Textbook of

Obstetrics and
Gynaecology
A life course approach

Editors:
Eric A.P. Steegers (editor-in-chief )
Bart C.J.M. Fauser
Carina G.J.M. Hilders
Vincent W.V. Jaddoe
Leon F.A.G. Massuger
Joris A.M. van der Post
Sam Schoenmakers
Textbook of Obstetrics and Gynaecology
Editors:
Eric A.P. Steegers (editor-in-chief)
Bart C.J.M. Fauser
Carina G.J.M. Hilders
Vincent W.V. Jaddoe
Leon F.A.G. Massuger
Joris A.M. van der Post
Sam Schoenmakers

Textbook of Obstetrics
and Gynaecology
A life course approach
ISBN 978-90-368-2130-8 ISBN 978-90-368-2131-5  (eBook)
https://doi.org/10.1007/978-90-368-2131-5

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Life cycle and structure of the book
The cover of the book shows a figure of the human
life cycle. It depicts a series of distinct, bounded life
stages through which an individual passes his or her
lifetime. A life course approach to women’s health
recognizes the long-term effects during these stages
of biological, behavioural – including lifestyle – and
social exposures on health later in life and across
generations. Life time health starts with preconcep-
tion parental gametogenesis and subsequent foetal
growth and development. After birth, neonatal
health is further built on during infancy and child-
hood. Health also becomes dependent on learned
habits and behaviours. During adolescence, the
child reaches puberty and becomes sexually aware.
This represents the inner circle of the cover figure.
In early adulthood the life cycle is initiated again –
in many but not all people – by the conception and
birth of one’s own children. With pregnancy the
conception
and
foetal health
introduction to
a life course
approach
maternal
adaptation to
pregnancy
V
woman’s body adapts to the needs of the growing
foetus. This affects reproductive aging and perimeno­­
pausal and postmenopausal health. Towards the end
of life, there is a decline in functional capacity and
health. The rate of decline depends on both contem-
porary influences and the level of peak function
attained earlier in life.
Applying the life course approach to a new textbook
of Obstetrics and Gynaecology implicates a funda-
mental change in the structure and contents of such
a volume. After an introduction to this approach,
parts II, III and IV of the book follow the inner cir-
cle of parental health, conception, foetal life, birth
and subsequent growth and development up to and
including reproductive age. Parts V, VI and VII of
the book follow the aging woman towards the post-
menopause and old age.
childhood
and reproductive
adolescence health
peri- & post-
reproductive menopausal
aging health
Foreword by Lucilla Poston
I find it immensely refreshing to see a textbook of
obstetrics and gynaecology that, uniquely, encom-
passes the continuum of health in women from the
early reproductive years through to the menopause
and beyond. I congratulate the editors and authors
for their vision, as it fulfils the need for a clinical
and educational response to modern thinking. The
traditional clinical ‘silos’ of obstetrics and gynaecol-
ogy do no service to the now widely appreciated ‘life
course’ approach to health, and thereby to disease,
which has arisen from more than two decades of
intensive research into the ‘Developmental Origins
of Health and Disease hypothesis’. As the health of
the early embryo is potentially the most modifiable
and effective means of ensuring a healthy start in life
for the next generation of children, all students and
healthcare professionals, and indeed all young peo-
ple, should understand the importance of the health
of young women (and men) well before conception.
This textbook emphasizes this essential perspective
on a healthy start to life, but does not stop there, as
the reader is taken through the cycle of health in
infancy, then adolescence, sexual health and towards
pregnancy in the next generation, illustrating that
none can be considered in isolation to the other.
Pregnancy may be just nine months in duration, but
complications in pregnancy do not inevitably end at
delivery, and may adversely influence the mother’s
health for many years beyond. By emphasizing that
we should look back across the life course of repro-
ductive health, as well as understand societal and
demographic health factors, this book also under-
pins the need for healthy aging and quality of life in
the contemporary management of postmenopausal
women, and those with gynaecological disease.
Unquestionably, as they read the chapters of this
well-constructed book, healthcare practitioners with
the responsibility for looking after women, whether
as adolescents, in pregnancy or in the post repro-
ductive years, will be left in no doubt that optimal
patient care will be predicated by both a multidisci-
plinary and life course approach.
Professor Lucilla Poston PhD, FRCOG, FMedSci
President, International Society for the Developmental
Origins of Health and Disease (DOHaD).

Foreword by Pauline Meurs
This Textbook of Obstetrics and Gynaecology: a life
course approach is one of the first educational text-
books adopting this approach to women’s health.
There has been growing recognition that using a life
course approach for women’s health is vital for the
prenatal period and has added value in early child-
hood. It also enhances health during reproductive
aging and perimenopause and postmenopause, and
may affect risks and outcomes of malignant disease.
Focusing on the life course means a paradigmatic
change of our view of how to treat women: it entails
a shift from disease management to health manage-
ment. Treatment and support are based on personal,
participative and context-based factors. Taking into
account the context means that alongside the evi-
dence based on randomized controlled trials and
other scientific research, other types of knowledge
have to be considered: the individual preferences of
women, underlying values, social, ethnic and cul-
tural aspects, clinical setting and living conditions at
home.
Context-based care is a continuous process of col-
lective learning and improvement, weighing vari-
ous different resources of knowledge and integrating
them into practice. It is essential to use the ‘patient
experience’ as an outcome variable when research-
ing the effectiveness of this approach.
The role of the gynaecologist, midwife, nurse, gen-
eral practitioner, social worker and other profes-
sionals involved in the care of (pregnant) women is
to provide information and help women in making
appropriate choices. Information regarding possible
benefits, potential risks and alternatives will allow a
woman to choose the most appropriate treatment in
line with her personal circumstances.
VII
This textbook gives excellent insight into what is
needed to deliver a good quality of care, care that is
based on research outcomes, on experiences of the
women treated and on a detailed analysis of the con-
text and preferences involved.
The authors make a very clear and compelling argu-
ment for the necessity of working together in teams
and of trespassing the borders of the disciplines
involved. Good care also means working from com-
munity to hospital and back: seamless care with a
responsible multidisciplinary team.
I am convinced that this textbook with its innova-
tive approach to women’s health will serve as a guide
for many students and gynaecology residents and
enable them to systematically take into account the
perspective of the patient and her context. Hope-
fully the textbook will also inspire other profession-
als who contribute to the improvement of women’s
health, and healthcare.
Professor Pauline Meurs
Health Care Governance
Erasmus University
Chair of the Council for Public Health and Society
in the Netherlands
Foreword by Lesley Regan
Over the course of my career as a clinical aca-
demic working in the specialty of Obstetrics and
Gynaecology, I have witnessed an important and
significant shift in attitudes towards the delivery of
women’s healthcare. When I graduated from medi-
cal school in 1980, the majority of doctors from my
generation had received a traditional training which
was geared towards delivering a disease intervention
service. With a few notable exceptions, we tended
to see our patients – both girls and women – only
when they developed a problem that needed to be
treated during their adolescent, reproductive or
post reproductive years. More recently this perspec-
tive has begun to be challenged, with the realiza-
tion that clinicians can serve girls and women much
more effectively by adopting a continuous life course
approach to the delivery of women’s healthcare.
This life course approach focuses on the promotion
of good health, wellbeing and the prevention of ill
health, instead of merely providing treatment options
for established disease. It also provides the opportu-
nity to respond appropriately to any contemporary
demographic challenges. For example, thanks to sig-
nificant improvements in infant and child health our
world now contains the largest population of adoles-
cents in history. We must address their sexual and
reproductive health needs as a matter of urgency,
since we know that this will have an important
impact on the quality of their lives and future health
requirements. Furthermore, as our life expectancy
increases, most women of my generation will need to
plan for the fact that they are likely to spend a longer
proportion of their lives in a post reproductive state
than they did in their reproductive era.
Most girls and women have predictable long-term
reproductive healthcare needs, which means that the
practical implementation of services to accompany
a life course approach is a relatively simple plan-
ning exercise, if logical solutions and pathways are
adopted. Helpfully, women tend to visit healthcare
practitioners more than men – frequently when they
are going through normal everyday life events, such
as requesting contraception, seeking advice about
menstrual issues, when trying to conceive, dur-
ing pregnancy, after the birth of their baby or while
­experiencing the menopause and transitioning into
post reproductive life. These various interactions offer
multiple opportunities for healthcare professionals
to provide women with consistent, evidence-based
information that allows them to make informed deci-
sions about their own healthcare choices. It is also an
opportunity to promote healthy lifestyles that will
have a positive impact on that woman’s future health
as well as that of any children she may have.
Organizations such as the Royal College of Obste-
tricians and Gynaecologists and the World Health
Organization have long advocated for a life course
approach to women’s healthcare to be adopted uni-
versally. Achieving this goal will require several
important shifts in emphasis and philosophy –
within the profession itself, among policy-makers,
and in the organization of both health and social care
services to ensure they are fully integrated and truly
woman-centred. Technological advances are help-
ing to support these changes in service delivery, with
more screening, advice, diagnostic services and one
stop clinical procedures being delivered in a day case
setting closer to the woman’s home, rather than in a
traditional hospital inpatient setting.
This new edition of the Textbook of Obstetrics and
Gynaecology is an important step towards engaging
the global medical profession and enthusing them
with the concept and the benefits of a life course
approach to women’s health. The authors empha-
size the importance of a multidisciplinary, public
health approach, demonstrating clearly to clinicians
the benefit of a life course perspective and what this
will mean for them in their day to day practice. This
is an invaluable addition to the literature on the
life course approach to women’s health, and I hope
it will do much to inspire current and future gen-
erations of obstetricians and gynaecologists to help
make the concept a reality.
Professor Lesley Regan MD, DSc, FRCOG
President, Royal College of Obstetricians and
Gynaecologists
Head of Department of Obstetrics & Gynaecology,
St Mary’s Hospital at Imperial College, London
Director Imperial Women’s Health Research Centre
Chair UK National Confidential Enquiry into
Patient Outcome and Death (NCEPOD).
 IX

Foreword by Jan MM van Lith

The Dutch College of Obstetrics and Gynaecology
(NVOG) aims to provide the best quality of care for
women of all ages (7 www.nvog.nl). We have adopted
Machteld Huber’s (2011) definition of health as our
perspective for women’s health. This entails the abil-
ity to adapt and self-manage in physical, mental
and social domains. The college defines and sets the
standards for continuous improvement of care using
its quality cycle.
Knowledge gaps are identified and defined, the sci-
entific agenda is set, research is stimulated, per-
formed and monitored. The outcomes are written
in standards for clinical practice, implementation
is facilitated and care is validated to close the circle
towards the identification of new knowledge gaps.
Prevention is one the most important issues in the
future of health, next to personalized and regenera-
tive medicine. Awareness and understanding of the
social context and its influence on health is of major
importance for professionals.
The approach of this textbook underlines and sup-
ports the aims of our college and will contribute to
improve women’s health.
Knowledge of these relationships and connections
is of great importance to understand the underlying
mechanisms. Students, trainees and professionals
should be educated in this way. This will contrib-
ute to improving doctors’ skills and ultimately lead
to the best quality of care for women of all ages.
This textbook underlines the importance of this
approach and will help to bring women’s health to
the next level by providing professionals with the
tools to do so.
This new textbook, following a long tradition of
Dutch textbooks, again proves that the Netherlands
is in the frontline of translating new insights into
clear concepts and making them available for pre-
sent and future generations of professionals active in
Obstetrics and Gynaecology.
Indeed, I highly recommend this textbook!
Professor Jan MM van Lith
President, Dutch College of Obstetrics and Gynae-
cology

From the perspective of the life course approach

this new textbook is completely in accordance with
social developments and views on medical care of
the future. Obstetrics and Gynaecology are pre-
eminently positioned in the cycle of life. Already
for decades, gynaecologists are involved in the care
of women from cradle to grave. More and more we
are becoming aware that all phases of life are linked.
Events in one phase may influence and/or can be
predictive for events in a later phase and even for
health and disease across generations. Such events
can be illnesses, genetic profiles, environmental
effects and healthy behaviour.
Preface editors
This new ‘Textbook of Obstetrics and Gynaecology: a
life course approach’ marks the end of seven very suc-
cessful editions of the Dutch Textbook ‘Obstetrie en
Gynaecologie, de voortplanting van de mens’. Since
the first edition was released in 1993, it has not only
been the leading textbook in the curricula of Dutch
medical and midwifery schools but has also played an
important role in the training of gynaecologists and
served as a book of reference for doctors of all speci-
alities as well as midwives. Its high standards can be
attributed to the vision and dedication of the succes-
sive editors Professor P.E. Treffers (first two editions)
and Professor M.J. Heineman (third to seventh edi-
tion) and a large team of vastly committed authors,
all leading Dutch gynaecologists in their fields.
These editions followed up on the textbook ‘De
voortplanting van de mens. Leerboek voor Obstetrie
en Gynaecologie’ edited by Professor G.J. Klooster-
man, the first edition of which was released in 1973.
The fast development of translational and clini-
cal research and changing perspectives in how care
should be provided made a new standard textbook
necessary in 1993.
effects intervention
conception & childhood & reproductive maternal adaptation
foetal health adolescence health
exposures
preconception antenatal
clinical care
care care
research developmental origins of
health and disease
education
.Figure 1  Shifts in paradigms related to a life course approach
The same is true now, as the current understanding
directs us towards a life course approach to women’s
health which should be leading in the way care is
provided. As illustrated by the life cycle figure on the
front cover, a woman’s life is a continuum composed
of a series of bounded life stages ‘from the cradle to
the grave’. This continuum biologically starts during
parental preconception gametogenesis and subse-
quent embryonic and foetal development and will
transpire throughout life. The different life course
stages of each individual consecutively prepare and
determine health outcome and wellbeing (. fig. 1).
Intrinsically, this is not limited to one’s own lifetime
as the reproductive health of couples also affects the
health of future generations.
Such a life course approach in obstetric and gynae-
cological patient care provides a path towards
healthy aging, with specific attention for lifestyle,
prevention and the social context. This requires a
change in mindset of women’s healthcare providers
to feel responsible not only for managing disease but
also for managing health. Both in clinical care and
research, development of new strategies will focus
on the earliest origins of life. On the other side of
burden of disease
healthy aging
peri- & post-
reproductive aging
to pregnancy menopausal health
biological, behavioural & social
multidisciplinary care & networking medicine
women-centred
blended learning programmes
 XI
Preface editors

the spectrum of life providing chronic care for women with
oncological disease and at old age will evolve towards improv-
ing and prolonging wellbeing and quality of life as long as
deemed acceptable (. fig. 2).
As a result, obstetricians and gynaecologists will provide future
care in a much more multidisciplinary fashion – gender ori-
ented and tailored to the individual – within hospitals. They
may also adapt a coordinating role in care within the com-
munity enabled by the developments of networking medicine
using the potential of digital technology and care.
This new textbook is a treatise on the clinical practice of obstet-
rics and gynaecology in which the life course approach has
been applied for the first time. The structure of the book and
contents of the chapters have been completely revised and
rewritten accordingly and the volume has been considerably
condensed by an outstanding team of largely new authors. As
international textbooks are increasingly used in medical curric-
ula, it was decided to publish in the English language, thereby
also making it available for an international audience. Special
attention has been given to renewing all the illustrative mate-
rial. The e-book version of the text incorporates modern mul-
timedia products such as 3D video animations on physical
examination and birth as well as leading edge films of five com-
mon operative procedures from a surgeon’s point of view.
The textbook should serve as a reference not only for medical
and midwifery students but also for gynaecologists in train-
ing and other clinicians who have the privilege of caring for
women and their families, from the earliest moments in life
onwards.
Eric A.P. Steegers
Bart C.J.M. Fauser
Carina G.J.M. Hilders
Vincent W.V. Jaddoe
Leon F.A.G. Massuger
Joris A.M. van der Post
Sam Schoenmakers

preconception early life adult life older life

reproductive health, maternal adaption to
gametogenesis conception, foetal health, adolescence pregnancy & reproductive aging peri- & postmenopausal health

parental health
health

threshold varies
disease threshold lifestyle & environment

disease rehabilitation
ensuring quality of life
age

.Figure 2  A life course perspective for maintenance of health (Adapted from: The implications for training
embracing a life course approach to health. World Health Organization 2000)
Supplementary online study information
Currently, most students make use of web- or cloud-
based information on computers or mobile devices
for studying purposes. Therefore, supplementary
online study tools are provided with this new study
book to benefit and support an active learning envi-
ronment with the possibility of regularly updating
these tools. This allows for the online information to
be dynamic and up to date, as compared to having
to wait for a new edition of the textbook.
It is our hope that this book will be used in a
blended course design, which means that classical
face-to-face training is combined with traditional
literature reading and online training programs. To
highlight the integration of the life course approach,
new illustrations have been made. To emphasize
the importance of each part in the life course, each
chapter will start with the illustration of the spe-
cific time period the chapter relates to. A variety of
instructional formats such as e-modules, video-lec-
tures and surgical 3D movies are used in this book
to stimulate a blended training program. Advantages
of this online study platform are a more flexible
and increased access to training (24/7), scalabil-
ity of training and the possibility of using regularly
updated tests or questionnaires.
The online study platform can be found on 7 mijn.
bsl.nl. It will be updated regularly with new or
adapted online study tools and material based on
new knowledge and insights. The following different
multimedia are used:
Anatomical illustrations and movies
New illustrations were drawn to specifically improve
anatomical knowledge. Animations in relation to
emergency obstetrics (for example childbirth in
breech position) are provided.
Surgical 3D movies
Five different gynecological surgical procedures are
explained step by step. Procedures are filmed from
a surgeon’s point of view and available in 3D. The
anatomical highlights and 3D inlays provide a bet-
ter understanding of different anatomical structures
and is more intuitive than pure static illustrations.
Furthermore, it's possible to evaluate your knowl-
edge by taking a test, which is included in the mov-
ies. In each course you will find information and
instructions about pre- and postoperative care,
objectives and learning goals. These movies are pro-
vided by the Incision Academy. (7 www.incision.care)
Clinical case scenarios
Different clinical case scenarios in relation to the
life course approach will be presented. For example,
the impact of hereditary breast cancer for a young
woman, her family and her offspring.
Knowledge tests
After each chapter your knowledge can be tested by
an online questionnaire.
Supplementary literature and websites
Suggestions for additional reading are given.
E-learning, tutorials
Specific topics will be explained in further detail by
video or presentation.
In order to keep supplemental online study informa-
tion up to date and innovative, suggestions and ideas
by users of the study book will be appreciated.
Multimedia Editors
Lindy Santegoets
Sam Schoenmakers
 XIII

Acknowledgements

This project could not have been completed without

the enthusiasm and professionalism of Ivonne Friis
and Anja Heida from our publisher Bohn Stafleu van
Loghum. Ron Slagter and Vincent Khouw beautifully
shaped the appearance of the book – and its digi-
tal version – by their contemporary illustrations and
video animations. We thank Charles Pallandt, CCO
from Incision Academy, for enabling the availability of
leading edge video instructions of 5 common
Obs&Gynae operative procedures filmed from a sur-
geon’s view in combination with 3D anatomical expla-
nations. The contribution of Dr Lindy Santegoets,
gynaecologist, has been indispensable for the compo-
sition of the multimedia material.

Eric A.P. Steegers

Bart C.J.M. Fauser
Carina G.J.M. Hilders
Vincent W.V. Jaddoe
Leon F.A.G. Massuger
Joris A.M. van der Post
Sam Schoenmakers
Contents

Part I  Introduction to a life course approach in obstetrics and gynaecology

1 Life course approach in women’s health. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Romy Gaillard, Keith M. Godfrey, and Vincent W.V. Jaddoe

2 Life course approach in obstetrics and gynaecology for patient care, education and research. . . . . . 17
Sam Schoenmakers, Bart C.J.M. Fauser, Mary E.W. Dankbaar, Carina G.J.M. Hilders,
Vincent W.V. Jaddoe, Leon F.A.G. Massuger, Joris A.M. van der Post and Eric A.P. Steegers

3 Reproductive medicine: ethical reflections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Guido M.W.R. de Wert and Wybo J. Dondorp

4 Anatomy of the pelvis, pelvic organs and reproductive system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

Marco C. DeRuiter, Gerrit-Jan Kleinrensink and Bernadette S. de Bakker

5 Essentials of history taking and physical examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

Emer Hageraats and Anna P. Gijsen

Part II  Conception and foetal health

6 Preconception health and care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

Sam Schoenmakers, Maria P.H. Koster and Régine P.M. Steegers-Theunissen

7 Embryonic, placental and foetal growth and development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

Wessel Ganzevoort, Rebecca C. Painter, Aleid G. van Wassenaer-Leemhuis, Bernadette S. de Bakker,
Régine P.M. Steegers-Theunissen and Marijke M. Faas

8 Birth and the neonatal period. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

Rob (H.R.) Taal, Irwin K.M. Reiss, Enrico Lopriore and Vincent W.V. Jaddoe

Part III  Childhood and adolescence

9 Paediatric and adolescent gynaecology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

Sabine E. Hannema and Marianne J. ten Kate-Booij

10 Sexual health. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177

Rik H.W. van Lunsen and Ellen T.M. Laan

11 Contraception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Frans J.M.E. Roumen, Rik H.W. van Lunsen and Suzy M. de Swart

Part IV  Reproductive health

12 The normal and abnormal menstrual cycle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229

Joop S.E. Laven and Nils B. Lambalk

13 Infertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
Jesper M.J. Smeenk and Simone L. Broer

14 Assisted reproductive technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263

Bart C.J.M. Fauser and Didi D.M. Braat

15 Sexually transmitted infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283

Henry J.C. de Vries and Gilbert G.G. Donders
 XV
Contents

Part V  Maternal adaptation to pregnancy

16 Routine antenatal care, antenatal testing and foetal therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307

Arie Franx, Mireille N. Bekker and Dick Oepkes

17 Maternal adaptations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321

Sicco A. Scherjon

18 Early pregnancy disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353

Rebecca C. Painter, Norah M. van Mello, Mariëtte Goddijn, Merel M.J. van den Berg, Christianne Lok,
Nienke van Trommel and Joris A.M. van der Post

19 Gestational disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371

Marjon de Boer, Pim W. Teunissen and Christianne J.M. de Groot

20 Chronic risk conditions and pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385

Marc E.A. Spaanderman, Hilmar Bijma, Johannes J. Duvekot, Mariëlle G. van Pampus,
Elisabeth van Leeuwen, Jerome M.J. Cornette, Titia A.T. Lely, Louis L.H. Peeters
and Chahinda Ghossein-Doha

21 Delivery and puerperium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415

Esteriek de Miranda, Corine J.M. Verhoeven, Petra C.A.M. Bakker and
Marianne Prins

Part VI  Reproductive aging

22 Abnormal uterine bleeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475

Marlies Y. Bongers, Peggy M.A.J. Geomini, Wouter J.K. Hehenkamp and Mark Hans Emanuel

23 Pelvic floor disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491

Huub (C.H.) van der Vaart, Pieternel Steures and Jan-Paul W.R. Roovers

24 Benign pelvic mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511

Toon van Gorp and Peggy M.A.J. Geomini

25 Cervical premalignancies and cervical cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525

Ruud L.M. Bekkers and Jurgen M.J. Piek

Part VII  Peri- and postmenopausal health

26 Breast cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545

Mirelle Lagendijk, Lindy A.M. Santegoets and Linetta B. Koppert

27 The menopause, the perimenopause and the postmenopause . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557

Dorenda K.E. van Dijken, Maryam Kavousi, Monique M.A. Brood-van Zanten, Loes Jaspers and
Mick A.A. van Trotsenburg

28 Uterine cancer and premalignant lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577

Hanny (J.M.A.) Pijnenborg, Koen K. van de Vijver and Roy F.L.P. Kruitwagen

29 Ovarian cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591

Marian J.E. Mourits, Florine A. Eggink, Mathilde Jalving, Marco de Bruyn,
Joost Bart and Hans W. Nijman
XVI Contents

30 Vulvar cancer and vulvar premalignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

Joanne A. de Hullu, Irene A.M. van der Avoort, Maaike H.M. Oonk and Mariette I.E. van Poelgeest

31 Care for the elderly woman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 617

Marcel G.M. Olde Rikkert and Didy E. Jacobsen

Supplementary Information. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633

Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 634
 XVII

Editors and Authors

Editors Bernadette S. de Bakker 

Professor Eric A.P. Steegers (editor-in-chief)  section Clinical Anatomy and Embryology, Amsterdam
Professor of Obstetrics and Gynaecology, Head of the
Department of Obstetrics and Gynaecology, Erasmus MC,
University Medical Center Rotterdam
Emeritus professor Bart C.J.M. Fauser  Center, Groningen
Professor Reproductive medicine, Department of
Reproductive medicine and Gynaecology, University
Medical Center, Utrecht
Professor Carina G.J.M. Hilders 
Professor Medical Leadership, Erasmus University
Rotterdam and Managing Director, Reinier de Graaf
Hospital, Delft, gynaecologist
Professor Vincent W.V. Jaddoe 
Professor of Paediatric epidemiology, The Generation R
Study Group, Department of Epidemiology, Department of
Pediatrics, Erasmus MC, University Medical Center Rotterdam
Clinical embryologist, Department of Medical Biology,
UMC, University of Amsterdam
Dr Joost Bart 
Pathologist, Department of Pathology, University Medical
Dr Mireille N. Bekker 
Associate Professor Obstetrics, Birth center, University
Medical Center, Wilhelmina children’s hospital, Utrecht
Dr Ruud L.M. Bekkers 
Gynaecological oncologist, Department of Obstetrics and
Gynaecology, Catharina Hospital, Eindhoven and Radboud
University Medical Center, Nijmegen
Merel M.J. van den Berg 
PhD candidate, Center for Reproductive medicine,
Amsterdam UMC, Amsterdam

Professor Leon F.A.G. Massuger  Dr Hilmar Bijma 

Professor Gynaecological oncology, Department of Gynaecologist, Department of Obstetrics and Gynaecology,
Obstetrics and Gynaecology, Radboud University Medical Erasmus MC, University Medical Center Rotterdam
Center, Nijmegen
Dr Marjon A. de Boer 
Professor Joris A.M. van der Post  Gynaecologist, Department of Obstetrics and Gynaecology,
Vice-head of the Department of Obstetrics and Amsterdam UMC, University of Amsterdam
Gynaecology, Amsterdam UMC, Amsterdam
Professor Marlies Y. Bongers 
Dr Sam Schoenmakers  Gynaecologist, Department of Obstetrics and Gynaecology,
Gynaecologist, Department of Obstetrics and Gynaecology, MSB Máxima Medical Center, Veldhoven/Maastricht
Erasmus MC, University Medical Center Rotterdam University Medical Center, Maastricht

Editors multimedia Professor Didi D.M. Braat 

Head of the Department Obstetrics and Gynaecology,
Dr Lindy A.M. Santegoets  Department of Obstetrics and Gynaecology, Radboud
Gynaecologist, Reinier de Graaf Groep, Delft Medical Center, Nijmegen

Dr Sam Schoenmakers  Dr Simone L. Broer 

Gynaecologist, Department of Obstetrics and Gynaecology, Gynaecologist, Department of Reproductive medicine and
Erasmus MC, University Medical Center Rotterdam gynaecology, University Medical Center, Utrecht

Authors Monique M.A. Brood-van Zanten 

Scientific adviser, Department of Obstetrics and
Dr Irene A.M. van der Avoort  Gynaecology, Amsterdam UMC, University of Amsterdam
Gynaecologist, Department of Obstetrics and Gynaecology,
Ikazia Hospital, Rotterdam Dr Marco de Bruyn 
Researcher, Department of Obstetrics and Gynaecology,
Dr Petra C.A.M. Bakker  University Medical Center, Groningen
Obstetrician-perinatologist, Department of Obstetrics and
Gynaecology, Amsterdam UMC, VU University Medical
Center, VU University, Amsterdam
XVIII Editors and Authors

Dr Jerôme M.J. Cornette  Dr Chahinda Ghossein-Doha 

Gynaecologist, Department of Obstetrics and Gynaecology, Medical doctor, Department of Cardiology, Maastricht
Erasmus MC, University Medical Center Rotterdam University Medical Center, Maastricht

Dr Mary E.W. Dankbaar  Dr Anna P. Gijsen 

Program manager e-learning/team coordinator, Erasmus Gynaecologist, Department of Obstetrics and Gynaecology,
MC, University Medical Center Rotterdam Elkerliek hospital Helmond, Helmond

Dorenda K.E. van Dijken  Professor Mariette Goddijn 

Gynaecologist, Department of Gynaecology, OLVG West, Professor Reproductive medicine, gynaecologist, Center for
Amsterdam Reproductive medicine, Amsterdam UMC, Amsterdam

Professor Gilbert G.G. Donders  Professor Keith M. Godfrey 

Gynaecologist, Department of Obstetrics and Gynaecology, Professor of Epidemiology and Human Development, MRC
Antwerp University Hospital, Femciare Clinical Research for Lifecourse Epidemiology Unit and NIHR Southampton
Women, Tienen, and RZ Heilig Hart Tienen, Belgium Biomedical Research Centre, University of Southampton
and University Hospital Southampton NHS Foundation
Dr Wybo J. Dondorp  Trust, United Kingdom
Associate Professor of Biomedical Ethics, Department of
Health, Ethics & Society, Maastricht University, Maastricht Dr Toon van Gorp 
Gynaecological oncologist, Department of Obstetrics
Dr Johannes J. Duvekot  and Gynaecology, Maastricht University Medical Center,
Gynaecologist, Department of Obstetrics and Gynaecology, Maastricht
Erasmus MC, University Medical Center Rotterdam
Professor Christianne J.M. de Groot 
Dr Florine A. Eggink  Gynaecologist, Head of the Department of Obstetrics and
PhD student, Department of Obstetrics and Gynaecology, Gynaecology, Amsterdam UMC, Free University, Amsterdam
University Medical Center, Groningen
Emer Hageraats 
Professor Mark Hans Emanuel  Skillsteacher, Skillslab FHML Maastricht University,
Gynaecologist, Department of Obstetrics and Gynaecology, Maastricht
University Medical Center, Utrecht
Dr Sabine E. Hannema 
Dr Marijke M. Faas  Paediatrician-endocrinologist, Department of Pediatrics,
Associate Professor, Department of Pathology and Medical Erasmus MC, University Medical Center Rotterdam and
biology, University Medical Center Groningen, University of Leiden University Medical Center, Leiden
Groningen
Dr Wouter J.K. Hehenkamp 
Professor Arie Franx  Gynaecologist, Department of Obstetrics and Gynaecology,
Professor of Obstetrics, Birth center, University Medical Amsterdam UMC, Amsterdam
Center, Wilhelmina children’s hospital, Utrecht
Dr Lianne Holten 
Dr Romy Gaillard  Senior-teacher, medical anthropologist, AVAG Midwifery
The Generation R Study Group, Department of academy Amsterdam and Groningen
Epidemiology, Department of Pediatrics, Erasmus MC,
University Medical Center Rotterdam Dr Joanne A. de Hullu 
Gynaecological oncologist, Department of Obstetrics
Dr Wessel Ganzevoort  and Gynaecology, Radboud University Medical Center,
Gynaecologist-perinatologist, Associate Professor, Nijmegen
Department of Obstetrics and Gynaecology, Amsterdam
UMC, Amsterdam Dr Didy E. Jacobsen 
Geriatrician, Department of Geriatric Medicine, Radboud
Dr Peggy M.A.J. Geomini  University Medical Center, Nijmegen
Gynaecologist, Department of Obstetrics and Gynaecology,
MSB Máxima Medical Center, Veldhoven
 XIX
Editors and Authors

Dr Mathilde Jalving  Dr Titia (A.T.) Lely 

Internist-oncologist, Department of Medical oncology, Gynaecologist, Department of Gynaecology, University
University Medical Center, Groningen Medical Center, Utrecht

Dr Loes Jaspers  Dr Christianne Lok 

Epidemiologist, Department of Infectious Diseases, GGD Gynaecological oncologist, Antoni van Leeuwenhoek
Utrecht, Zeist Hospital, Amsterdam

Dr Marianne J. ten Kate-Booij  Professor Enrico Lopriore 

Gynaecologist, Department of Gynaecological oncology, Paediatrician-neonatologist, Department of Neonatology,
Erasmus MC, University Medical Center Rotterdam Leiden University Medical Center, Leiden

Dr Maryam Kavousi  Dr Rik (H.W.) van Lunsen 

Epidemiologist, Department of Epidemiology, Erasmus MC, Sexual health, Department of Sexuology & Psychosomatic
University Medical Center Rotterdam Gynaecology, Amsterdam UMC, Amsterdam

Professor Gerrit-Jan Kleinrensink  Dr Norah M. van Mello 

Professor Anatomy, Department of Neuroscience & Gynaecologist, Department of Obstetrics and Gynaecology,
Anatomy, Erasmus MC, University Medical Center Amsterdam UMC, Amsterdam
Rotterdam
Dr Esteriek de Miranda 
Dr Linetta B. Koppert  Senior-researcher/midwife, Department of Obstetrics and
Oncological surgeon, Department of Surgical oncology, Gynaecology, Amsterdam UMC, University of Amsterdam
Erasmus MC, University Medical Center Rotterdam
Professor Marian J.E. Mourits 
Dr Maria P.H. Koster  Gynaecological oncologist/Professor Gynaecological
Assistant Professor, Department of Obstetrics and oncology, Department of Obstetrics and Gynaecology,
Gynaecology, Erasmus MC, University Medical Center University Medical Center, Groningen
Rotterdam
Professor Hans W. Nijman 
Professor Roy F.L.P. Kruitwagen  Gynaecological oncologist/Professor Gynaecological
Gynaecological oncologist, Department of Obstetrics oncology and immunotherapy, Department of Obstetrics
and Gynaecology, Maastricht University Medical Center, and Gynaecology, University Medical Center, Groningen
Maastricht
Professor Dick Oepkes 
Professor Ellen T.M. Laan  Department of Obstetrics, Leiden University Medical Center,
Professor Sexual health, Department of Sexuology & Leiden
Psychosomatic Gynaecology, Amsterdam UMC, Amsterdam
Professor Marcel G.M. Olde Rikkert 
Mirelle Lagendijk  Full Professor in Geriatric Medicine & Chair Geriatric
Surgical resident in training, Department of Surgery, Department, Department of Geriatric Medicine, Radboud
Erasmus MC, University Medical Center Rotterdam University Medical Center, Nijmegen

Professor Nils B. Lambalk  Dr Maaike H.M. Oonk 

Division of Reproductive Medicine, Department of Gynaecological oncologist, Department of Obstetrics and
Obstetrics and Gynaecology, Amsterdam UMC, Amsterdam Gynaecology, University Medical Center, Groningen

Professor Joop S.E. Laven  Dr Rebecca C. Painter 

Division of Reproductive Medicine, Department of Gynaecologist-perinatologist, Associate Professor,
Obstetrics and Gynaecology, Erasmus MC, University Department of Obstetrics and Gynaecology, Amsterdam
Medical Center Rotterdam UMC, Amsterdam

Dr Elisabeth van Leeuwen  Dr Mariëlle G. van Pampus 

Gynaecologist, Department of Obstetrics and Gynaecology, Gynaecologist, Department of Obstetrics and Gynaecology,
Amsterdam UMC, Amsterdam OLVG , Amsterdam
XX Editors and Authors

Dr Louis L.H. Peeters  Dr Pieternel Steures 

Gynaecologist, Division of Perinatology and Gynaecology, Urogynaecologist, Department of Obstetrics and
University Medical Center, Utrecht Gynaecology, Jeroen Bosch Hospital, ‘s-Hertogenbosch

Dr Jurgen M.J. Piek  Suzy M. de Swart 

Gynaecological oncologist, Department of Obstetrics and General practitioner, Urogynaecology, General practice de
Gynaecology, Catharina Hospital, Eindhoven Swart en Nieuwenhuis, ’s-Hertogenbosch

Dr Hanny (J.M.A.) Pijnenborg  Dr Rob (H.R.) Taal 

Gynaecological oncologist, Department of Obstetrics Pediatrician, fellow neonatology, Department of
and Gynaecology, Radboud University Medical Center, Neonatology, Erasmus MC, University Medical Center
Nijmegen Rotterdam

Dr Mariette I.E. van Poelgeest  Professor Pim W. Teunissen 

Gynaecological oncologist, Department of Obstetrics and Gynaecologist, Department of Obstetrics and Gynaecology,
Gynaecology, Leiden University Medical Center, Leiden Amsterdam UMC, Free University, University of Maastricht

Marianne Prins  Dr Nienke van Trommel 

Senior-teacher, AVAG Midwifery academy Amsterdam and Gynaecologist, Antoni van Leeuwenhoek Hospital,
Groningen Amsterdam

Professor Irwin K.M. Reiss  Dr Mick A.A. van Trotsenburg 

Paediatrician-neonatologist, Department of Neonatology, Gynaecologist, Department of Gynaecology and Obstetrics,
Erasmus MC, University Medical Center Rotterdam Universitätsklinikum St. Pölten-Lilenfeld, Austria

Professor Jan-Paul W.R. Roovers  Professor Huub (C.H.) van der Vaart 
Urogynaecologist, Professor Gynaecology, Department of Professor Urogynaecology, Division Woman and Baby,
Obstetrics and Gynaecology, Amsterdam UMC, Amsterdam University Medical Center, Utrecht

Dr Frans J.M.E. Roumen  Corine J.M. Verhoeven 

Gynaecologist (n.p.), Department of Obstetrics and
Gynaecology, Zuyderland Medical Center, Heerlen-Sittard
Professor Marco C. DeRuiter  Veldhoven
Professor Anatomy and embryology, Department of
Anatomy and Embryology, Leiden University Medical
Center, Leiden
Professor Sicco A. Scherjon 
Professor Obstetrics, Department of Obstetrics and
Gynaecology, University of Groningen, and perinatologist,
Department of Obstetrics and Gynaecology, University
Medical Center Groningen, Groningen
Senior-researcher/clinical midwife, Department of
Midwifery Science/Obstetrics, Amsterdam Public Health
research institute, Amsterdam/Máxima Medical Center,
Dr Koen K. van de Vijver 
Pathologist, Department of Pathology, Antoni van
Leeuwenhoek Hospital, Amsterdam
Professor Henry J.C. de Vries 
Dermatologist and Professor of skin infections, Amsterdam
UMC, University of Amsterdam, and Public Health Service
(GGD Amsterdam), Amsterdam

Dr Jesper M.J. Smeenk  Dr Aleid G. van Wassenaer-Leemhuis 

Gynaecologist, Department of Obstetrics and Gynaecology, Neonatologist, long-term follow-up, Department of
Elisabeth TweeSteden Hospital, Tilburg Neonatology, Amsterdam UMC, Amsterdam

Professor Marc E.A. Spaanderman  Professor Guido M.W.R. de Wert 

Gynaecologist-perinatologist, Head of the Department of Professor of Biomedical Ethics, Department of Health,
Obstetrics, Maastricht University Medical Center, Maastricht Ethics & Society, Maastricht University, Maastricht

Professor Régine P.M. Steegers-Theunissen 

Professor in Periconceptional epidemiology, Department of
Obstetrics and Gynaecology, and Pediatrics/Neonatology,
Erasmus MC, University Medical Center Rotterdam
 1 I

Part I Introduction to
a life course approach in
obstetrics and gynaecology
Chapter 1 Life course approach in women’s health – 7
Romy Gaillard, Keith M. Godfrey and Vincent W.V. Jaddoe

Chapter 2 Life course approach in obstetrics and gynaecology for patient

care, education and research – 17
Sam Schoenmakers, Bart C.J.M. Fauser, Mary E.W. Dankbaar,
Carina G.J.M. Hilders, Vincent W.V. Jaddoe, Leon F.A.G.
Massuger, Joris A.M. van der Post and Eric A.P. Steegers

Chapter 3 Reproductive medicine: ethical reflections – 27

Guido M.W.R. de Wert and Wybo J. Dondorp

Chapter 4 Anatomy of the pelvis, pelvic organs and reproductive

system – 51
Marco C. DeRuiter, Gerrit-Jan Kleinrensink and Bernadette
S. de Bakker

Chapter 5 Essentials of history taking and physical examination – 85

Emer Hageraats and Anna P. Gijsen

Future perspectives
Eric A.P. Steegers

Life course approach

A life course perspective offers a novel opportunity to optimize women’s health and
woman-centred care. It involves all interrelated stages of a woman’s life taking into
account the short-term and long-term effects of biological, behavioural and social expo-
sures during the preconception period, gestation, childhood, adolescence, adulthood
and old age. This will impact the way healthcare for women will be provided (.fig. 1).
Gynaecologists will work in multidisciplinary teams, linking hospital care and community
services and crossing different working environments. Networking medicine also offers
possibilities for initiating preventive interventions, such as for folic acid supplementa-
tion and nutritional intake, stop smoking and alcohol use and discuss contraception at a
young age, encouraging a healthy lifestyle and enabling women to take control of their
own health behaviours. Applications of information and internet technology – e-health
– have a huge potential to do this. Medicine will move beyond treating and curing sick
people into improving public health and well-being. The quality of health services and
professionals will be increasingly judged by measures of health status which matter to
and are reported by women themselves instead of indicators such as survival or com-
plications of treatment only. Participatory medicine will further evolve. In value-based
healthcare such values will be defined relative to costs and effectiveness in providing
care should therefore be continuously monitored and subject to improvement.
 3

developmental
environment
influences
on skills &
individual knowledge
work, expertise
& experience

prenatal infancy childhood adolescence adulthood old age

c ore s
management

specia es
of specialist

servi
menopause uro-
health agriculture

er
gynaecology

li s t
care
c

vi c
contraception & food
services production

es
preconception care sexual chronic disease
psychosexual initial investigation antenatal care health care
counseling of subfertility
community familial cancer
gynaecological gynaecology genetics
specialist
cancer screening paediatric and
uro-
gynaecology adolescentt
water and gynaecology
reproductive
sanitation education
medicine neonatology
foetal medicine gynaecological
high risk obstetrics cancer
assisted conception
in di ors
vid u al l
ifestyle fact work
soc
unemployment ial a n r ks environment
d c o m m u n i t y n e t wo

living and working

conditions

. Figure 1  What women seek from healthcare. Life course view of a health service for women (adapted from:
Royal College of Obstetricians and Gynaecologists. Scientific Impact paper No.27. August 2011. Why should we
consider a life course approach to women’s health care?)

Precision medicine for women

On 20 January 2015, President Barack Obama launched the Precision Medicine Initiative
in his State of the Union address. It may be assumed that its development will further
contribute to gynaecological clinical practice and women’s health and wellbeing at
a population level. It means that in prevention and treatment strategies, individual
variability is taken into account. This has become feasible by the impressive develop-
ments in host-omics biology approaches such as genomics, proteomics, metabolomics
and microbiomics as well as in information technology. A person’s personal genetic
and biological systems interact with the environment. Individual characteristics at a
micro-level together with more holistic information of the environment at a macro-
level (.fig. 2) may therefore enhance predictive, preventive, personalized and partici-
patory medicine. Each person will be surrounded by a ‘virtual cloud’ of billions of data
points, including data from mobile devices, which can be applied in providing precision
medicine, tailored to the individual and living environment (.fig. 3). In this way infor-
mation and data can also be stratified by sex and gender, improving the care women
are offered. History taking classically aims to obtain information useful in formulating
a diagnosis and providing medical care to the patient. Using the newly developed –
and rapidly available at the bedside – detailed individual biomedical characteristics
and information on the social environment, history taking will evolve into predictive
modelling. In this way patient-centred precision medicine in the 21st century has the
potential to significantly improve individualized preventive and treatment strategies in
 environment

co

el
ev
m

l
m

ro
un

ac
ity

m
life course
women’s
wellbeing

m
l
ua

ic
ro
d
vi

l
ev
di

el
in

H o s t- o m ic s

. Figure 2  Micro and macro level determinants of women’s wellbeing and health

precision foetal maternal care

social domain

periconception care external environment

lifestyle & nutrition

tailored to the individual

& neighborhood precision foetal-maternal care

foetal + medical history

antenatal care internal environment

host-omics

. Figure 3  Precision medicine for women

the future. Regenerative medicine, tissue transplantation and pharmacogenomics are

just some of the many examples. In doing so, ethically one has to deal with questions
on the protection of patient confidentiality and privacy and find ways to guarantee
conscientious procedures for obtaining informed consent.

Woman-centred life course research

Better care starts with new scientific knowledge. Life course research and epidemiology
require long-term birth cohorts, preferably from the preconception period up to old age,
and routine data linkage with multidisciplinary information on biological, physical, psy-
chological, behavioural and social determinants of women’s health, functional capacity
and aging over time. Open data sharing and accessibility to the participants themselves
will become commonplace. It comprises the identification of ‘critical periods’ during the
lifetime when biological changes are wholly or partially irreversible. The same is true for
the importance of interaction, clustering and accumulation of risks along the life course.
Research should be more context based. This implies that more attention is paid to the
effects of age, ethnicity, education, living conditions (such as marital status, household,
neighbourhood) and working conditions. Both in animal and human studies, sex should
always be included as a biological variable. Also governmental policies and local practice
 5

within which healthcare is provided should be taken into account. In advancing this
field of science women should be increasingly involved as active collaborators – making
optimal use of their knowledge and willingness to participate in clinical trials. This kind
of research will lead to a greater understanding about risk factors for women’s health
and disease such as subfertility, onset of menopause and related disorders such as post-
menopausal symptoms and osteoporosis as well as oncological diseases of the breasts,
uterus and ovaries. It will also provide insights into the gender specificity of symptoms
and treatment modalities of chronic conditions such as metabolic and cardiovascular
disease. In this way, new knowledge can be used to more effectively tackle major issues
in women’s health. Future research should also increasingly focus on the origins of
disparities in health which are often related to poor health literacy and social circum-
stances. This includes the intergenerational cycle of adverse effects of poverty. It could
be said that academics have a moral obligation to do so as these effects may be avoid-
able and they are unfair and unjust. Linking up medicine and public health is a prereq-
uisite for this. It also requires a change in the practice in research in which new scientific
discoveries and technology are applied much more quickly for the benefit of the wellbe-
ing and health of patients within hospitals but also for the community at large. This can
be designated as societal valorization of knowledge. It also facilitates translation of new
knowledge into local and national policy recommendations.

Education and training

Women’s healthcare providers of tomorrow, and gynaecologists in particular, have to be
prepared for a different way of practice. The life course approach should be implicitly used
as a framework within education and lifelong learning. This also involves, among other
things, the teaching of embryology, medical sociology and geriatrics. The potential of
preventive intervention in addition to cure and palliation should be clear. New curricular
materials have to be developed using sex- and gender-based evidence. The use of host-
omics data in daily practice and the complexity of the heterogeneity of the aetiology of dis-
ease may necessitate integration of pre-clinical and clinical teaching programs combining
basic science and clinical medicine. Future doctors and gynaecologists have to be taught
not only how to act in a hospital environment, but also how to serve the local healthcare
needs of the population. Overcoming societal challenges will prove vitally important in
improving individual and public health. Students need to be aware of the different living
conditions of people, as for example in deprived neighbourhoods. The accelerating growth
in basic, translational and clinical scientific knowledge and information technology again
stresses the importance of continuing professional development. Multimedia technologi-
cal innovations and virtual reality techniques enable powerful simulation drills improving
patient safety. This will also deepen competences such as 3D anatomical insights into
embryogenesis and complicated oncological surgical procedures. Finally, the teaching of
academic principles remains central. Training programs need to be flexible and tailored to
students so that they can excel in their early 30s when they are at the top of their game.
This coming new generation will steer all the new exciting scientific and technological
advances towards better health and wellbeing for all women and their families.
 1. Ben-Shlomo Y, Kuh D. A life course approach to chronic disease epidemiology; con-
ceptual models, empirical challenges and interdisciplinary perspectives. Int J Epide-
miol. 2002;31:285–93.
2. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med.
2015;372(9):793–5.
3. The Council for Public Health and Society. No evidence without context. About the
illusion of evidence-based practice in healthcare. The Hague, June 2017.
4. Khoury MJ, Gwinn ML, Russell E, Glasgow RE, Kramer RE. A population approach to
precision medicine. Am J Prev Med. 2012;42:639–45.
5. Kuh D, Ben-Shlomo Y, Lynch J, Hallqvist J, Power C. Life course epidemiology. J Epide-
miol Community Health 2003;57:778–83.
6. Porter ME. What is value in health care? N Engl J Med. 2010;363:2477–81.
7. Royal College of Obstetricians and Gynaecologists. Scientific Impact paper No.27.
August 2011. Why should we consider a life course approach to women’s health
care?
8. Royal College of Obstetricians and Gynaecologists. Working Party Report. September
2012. Tomorrow’s Specialist.
9. Steegers EA, Barker ME, Steegers-Theunissen RP, Williams MA. Societal valorisation of
new knowledge to improve perinatal health: time to act. Paediatr Perinat Epidemiol.
2016;30(2):201–4.
10. World Health Organization (WHO). The implications for training embracing a life
course approach to health. 2000.
 7 1

Life course approach in women’s

health
Romy Gaillard, Keith M. Godfrey and Vincent W.V. Jaddoe

! Life course
A life course approach in women’s health focuses on the influence of exposures and
events on health outcomes at different life stages throughout their own lives and in future
generations. Women’s reproductive health develops across the life course from menarche
to menopause and is influenced by sociodemographic, psychosocial, lifestyle, genetic and
prenatal factors.

Summary
Women’s reproductive health is a major determinant for pregnancy outcomes and their
risk of various non-communicable diseases in later life. Besides the consequences for
a woman’s own health, it also has important health consequences for her offspring.
Adverse maternal exposures during pregnancy may adversely affect foetal development,

 lectronic supplementary material

E
The online version of this chapter (7 https://doi.org/10.1007/978-90-368-2131-5_1) contains supplementary
material, which is available to authorized users.

© Bohn Stafleu van Loghum is een imprint van Springer Media B.V., onderdeel van Springer Nature 2019
E. A. P. Steegers et al. (Eds.), Textbook of Obstetrics and Gynaecology, https://doi.org/10.1007/978-90-368-2131-5_1
leading to permanent developmental adaptations which predispose offspring to
an increased risk of non-communicable diseases in adulthood. Using this life course
approach to women’s health, we need to identify and create opportunities to improve
women’s health through their life course and the health of future generations both at
a population level as well as in patient care by using a multidisciplinary approach from
early life onwards.

1.1 Introduction – 9

1.2 Determinants of reproductive health – 9

1.3 Reproductive health and risk of chronic disease in women’s

later life – 10

1.4 Maternal reproductive health and the risk of chronic disease in the

offspring – 12

1.5 Critical periods of developmental programming – 12

1.6 Mismatch between life periods – 13

1.7 Developmental adaptations – 14

1.8 Social context – 15

Acknowledgements – 16

Glossary – 16

Key references – 16
1.2 · Determinants of reproductive health
1.1 Introduction
A 7life course approach in women’s health focuses on the influ-
ence of exposures and events on health outcomes at different
life stages throughout their own life course and in future gen-
erations. Women’s reproductive health, which includes the
period from menarche to menopause, is relevant for all women
and develops across the life course. This marks the importance
of taking a life course approach to use all opportunities to
improve women’s health.
It is well known that women’s reproductive health is a major
determinant of their overall health and quality of life. Besides
genetic determinants of reproductive health, accumulating evi-
dence suggests that exposures from early life onwards, including
prenatal, sociodemographic, psychosocial and lifestyle related
factors, are also important determinants of various reproductive
health outcomes throughout the life course. In past decades, it
has become increasingly clear that maternal reproductive health
is also a major determinant for offspring health outcomes. The
life course approach for women’s reproductive health thereby
underlines the developmental process of chronic disease
throughout the life course and the potential for early life inter-
ventions to reduce the risk of non-communicable diseases in
their later life and in future generations (.fig. 1.1). This chapter,
based on our previous review (Further reading Gaillard R et al.
submitted), is focused on determinants of women’s reproductive
health and the associations with long-term health outcomes in
women and their offspring. Results from large population-based
studies, potential underlying mechanisms and implications for
population health and clinical practice are discussed.
1.2 Determinants of reproductive health
Women’s reproductive health develops through the life course.
Age at menarche, marking the onset of the female reproductive
cycle, and age at menopause, marking the final stage of ovar-
ian aging, are major components of women’s reproductive
health. Throughout the 20th century an earlier onset of puberty
has been observed in mainly high income countries, which
has been attributed to major improvements in socioeconomic
circumstances and the general health of populations. These
secular patterns are less clear for age at menopause, although
some prospective cohort studies seem to suggest that age at
menopause has increased over recent decades. In addition,
the mean age at natural menopause is around 51 years in high
income countries, as compared with 48 years in low and mid-
dle income countries, suggesting that socioeconomic condi-
tions and the general health of the population are also related
to age at menopause.
The age at menarche and at menopause are determined by
the combination of genetic predisposition and environmental
factors. Although specific genetic determinants remain under
active investigation, studies focused on hereditary influences
of age at menarche suggest that maternal age at menarche
is a major determinant of offspring’s age at menarche and
approximately half of the variation can be explained by genetic
9 1
influences. The influence of genetic determinants on age at
menarche has decreased in past decades, suggesting strong
environmental influences or gene-environment interactions.
Similarly, a mother’s age at menopause is related to her daugh-
ter’s age at menopause, but these associations seem weaker than
for age at menarche, suggesting that environmental factors
play an important role. Recent genome-wide association stud-
ies have identified around 30 genetic loci for age at menarche
and around 17 for age at natural menopause. However, these
genetic loci still account for a very small fraction of the overall
heritability of these traits.
Environmental factors throughout a woman’s life course
influence age at menarche and menopause. Ovarian devel-
opment in utero and maintenance of primordial oocytes
throughout childhood are essential for subsequent reproduc-
tive function. It has been suggested that an altered in-utero
endocrine environment due to excessive maternal weight gain,
gestational diabetes, smoking during pregnancy and expo-
sure to endocrine environmental disruptors, is related to age
at menarche in female offspring. A low birth weight, especially
when followed by rapid postnatal growth, and a high birth-
weight have been linked to earlier age at menarche, although
findings are not consistent. In small for gestational age infants,
it has been suggested that altered hormone levels, such as a high
serum level of the androgen dehydroepiandrosterone sulphate
(DHEAS), may lead to earlier sexual maturation. A high body
mass index, and especially a high body fat mass, in infancy and
childhood is an important postnatal risk factor for earlier age
at menarche, possibly due to altered leptin levels, which influ-
ence pulsatile release of gonadotropin-releasing hormone in the
hypothalamus. Other sociodemographic and lifestyle related
characteristics, such as low socioeconomic status, physical
activity, nutritional factors and physiological factors such as
disrupted family life, may also influence age at menarche. Com-
parable associations are weaker and less consistent for age at
menopause. A higher body mass index throughout adulthood
and weight gain are related to a later age at menopause and a
longer reproductive lifespan, most likely through increased
oestrogen levels. Also, lifestyle related factors in adulthood,
including smoking, alcohol consumption and dietary hab-
its, such as an extreme calorie restriction diet, may be related
to age at menopause although these associations are not rep-
licated across all studies. Smoking is most consistently related
to a younger age at menopause, possibly due to a toxic effect
of smoking on the ovarian follicles. In addition, nulliparous
women have a younger age at menopause as compared with
multiparous women. Not all women have a natural menopause;
around 20 % of women undergo surgical procedures such as a
hysterectomy, leading to medically induced menopause.
Maternal health during the reproductive period is of
major importance for the entire course of pregnancy. Infertil-
ity is a common problem during the reproductive period, with
recent prevalence estimates as high as 9–18 % in the general
population. Infertility and subfertility rates and causes vary
across women from different ethnic backgrounds, with higher
rates of tubular infertility among African-American and His-
panic women and higher rates of endometriosis among white
 10 Chapter 1 · Life course approach in women’s health
1 offspring health outcomes
early life factors
age at
(e.g. parental characteristics, birth, gynaecological health,
menarche
birth characteristics, growth) pregnancy outcomes
genetic, social and environmental factors
. Figure 1.1  Life course approach in women’s health
women. Important risk factors for infertility and subfertility
among women are obesity, polycystic ovary syndrome, endo-
metriosis and a history of pelvic inflammatory disease. Espe-
cially during adolescence and first sexual contact, women are
at risk of sexually transmitted infections which influence repro-
ductive function by causing pelvic inflammatory disorders
and subsequent reduced fertility and increased risks of ectopic
pregnancy. Also, other sociodemographic factors and multiple
unhealthy maternal lifestyle characteristics, such as low educa-
tional level, a Western dietary pattern, smoking, alcohol con-
sumption and low physical activity are associated with reduced
fertility. Remarkably, although reduced fertility is more com-
mon among women with a low educational level and socioec-
onomic status, women with a high educational level are more
likely to receive assisted reproductive therapy. Women with
reduced fertility who become pregnant subsequently have an
increased risk of pregnancy complications, including miscar-
riage, gestational diabetes, and delivering a low birth weight
infant.
Besides reduced fertility, suboptimal maternal health, char-
acterized by maternal obesity, type 1 or type 2 diabetes, pre-
existing hypertension or unhealthy lifestyle characteristics,
is also a major risk factor for maternal and neonatal morbid-
ity and mortality during pregnancy. Maternal pre-pregnancy
obesity and to a lesser extent excessive gestational weight gain
lead to strongly increased risks of gestational hypertensive dis-
orders, gestational diabetes, foetal death, congenital anomalies,
preterm birth and macrosomia. Maternal diabetes before or
during pregnancy is a well-known risk factor for miscarriage,
congenital anomalies and neonatal hypoglycaemia. Pre-exist-
ing hypertension or gestational hypertensive disorders lead to
increased risks of maternal mortality, stroke, liver rupture and
delivering a preterm born infant or low birth infant. Infec-
tions with sexually transmitted diseases during pregnancy,
such as HIV and chlamydia, lead to increased risks of mater-
nal and neonatal morbidity and mortality, such as miscar-
riage, stillbirth and transmission of infection to the newborn.
Importantly, these suboptimal maternal health characteristics
are more frequent among women from ethnic minority groups
(e.g. birth characteristics, chronic disease risk)
chronic disease risk
fertility, age at child
age at (e.g. cardiovascular disease,
menopause type 2 diabetes, cancers,
osteoporosis)
and with a low socioeconomic status, predisposing to increased
risks of pregnancy complications in these groups.
Thus, reproductive health is influenced by genetic factors
and environmental factors during the prenatal period, child-
hood and adulthood. Maternal health in the entire reproduc-
tive period is a critical factor for the course of pregnancy and
the risk of pregnancy complications.
1.3  eproductive health and risk of chronic
R
disease in women’s later life
A woman’s reproductive health is a major determinant for the
risk of non-communicable diseases in later life (.tab. 1.1).
The timing of age at menarche and menopause, indicators
of ovarian function and aging, are related to women’s health
throughout the life course. A younger age at menarche has
both behavioural and physical consequences. A younger age
at menarche is related to health risk behaviours and increases
the risk of premature death, obesity, cardiovascular disease
and insulin resistance. Both a younger age at menarche and an
older age at menopause are associated with increased risks of
breast cancer and endometrial cancer. An earlier age at men-
opause is also associated with increased risks of osteoporosis,
cardiovascular disease and overall cause mortality, although
this effect is small. The interval between age at menarche and
age at menopause itself is also related to an increased risk of
chronic diseases later in life.
Sexually transmitted infections (STI) are an important fac-
tor related to the risk of chronic diseases in women’s later life,
especially in low income countries where treatment options are
limited. The most well-known example is a persistent human
papilloma virus infection, which may cause cervical carcinoma
later in life. HIV infection reduces life expectancy and people
living with HIV infection have increased risks of secondary
infections and various chronic diseases, including kidney dis-
eases, cardiovascular disease and various types of cancers.
Alongside these maternal reproductive health character-
istics, infertility and pregnancy are strongly related to the risk
of non-communicable diseases in later life. Increasing evidence
1.3 · Reproductive health and risk of chronic disease in women’s later life
11 1

. Table 1.1  Adverse reproductive health characteristics and associated future disease risk

women’s reproductive characteristics throughout associated future disease risk in women

the life course

menarche
– younger age at menarche obesity, cardiovascular disease, metabolic syndrome breast and endometrial cancer,
premature mortality
– older age at menarche lower bone mineral density
sexually transmitted infections reduced fertility, different types of cancers
infertility/PCOS/fertility therapy failure cardiovascular disease, endometrial cancer, depression and anxiety disorders
pregnancy
– excessive gestational weight gain obesity, hypertension
– gestational diabetes type 2 diabetes, cardiovascular disease, metabolic syndrome
– gestational hypertensive disorders cardiovascular disease
– preterm birth and low birth weight cardiovascular disease
menopause
– younger age at menopause cardiovascular disease, osteoporosis, premature death
– older age at menopause breast and endometrial cancers

suggests that infertility, especially when related to polycystic
ovary syndrome, is associated with an increased risk of endo-
metrial cancer, psychiatric disorders and cardiometabolic dis-
ease in later life. Pregnancy is a period which involves major
maternal physiological adaptations to accommodate the
increasing needs of the developing foetus. The cardiac out-
put increases, blood volume expands, and peripheral vascu-
lar resistance decreases during the first half of pregnancy and
increases thereafter. There are also major adaptations in glucose
homeostasis, insulin sensitivity, lipid metabolism and protein
metabolism. Pregnancy is therefore often considered to be a
physiological stress model in which pregnancy imposes an
increased physiological burden on the woman’s body in order
to sustain foetal growth and development. Pregnancy com-
plications may develop due to maternal inability to adapt to
pregnancy or due to suboptimal maternal adaptations during
pregnancy and may thereby reveal a woman’s vulnerability for
the development of non-communicable diseases in later life. In
line with this hypothesis, it has been shown that women with
excessive gestational weight gain or who develop gestational
diabetes or gestational hypertensive disorders have a strongly
increased risk of obesity, type 2 diabetes and cardiovascular
disease in later life. For example, women who develop gesta-
tional hypertension have a fivefold higher risk of developing
chronic hypertension in later life. These women who develop
chronic hypertension after gestational hypertension subse-
quently have an approximately 20 % risk of a cardiovascular
event. A large meta-analysis among 3,488,160 women showed
that women with preeclampsia have a fourfold higher risk of
hypertension and a twofold higher risk of ischaemic heart dis-
ease, stroke and venous thromboembolism after at least 5 years
of follow-up. A US study among 14,403 women showed that
after 30 years of follow-up, at a median age of 56 years, the
cumulative cardiovascular disease survival for women with
early preeclampsia was 85.9 %, as compared with 98.3 % for
women with late preeclampsia and 99.3 % for women without
preeclampsia. A meta-analysis among 20 cohort studies showed
that women who develop gestational diabetes have a seven-
fold higher risk of developing type 2 diabetes in later life. Also,
women who deliver a preterm or low birth weight infant have
an approximately twofold higher risk of themselves developing
cardiovascular disease in later life. This effect is seen for both
induced and spontaneous preterm birth. Since pregnancy has
a strong influence on a woman’s body, it has been suggested
that higher maternal parity might also be a risk factor for non-
communicable diseases in later life. Indeed, maternal parity
itself has been associated with the risk of cardiovascular disease
and certain cancers in later life, although findings are incon-
sistent. It seems that both women without children as well as
women with a high number of children have an increased risk
of chronic diseases in later life.
The mechanisms underlying the associations of maternal
reproductive health with the risk of chronic diseases remain
to be further elucidated. It is likely that a common underly-
ing predisposition or already present risk factors and sub-
clinical disease play key roles in these observed associations.
Whether there is an additive effect of markers of reproductive
health, such as vascular damage, inflammation and endothelial
dysfunction due to pregnancy complications, on later risk of
chronic disease, remains to be determined.
The menopause and postmenopausa l phase is character-
ized by a decline in ovarian function. Menopause is defined as
amenorrhoea for one year. Before this period, women experi-
ence alterations in their menstrual cycle and various physi-
cal and psychological complaints. As oestrogen is important
for a variety of organ systems, postmenopausal women have
 12 Chapter 1 · Life course approach in women’s health
increased risks of urogenital symptoms, osteoporosis and car-
1 diovascular disease. Alongside physical changes, also vari-
ous social changes occur such as in the family situation and
employment. Both components strongly influence health and
wellbeing of menopausal and postmenopausal women.
1.4  aternal reproductive health and the risk
M of respiratory infections, cardiometabolic disease, lower cogni-
of chronic disease in the offspring
Maternal health during pregnancy also affects long-term health
outcomes of offspring. In past decades, large-scale epidemio-
logical studies have shown that children born with a low birth
weight have increased risks of cardiovascular diseases, meta-
bolic diseases, osteoporosis and certain types of cancers. More
recent studies suggest that a high birth weight and preterm
birth, independent of size at birth, are also associated with
increased risks of obesity, hypertension, type 2 diabetes and
asthma in later life. These associations are apparent across the
full range of birth weight and gestational age at birth and are
independent of sociodemographic and lifestyle related risk fac-
tors for non-communicable diseases. Based on these findings,
the 7development origins of health and disease hypothesis has pro­
posed that adverse health outcomes in adulthood originate in
early life. This hypothesis proposes that adverse exposures, act-
ing at different stages of foetal and early postnatal development,
lead to permanent adaptations in the structure, physiology and
function of various organ systems. These developmental adap-
tations may contribute to short-term survival, but increase
susceptibility to disease in later life. This hypothesis is not
only supported by observational studies showing associations
between birth outcomes and adverse health outcomes in adult-
hood, but also by experimental studies in animals, leading to
the term ‘developmental programming’.
It is clear that low and high birth weight and preterm birth
are not the causal factors per se leading to non-communicable
diseases in later life. Birth weight and gestational age at birth
are merely proxies of different foetal exposures and growth
patterns and the starting point of childhood growth. Mater-
nal health during pregnancy and lifestyle related factors as
well as placental function throughout pregnancy are major
determinants of the in-utero environment for the developing
foetus. Indeed, multiple studies have shown that maternal nul-
liparity, malnutrition and smoking during pregnancy lead to
a restricted in-utero environment and are associated with low
birth weight, hypertension, reduced kidney function and cardi-
ovascular disease in the offspring. Maternal obesity, gestational
diabetes and excessive gestational weight gain, leading to an
excessive nutritional in-utero environment, are associated with
increased risks of macrosomia, childhood and adulthood obe-
sity, insulin resistance and type 2 diabetes in the offspring. The
placenta is the active interface between the maternal and foetal
environment and the key regulator of foetal nutrition, growth
and cardiovascular development. Impaired placental vascular
function during pregnancy, low placental weight and reduced
placental surface area at birth are associated with impaired foe-
tal growth, adverse birth outcomes, adverse childhood body
composition and hypertension in later life. In the postnatal
period, rapid infant weight gain has been especially associated
with an increased risk of obesity, higher fat mass levels, cardio-
vascular disease and metabolic dysfunction in later life. Also,
formula feeding instead of breastfeeding may increase the risk
tion, asthmatic disorders and allergies throughout childhood
and adulthood, although findings are inconsistent and some
are at least partly explained by confounding by other sociode-
mographic and lifestyle factors. The online case for this chapter
provides a detailed example of offspring consequences of devel-
opmental programming.
Thus, adverse exposures during foetal development leading to
a restricted or excessive nutritional environment in utero and in
infancy are associated with increased risks of non-communicable
diseases in later life. Many of these associations seem to be inde-
pendent or further amplified by sociodemographic and lifestyle
related characteristics in childhood and adulthood.
1.5  ritical periods of developmental
C
programming
With regards to developmental programming of long-term
health outcomes of offspring, the timing of the exposure seems
to be critical for establishing the phenotype of the offspring.
Critical periods seem to differ depending on specific maternal
exposures and the offspring outcomes studied and are related
to the development of specific organ systems. Animal stud-
ies provide insights into the critical periods for adverse influ-
ences of maternal factors on offspring development, although
differences in developmental timings between species need to
be born in mind. Studies in rodents have shown that already
suboptimal maternal dietary intake, undernutrition and obe-
sity in the preconception period influence the development of
cardiovascular and metabolic dysfunction in offspring in later
life, possibly through reduced oocyte quality and suboptimal
embryonic development. In addition, animal studies specifi-
cally exploring the effects of maternal nutritional intake during
pregnancy and in the lactation period by using cross-fostering
have also shown that a suboptimal maternal dietary intake,
for example a high fat diet, in both periods is independently
associated with cardiovascular and metabolic dysfunction
and altered hypothalamic programming in the offspring. On
the other hand, for example, foetal overexposure to increased
glucocorticosteroids in late pregnancy leads to higher risks of
hypertension, altered renal and cardiac development, hyper-
glycaemia and altered behaviour in offspring in various animal
models.
Large population-based human studies with long-term
follow-up have also provided further insight into critical peri-
ods of development programming. Several older studies have
shown that infants who are proportionately small at birth,
1.6 · M
 ismatch between life periods
which may suggest that these infants have been exposed to an
adverse in-utero environment already in early pregnancy, have
different risks of chronic disease in adulthood than infants who
are disproportionately small at birth, possibly due to exposure
to an adverse in-utero environment in late pregnancy. Fur-
ther insight into critical periods for developmental program-
ming in humans has been derived from the Dutch Famine
Study, one of the most well-known human cohorts focussing
on developmental adaptations, which explored the influence
of maternal famine during the Second World War on vari-
ous long-term offspring outcomes. This study showed that the
timing of exposure to the famine was critical for the develop-
ment of adverse offspring health outcomes. Offspring exposed
to maternal famine in early pregnancy had increased risks of
schizophrenia, central obesity, coronary heart disease and dys-
lipidaemia, whereas exposure to famine in mid-gestation led
to an increase in microalbuminuria, reduced creatinine clear-
ance and pulmonary disease in adulthood; exposure to famine
in late gestation was most strongly related to impaired glucose
tolerance in adulthood. Findings from more recent popula-
tion-based prospective cohort studies focused on less extreme
exposures have shown that early pregnancy, which involves the
embryonic period when human growth and developmental
rates are highest, may be a specific critical period in pregnancy
for developmental programming. In both naturally conceived
pregnancies and pregnancies after assisted reproductive ther-
apy, foetal growth restriction in the first trimester of pregnancy
is associated with an increased risk of adverse pregnancy out-
comes and related to an adverse cardiovascular profile in child-
hood. A higher maternal pre-pregnancy body mass index, early
pregnancy weight gain and specific early pregnancy dietary
characteristics, such as a high glycaemic index, are specifically
associated with increased risk of obesity and cardiometabolic
dysfunction in offspring. Alongside this, it is known that foe-
tal dexamethasone exposure in the last trimester of pregnancy
improves neonatal pulmonary function and neonatal survival,
but might lead to a higher blood pressure and altered insulin-
glucose metabolism in offspring in later life. In the postnatal
period, both poor and rapid infant growth in the first 2 years
of life, and especially in the first 6 months of life, predisposes to
increased risks of obesity, hypertension, coronary heart disease
and type 2 diabetes in later life.
Sex-specific differences in response to adverse exposures
during periods of critical developmental might be present,
as many studies have shown that male and female offspring
develop different phenotypes following influences by adverse
exposures. This may be explained by different in-utero
responses to an adverse environment. Boys grow faster than
girls from an early stage of gestation onwards and invest less in
placental development, which makes them more vulnerable to
a suboptimal intrautero environment. Indeed, it is well known
that boys are at a higher risk of adverse birth outcomes, such as
low birth weight. On the contrary, girls are more likely to show
13 1
adaptations in response to the intrauterine environment. Also,
the development of chronic diseases differs among men and
women, which may lead to differences in phenotypes as a con-
sequence of developmental adaptations.
Thus, animal and human studies have shown that precon-
ception, embryonic development, foetal development and
infancy are independent and critical periods for developmental
programming. The critical periods depend on human growth
rates, development of specific organ systems and the specific
maternal exposures studied.
1.6 Mismatch between life periods
During the foetal period and infancy, the most important periods
of developmental plasticity, an individual adapts to early environ-
mental cues to develop a phenotype best suited for survival in
the particular environment. When the subsequent environment
in childhood and adulthood is similar to the early life environ-
ment and the individual’s phenotype is appropriately matched,
an individual is likely to remain healthy. However, when there
is a mismatch between the early life environment and the child-
hood and adulthood environment, individuals are at increased
risk of adverse health outcomes. This is described as the 7mis-
match hypothesis, which suggests that a developmental mis-
match between the environment during foetal life and infancy
and the subsequent environment in childhood and adulthood
leads to a strongly increased risk of chronic diseases in later life
(.fig. 1.2). Large longitudinal studies have shown that the risks
of obesity, hypertension, cardiovascular disease and type 2 diabe-
tes are highest among individuals born with a low birth weight
and rapid postnatal weight gain. Thus, these results suggest that
a low birth weight as a result of restricted foetal environment
may specifically lead to cardiometabolic disease in later life when
postnatal life is characterized by a relatively high body mass index
as a result of an affluent environment. This type of mismatch can
arise from various circumstances. This may involve adverse expo-
sures during pregnancy limiting the foetal nutrient supply, such
as impaired placental function, or a strongly obesogenic environ-
ment in later life. Similarly, the hygiene hypothesis is an example
of developmental mismatch. Optimal functioning of the immune
system may be influenced by changes in the environment aris-
ing from reduced exposure to microbial products and infections
in early life, which leads to increased risks of atopy in later life.
Given the various circumstances that can lead to development
mismatch, this is an important hypothesis to consider in both
affluent countries and developing countries going through rapid
socioeconomic transitions.
Thus, developmental adaptations in response to a subopti-
mal environment during early life may particularly lead to an
increased risk of chronic diseases when there is a mismatch
between the predicted environment in early life and the actual
environment in childhood and adulthood.
 14 Chapter 1 · Life course approach in women’s health

1 suboptimal maternal
nutritional environment

placental nutrient transfer

adaptations

impaired foetal nutrition

foetal developmental
adaptations

match between induced phenotype mismatch between induced pheno-

and postnatal environment type and postnatal environment
(e.g. low nutrition, high activity levels) (e.g. affluent environment with high
nutrition/low activity levels)

normal disease risk increased disease risk

. Figure 1.2  Mismatch hypothesis

1.7 Developmental adaptations
The mechanisms underlying the associations of developmental
adaptations in response to a suboptimal in utero and infancy
environment remain to be established and have mainly been
explored in animal models. Results from these animal stud-
ies suggest that physiological and epigenetic mechanisms play
important roles.
Epigenetic mechanisms involve modifications to the DNA
which do not affect the DNA sequence but do affect gene
expression. Epigenetic mechanisms involve the processes of
DNA methylation, histone modifications and non-coding
RNAs, of which DNA methylation is most widely studied.
During gametogenesis and embryogenesis, de-methylation
and re-methylation occur and these periods may be critical
for epigenetic modifications in response to environmental fac-
tors. Animal studies have shown that epigenetic modifications
in placental tissue and offspring occur in response to mater-
nal dietary alterations, maternal obesity and reduced utero-
placental blood flow, but this remains little explored in large
human studies. Studies among pregnant women have shown
that maternal obesity, impaired maternal glucose tolerance and
maternal folic acid supplement use induced epigenetic changes
of placental genes and in offspring cord blood. Results from the
Dutch Famine Study showed that exposure to the Dutch hun-
ger winter at preconception or in utero was associated with
altered methylation of the promotor regions of imprinted and
non-imprinted genes in the later life. Epigenetic modifications
together with other mechanisms may thus be involved in devel-
opmental adaptations.
Animal and human studies have shown that alterations
in foetal nutrient and oxygen supply affect foetal growth and
development of various organs and tissues. This may occur
as organs and tissues not essential for foetal survival have a
lower priority for nutrient supply than essential organ and tis-
sue systems. Across a wider range of foetal growth than usually
acknowledged, this may result in foetal brain sparing, in which
foetal blood flow redistribution with a preferential foetal blood
flow to the brain and heart occurs at the expense of the lower
body parts. This may subsequently lead to asymmetrical foetal
growth restriction, characterized by a relatively larger head size
than body size at birth, and predispose to an increased risk of
chronic disease in later life. However, developmental adapta-
tions in various organs and tissue systems may also occur in
response to different maternal and placental exposures. For
example, animal studies have suggested that maternal obesity
during pregnancy may affect offspring adipocyte morphol-
ogy and metabolism, which may influence the development of
obesity and insulin resistance in later life. Results from a large
population-based prospective cohort study in Rotterdam, the
Netherlands, showed that a small increase in umbilical artery
vascular resistance was associated with reduced foetal growth,
rapid postnatal growth and higher fat mass and blood pressure
at the age of 6 years.
1.8 · Social context
15 1

Developmental changes in the homeostatic set-points for

Perspectives: The potential for populations and
many hormones and alterations in tissue sensitivity to these
patients
hormones have also been shown in various animal models. For
Life course research focused on women’s health throughout
example, in rats, reduced placental 11-hydroxysteroid dehy-
the life course and the health of the next generations
drogenase type 2 activity is associated with increased blood
has led to a better understanding about risk factors and
pressure in the offspring during adult life, possibly due to pre-
the development of chronic disease. Currently, we are
mature activation of the foetal hypothalamic-pituitary-adrenal
challenged with using this knowledge to identify and
(HPA) axis. Similar mechanisms may play a role in human
create opportunities to improve women’s health through
pregnancies and could explain the relations between maternal
the life course and the health of future generations both
influences and alterations of adrenocortical function in the
at a population level as well as in patient care by using a
offspring. Animal studies have also suggested that a maternal
multidisciplinary approach.
hypercaloric diet during pregnancy and overfeeding in the
First, health education needs to focus on women’s health
foetal and early postnatal period may lead to hyperphagia and
from an early age onwards to improve their pre-conception
altered satiety mechanisms through adverse programming of
health to optimize women’s fertility chances, the course
the hypothalamus by high foetal and infant leptin and insulin
of pregnancy and to improve long-term health outcomes
levels. These alterations in satiety mechanisms may play a key
in offspring. Improving health education and health
role in the development of obesity in offspring in later life.
behaviour, for example by targeting obesity, alcohol
Thus, animal studies have provided insight into potential
consumption and smoking among teenagers and women
developmental adaptations playing a key role in the develop-
of reproductive age, at a population level is important to
mental origins of non-communicable diseases in later life. These
increase its impact and chance of success. As the risk of
mechanisms remain to be further explored in large human studies.
adverse reproductive outcomes is higher among women
from ethnic minority groups and with a low socioeconomic
1.8 Social context status, health education should also specifically target
these more vulnerable groups. Second, since there is
accumulating evidence that a woman’s reproductive
The described life course trajectories are strongly influenced by
history is related to the risk of chronic disease in later life,
social contexts. Over the past decades, the social, economic and
a woman’s reproductive history should raise awareness
political position of women has changed dramatically and still
among clinicians and serve as an indicator for preventive
varies widely across countries. Especially in Western countries,
therapy and follow-up in clinical practice. Currently, the
women have more opportunities with regards to education and
American Diabetes Association recommends additional
employment, and their life expectancy has increased. Women
glucose testing among women with a history of gestational
are also less likely to be married, divorce rates have increased
diabetes. The diagnosis of gestational diabetes also
and childbearing is being increasingly delayed. Society expecta-
provides an opportunity to stimulate women to make
tions of women have also changed considerably, which has cre-
lifestyle changes, since the risk of type 2 diabetes can
ated more opportunities for women but also increases pressure
be reduced by lifestyle modification. It is estimated that
on women. The societal changes influence the development of
only 5–6 women with a history of gestational diabetes
diseases and interact with risk factors for disease throughout
need to be treated to prevent one case of diabetes in the
the life course, but the pathways still need to be explored in fur-
next 3 years. Similarly, the American Heart Association
ther depth. For example, it is well known that educational level
recommends that women who develop gestational
is a major determinant of health behaviour and development
hypertensive disorders should have careful monitoring
of disease throughout the life course. However, not all women
and treatment of cardiovascular risk factors postpartum.
are able to reach their educational potential due to family based
In addition, the American Heart Association recommends
and societal influences. Or for example, the influence of divorce
that healthcare professionals should take a woman’s
on women’s psychological well-being and health throughout
history of pregnancy complications into account when
the life course may vary depending on how common divorce
assessing disease risk later in life. Third, the risk of
is in a certain community. The area where women and their
non-communicable diseases in the next generations may
children live is also a major determinant of health and health
be reduced by improving the intrauterine environment
behaviour through influences such as social inequality within
and the environment during infancy. Children with known
and between neighbourhoods and social problems which tend
risk factors in early life for non-communicable diseases in
to cluster together in neighbourhoods.
later life may especially benefit from interventions in early
Thus, women’s life course trajectories are strongly influ-
life, focused for example on optimal nutritional intake
enced by the social, economic and political environment.
and prevention of obesity from early life onwards. Finally,
Their combined effect and interaction with well-known life-
further research is needed to obtain more insight into the
style related risk factors on women’s health throughout the life
critical periods in women’s reproductive health across the
course and health of their offspring remains to be examined in
life course, the potential for diagnostic and preventive
detail.
 16 Chapter 1 · Life course approach in women’s health
1 interventions during these time periods and the influence
on health outcomes in future generations. Especially
follow-up of women and their children participating in both
historic and more contemporary birth cohorts from the
prenatal period until death will provide valuable insights
into the life course approach on women’s health.
Highlights
5 A life course approach in women’s health focuses on the
influence of exposures and events on health outcomes
at different life stages throughout women’s own life
course and in future generations.
5 Pregnancy can be considered as a physiological stress
model in which pregnancy imposes an increased
physiological burden on the woman’s body in order
to sustain foetal growth and development. Pregnancy
complications may thereby reveal a woman’s
vulnerability for the development of non-communicable
diseases in later life.
5 The development origins of health and disease
hypothesis suggests that adverse health outcomes in
adulthood originate in foetal life or early postnatal life
through developmental adaptations in response to an
adverse intrauterine or early postnatal environment.
5 Developmental mismatch between the early life
environment and subsequent environment in childhood
and adulthood may especially increase the risk of
non-communicable diseases in adulthood.
5 The life course approach underlines the potential to
improve women’s health throughout the life course and
health of future generations on a population level and
in patient care by using a multidisciplinary approach.
Acknowledgements
The authors received funding from the European Union’s Seventh
Framework Programme (FP7/2007–2013), project EarlyNutrition under
grant agreement n°289346. KMG is supported by the National Institute
for Health Research through the NIHR Southampton Biomedical Research
Centre and by the European Union’s Seventh Framework Programme
(FP7/2007–2013), project ODIN under grant agreement number 613977.
VWVJ received a grant from the Netherlands Organization for Health
Research and Development (VIDI 016. 136. 361) and a European Research
Council Consolidator Grant (ERC-2014-CoG-648916). RG received funding
from the Dutch Heart Foundation (grant number 2017T013) and the Dutch
Diabetes Foundation (grant number 2017.81.002).
Glossary
Life course approach (also known as life course perspective or life course
theory)  A life course approach is the assessment of the influence of expo-
sures and events at different stages in life (gestation, childhood, adolescence,
young adulthood and midlife) on health outcomes throughout the life
course and in future generations. It aims to identify underlying biological,
behavioural and psychosocial processes that operate across the life span and
the potential for interventions in populations and individuals
Development origins of health and disease hypothesis  This hypothesis
proposes that adverse exposures at different stages of foetal and early
postnatal development lead to permanent adaptations in the structure,
physiology and function of various organ systems, which may contribute to
short-term survival, but increase susceptibility to disease in later life
Mismatch hypothesis  This hypothesis proposes that developmental mis-
match between the early life environment and the subsequent environment
in childhood and adulthood leads to an increased risk of non-communicable
diseases in later life
Key references
1. American Diabetes A. 13. Management of Diabetes in Pregnancy.
Diabetes care. 2017;40(Suppl 1):S114–9.
2. Forman MR, Mangini LD, Thelus-Jean R, Hayward MD. Life-course
origins of the ages at menarche and menopause. Adolesc Health Med
Ther. 2013;4:1–21.
3. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero
and early-life conditions on adult health and disease. The New England
journal of medicine. 2008;359(1):61–73.
4. Godfrey KM, Inskip HM, Hanson MA. The long-term effects of prenatal
development on growth and metabolism. Semin Reprod Med.
2011;29(3):257–65.
5. Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, Hotaling J.
Female infertility, infertility-associated diagnoses, and comorbidities:
a review. J Assist Reprod Genet. 2017;34(2):167–77.
6. Hanson M, Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD.
Developmental plasticity and developmental origins of non-
communicable disease: theoretical considerations and epigenetic
mechanisms. Progress in biophysics and molecular biology.
2011;106(1):272–80.
7. Mishra GD, Cooper R, Kuh D. A life course approach to reproductive
health: theory and methods. Maturitas. 2010;65(2):92–7.
8. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones
DM, et al. Effectiveness-based guidelines for the prevention of
cardiovascular disease in women–2011 update: a guideline from the
american heart association. Circulation. 2011;123(11):1243–62.
9. Park K, Wei J, Minissian M, Bairey Merz CN, Pepine CJ. Adverse
Pregnancy Conditions, Infertility, and Future Cardiovascular
Risk: Implications for Mother and Child. Cardiovasc Drugs Ther.
2015;29(4):391–401.
10. Stephenson DK, J. Shawe, D. Lawlor, N.A. Sattar, J. Rich-Edwards, et al.
Why should we consider a life course approach to women’s health
care? (Scientific impact paper no. 27). Royal College of Obstetricians
and Gynaecologists. 2011.
 17 2

Life course approach in obstetrics

and gynaecology for patient care,
education and research
Sam Schoenmakers, Bart C.J.M. Fauser, Mary E.W. Dankbaar, Carina G.J.M. Hilders,
Vincent W.V. Jaddoe, Leon F.A.G. Massuger, Joris A.M. van der Post and
Eric A.P. Steegers

! Life course
A woman’s life is a continuum composed of a one-way direction sequence of the life course
stages. This continuum biologically starts during maternal and paternal preconception
gametogenesis and will carry on throughout life. The different life course stages of each
individual consecutively prepare and determine health outcome and wellbeing. The life
course approach in obstetric and gynaecological patient care should be personalized,
providing a path towards healthy aging, with specific attention for prevention and the
social environment.
Such a life-long integrated approach involves reorganization of medical training programs
and the healthcare system, necessitating integrated, transmural and multidisciplinary care,
crossing medical and social domains. Future research has to take into account both ­­

 lectronic supplementary material

E
The online version of this chapter (7 https://doi.org/10.1007/978-90-368-2131-5_2) contains supplementary
material, which is available to authorized users.

© Bohn Stafleu van Loghum is een imprint van Springer Media B.V., onderdeel van Springer Nature 2019
E. A. P. Steegers et al. (Eds.), Textbook of Obstetrics and Gynaecology, https://doi.org/10.1007/978-90-368-2131-5_2
 short- and long-term effects of biological, behavioural psychological, socioeconomic and
cultural factors on reproductive, obstetric and gynaecological health and disease during the
whole life course and across generations.

Summary
The life course approach in obstetrics and gynaecology respects the continuum of a
woman’s life. The continuum is a one-way direction, which already starts preconception-
ally with gametogenesis in the parental reproductive organs and is followed by consecu-
tive life course stages, such as conception, foetal and placental growth and development,
menopause and geriatric aging. Each individual’s life course is unique. Therefore, the
life course approach should be personalized and context-based, providing an individu-
alized path towards healthy aging, with specific attention for prevention, the social
environment and the next generation. A life course-long healthcare approach neces-
sitates reorganisation of the current health care system, research and medical training
programmes, involving integration and transcendence of transmural and multidiscipli-
nary care as well as crossing medical, paramedical and social domains.

2.1 Introduction – 19
2.1.1 The life course approach in obstetrics and gynaecology: linking past, present
and future – 19

2.2 Life course approach in patient care in obstetrics and 

gynaecology – 19
2.2.1 Woman-centred, personalized medicine – 20
2.2.2 Linking the medical with the social domain – 20
2.2.3 Multidisciplinary networking-medicine – 21
2.2.4 Measure quality of care by health outcomes that matter most to patients – 21

2.3 The life course approach in education and training – 22

2.3.1 Learning goals and target groups – 22
2.3.2 Instructional design and formats – 22
2.3.3 Educational principles – 22
2.3.4 Blended training program – 23

2.4 The life course approach in scientific research – 23

Glossary – 24

Key references – 24
2.2 · Life course approach in patient care in obstetrics and gynaecology
19 2
2.1 Introduction
access to
2.1.1  he life course approach in obstetrics
T public goods
ho
and gynaecology: linking past, present rk us
wo i
and future own foetal

ng
history re
pr
h

alt l

od tory
he nta
The life course approach in general appreciates the continuum

is
uc
my

me

tive
of wellbeing and health in time in relationship to human con-

envir icity
econo
stitution, behaviour and the social environment (.fig. 2.1). It

tox
onmental
life course
focusses on the influence of exposures and events at different women’s wellbeing

s ex u a l
h e a lt h

nutritio
developmental stages on individual women’s health outcomes and health
from conception, embryonic and foetal development, childhood

educ

n
up to the menopause and geriatric aging (.fig. 2.2). It inte-

atio

a lt n it y
grates and transcends all medical, paramedical and social disci- ch le
d is r o n i c sty

he mu
n
plines and involves a transition in healthcare in which the focus life

h
ease

m
is shifted to management and maintenance of health instead of co
re fa
la t m ily
disease only. Health of maternal and paternal gametes deter- io n to
shi access e
mines the commencement of the life course of their offspring. ps
h e alth c a r
The future gynaecologist has to acknowledge that the early
life stages, including prenatal and birth characteristics, soci-
odemographic, lifestyle related and genetic factors determine
. Figure 2.1  Determinants of women’s wellbeing and health
a variety of interdependent health outcomes and wellbeing
throughout a woman’s life course. The gynaecologist has to
understand the potential for preventive measures to reduce
the risk of 7non-communicable diseases in later life and future
» Life course approach: Most nephrons form during the
3rd trimester; intrauterine growth restriction, preterm
generations. Especially with increased longevity in mind, a new
birth and low birthweight are associated with a small
health and patient care attitude in obstetrics and gynaecology
number of nephrons. In addition, prematurity and very
is therefore needed. This requires reorganization of the current
low birth weight are major risk factors for neonatal
medical training programs and the healthcare system.
acute kidney injury. All factors taken together indicates
an increased risk of chronic kidney disease in later life.
Box 1: Case
In 1980 a term pregnancy is complicated by eclampsia and
a healthy girl, Natasha, with a weight of 3,100 grams is born
via caesarean section. 2.2  ife course approach in patient care
L
In 2008, Natasha’s first pregnancy is complicated by severe in obstetrics and gynaecology
early preeclampsia and she delivers at 29 weeks.

A life course approach to women’s health implicates a patient-

» Life course approach: Women have a relative risk of
centred transition in healthcare towards management of health
2.9 of developing preeclampsia with a positive family
instead of disease only, enabling intervention strategies to pre-
history of preeclampsia (mother or sister).
vent and reduce future health risks, regardless of whether the
A growth-restricted son, Dilano, is born with a
woman in question will or will not have children. To maxi-
birthweight of 859 grams and admitted to the neonatal
mize the benefit from the life course approach, women should
intensive care unit. After 12 weeks Dilano is discharged
be entitled to a digital personalized life course passport, which
in a good condition. Six months postpartum, both
they own and control themselves. It keeps a record of all medi-
mother and son are in such a good condition that they
cal, social and personal events, including the preconception
are discharged from follow-up and referred to their
period, and serves as a lifelong digital medical record. Also in
general practitioner for future health issues.
view of the increased longevity of current and future female
In 2035, both Natasha and Dilano, being 55 and 27 years of
generations, a new attitude towards health and patient care in
age, respectively, are admitted to the hospital. Natasha has
obstetrics and gynaecology is required. The current fragmented
suffered a stroke due to undiagnosed chronic hypertension
health services in general, being organized according to age,
and Dilano has to undergo daily dialysis for chronic kidney
discipline and organ oriented, need to be proactive and inte-
insufficiency and is awaiting a kidney transplantation.
grated, taking environmental, social and cultural perspectives
into account. This will have an influence on the healthcare
» Life course approach: Women with a history
organization in which -as in an ecosystem- a team-based
of preeclampsia are at increased risk for future
approach and a change in reimbursement models is needed to
cardiovascular disease.
really engage with the needs of the patient and population.
 20 Chapter 2 · Life course approach in obstetrics and gynaecology for patient care, education and research

percentage of women
2 in age range taking up
maternal and foetal screening
service
100 %
newborn
wborn blood contraception, sexual
90 % screening health & cervical screening

80 %

70 %

60 %
childhood chlamydia preconception antenatal chron disease
chronic
50 % vaccinations screening care care screening
sc

40 %

30 % sexual health
hea menopause
education

20 %

HPV
10 % assisted conception
on
vaccination

source RCOG, 2011. 0 %

–2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70
age (years)

. Figure 2.2  Population view of women’s healthcare needs across the life course (adapted from RCOG 2011)

The following aspects are essential for future healthcare in
obstetrics and gynaecology following the life course approach.
2.2.1 Woman-centred, personalized medicine
A woman’s journey through the healthcare system needs to be
woman-centred and tailored by multidisciplinary guidelines
and protocols, preparing her for what to expect in advance.
Current developments of the digital world have opened up
many possibilities to timely inform and educate women about
their health issues. The most important step is to make women
aware of and take responsibility for their own health. Women
have to be educated, stimulated and guided with understand-
able, accessible and reliable information about disease preven-
tion and health promotion. Women should be made aware of
the impact their lifestyle and behaviour will have on their own
life course. Self-reliance has to be encouraged by combined
efforts of local and national governments, healthcare provid-
ers and health insurance companies. It should be a co-creation
in helping women to manage themselves by raising awareness.
Women should be well prepared for a healthcare consultation
by means of good information and decision aids, allowing for
shared decision-making. Outpatient clinics should adopt a one-
stop model as far as possible and investigate how such services
can be taken to the community.
Woman-centred, personalized care necessitates the need
to divert from mono-disciplined speciality-oriented disease
management towards a multidisciplinary approach, including
gender-oriented medicine. Men and women differ, not only
in chromosomal constitution, gonadal differentiation or psy-
chological gender aspects, but also in susceptibilities for heart
disease, obesity or depression. Further development and
healthcare integration of personal 7‘omics’ characteristics such
as those related to genomics, nutrigenomics, pharmacogenom-
ics and metabolomics, will contribute to individual health pro-
motion and interventions in the future.
2.2.2  inking the medical with the social
L
domain
A woman’s health status cannot be fully appreciated without
viewing it in the context of her social environment as this also
determines health and wellbeing to a great extent (.fig. 2.1).
Identifying and incorporating the social determinants during
the different stages of the life course is imperative to adequately
anticipate and prevent women’s morbidity and mortality in
later life. For example, disparities in perinatal outcomes are
known to be related to lifestyle, education, working conditions,
experience of violence, geography, socioeconomic status of
couples and living in deprived districts.
In light of the lifelong consequences of perinatal morbid-
ity, timely identification and support of socioeconomically
vulnerable pregnant women is essential. A multidisciplinary
approach, involving local healthcare and municipalities, is nec-
essary to break the vicious circle that creates a poverty trap.
Both perinatal health as well as health in adult life will benefit
2.2 · Life course approach in patient care in obstetrics and gynaecology
society
ity and hospital ca
mun re
com
he alth care
innovation
l pr
en ra
sci smu
ce
tran
tiary care
ter
society
scie n c e
edu
ca
n Although multidisciplinary teams already exist within the field
ti o
co p o lic y
mm
u n it y
a n d h o s p it a l
s o c i et y
. Figure 2.3  7Societal valorisation of new knowledge
from this approach. We have to co-design the healthcare sys-
tem and actively reach out for the communities with lower
healthcare outcomes. To make this happen 7societal valorisa-
tion programs should be initiated and new incentives should be
aligned and supported by universities, hospitals and local and
national governmental bodies. By doing so, university medical
centres can take up the responsibility for applying new knowl-
edge for improved patient care throughout the healthcare sys-
tem, for better teaching curricula and for local and national
governmental policies (.fig. 2.3).
2.2.3 Multidisciplinary networking-medicine
The current healthcare system is based on a pyramid-like
organizational structure, which from the bottom up involves
community healthcare including general practitioners and
midwives and municipal public health services. If specialized
hospital care is needed, the woman needs to be referred by the
primary healthcare provider to a secondary care hospital. The
next level is the tertiary hospital, which is structured by depart-
ments of specialized and super-specialized healthcare. An
extension of the tertiary care is the quaternary care, with even
more highly subspecialized medical care.
In order to maintain the high quality of the current health-
care system and simultaneously keep it accessible and afford-
able, a shift from institutionalized to community (or ‘closer
to home’) based healthcare is necessary, and hospitals have to
become community partners. Hospital stays are becoming
shorter, leaving much care to be provided by other caregiv-
ers within the 7transmural chain of care. This also constitutes
the shift of less-complex high-volume care from tertiary to
21 2
secondary hospitals. Networking medicine enables the regional
institution of patient-centred care pathways, in which we shift
the incentive system to really meet the needs of the population
in a matrix of public health, chronic, hospital and acute care.
It should be clear which organization is responsible. All dif-
ferent participants at different moments in the woman’s life
ev dici
course have added value for the healthcare of this specific
m
en ne
e
tat
woman and may include medical specialists, psychologists,
ive
nurses, midwives, general practitioners, pharmacists and com-
society
munity social workers. The active participation of family and
peers enables more social visits, probably leading to better
quality of life and quicker recovery. For the elderly woman, a
y
nursing home could be an option before definitive discharge.
om
on
ec
of oncology, it is of utmost importance that such an approach
becomes the standard within all fields of obstetrics and gynae-
e
car cology. Effective teamwork is essential, requiring clearly defined
leadership, designated individual roles and expectations within
the team, willingness to share information and a supportive
staff. One member of each team should be appointed as the
advisor for communication and navigation for each individual
woman. This person is responsible for keeping an overview and
tracking the health problems that require attention and at the
same time coaches the patient.
The use of video communication allows the members of
multidisciplinary teams to be in close contact with each other.
This makes it possible to keep track of the recovery process
and to have access to each other’s expertise, thereby minimiz-
ing the risks of unnecessary referrals and treatments. In addi-
tion, flexibility within the local workforce and the team allows
the members to move within and between different centres
and closer to the woman’s home. When at home, virtual health
solutions such as e-consultations with the pharmacist or medi-
cal specialist should be offered as well as online platforms for
home monitoring. In addition, community groups can be used
for local non-medical and social care to support adequate and
optimal physical and mental recovery. We expect that in the
near future community groups will probably be more effective
in connecting with these people than the medical personnel at
institutions.
2.2.4  easure quality of care by health
M
outcomes that matter most to patients
In measuring quality of care, we are experiencing a shift in
‘what is the matter’ to ‘what matters to you’. The relevance of
today of being more self-responsible reflects on determin-
ing the personalized healthcare outcomes. The International
Consortium for Health Outcomes Measurement (ICHOM)
involves patients directly in defining health outcomes, since
they are the ones experiencing the defined outcomes first-
hand. The ICHOM defines health outcomes as the results that
matter the most to people when they seek treatment, includ-
ing the quality of life such as functional improvement and the
ability to live a normal and productive life. Simultaneously,
 22 Chapter 2 · Life course approach in obstetrics and gynaecology for patient care, education and research
ICHOM focusses on reduction of the worldwide ever-increas-
2 ing costs of healthcare, support of informed decision-making,
improving healthcare quality and on strong international
collaboration.
2.3  he life course approach in education
T applies to a large variety of learners, learning contexts (medi-
and training
2.3.1 Learning goals and target groups
If the life course approach is to be leading in the approach to
women’s healthcare, more integrated healthcare and interact-
ing healthcare providers are needed. With the focus on patient-
centred care, common virtues to provide care with skills and
passion, to really listen to the patient and being worthy of
their trust are becoming more predominant. Seeing the person
in addition to treating the illness will lead to more integrated
knowledge and skills. What are the consequences of a life
course approach and patient centered care for training health-
care professionals? What new knowledge and skills are required
and how can these be trained? Learning goals of such a training
program can be described as:
1. Know how disease risks interact with biological, social and
other processes regarding women’s health outcomes and
what interventions can be effective.
2. Being able to implement a woman-centred approach in
healthcare (using shared decision-making principles and
information on her social and professional context).
3. Being able to collaborate with healthcare professionals (e.g.,
nurses, obstetricians) and community workers in order to
offer interprofessional and transmural healthcare.
These learning goals are relatively new to most medical cur-
ricula, although training in shared decision-making and
interprofessional collaboration is beginning to appear. The
target groups for the life course approach are different types of
healthcare professionals, acting in women’s healthcare: medi-
cal specialists, residents, nurses, obstetricians, and general
practitioners. Considering the varying starting level in knowl-
edge and skills, a comprehensive, modular training program
is needed. Entrance tests may be used to determine the level
of knowledge. The specific context and tasks of the learner
determine which modules are obligatory, optional or can be
skipped.
What instructional design and formats are suitable, and
what educational principles should be implemented? An
instructional design is aimed at choosing methods that make
learning effective, efficient, and appealing in a specific context.
2.3.2 Instructional design and formats
As the target groups of this training program are healthcare
workers with limited time for classroom training, a blended
training program (a combination of online and face-to-face
training) is most appropriate. Advantages of online learning
are: more flexible and increased access to training (24/7), scal-
ability of training (no extra costs for extra students, once the
material is developed) and the possibility to make training
adaptive (using tests or questionnaires). Extensive research
shows that online instruction is just as effective as tradi-
tional instruction; it can achieve similar learning results. This
cal and non-medical), topics and learning outcomes, such as
knowledge, skills and attitudes. In a blended model learners
can develop knowledge and cognitive skills online, at home
or during quiet periods at work. Classroom time can then be
dedicated to training skills on a higher level, enabling reduced
face-to-face training time. Blended learning is not a single con-
cept; different mixes of online and face-to-face training and
different online formats exist. Systematic reviews have shown
that blended learning is at least as effective as traditional, face-
to-face learning. Learners evaluate it as equally attractive, but
sometimes as more demanding.
In a blended course design, a variety of instructional for-
mats such as e-modules, video-lectures, simulations and seri-
ous games can be used. E-modules and video-lectures are the
counterparts of traditional lectures, appropriate for developing
knowledge. Simulation programs and serious games are the
counterparts of simulation training and role-play, appropri-
ate for developing skills, without risks for the patient. They can
offer learning tasks in a realistic, engaging online environment,
where learners directly experience the consequences of their
decisions.
2.3.3 Educational principles
For the development of training modules, a number of evi-
dence-based educational principles can be implemented:
5 Learning is promoted when learners are engaged in a
task-centred approach including demonstration of worked
cases and application in open cases in a variety of problems.
‘Whole’ learning tasks that are based on complex real-life
experiences foster transfer to clinical practice. They can be
presented from simple to more complex, with diminishing
guidance.
5 Clinical competencies are based on a combination of
specific clinical knowledge and a general problem-solving
ability. Domain-specific knowledge is just as essential as are
domain-general skills.
5 Distributed learning over time (‘spacing’: spreading
out study time) typically benefits long-term retention
more than does massing learning opportunities in close
succession.
5 Feedback is one of the most powerful learning principles.
Appropriate feedback allows learners to verify their answers
or actions, determine the cause of errors and it motivates
learners to remain involved in the learning tasks. It should
be directed to the task, process and/or regulation and not to
the self-level.
2.4 · The life course approach in scientific research
2.3.4 Blended training program
An effective and efficient training program in the life course
approach is a blended course design, with course components
for different target groups. The online instructional mate-
rial relating to the first learning goal is aimed at knowledge
acquisition. It will include e-modules, text and video-lectures
on disease risks and the interactions between biological and
social processes, discussing possible intervention and preven-
tion strategies. The e-modules are highly interactive; the vid-
eos contain cases with examples of how interactions may work
out for women in different contexts and which interventions
can be considered. Knowledge tests enable learners to enter this
material at the required level. In the classroom sessions, more
complex cases and possible interventions are discussed. The
assessment will contain assignments with open cases, where
learners have to show they understand the interactions related
to health management and disease risks and are able to define
effective interventions.
The online material relating to the second and third learn-
ing goal is aimed at complex skills learning. It will include a
simulation program or simulation game, enabling learners to
practise with shared decision-making principles and interpro-
fessional collaboration. A variety of cases (tasks) are offered, at
different complexity levels. Learners work on these cases partly
individually and in small groups. They are invited to discuss
their strategies in a discussion forum, and add cases from their
own clinical experience. In the face-to-face training sessions,
the online discussions are briefly reviewed, and new cases are
used for role-play and debriefing. The assessment will contain
role-play with new cases, where learners are evaluated on their
individual and team performance.
Learners are stimulated to use the online material fre-
quently over time, related to the challenges in their work, and
continue sharing experiences in intervention strategies.
2.4  he life course approach in scientific
T 2. Implementation of knowledge: Knowledge and awareness
research
The only way forward to improve quality of life and healthcare
is creating and applying new knowledge by scientific research
(.fig. 2.3). Based on the many challenges mentioned above,
the focus of research leading to changes in clinical practice
of women’s health is in need of a major revision. In doing so,
we should acknowledge that the current healthcare system is
predominantly gender non-specific (i.e. men and women are
treated alike) which should change. Much data support the
contention that at present women are significantly less well
served in the healthcare system.
The life course approach stresses that a given stage in the
life of human beings has distinct implications for health in
later life. The concept of early detection of risk factors and pri-
mary or secondary prevention of disease in later life stresses
the development of concepts away from the argument that
many disease conditions can be cured. The imperative focus on
23 2
health management by early detection and disease prevention
stresses the need for fundamentally different research strate-
gies away from the evidence-based medicine dogma of rand-
omized controlled trials in homogeneous groups of patients
ignoring major differences in environmental and social context
and patients themselves. Instead, prospective cohort follow-up
studies may identify patient characteristics upon initial screen-
ing associated with more long-term disease outcomes. New
statistical tools have been developed (multivariate prediction
models) to guide precision medicine. Research strategies guid-
ing the practice of gender-sensitive medicine often require
multidisciplinary and transmural approaches in the context of
networking medicine.
The current healthcare system as we practise today is both
predominantly studied by men, but also chiefly developed for
men. This dates back to the 1950s when it was believed that
gender did not matter when general disease conditions were
concerned. Many such initial studies were performed exclu-
sively in men (mainly due to uncertainties of unintended
pregnancies and possible teratogenic effects of studied drugs),
under the assumption that findings would be equally applicable
to women. Abundant evidence now convincingly demonstrates
that this concept is incorrect. This holds true for many systems
in the body such as bone, cardiovascular, brain as well as for
pharmacotherapy and many others.
In order to ensure that future research will contribute more
substantially to women’s health, the following principles need
to be acknowledged:
1. Women are underserved: National and international data
demonstrate that women are less well served in the present
healthcare system than men. Women more frequently visit
a general practitioner, use medication more often, more
often suffer from chronic disease, are admitted more to the
hospital, and assess their quality of life less favourably com-
pared with men when growing older. Healthcare expendi-
ture favours women and older age, but the added value in
terms of quality of life remains uncertain.
in the science community concerning the relevance of
female-specific issues in medicine is slowly growing, but
this is often not translated into modified and more gender-
sensitive practice guidelines. Therefore, we should aim our
efforts towards translating recent knowledge into clinical
care much more quickly.
3. Knowledge gap: It should also be acknowledged that often
insufficient knowledge is available with regard to gender-
specific medicine. This knowledge gap should be decreased
by more research in this area. In the Netherlands, this area
of research has been prioritized by funding bodies and
money is allocated with the aim to bridge this gap. This
includes bridging the knowledge gap in the education of
professionals and implementation of specific insights into
the medical curricula.
4. Gender differences in healthy aging: Women live longer
than men, but the number of years with a good quality of
life (self-assessed by women) is actually less than in men.
 24 Chapter 2 · Life course approach in obstetrics and gynaecology for patient care, education and research
Hence, women live longer, however in suboptimal quality
2 of life. Gender (male versus female) differences and the role
of sex steroids in active healthy aging should be prioritized
in terms of a knowledge gap with potentially major clinical
implications.
5. Women’s health: We need to focus more on women’s health
in general disease conditions such as cardiovascular dis-
ease, psychiatric disease, migraine, epilepsy, endocrinology,
autoimmune disease and related gender-specific aspects of
such conditions.
6. Female-specific disease: Moreover, common women-specific
conditions such as fibroids, endometriosis, and menopause
should be studied further, ultimately filling the current gap
of unmet needs.
7. Women’s wellbeing and health should be studied and inter-
preted in the context of their social and cultural environ-
ment and background. The methodology of studies should
be structured towards outcomes of quality of life and
healthy aging. Prioritization of studies should be driven
by the ambition to improve health instead of only curing
disease.
8. Novel research strategies need to be developed not only
enabling evidence-based medicine, but 7context-based
medicine in general as well as studying patients in their
individual context. The awareness that every phase in the
life course of a human being has major implications for
subsequent health requires follow-up studies. At the very
beginning of the life course sex-specific development of
the foeto-placental unit as well as maternal adaptation to
pregnancy should already be taken into account in studying
these phenomena. Focus on contemporary risk assessment
tools (genomics, microbiomics, metabolomics) will further
aid in developing gender specific personalized care.
Highlights
1. The life course approach in obstetrics and gynaecology
appreciates the continuum of wellbeing and health in
time in relationship to human constitution, behaviour
and the social environment and starts off with the
health of maternal and paternal gametes.
2. Woman-centred, personalized medicine focusses on
management of health instead of disease only, with
women owning and controlling a digital personalized
life course passport.
3. Multidisciplinary, networking medicine will support
a shift from institutionalized- to community-based
healthcare to meet the needs of the population.
4. Blended learning training programs will be designed for
different target groups.
5. Novel research strategies need to be developed not only
enabling evidence-based medicine, but context-based
medicine in general as well studying patients in their
individual context.
Glossary
Non-communicable disease (NCD)  Chronic disease tending to be of long
duration and slow progress, non-infectious and non-transmissible. They
are the result of a combination of genetic, physiological, environmental
and behavioral factors. The main types of NCDs are cardiovascular disease,
chronic respiratory disease, diabetes and cancer. Importantly, people in low-
and middle-income countries are disproportionately affected by NCDs (more
than three quarters of global NCD deaths; approximately 32 million persons)
Omics  Refers to a field of study in biology ending in -omics, such as genom-
ics, metabolomics and transcriptomics. It aims at the collective characteriza-
tion and quantification of pools of biological molecules that translate into
the structure, function, and dynamics of an organism or organisms
Transmural chain of care  Interfaces between primary, secondary and ter-
tiary care in medicine. Various institutions and health professionals work
together on particular care pathways
Societal valorisation  Application of new scientific discoveries and technol-
ogy for the advantage of the wellbeing and health of patients within hospi-
tals but also for the community at large
Context-based medicine  Individual patients’ care by which healthcare
professionals adjust the practice of shared decision making to fit within the
context of the individual patient. This indicates practicing medicine beyond
the local implementation of external knowledge and purely evidence based
medicine. Healthcare professionals coordinate actively joint decision making
within the context of the patient and the social environment and focus on
paying attention to listening instead of solely providing information
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3. Dankbaar MEW. Serious Games and Blended Learning; Effects
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Improving students’ learning with effective learning techniques:
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learning in health professions: systematic review and meta-analysis.
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learning: the 4C/ID-model. Educ Technol Res Dev [Internet].
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healthcare delivered at the primary-secondary interface: how
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education. Acad Med [Internet]. 2006;81(3):207–12.
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effectiveness of web-based and classsroom instruction: a meta-
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Czabanowska K, et al. The promised land of blended learning: quizzes
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 27 3

Reproductive medicine: ethical

reflections
Guido M.W.R. de Wert and Wybo J. Dondorp

! Life course
This book takes a life course approach, which is a new and valuable concept in Obstetrics
and Gynaecology. However, a full integration of this approach in a chapter on Ethics that
would meaningfully cover the ethical aspects of all specific issues arising in women’s health
would have required far more space than is available. It would have required discussing
the diverse moral frameworks, the concrete dilemmas, the specific views and positions
taken in current ethical debates on issues ranging from the ethics of healthcare for little
girls and female adolescents (including possible tensions between parental and children’s
decision-making authority) via debates about gender identity challenges and reproductive
health concerns (including women’s right to safe abortion), to issues linked with
reproductive aging as well as with perimenopausal and postmenopausal health (including
the ethics of clinical trials and the ethics of next generation sequencing in oncology
patients as part of personalized medicine) and ending with end-of-life decisions, especially
euthanasia and assisted suicide, in the context of the provision of care for women affected
with, for example, gynaecological cancer.

 lectronic supplementary material

E
The online version of this chapter (7 https://doi.org/10.1007/978-90-368-2131-5_3) contains supplementary
material, which is available to authorized users.

© Bohn Stafleu van Loghum is een imprint van Springer Media B.V., onderdeel van Springer Nature 2019
E. A. P. Steegers et al. (Eds.), Textbook of Obstetrics and Gynaecology, https://doi.org/10.1007/978-90-368-2131-5_3
Summary
In this chapter we focus on the ethics of current developments in the context of human
reproduction, ranging from preconception care to assisted reproduction, and from
embryo selection to foetal therapy. What makes the ethical debate in this field so chal-
lenging is that many issues arise from the fact that the interests of several stakeholders
beyond the patient may need to be taken into account. For instance: lifestyle choices in
pregnancy are not just a matter of women’s autonomy, but also of parental responsibility.
And in decision-making concerning genomic information the interests of family members
may be at stake as well. Many of the issues that will be discussed in this chapter require
further research of relevant empirical questions (preferences, impacts, etc.) as well as
ethical analysis and societal debate. Although in some of these debates societal concerns
about the ‘acceptability per se’ of a new development, such as germline genome editing
(GLGE), may have to be addressed, ethical reflection and debate should not be regarded
as limited to such questions. Beyond issues of acceptability, challenging ethical questions
relate to the conditions under which a specific technology or intervention (such as
preconception carrier screening) can responsibly be introduced and offered. In these
debates, the input of all stakeholders (patients, professionals, society at large) is essential.

3.1 Introduction – 29
3.2 Ethics of preconception care – 29
3.2.1 PCC (Preconception Care) for women or couples at a known higher
than average risk – 29
3.2.2 PCC for the general population of women or couples of reproductive age – 31
3.2.3 Preconception carrier screening – 32
3.2.4 Fertility preservation – 33

3.3 Fertility treatment – 33

3.3.1 Fundamental objections? – 33
3.3.2 Conditions for the responsible provision of assisted reproduction – 34
3.3.3 Access and justice – 35
3.3.4 Ethical aspects of third-party reproduction – 36

3.4 Preimplantation genetic testing (PGT) – 39

3.4.1 Ethics of PGD (Preimplantation Genetic Diagnosis) – 39
3.4.2 Ethics of PGS (Preimplantation Genetic Screening) – 40
3.4.3 Blurring the boundary between PGD and PGS – 41
3.4.4 Germline genome editing: from selection to modification? – 42

3.5 Prenatal testing – 42

3.5.1 Ethics of PD – 43
3.5.2 Ethics of prenatal screening – 43

3.6 Conclusion – 46
Glossary – 46
Key references – 47
3.2 · Ethics of preconception care
3.1 Introduction
As we had to make choices, we decided to focus on the eth-
ics of a series of reproductive issues, taking a broad scope and
focusing on four domains: the ethics of individual and univer-
sal preconception care, the ethics of reproductive medicine,
and the ethics of selective reproduction, concentrating on
both preimplantation and prenatal diagnosis and screening,
including a brief section on the ethics of experimental foetal
therapy. Our chapter not only acknowledges the importance
of an integrated life course perspective, for instance when
discussing fertility preservation for prepubertal girls needing
cancer treatment, but also moves this perspective to the next
generation when discussing issues of in utero programming or
reproductive selection. While concentrating on ethical guid-
ance relevant to the professional-patient relationship in these
four domains, we regularly also refer to the societal context.
For instance: while the ethics of preconception care mostly
focus on individual responsibility of prospective mothers,
this should not lead to ignoring social determinants of health
and the linked societal responsibility of other stakeholders,
including government, employers, and healthcare institutions.
Unequal access to healthcare and poverty are important deter-
minants of periconception and foetal health, with significant
implications for health later in life (7 sect. 3.2). And, to give a
second example, when speaking about the handling of genetic
risks for future children, it should not be forgotten that societal
and medical support for families with affected children is and
will continue to be of major importance, both as a matter of
justice, and as a material condition for real reproductive free-
dom (7 sect. 3.5).
3.2 Ethics of preconception care
Preconception care (PCC) is understood as the ‘entire range
of measures designed to promote the health of the expect-
ant mother and her child which, in order to be effective, must
­preferably be adopted prior to conception’ [1]. These measures
can consist of a) collective interventions such as rubella vacci-
nation, iodine fortification of food products, housing and occu-
pational health measures, or information campaigns promoting
the timely use of folic acid by women planning a pregnancy, b)
an individual offer of information and counselling relevant to
the behaviour and decision-making of future parents. This can
either be targeted, i.e. PCC offered to women or couples at a
known higher than average risk of an adverse pregnancy out-
come or general, i.e. PCC offered to the general population of
women or couples of reproductive age. The latter form of PCC
may also involve screening for carrier status of recessive disor-
ders. For the sake of space, we will refrain from discussing col-
lective interventions.
29 3
3.2.1  CC (Preconception Care) for women or
P
couples at a known higher than average
risk
The importance of targeted PCC is beyond debate. Ethical
issues concern not so much the desirability of making this
a standard part of good medical care, but the primary aim of
doing so as well as the conditions for responsible application.
It seems that depending on the precise context, there may in
fact be different aims of targeted PCC. An important further
distinction is between PCC for those at a known risk of trans-
mitting a genetic disorder and PCC for those at a higher risk of
adverse pregnancy outcomes that allow for timely preventative
or therapeutic measures.
PCC as reproductive genetic counselling
To the extent that targeted PCC looks at genetic risks, it
encompasses the classical practice of reproductive genetic
counselling offered to couples who, because of their earlier
reproductive history, a positive genetic test, or a positive family
anamnesis, are known to be at a higher risk of having a child
with a specific genetic disorder. Sometimes further testing will
first be needed in order to determine the precise at risk status
of the client or couple. Given that timely knowledge of such
risks can help to avoid that outcome only by enabling the cou-
ple to either refrain from having genetically related children
or to resort to forms of selective reproduction (see below), the
ethical question is with what aim this form of PCC should be
offered. There are two possible answers. According to what we
will refer to as the 7‘prevention view’, the aim is to reduce the
number of children born with severe genetic disorders. This
may be motivated by an ethical (prevention of suffering) or a
health economic (reducing societal costs) concern, or by both.
However, this has been criticized as potentially leading the
practice into a problematic form of population eugenics [2].
According to the dominant 7‘autonomy view’, reproductive
genetic counselling is meant to provide couples with individ-
ual opportunities for reproductive choice that fit in with their
own situation, values, and ideals [3]. An important reason for
stressing that the privacy and personal nature of reproductive
choices should, in principle, be protected, even when this may
lead to the birth of children with genetic disorders, is that such
choices are fraught with moral and ideological ambivalence.
The professional ethos of ‘non-directive’ genetic counsel-
ling is closely connected with the latter understanding of the
aim of the practice [4]. It is a normative ideal that requires pro-
fessionals to create a climate in which applicants are empow-
ered to make their own choices as far as possible with regard
to the different reproductive options available to them. These
may include risk acceptance, deciding not to have children,
having children with donor gametes (7 sect. 3.3.4), starting
a pregnancy and opting for prenatal diagnosis (7 sect. 3.5.1),
or choosing preimplantation genetic diagnosis (7 sect. 3.4.1).
Ethical arguments for upholding this ideal are that direc-
­
tive counselling fails to reflect due respect for the applicants’
 30 Chapter 3 · Reproductive medicine: ethical reflections
autonomy, that it may undermine the fabric of the professional-
3 client relationship, and that very different views are possible
with regard to which reproductive risks are still acceptable and
which are not. This is not to deny that there may be exceptional
situations where unsolicited professional advice would be justi-
fied. These could be severe risk situations where the chances of
having an affected child are very high and where the disorder
in question would entail serious suffering for the child to be. In
such cases, the professional should make it clear that her advice
reflects her own view of the matter and limit herself to rational
persuasion.
As the ideal of non-directive counselling should be
regarded as the practical translation of the ethical principle of
respect for reproductive autonomy, and as autonomy presup-
poses competence, good counselling must be guided by dif-
ferent principles when clients are not or not fully competent.
Competence refers to a person’s ability to make decisions in the
light of a reasonable assessment of his or her relevant interests.
This not only presupposes a person’s ability to reason and delib-
erate, but it also follows that competence is always specific to
the decision at hand [5, 6]. Where this decision-specific compe-
tence is absent, the principle of the client’s best interests should
be the primary perspective. Counselling may then take the
form of discouraging choices or behaviour that would clearly
be at odds with this perspective, for instance: having children
while being unable to properly care for them. But in this con-
text, considerations of justified paternalism are not the only
relevant perspective. Clearly, concerns about the wellbeing of
those future children may provide an important further reason
for professionals to discourage cognitively impaired clients or
couples from reproducing.
Beyond discouragement, is it ever acceptable to consider
non-voluntary anticonception or even sterilization? Such meas-
ures are regularly requested by parents of fertile daughters
with a serious cognitive impairment who may become sexually
active. As they entail an infringement on basic rights of self-
determination and bodily integrity, such measures require not
only ethical but also legal justification. Essential elements are
that the impaired person is indeed incompetent with regard to
reproduction and parenting, that the relevant measure is clearly
in her or his best interest, and that the least invasive measure
is chosen. In cases where the condition entailing incompetence
is deemed irreversible, sterilization may be less invasive than
repetitive administration of long-acting contraception.
Confidentiality is a general condition of the doctor-patient
relationship. Its purpose is not only to protect the patient’s pri-
vacy, but also to ensure that those who are in need of healthcare
will not be kept away from doctors for fear that their secrets
will not be safe. However, in the context of genetic counselling
dilemmas may arise when information emerges that is highly
relevant for the health prospects of the client’s or patient’s rel-
atives. In such cases the client will be asked, and if necessary
helped, to inform those relatives. But what if for whatever rea-
son he or she refuses to take such steps while also rejecting the
professional’s request to be relieved of the duty of confidenti-
ality’? May professionals in such cases break this duty? As a
way out of this dilemma, it has been suggested that in an era of
increasing importance of genetics, families rather than individ-
ual patients should be regarded as the ‘unit of confidentiality’.
This ‘solution’ is generally rejected in the health law and ethics
literature [3, 7–9]. Still, the dominant view is that profession-
als may find themselves in a conflict of duties where informing
the relatives without the client’s permission could under condi-
tions be justifiable. To inform the weighing in individual cases,
the following criteria have been formulated: ‘everything reason-
ably possible has been tried to obtain permission; maintaining
confidentiality will lead to serious harm for a third person; the
professional is conscience-stricken by keeping the secret; there
is no other way to solve the problem but by breaking it; it is vir-
tually certain that by breaking the secret the harm in question
can be prevented or reduced; not more of the secret is revealed
than is necessary’ [10].
PCC as primary prevention
PCC may also be targeted to women at a higher risk of adverse
pregnancy outcomes that allow for timely preventative or ther-
apeutic measures. Examples here are the importance of control-
ling phenylalanine levels already prior to pregnancy in women
with maternal phenylketonuria (PKU; a rare genetic disorder
disabling the body from breaking down the amino acid pheny-
lalanine) in order to avoid pregnancy complications and foe-
tal abnormalities, optimization of folic acid status in women
at a higher risk of having a child with a neural tube defect, or
lifestyle modification in women known to have an addiction
problem.
The relevant ethical framework is different from that
of reproductive genetic counselling for the following rea-
sons. Firstly, the moral problems connected with the ‘preven-
tion view’ do not apply here: there is nothing problematically
‘eugenic’ in trying to ensure that children are born without
avoidable health problems. Secondly, as parents-to-be, preg-
nant women have a responsibility to protect their future chil-
dren from harm to the extent that doing so is reasonably
possible. This means that PCC for primary prevention is not
morally non-committal: pregnant women, and their partners,
may be expected to heed professional advice about relevant
medication or lifestyle choices and behaviour. As most women
want to have healthy children, they will usually take this advice
to heart, meaning that PCC need not be explicitly directive. But
when they do not, directive counselling is not as such ethically
problematic.
A challenging group for PCC is women with a high-risk
lifestyle due to multidrug dependency, often in combination
with further psychiatric problems and challenging living con-
ditions, such as bad housing, unhealthy food, and stress. Con-
cerns relate to a) health damage already occurring in utero as
a result of foetal exposure to toxic substances (prenatal harm),
b) health damage occurring at birth as a result of avoidance or
refusal of necessary obstetric care (perinatal harm), c) imme-
diate and possible long-term harm if withdrawal symptoms are
left untreated (postnatal harm), and d) damage to the future
child’s health and welfare as a result of being raised in unsafe
circumstances (postnatal harm). It is clear that in such cases
not much is to be expected from PCC in the sense of informing
3.2 · Ethics of preconception care
and advising, even apart from the fact that many pregnancies
in this high-risk population are not in fact planned. Societal
concerns about ‘failed parenthood’ have led to debate about the
desirability of coerced anticonception for those with a record
of child protection measures. In view of relevant European law,
there is no legal scope for this, at least with regard to women
who are competent; and with regard to those who are incom-
petent this could only be considered when doing so was clearly
in their own best interests, but not with an eye to those of the
future child.
Prenatal child protection measures
If a pregnancy has occurred, the question arises how the future
child can be protected from avoidable harm. Although this is
beyond the scope of PCC we discuss this issue here because it
directly connects to the preceding. It is in line with the above
ethical framework that measures beyond directive counselling
may be justified under certain conditions. This involves steps
on an escalation ladder of pressure and coercion [11]. Pressure
involves trying to influence a person’s behaviour but, unlike
coercion, without completely denying her a choice in the mat-
ter. Forms of pressure may for instance include promises and
threats connected to regular healthcare visits and controls. At
the top of the ladder, coercion may consist of coerced hospi-
talization to avoid further exposure or avoidance of perina-
tal care. Any steps on this ladder require a) that the relevant
measures will effectively protect the child from highly plausi-
ble harm (effectiveness and harm probability), b) that the level
of infringement on the woman’s liberty is proportional to the
magnitude of the harm to be prevented (proportionality), and
c) that the least drastic measure must be chosen (subsidiarity).
As coerced hospitalization infringes on a legal right to self-
determination, it always also requires a legal title. These con-
ditions reflect that prenatal child protection measures do not
bring their own justification, regardless of the interests of the
pregnant woman. In view of this sensitive balance, it is essential
that the underlying empirical claims are evidence-based.
It has been suggested that in order not to interfere with
women’s right to have a termination, prenatal child protection
measures can only be taken after the legal limit for abortion has
been reached. Care professionals have protested that if meant
to avoid harm resulting from exposure to prenatal drug abuse,
this is simply too late, as these effects will already occur in
early pregnancy. However, this legal deadlock only arises if it is
assumed that protecting the as yet unborn child equals protect-
ing the foetus. The problem disappears if prenatal child protec-
tion is not about protecting the foetus, but about protecting the
health and wellbeing of the future child.
3.2.2  CC for the general population of women
P However, it does not follow that individual responsibility can
or couples of reproductive age
PCC for the general population differs from targeted PCC in
being a public-health initiative rather than a healthcare inter-
vention. Whereas healthcare interventions respond to com-
plaints or address known risk factors in individuals with a
31 3
positive medical history, family anamnesis or test result, public
health measures are typically aimed at healthy individuals with
an average risk profile. PCC intends to provide them with rel-
evant general information about prevention of subfertility [12],
reproductive health including about adequate folic acid intake,
cessation of smoking and alcohol consumption as well as the
use of any other drugs, physical exercise, bringing body mass
index (BMI) down to a healthy level, etc. Those found to be at
higher risks on the basis of their medical or family history will
be referred for targeted PCC (7 sect. 3.2.1). PCC for the general
population may also include information about preconception
carrier screening for recessive disorders (7 sect. 3.2.3).
PCC for those with an average risk profile has been criti-
cized as a form of 7 ‘medicalization’. This term is often used to
express the tendency that more and more aspects of human
life are brought under a ‘medical gaze’ and defined as requiring
medical control and intervention [13]. Examples are the medi-
calization of deviant behaviour, of sexuality, of pregnancy, the
menopause, old age, etc. In addition to this we now have ‘the
medicalization of the pre-pregnancy period’ [14, 15]. Although
the term may suggest a mere descriptive perspective, it has a
strong connotation of moral disapproval. As such, medicaliza-
tion is like ‘violence’ or ‘discrimination’: by referring to ‘facts’
that are supposedly wrong by definition, such ‘moral species
terms’ [16] serve as arguments that seem to need no further
justification, which makes them extremely useful for rhetori-
cal purposes. The best way to deal with this criticism of PCC is
therefore to unpack and consider the underlying concerns and
objections [17]. So what is behind the medicalization charge? A
main objection seems that the biomedical perspective of PCC
comes with an emphasis on individual responsibility for health
that ignores the role of social determinants and constraints.
According to a further criticism PCC medicalizes women’s lives
while tending to be silent about the responsibilities of fathers-
to-be. PCC would also reduce women to a state of ‘anticipatory
motherhood’ [15].
These criticisms point to important ways in which PCC
programmes could derail. But instead of bringing the con-
cept under the sweeping sentence of medicalization, they call
for conditions aimed at securing its balanced implementation.
For instance, it is essential that as part of the collective meas-
ures that belong to a comprehensive approach to PCC, factors
such as housing circumstances or work environment are taken
into account as well. This is not something new (the influen-
tial definition of PCC given by the Centers of Disease Con-
trol and Prevention does in fact incorporate ‘social risks’ [18])
although it clearly requires more attention. As has been pro-
posed, those in a position to address those socioenvironmen-
tal factors, such as employers, local councils, should be invited
to regard themselves as stakeholders in this endeavour [19].
be completely dismissed as relevant when dealing with repro-
ductive health. Clearly this should then be regarded and pre-
sented as a responsibility not just of women, but also of their
partners. And whereas women of a reproductive age should
not be reduced to mothers in waiting, it does not follow that
new insights pertaining to the prenatal and preconception
 32 Chapter 3 · Reproductive medicine: ethical reflections
determinants of health should not be actively shared with those
3 who may become parents, precisely to empower them to take
their responsibility to the extent that doing so can reasonably
be expected from them.
Funding for PCC as a public health program may not seem
obvious for governments wrestling with rising healthcare costs
in the absence of clear evidence that this will effectively bring
down perinatal mortality. However, leaving this to individual
health practitioners and motivated couples will lead to unequal
access and risks of prejudicing those who might benefit most.
It also stands in the way of implementing a comprehensive
approach to PCC that avoids the pitfall of reducing reproduc-
tive health to a matter of individual responsibility. Moreover
it will continue and entrench the fragmentation between ele-
ments of reproductive care that would ideally form a chain
linking preconception, prenatal and neonatal care.
3.2.3 Preconception carrier screening
PCC for the general population may also include information
about preconception carrier screening for autosomal recessive
disorders. These disorders usually present in families where
there is no history of the disease. In about 1-2 in the 100 cou-
ples, both partners are carriers of the same recessive disease
[20]. This means that they have a 1 in 4 chance of having a
child with the disorder. As carriers themselves are healthy,
carrier couples will very often be unaware of their reproduc-
tive risk. In those cases it is only after a child with the disease
is born that parents are able to avoid recurrence in further
pregnancies. Carrier testing makes it possible for individuals
or couples to find out about their carrier status. Knowing this
prior to pregnancy gives carrier couples reproductive options
that will allow them to avoid the birth of an affected child. As
part of reproductive genetic counselling (7 sect. 3.2.1), the offer
of such testing is standard practice in most countries for those
with an a priori increased risk based on the personal or fam-
ily disease history of themselves or their partner. This practice
should be distinguished from carrier screening, which is the
offer of carrier testing to those without a similar disease his-
tory based indication [21]. Although carrier screening can
still be done during pregnancy, as a form of prenatal screening
(7 sect. 3.5.2), it is ideally performed at the preconception stage,
as this will provide the couple with more time for deliberation
as well as more reproductive options than only prenatal diag-
nosis and possible termination of pregnancy (7 sect. 3.5.1).
Since the 1970s, carrier screening has been offered to
individuals or couples in specific ethnic groups with a higher
frequency of recessive disorders associated with significant
morbidity and reduced life-expectancy. Well-known examples
are beta-thalassaemia carrier screening in several high-risk
populations in the Mediterranean region, and carrier screen-
ing in Ashkenazi Jewish populations for Tay Sachs disease
and other recessively inherited conditions in those groups. A
first step towards ‘universal’ screening (addressing all preg-
nant women and couples of reproductive age) was taken in
guidelines of American professional societies. This was based
on the consideration that multi-ethnic backgrounds make
it increasingly difficult to determine who does or does not to
belong to a higher risk group. In Europe, initiatives for offering
carrier screening beyond ethnicity-based higher risk groups,
including communities with a high burden of recessive disease
due to founder-mutations, have until now been limited.
With the advent of new genomic technologies it has now
become possible to think of expanded universal carrier screen-
ing: an offer to all couples or persons of reproductive age to
have themselves tested for carrier status for up to several hun-
dred recessive disorders. Although individually rare, together
these amount to a reproductive risk comparable to that of a
36-year-old woman having a child with Down syndrome, a risk
for which screening programs have already been available for
several decades. Commercial laboratories in North America,
Australia and Europe have started offering expanded universal
testing to interested clients. Public health authorities in several
countries are currently considering policy options. However, it
is still an open question whether a screening offer along these
lines will respond to a need among the general population
[22]. If it does, its implementation should be subject to condi-
tions for responsible screening as discussed in, amongst oth-
ers, a recent position paper of the European Society of Human
Genetics [21].
What should the aim of carrier screening be? This leads
back to our earlier discussion of the ‘prevention’ and the ‘auton-
omy’ view. Whereas traditional ethnicity-based carrier screen-
ing programs were – and are – explicitly aimed at prevention
in the sense of reducing the burden of disease in the relevant
community [23], screening authorities in Western countries
tend to embrace the alternative autonomy view, according to
which carrier screening, and reproductive screening in gen-
eral, is meant to provide couples with meaningful reproduc-
tive options [21]. As mentioned in our earlier discussion (see
above), the prevention view is thought to raise the spectre
of ‘eugenics’. However, as a notion of moral condemnation,
‘eugenics’ has the same rhetorical properties as ‘medicaliza-
tion’. If we try to unpack the underlying concerns, a first issue
is the felt need to protect reproductive decisions against inter-
ference by the state or societal institutions [24]. For the same
reason, reproductive counselling should be non-directive,
couples should not, however subtly, be pressured to undergo
reproductive screening. A second issue concerns the wish to
steer free of what is known as the ‘disability rights critique’,
according to which reproductive screening programs send the
message that persons living with the disorders in question are
not welcome in society [25]. While these considerations are
certainly morally relevant, it does not necessarily follow that
prevention-aimed carrier screening is always ethically prob-
lematic. Examples would be programs such as those set up on
the initiative of the Azhkenazi Jewish community determined
to end the suffering of its children and families caused by a
small number of high-impact disorders with a high frequency
in that population. However, with regard to forms of expanded
carrier screening that would be offered or made available in the