds of physicians and biologists, and a solid rock on which to build newer
edifices of scholarship.
Douglas R. Shanklin, M.D., F.R.S.M.
Professor of Pathology and of Obstetrics and Gynecology
University of Tennessee, Memphis;
Chief ofP erinatal Pathology and ofD evelopmental Neuropathology;
Formerly, Pathologist-in-Chief,
Chicago Lying-In Hospital,
University of Chicago
References
1. Megory E, Weiner E, Shalev E, Ohel G. Pseudomonoanmiotic twins with cord
entanglement following genetic puncture. Obstet Gynecol1991 ;78:915-917 .
2. Ahn MB, Phelan JP. Multiple pregnancy: antepartum management. In: Gall SA (ed).
Twin Pregnancy. Clinics inPerinatology 1988;15:55-69.
Preface
The pathology of having more than one human conceptus at a time has been
referred to as the history of sibling rivalry before birth. 1 In addition to the
psychosocial, sociological, and ethical issues raised by human multiples, or twins
and supertwins as they are also called,2 the scientific aspects of human twinning
and higher multiples are part of a number of disciplines. In addition to all the
concepts of disease and developmental disorders encountered in singleton infants,
the pathology of multiple pregnancy includes considerations of basic processes in
reproduction and embryology, normal development and teratology, and genetic
and environmental influences on development. Similarly, the placentology of
multiple conceptions adds several dimensions to the interpretations required in
singletons. It is no wonder that multiple reproduction has attracted medical
attention over the years.
The quality and usefulness of much of the information that has been reported
concerning multiple gestations is in direct proportion to the precision and
completeness of the pathology-the descriptions and interpretations. Many
pathologis1$ have contributed to our knowledge of the scope of the pathology of
mUltiple pregnancy, and the pediatric pathologist particularly has had a special
interest and background on which to draw. In addition, a number of astute
obstetricians, pediatricians, neonatologists, and perinatologists have provided
valuable in$ights, and research scientists have deepened our understanding of the
basic processes. My debt to these excellent contributions is acknowledged by
references to their work on which I have been privileged to build.
The stimulus for this monograph came from the research for a chapter on the
pathology of multiple pregnancy for Wigglesworth and Singer's3 Textbook of
Fetal and Perinatal Pathology. When the editors gently indicated that they could
not possibly accept everything I wanted to include, valuable though it was, it
occurred to me that it would be helpful to have a single volume that provided an
expansion of the information available on the pathology of twins and higher
multiples. Parents of multiples, their families, and the multiples themselves, are
becoming more active in their search for information, as witness the proliferation
of twin societies, associations of parents of multiples, and lay publications related
to multiple births. As a result, in addition to the questions arising from the
scientific curiosity of those who care for multiples, there is an increasing need for
these caregivers to be able to answer their patient's questions, accurately and
understandably. Also, as part of the enhanced concern regarding management
xi
Xll Preface
liability in human reproduction in general, there has been an increasing focus on
problems of outcome in mUltiple gestation in particular. Thus, it has been my plan
in this volume to provide useful information across the spectrum of the pathology
of multiple pregnancy, based on information from the literature and a review of a
large number of related cases.
It is for all those interested in human multiple reproduction that this monograph
is intended, including direct caregivers and indirect support staff, and particularly
those in a position to interpret the pathologic findings when problems occur. It is
my hope that they will find something interesting and useful in these pages.
References
1. Gonzales-Crussi F. Notes of an Anatomist. London: Pan Books; 1986:19.
2. Noble E. Having Twins. A Parent's Guide to Pregnancy, Birth and Early Childhood.
Boston: Houghton Mifflin; 1991:3.
3. b.u~win VJ. Pathology of multiple pregnancy. In: Wigglesworth JS, Singer DB, eds.
Textbook of Fetal and Perinatal Pathology. Oxford: Blackwell Scientific; 1991:221-
262.
