Maternal influence on fetal size and use of longitudinal fetal surveillance in predicting adverse

96 Pages·2016·1.53 MB·English

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Dissertation for the degree of philosophiae doctor (PhD)
at the University of Bergen
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Dissertation date: (cid:20)(cid:24)(cid:17)(cid:19)(cid:25)(cid:17)(cid:21)(cid:19)(cid:20)(cid:25)

Scientific environment

Clinical Fetal Physiology Research Group, Department of clinical science, University
of Bergen

Fetal Medicine Unit, Department of Obstetrics and Gynecology, Haukeland University
Hospital, Bergen

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Contents
Page
Acknowledgements………………………………………………………………………… 8
List of abbreviations……………………………………………………………………..….10
Abstract………………………………………………………………………………………12
List of papers I – III…………………………………………………………………...……14
1 Introduction ........................................................................................................... 15
1.1 Prenatal care in a historical perspective .......................................................... 15
1.2 Gestational age ................................................................................................ 17
1.3 Normal fetal growth ........................................................................................ 18
1.4 Methods ........................................................................................................... 19
1.5 Maternal influence on fetal size and growth ................................................... 21
1.5.1 Genetic influence on birthweight ............................................................. 21
1.5.2 Maternal constraint ................................................................................... 22
1.5.3 Maternal anthropometric measures .......................................................... 22
1.5.4 Gestational weight gain ............................................................................ 23
1.5.5 Other lifestyle related factors influencing fetal growth ............................ 24
1.6 Fetal growth restriction ................................................................................... 24
1.6.1 Definition .................................................................................................. 24
1.6.2 Etiology of fetal growth restriction .......................................................... 26
1.6.3 Surveillance of IUGR ............................................................................... 26
1.7 Doppler ultrasound assessment of placental and fetal circulation .................. 27
1.7.1 Maternoplacental circulation .................................................................... 28
1.7.2 The umbilical artery .................................................................................. 29
1.7.3 The blood flow of the middle cerebral artery ........................................... 30
1.7.4 The Ductus Venosus ................................................................................. 30
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1.7.5 Circulatory redistribution in compromised fetuses .................................. 31
1.7.6 Intrapartum care ........................................................................................ 33
1.8 Consequences of IUGR ................................................................................... 33
1.8.1 Short term consequences .......................................................................... 33
1.8.2 Long term consequences .......................................................................... 35
1.9 Ultrasound physics .......................................................................................... 36
1.10 Ultrasound safety ......................................................................................... 37
2 Aims of the studies ................................................................................................ 39
3 Materials and methods ........................................................................................... 40
3.1 Study I ............................................................................................................. 40
3.1.1 Study population ....................................................................................... 40
3.1.2 Examinations ............................................................................................ 40
3.1.3 Statistical method ..................................................................................... 41
3.2 Study II and III ................................................................................................ 41
3.2.1 Study population ....................................................................................... 41
3.2.2 Examinations ............................................................................................ 41
3.2.3 Statistical methods .................................................................................... 43
4 Results ................................................................................................................... 45
4.1 Study I ............................................................................................................. 45
4.2 Study II ............................................................................................................ 46
4.3 Study III ........................................................................................................... 50
5 Discussion .............................................................................................................. 55
5.1 Methodological consideration ......................................................................... 55
5.1.1 Study design ............................................................................................. 55
5.1.2 Biometry and Doppler measurements ...................................................... 55
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5.1.3 Internal validity ......................................................................................... 56
5.1.4 External validity ....................................................................................... 58
5.2 Discussion of results ........................................................................................ 59
6 Conclusions ........................................................................................................... 62
7 Future aspects ........................................................................................................ 63
8 References ............................................................................................................. 65

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Acknowledgements
The present work was carried out at the Section for Fetal Medicine and Ultrasound
Diagnostics, Department of Obstetrics and Gynecology, Haukeland University
Hospital and at the Department of Clinical Medicine, University of Bergen. I offer my
sincere thanks to the heads of the department Per Børdahl and Susanne Albrechtsen
and section leader Synnøve Lian Johnsen who provided the facilities and support
necessary to accomplish the project. From January 2012 I have been founded by a
scholarship from the University of Bergen. Several people have contributed to this
work and I would like to thank all of you.

Synnøve Lian Johnsen, my co-supervisor from the very first beginning until you
became my principal supervisor from June 2014. I am very grateful for your
contagiously encouragement and I always feel very motivated after our meetings. I
appreciated that you enabled me to combine research and clinical work, and you have
been a great support in both settings. Thank you for let me be a part of The Fetal
Medicine Unit and for believing in me.

Torvid Kiserud, my principal supervisor until June 2014, and further as co-supervisor
to the very end. Thank you for inviting me into your inspiring research group. I
appreciate your wide experience and your ability to think in new ways. Your linguistic
talent is enviable. Despite the fact that you are a very busy man, I have always felt that
I have been given priority and your thorough and quick revisions have been very
valuable.

Svein Rasmussen, my co-supervisor and my statistical advisor. Thank you for
patiently trying to learn me somewhat complicated statistics. Your contribution into
this has been of great value.

I also want to express my thanks to Cathrine Ebbing for your contribution in paper III.
I appreciates that your door is always open and for letting me bother you with all my
professional and private concerns, your support has been very valuable.
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My friend and colleague Liv Cecilie Thomsen, you have contributed to this thesis in
several ways by shearing of your own research experience and your knowledge on
how to write a thesis. I also appreciate your care and our meetings outside
Kvinneklinkken.

Per Børdahl, thank you for your support in the very beginning of my research carrier.
I appreciate your engagement when I asked for help finding literature of obstetric
history.

I am very grateful to have been allowed to work with so many good colleagues at The
Fetal Medicine Unit, all have been very helpful and supportive. I will thanks the
midwifes for their eagerly help with recruitment. Jorunn, Anita and the office staff
deserves thanks for making the days go smoothly. Especially thanks to all the doctors
at the Fetal Medicine Unit for patiently giving me professional advice and for shearing
of their experience.

Thanks to all the women who agreed to participation and made this study possible.

To all of my valuable friends, thank you for all your support over the last years.
Whiteout you my life had been considerably less fun.

Finally, my warmest tanks to my always supporting parents, I am grateful for all your
help and for believing in me. My dearest two children, Magnus and Martin, you are
my bright spots in life, and I am thankful for your patience and love. Finally I also
want to thank Frank; you have managed to distract me from tough days and
contributed to a lot of joy. Thank you for all your patience and support.

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List of abbreviations

AC Abdominal circumference
AED Absent end diastole
AGA Appropriate for gestational age
ARED Absent and reversed end diastole
aRR Adjusted relative risk
BMI Body mass index
BPD Biparietal diameter
CI Confidence interval
CPR Cerebroplacental ratio
CRL Crown rump length
CTG Cardiotocography
DV Ductus venosus
EFW Estimated fetal weight
FL Femur length
HC Head circumference
IgF Insulin-like growth factor
IUGR Intrauterine growth restriction
IVF In vitro fertilization
LGA Large for gestational age
LMP Last menstrual period
MCA Middle cerebral artery
MBR Medical birth registry
NICU Neonatal intensive care unit
NPV Negative predictive value
PE Pre-eclampsia
PI Pulsatility index
PPV Positive predictive value
RR Relative risk
SD Standard deviation
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