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FACULTY OF HEALTH AND MEDICAL SCIENCES

UNIVERSITY OF COPENHAGEN

PhD thesis
Anna J. M. Aabakke

Surgical techniques for caesarean section


Short- and long-term consequences
FACULTY OF HEALTH AND MEDICAL SCIENCES
UNIVERSITY OF COPENHAGEN

PhD thesis
Anna J. M. Aabakke

Surgical techniques for caesarean section


Short- and long-term consequences

Academic advisors:

Lone Krebs, Associate Professor, MD, DMSC


Niels Jrgen Secher, Honorary Professor, MD

This PhD thesis has been submitted to the Graduate School of The Faculty of Health
and Medical Sciences, University of Copenhagen on the 4. June 2014 and has been
approved for public defence on the 27. August 2014.

The public defence will take place at University of Copenhagen, Holbk Hospital on
the 19. September 2014.
Author

Anna J. M. Aabakke, MD

Department of Obstetrics and Gynaecology


University of Copenhagen, Holbk Hospital

Institute for Gynaecology, Obstetrics and Paediatrics


Faculty of Health and Medical Sciences
University of Copenhagen

Academic advisors

Associate Professor Lone Krebs, MD, DMSC


Department of Obstetrics and Gynaecology
University of Copenhagen, Holbk Hospital, Denmark

Honorary Professor Niels Jrgen Secher, MD


Faculty of Health
Aarhus University, Denmark

The Research Unit Womens and Childrens Health


The Juliane Marie Center
Copenhagen University Hospital, Denmark

Assessment Committee

Associate Professor Thomas Bergholt, MD, PhD (Chairperson)


Department of Obstetrics and Gynaecology
University of Copenhagen, Hillerd Hospital, Denmark

Department Clinical Medicine


University of Copenhagen, Denmark

Professor Per Olofsson, MD, PhD, BSc


Department of Obstetrics and Gynaecology
Skne University Hospital, Sweden

Professor Philip J. Steer, BSc, MD, FRCOG


Department of Obstetrics and Gynaecology
Chelsea and Westminster Hospital, United Kingdom

Title page illustration by May C. M. Aabakke, 2014


the Caesarean section per se, as do other
operations, continues to carry a small risk; the
indications must still be carefully considered.
Nor shall the knowledge that a womans
obstetrical future is prejudice by the uterine
scar be forgotten.

Dyre Trolle, 19821


Contents
PREFACE ........................................................................................................................... III

Studies ............................................................................................................................................................................. III

ENGLISH SUMMARY ....................................................................................................... IV

DANSK RESUM (SUMMARY IN DANISH) ..................................................................... VI

ABBREVIATIONS ........................................................................................................... VIII

INTRODUCTION ................................................................................................................. 1

BACKGROUND .................................................................................................................. 3

Caesarean section surgical techniques ............................................................................................................................ 3


Skin closure techniques.................................................................................................................................................. 6
Methods to incise the fascia ........................................................................................................................................... 7

Long-term consequences of Caesarean section .............................................................................................................. 8


Incisional hernia ........................................................................................................................................................... 11

Randomised controlled trial in which each participant is his/her own control ......................................................... 11

AIMS .................................................................................................................................. 14

METHODS ......................................................................................................................... 15

Study I & II ..................................................................................................................................................................... 15


Design: Randomised controlled trial in which each participant is her own control ..................................................... 15
Participants................................................................................................................................................................... 15
Procedures .................................................................................................................................................................... 15
Outcomes ..................................................................................................................................................................... 15

Study III .......................................................................................................................................................................... 16


Register data ................................................................................................................................................................ 16

Ethics ............................................................................................................................................................................... 17

Statistics ........................................................................................................................................................................... 17
Studies I & II................................................................................................................................................................ 17
Study III ....................................................................................................................................................................... 18

RESULTS .......................................................................................................................... 19

Study I.............................................................................................................................................................................. 19

Study II ............................................................................................................................................................................ 20

I
Study III .......................................................................................................................................................................... 21

DISCUSSION .................................................................................................................... 22

Skin closure techniques .................................................................................................................................................. 22

Methods to incise the fascia............................................................................................................................................ 25

Randomised controlled trial in which each participant is his/her own control ......................................................... 27

Incisional hernia ............................................................................................................................................................. 30

CONCLUSIONS ................................................................................................................ 34

CLINICAL RECOMMENDATIONS .................................................................................... 35

REFERENCES .................................................................................................................. 36

ACKNOWLEDGEMENTS ................................................................................................. 47

Funding ............................................................................................................................................................................ 48

APPENDIX ........................................................................................................................ 49

Article I ............................................................................................................................................................................ 49

Article II .......................................................................................................................................................................... 57

Article III ......................................................................................................................................................................... 64

II
Preface

Preface
This PhD thesis was conducted during my employment at the Department of Obstetrics and
Gynaecology, University of Copenhagen, Holbk Hospital, from 2010 to 2014. Study II was
conducted in collaboration with the Department of Obstetrics and Gynaecology, University of
Copenhagen, Hvidovre Hospital.

Studies
The thesis is based on the following three articles generated from three studies:

I. Aabakke AJM, Krebs L, Pipper CB, Secher NJ. Subcuticular Suture Compared with Staples
for Skin Closure After Cesarean Delivery: A Randomized Controlled Trial. Obstet Gynecol
2013;122:878-84.

II. Aabakke AJM, Hare KJ, Krebs L, Secher NJ. Sharp Compared with Blunt Fascial Incision
at Cesarean Delivery: A Randomized Controlled Trial with Each Case as her Own Control.
Eur J Obstet Gynecol Reprod Biol 2014; 172:40-45.

III. Aabakke AJM, Krebs L, Ladelund S, Secher NJ. The Incidence of Incisional Hernia after
Cesarean Delivery: A Register-based Cohort Study. Plos One 2014; (In press).

The articles are referenced to by their Roman numerals in the text.

There are no potential conflicts of interest in any of the three studies.

III
English Summary

English Summary
Caesarean section is a common surgical procedure performed on young, otherwise healthy women,
which can have both short- and long-term consequences for the mother. These may be modified by
the techniques used at each step of the caesarean section, and therefore evidence behind the surgical
techniques is essential.

This thesis is based on three studies which explore surgical techniques to open the fascia and close
the skin at caesarean section as well as the long-term risk of incisional hernia requiring surgical
repair after caesarean section. The two randomised trials used a study design in which each patient
was her own control, i.e. women were randomised to a side distribution of the two techniques
(technique A right and technique B left, or technique B right and technique A left).

In study I, we compared subcuticular absorbable sutures with staples for skin closure after
caesarean section. The primary outcome was the overall preferred side of the scar after 6 months.
Additional outcomes were differences in objective cosmetic scores (assessed by two plastic
surgeons), differences in pain scores, and the rate of separation and infection. Significantly more
women preferred the stapled side, both overall and cosmetically, and reported staples as their
preferred technique. There were no significant differences in pain scores at any time. One plastic
surgeon preferred the stapled side, while the other found no significant difference. In the evaluation
of skin closure techniques for caesarean section, both objective and subjective measures have to be
considered. We found subjective and cosmetic outcomes in favour of staples, whereas meta-
analyses of previous studies have found that the use of staples increased the rate of separation.
Future studies are needed that explore the influence of the time of removal of staples on separation,
infection, and long-term cosmetic results; that grade the severity of separation and explore the
various consequences; and that study outcomes in women with higher BMIs.

In study II, we compared blunt opening of the fascia by manual traction with sharp incision with
scissors. Primary outcome was patient preference for the right or left side of the scar 3 months
postoperatively. Secondary outcomes were differences in pain between the two sides. The study
showed no difference in patient preference or any differences in pain scores after either technique
up to 3 months postoperatively.

IV
English Summary

A study design in which each patient is her own control is rarely implemented. We showed that the
design significantly reduced sample variance of the objective cosmetic scores in study I, thus
confirming that the design reduces the influence of confounders. The design is therefore suitable for
trials of surgical techniques; especially trials with cosmetic outcomes can benefit from the design.

Study III is a prospective register-based cohort study estimating the incidence of incisional hernia
requiring surgical repair after caesarean section over a 10-year period. The cumulated risk in the
Danish population was less than 2 per 1000 caesarean sections. Most hernias were in midline
incisions in a population in which the transverse incision was the primary approach at caesarean
section. Consequently, the risk is very low of developing a hernia requiring repair in a transverse
caesarean section incision following current surgical recommendations.

Several studies have compared groups of caesarean procedures for abdominal incision without
differentiating between the individual steps. We recommend that studies be performed that evaluate
the individual surgical steps and their long-term consequences.

V
Dansk Resum (Summary in Danish)

Dansk Resum (Summary in Danish)


Kejsersnit er et hyppigt kirurgisk indgreb som udfres p unge, i vrigt raske kvinder. Kejsersnit
kan dog have konsekvenser for moderen bde p kort og langt sigt, hvilket til dels afhnger af de
kirurgiske teknikker, der er anvendt ved operationen. Derfor er det af stor betydning, at
operationsteknikkerne er evidensbaserede.

Denne Ph.D.-afhandling er baseret p 3 studier om kejsersnit, som undersger kirurgiske teknikker


til bning af muskel-fascien og lukning af huden, og estimerer risikoen for senere at udvikle et brok,
der krver operation.
I afhandlingen indgr to randomiserede studier, der har et design, hvor hver enkelt patient er sin
egen kontrol. Kvinderne blev randomiseret til sidefordelingen af de to operationsteknikker, som
blev undersgt (teknik A til hjre og teknik B til venstre, eller teknik B til hjre og teknik A til
venstre). Et sdan design har den fordel, at det reducerer betydningen af forskelle blandt deltagerne
og dermed nedstter det ndvendige deltagerantal.

I det frste studie sammenlignede vi klips med intrakutan selvabsorberende sutur til lukning af
huden efter kejsersnit. Det primre effektml var patientens foretrukne side af arret 6 mneder efter
operationen. vrige effektml var forskellen mellem de objektive kosmetiske vurderinger af de to
sider af arret, som blev udfrt af to plastikkirurger blindet til randomiseringen. Desuden evaluerede
vi patienternes oplevelse af smerte, samt forekomsten af infektion og spaltning. Studiet viste, at
signifikant flere kvinder foretrak den side af arret, som blev lukket med klips bde overordnet og
kosmetisk, og angav klips som deres foretrukne metode. Der var ingen forskel i forekomsten af
smerter i relation til de to hudlukningsmetoder. Ved den objektive vurdering foretrak den ene
plastikkirurg oftere den klipsede side, mens den anden ikke fandt en signifikant kosmetisk forskel.
Bde objektive og subjektive faktorer skal tages i betragtning i en vurdering af operationsteknikker.
Vi fandt at det subjektive og kosmetiske resultat var bedre ved anvendelse af klips, hvorimod meta-
analyser af tidligere studier har fundet, at risikoen for spaltning af arret er hjere ved brug af klips.
Der mangler fortsat viden om, hvorledes tidspunktet for fjernelse af klips pvirker forekomsten af
spaltning, infektion og det langsigtede kosmetiske resultat. Desuden br fremtidlige studier
klassificere graden af spaltning og vurdere den langsigtede konsekvens af spaltning, samt omfatte
kvinder med hjt BMI.

VI
Dansk Resum (Summary in Danish)

I det andet studie sammenlignede vi to metoder til bning af fascien ved kejsersnit - skarp incision
med saks og stump spaltning med fingrene. Det primre effektml var patientens overordnet
foretrukne side af arret 3 mneder efter operationen. Det sekundre effektml var forskelle i
oplevelsen af smerte imellem de to sider af arret. Studiet viste ingen forskel imellem de to
operationsmetoder postoperativt eller ved opflning efter 3 mneder.

Et studiedesign, hvor patienten fungerer som sin egen kontrol, anvendes sjldent. Vi viste i studie I,
at designet signifikant reducerede variansen i de objektive kosmetiske scores og sledes at designet
reducerede betydningen af confoundere. Designet er velegnet til randomiserede studier af kirurgiske
teknikker, og isr til studier med kosmetiske effektml.

Det tredje studie er et register-baseret kohorte studie, hvor vi estimerede forekomsten af brok i
kejsersnitar, som krvede operation indenfor 10 r efter kejsersnitet. Vi fandt en kumuleret risiko i
vores studiepopulation p 2 pr. 1000 kejsersnit. De fleste af de kvinder, der udviklede
operationskrvende brok, havde fet foretaget kejsersnit gennem en midtlinjeincision i en periode,
hvor det var almindelig procedure at foretage kejsernit gennem tvrsnit. Vi konkludererde derfor, at
risikoen for at udvikle et brok efter kejsersnit er uhyre lav, nr kejsersnit udfres i henhold til
aktuelle anbefalinger.

VII
Abbreviations

Abbreviations
BMI Body Mass Index (calculated as weight (kg) / [height (m)]2)

CI Confidence Interval

CONSORT CONsolidated Standards Of Reporting Trials

OR Odds Ratio

RCT Randomized Controlled Trial

RR Relative Risk

STROBE STrengthening the Reporting of OBservational studies in Epidemiology

VAS Visual Analogue Scale

WHO World Health Organization

VIII
Introduction

Introduction
The term caesarean section historically originates from the Roman legal text Lex Caesarea that
forbade burial of pregnant women before the child was extracted from the womb,2 and the term was
first used in connection with abdominal birth in Roussets book from 1581.3 Caesarea derives from
the Latin verb caedare to cut.4
Legal texts from the ancient world document the early use of the caesarean section, primarily for
post-mortem delivery of living or dead children.5 The same indication prevailed for religious and
cultural reasons during the Medieval period, and it was not until the late 16th century that caesarean
section became a medical procedure.2;4 However, the procedure was rarely performed on living
women due to the high risk of maternal mortality caused by haemorrhage and infection.3 With the
introduction of anaesthesia and aseptics in the 19th century and antibiotics and uterotonics in the
20th century, the safety of the procedure improved significantly.4 Later, a shift from general to
regional anaesthesia and an awareness of early mobilisation to prevent thromboembolic events have
further improved safety.6
The increased safety of the caesarean section has changed the indications for the procedure and
resulted in an increased frequency. Today, caesarean section is an obstetric intervention for
preventing maternal and neonatal mortality and morbidity. However, it is increasingly accepted to
perform caesarean section on maternal request without clear medical indications, although there is
increasing evidence that caesarean sections can have negative consequences.7;8 Both very low and
very high rates of caesarean section can be dangerous, but the optimal rate is unknown.9 In 1985 the
World Health Organisation made a consensus statement recommending that caesarean section rates
should not exceed 15%.10 Nevertheless, rates are presently over 30% in the United States, Latin
America, several European countries, and
Australia, and much higher in private than in
public facilities in especially Latin America and
Asia.11-15 It has been argued that we are
experiencing a worldwide caesarean section
epidemic.6;16 And since there is no evidence of a
decrease in the maternal and neonatal morbidity
and mortality concomitant with the increasing
rates, the American College of Obstetrics and
Gynecology recently suggested measures to
Figure 1. Caesarean section rates in Denmark 1997
prevent overuse of caesarean sections.17 In 2012.16 CS: Caesarean section.

1
Introduction

Denmark, the caesarean section rate passed the 15% landmark in 2000, but the rate has stayed
relatively stable between 21% and 22% since 2006 (Figure 1).18

Irrespective of optimum rates, caesarean section is a common surgical procedure performed on


young, otherwise healthy women. And therefore it is essential the surgical techniques used be
carefully evaluated.19 A caesarean section consists of several individual surgical steps based on the
anatomical layers to be incised before and closed after the baby is extracted (Figure 2). The surgical
techniques used at each step of the caesarean section may influence both short- and long-term
maternal morbidity.
The short-term maternal risks of a caesarean section including infection, bleeding, and
thromboembolic events, are well known.8;20 But recently there has also been an increasing
awareness of the long-term consequences of caesarean section.7;21

The studies on which this thesis is based explore surgical techniques to open the fascia and close the
skin as well as the long-term risk of incisional hernia requiring repair after caesarean section.

In the following section, the primary subjects of the thesis are described: 1) Caesarean section
surgical techniques. 2) The maternal long-term consequences of caesarean section. 3) A trial design
in which each participant is his/her own control.

Figure 2. Transverse
Skin
section of the abdomen at
Subcutaneous fat
the level where the
Fascia
Rectus muscle
caesarean section is done,
Preperitoneal fat illustrating the anatomical
Parietal peritoneum
layers of the abdomen.
Visceral peritoneum Drawing by Randi Iversen.
Adapted from Figure 17.1
in: Srensen JL, Ottesen B,
Myometrium
Weber T, editors. Ars
Amniotic fluid Pariendi - hndgreb og akut
behandling ved fdsler.
Fetus Kbenhavn: Munksgaard
Danmark, 2011: 195. With
permission from Jette Led
Srensen.

2
Background

Background

Caesarean section surgical techniques


The surgical techniques used at caesarean section stayed unchanged until the introduction of
anaesthesia around 1850, which allowed for a shift in priority from speed to careful surgical
technique.4;22
Historically, many types of abdominal incisions have been suggested for caesarean section.5 The
introduction of the midline incision through the linea alba was the first improvement and had the
advantage of reducing bleeding.5 At the turn of the 19th century, the skin incisions were increasingly
transverse, while the fascia was incised longitudinally.4;5 In 1900, Pfannenstiel advocated the
transverse incision of the fascia, which provided more secure closure and less postoperative pain.
The transverse abdominal incision was modified by Maylard in 1907 and Joel-Cohen in 1972.5
However, in Denmark the transverse abdominal incision did not become the incision of choice until
the early 1980s.
In the past, the uterine incision was not sutured based on the belief that the edges would
automatically be approximated as the uterus contracted4;22 Snger and Kehrer introduced uterine
suturing with silver wire sutures in 1882. 4;22 The uterine incision was traditionally longitudinal, but
already in 1882 Kehrer advocated for a low transverse incision.4 However, the transverse incision of
the uterus with the advantage of less haemorrhage and reduced risk of uterine rupture in subsequent
pregnancies did not become widespread until re-introduced by Kerr in 1926.4
These were the initial improvements of the surgical techniques for caesarean section. Over the past
3 decades there has been an increasing focus on the necessity of scientific evidence behind the
surgical techniques, and as a result, several studies have been published about various techniques.
Below is a short review of the current recommendations and the evidence behind them.

Prophylactic antibiotics at caesarean section reduce the incidence of febrile morbidity, wound
infection, endometritis, and serious maternal infectious complications.23 Both cephalosporins and
penicillins may be used.24 Different administration times have been compared, and preoperative
administration before skin incision has been shown to significantly reduce the rate of endometritis
compared to intraoperative administration after cord clamping.25 No neonatal side effects including
neonatal sepsis or intensive-care unit admission have been shown. However, there is a lack of
evidence regarding the long-term consequences for the child of different administration times.

3
Background

For abdominal incision, a transverse


incision is recommended and preferred
in the Western world. Compared to a
midline incision, the risk of dehiscence,
herniation, disruption, and
postoperative pain is reduced, and the
cosmetic result is better (Figure 3).26
However, vertical midline incisions are
still used in some places and even
Figure 3. The advantages of the midline and transverse incisions mentioned in the current WHO
for caesarean section. Adapted from Figure 1 in Maale et al., Int
J Gynecol Obstet 2014.26 guidelines.27 A recent study has
indicated that the midline incision
might prove advantageous for women with a body mass index (BMI) over 40, although further
studies are needed to confirm these findings.28 Two types of transverse abdominal incisions
Pfannenstiel and Joel-Cohen have been compared in several studies which have examined the
short-term postoperative outcomes.29-32 The two techniques comprise a combination of surgical
techniques to open the various layers of the abdomen. The Pfannenstiel incision is located two
fingerbreadths above the pubic symphysis, the subcutaneous tissue is incised sharply with a scalpel,
the fascia is cut open with scissors and separated from the underlying muscles, and the peritoneum
is opened and widened sharply with scissors.31 The Joel-Cohen incision is placed 3 centimetres
below the line joining the anterior superior iliac spines, the subcutaneous tissue and the fascia are
incised in the midline only, the fascial incision is extended with the tip of a pair of scissors below
the fat tissue, the rectus muscles are separated by manual traction, and the peritoneum is entered
transversely with the finger tips.31-33 The studies have concluded that the Joel-Cohen method causes
significantly less postoperative morbidity, including fever, pain, and analgesic use; shorter
operating time; and shorter duration of the postoperative hospital stay.29-32 However, it is not known
whether the various steps of the two abdominal entry methods have differential outcomes.
Methods to open the parietal peritoneum have not been studied separately, and the evidence is based
on the above-mentioned studies of abdominal entry thus blunt entry is recommended. The visceral
peritoneum is incised 1 cm above the bladder fold, and there is no evidence supporting the
development of a bladder flap.34 However, the formation of a bladder flap might be beneficial when
the fetal head is deep in the pelvis as in the case of an acute caesarean section during labour or if the

4
Background

bladder is attached above the uterine segment due to adhesions. Recently, an interest in the
extraperitoneal approach to the caesarean section has been revived, with the postulate that it might
reduce acute postoperative pain, but further studies are needed.35
The uterus is opened with a transverse incision in the lower segment, and the incision expanded
bluntly by the surgeon separating the fingers in a cephalad-caudal direction. Blunt expansion causes
less blood loss, and expansion in the cephalad-caudad direction causes fewer unintended extensions
and cases of major blood loss.36;37
After the delivery of the baby, the placenta is extracted spontaneously by gentle cord traction and
uterine massage. Manual extraction causes more blood loss, postpartum endometritis, and longer
hospital stay.38
The uterotonic agent oxytocin reduces postpartum haemorrhage by 40% at vaginal delivery,39 but
optimal dosage and how it should be administered at caesarean section are unknown. The dose
requirement is higher at emergency caesarean section for labour arrest after augmentation than at
elective caesarean section.40 Oxytocin is a vasodilator with numerous dose-dependent side effects,
such as hypotension, tachycardia, nausea, and vomiting, which have to be weighed against higher
dosage. The English guideline from the National Institute for Health and Clinical Excellence from
2011 recommends a 5 iu bolus administered by slow intravenous injection.41 Two current reviews
recommend a lower dosage of 0.33 iu at elective and 3 iu at emergency caesarean sections, if
necessary repeated or accompanied by an infusion.42-44
The uterus can either be left in situ or exteriorised while the uterine incision is sutured. Neither a
meta-analysis (n = 3183) nor a large randomised trial (n = 9795) found any differences in intra- or
postoperative complications between the methods, but some studies have shown that exteriorisation
causes more pain.45;46 However, exteriorising the uterus may ease the overview during uterine
closure.
The uterine incision can be closed with a single- or double-layer suture. Two large trials found no
difference in the short-term outcomes of the two methods.45;47 But the role of the two methods in
reducing the long-term risk of uterine rupture is controversial and has not yet been evaluated in
randomised trials. A cohort and a case-control study found a 2 to 4 times increased risk of rupture
after closure with a single- compared to a double-layer suture.48;49 And a review found a higher risk
of rupture after closure with a single-layer locked suture, but not unlocked suture, compared to
double-layer closure.50 Additionally, a follow-up study found more frequent bladder adhesions after
single-layer versus double-layer hysterotomy closure.51 Thus, in women with no wish for future

5
Background

fertility (e.g. women who are sterilised during the caesarean section) there may not be any
additional benefit of a double-layer closure, but no definite recommendations can be given.
Inclusion of the endometrial layer in the suture has been discussed. A small study (n = 78) found
fewer healing defects 6 weeks postpartum when the endometrium was included, but further
evidence is needed before any recommendations can be given.52
The peritoneal layers can either be sutured or left open. An older Cochrane review (n = 2908) found
a reduction in operating time, postoperative stay in hospital, postoperative fever, and postoperative
analgesic use when the peritoneal layers were left unsutured.53 However, two larger multifactorial
trials of 2995 and 9675 women found no short-term differences. 45;47 Two reviews and meta-
analyses found an increased risk of intra-abdominal adhesions in subsequent caesarean sections
when the peritoneum was left unclosed.54;55 Thus, the short- and long-term consequences have to be
weighed against each other until further results are available.
Methods to close the fascia are well documented for midline incisions but have never been studied
in lower transverse incisions. In midline incisions, a suture technique with continuous sutures
placed 1 cm apart and 1 cm from the incision using a suture 4 times the length of the incision has
been shown to prevent hernias.56 Additionally, a meta-analysis of closure of the fascia after midline
laparotomies found that a continuous suture with a suture material that was slowly absorbable (i.e.
polydioxanone [PDS] and polyglyconate [Maxon]) compared to rapidly absorbable (i.e. polyglactin
[Vicryl] and polyglycolic acid [Dexon]) caused significantly less hernias.57 Until studies about
fascial closure of transverse incisions are available, a similar suture technique with slowly
absorbable sutures is recommended for caesarean sections.
Suturing of the subcutaneous fat reduces the risk of haematoma, seroma, and wound complications
if the fat layer is more than 2 cm thick.58;59 A meta-analysis found no such effect if the
subcutaneous fat was less than 2 cm.59 It has not been reported whether the sutures should be
continuous or disrupted. Subcutaneous drainage has no preventive effect against infection,
haematoma, and seroma and can therefore not be recommend.60

Skin closure techniques

Several methods and materials can be used for closing the skin after caesarean section. A survey of
American obstetricians in 2011 found that only 4% use methods other than absorbable sutures and
metal staples.61 Of those remaining, 39% primarily use absorbable suture, 48% primarily use metal

6
Background

staples, and the remaining 13% use both with equal preference. Metal staples and absorbable
sutures are also the two methods that have primarily been compared in randomised trials.

The ideal technique for skin closure should be quick, cost-effective, and simple, while maximising
wound cosmesis and patient satisfaction.62 Thus, both objective and subjective measures should be
evaluated.
When study I was initiated in 2010, only three randomised trials with a total of 251 patients had
been published that compared staples and subcuticular suture for skin closure after caesarean
section.63-65 These studies evaluated time for skin closure, infection rate, cosmetic results, patient
satisfaction, and pain. The only outcome on which the three trials agreed was that staples
significantly reduce the time of skin closure. Cosmetic results, pain, and patient satisfaction were
evaluated with different outcome measures and with diverging results. Two studies found no
difference in cosmetic outcomes or patient satisfaction, while one study found sutures to be
superior. And in regard to pain, one study found that staples and another study that sutures caused
more pain.63;65 Additionally, the cosmetic results of the scars were evaluated at different times from
6 weeks to 4 months postoperatively, although it is recommended that cosmetic evaluation of a scar
be postponed until 1 year after surgery to be reliable.66 Thus, these outcomes could not be
compared between the studies.
During the course of study I, an additional two studies67;68 and three meta-analyses69-71 of skin
closure techniques for caesarean section were published. The meta-analyses confirmed that the
outcomes regarding cosmetic results, pain, and patient satisfaction could not be quantitatively
combined because of diverging outcomes.69;70 The primary outcome of the meta-analyses was a
composite wound complication rate including infection and separation. Prior to the initiation of
study I, a cohort and a case-control study had evaluated risk factors of infection after caesarean
section and indicated that staples increased the risk of wound infection after caesarean section.72;73
However, the randomised trials available at the time could not evaluate infection due to small
sample sizes.63-65

Methods to incise the fascia

At abdominal incision, the fascia can be opened either sharply with scissors or bluntly by manual
traction (Figure 4). In both the Pfannenstiel and Joel-Cohen approach to abdominal entry, the fascia
is incised sharply with scissors. To the authors knowledge, no studies had focused solely on
techniques to incise the fascia before the initiation of study II. Additionally, blunt opening of the

7
Background

A B

Figure 4. A) Sharp opening of the fascia with scissors and B) blunt opening of the fascia by manual traction.

fascia by manual traction had not been described previously. It needs to be noted that the Joel-
Cohen method of abdominal opening has been described as blunt compared to the Pfannenstiel
method. However, the Joel-Cohen method of opening the fascia is equivalent to the sharp method
used in study II.

Long-term consequences of Caesarean section


Delivery by caesarean section has some long-term consequences for later pregnancies and the
woman.

Fertility is reduced and there is an increased birth and inter-pregnancy interval after a caesarean
section compared to after a vaginal delivery.74;75 However, the association may be partly causal due
to confounding by indication.
In a later pregnancy the embryo may implant in the caesarean section scar and become a so-called
scar pregnancy. It is a rare complication (<2) of a previous caesarean section and is associated
with high risk complications, including uterine rupture and abnormal placentation.76;77

Uterine rupture is associated with high perinatal morbidity and mortality, and primarily occurs in
pregnancies after a previous caesarean section, with an incidence of 0.10.3%.78;79 There is also a
risk of uterine rupture among women with a previous caesarean section undergoing second
trimester abortion with misoprostol, although the incidence is low (0.280.43%).80;81

8
Background

Abnormal placentation is associated with previous caesarean section. Placenta previa, where the
placenta lies over the internal cervical os, is more frequent after one previous caesarean section
compared to after vaginal delivery, with an odds ratio (OR) 1.5 (95% confidence interval [CI] 1.4
1.7).82 The risk increases with the number of previous caesarean sections.83 A meta-analysis found
an incidence of 1% after one previous caesarean section that increased to 2.8% after 3 previous
caesarean sections.21 Women with both a previous caesarean section and a current placenta previa
are at increased risk of maternal complications, including postpartum bleeding, hysterectomy,
venous thromboembolism, and admission to an intensive care unit. And the risk increases from 15%
among women with no previous caesarean sections to 83% among those with 3 caesarean
sections.21
Placenta previa and previous caesarean section are independent risk factors for placenta
accreta,increta, and percreta where the placenta becomes abnormally adherent to the
myometrium.84;85 The rate among women with one previous caesarean section is 0.30.6% (3.34%
among women with concomitant placenta previa), and the risk increases with the number of
previous caesarean sections.21 The removal of an abnormally adherent placenta is complicated by
the adherence and is thus associated with an increased risk of bleeding, blood transfusion,
hysterectomy, and admission to an intensive care unit (Figure 5).20
Placental abruption is likewise associated with previous caesarean section (OR 1.4, 95% CI 1.36
1.45), with an incidence of 1.01.5% after 1 previous caesarean section.21;86 The risk is not related
to the number of previous caesarean sections.21
Caesarean section also increases the risk of retained placenta (OR 1.5, 95% CI 1.31.6).87 Since the
placenta has to be removed
manually, a retained placenta
is associated with postpartum
bleeding and endometritis.
Hysterectomy is the last
resort when other treatments
have failed to stop
postpartum bleeding. The
risk of hysterectomy is
increased after previous
Figure 5. Removal of a placenta percreta after the birth of the baby.
caesarean section and Picture courtesy of the Department of Obstetrics and Gynecology,
Copenhagen University Hospital.

9
Background

increases with the number of previous caesarean sections from 0.65% after 1 to 8.99% after 6.88;89

Caesarean section is also associated with some long-term consequences for the mother independent
of pregnancy. Chronic pain is less frequent after caesarean section than after other surgical
procedures.90 Nevertheless, 418% have chronic pain 1 year after caesarean section, and 16% have
pain on a daily basis.91-93 The pain interferes with daily activities in 1.414%.91-93 Pain is primarily
located at the incision, and the risk is related to the number of previous caesarean sections.94
Endometriosis is possibly associated with previous caesarean section. A recent study found a hazard
ratio of 1.8 (95% CI 1.71.9) and an incidence of 0.6% 95
Occurrence of adherences is a well-known and common surgical complication. After one caesarean
section, the incidence is 2446%, and the occurrence and density increases with the number of
caesarean sections.96-100 The risk of being admitted to hospital due to adhesions or intestinal
obstruction is doubled after caesarean section compared to after vaginal delivery,96 and adherences
may cause sub-fertility, intestinal obstruction, and pain.96;100;101 Adherences complicate later
surgery, including caesarean sections, and caesarean section has been shown to increase the risk of
complications at hysterectomy (i.e. cystotomy and conversion to laparotomy).102;103

A few studies have examined the long-term complications of certain caesarean section surgical
techniques. The risk of uterine rupture has been associated with the number of uterine suture layers
as previously described (Pg. 5), but the evidence is controversial. Additionally, a follow-up study
found bladder adhesions to be more frequent after single-layer versus double-layer hysterotomy
closure as described on page 5.51 Further studies are needed to evaluate the association between
method of uterotomy closure and both uterine rupture and the risk of adhesions. Closure of the
peritoneum has also been associated with a reduction in adhesions.54;55 However, long-term follow-
up studies of randomised trials of caesarean section techniques are few. Currently, two large multi-
factorial randomised trials comparing seven different surgical techniques, the CAESAR and
CORONIS trials, are planning long-term follow-up.47;104 Both studies have compared single-
versus double-layer closure of the uterine incision, and closure versus non-closure of the visceral
peritoneum (CAESAR) and both layers of the peritoneum (CORONIS) without finding any short-
term differences between the techniques.45;47 The studies also compare blunt versus sharp
abdominal entry, exteriorisation of the uterus for repair versus intra-abdominal repair, chromic
catgut versus polyglactin-910 for uterine repair, and restricted versus liberal use of sub-sheath drain.

10
Background

The long-term results of the trials may clarify differences between these surgical techniques. The
CAESAR study, which is run primarily in the United Kingdom, accesses outcomes during a
consecutive pregnancy and caesarean section or surgery, and is thus able to access outcomes such as
adhesions and uterine rupture objectively and in a standardised fashion.47 The CORONIS trial,
which is being conducted in low- and middle-income countries, accesses a variety of long-term
outcomes assessed through face-face interviews with the participants.104 The trial can therefore
assess pain, which is a personal experience, while objective outcomes can only be evaluated
indirectly (e.g. adhesions through ectopic pregnancies). Additionally, the long-term outcomes of the
CORONIS trial could be influenced by recall bias. Nevertheless, the two trials are well planned,
well managed, and have an unprecedented focus on the long-term outcome of caesarean section
techniques and the results are awaited with much interest.105

Incisional hernia

Incisional hernia is a long-term complication of abdominal surgery which may lead to potentially
life-threatening events such as incarceration or intestinal obstruction. But the incidence of incisional
hernia after caesarean section is unknown. A single study found an incidence of 3.1% among 701
patients within 612 months of the caesarean section.106 All hernias occurred in midline incisions,
accounting for 421 of the caesarean sections, while there were no incisional hernias in the 280
transverse incisions. Similarly, studies exploring the rate of incisional hernias in Pfannenstiel
incisions after gynaecological surgery have found incidences of 0% after 15 years in 232
women.107;108 Studies have found that more than 50% of incisional hernias occur more than 1 year
after surgery, indicating that the incidence of incisional hernia in lower transverse incisions after
caesarean section might be underreported.108;109 In study III, we therefore estimated the incidence
in a large cohort over a 10-year period after the caesarean section.

Randomised controlled trial in which each participant is his/her own control


A randomised controlled trial (RCT) has a study design where participants are allocated at random
to one of several different interventions. Compared to other study designs, the advantages of the
RCT are a reduction of allocation bias and the possibility of blinding. Disadvantages of the RCT are
that it is less suitable for studies of rare outcomes or long-term effects of the interventions.111

11
Background

If each patient is his/her


own control in a RCT,
patient variation is
removed, making the trials
potentially more efficient
than a similarly sized
parallel group design study
where each patient receives Figure 6. Study patient from study I on the second postoperative day.
Study I had a design where each patient was her own control. This patient
only one intervention.112 In was randomised to skin closure with staples on the right side and
subcuticular sutures on the left side of the skin incision.
a RCT, the patients can be
their own control in two types of designs. 1) The crossover trial where the participants receive all
interventions in a certain sequence and are randomised to the sequence of interventions. The
crossover trial requires a constant baseline and no influence of time, and is not suitable for trials of
surgical techniques. 2) A design where the participants receive both interventions at the same time
and are randomised to side or location (Figure 6).113 This design is suitable for trials of surgical
techniques, however limited by anatomic considerations. Trials with such a design are limited in
number and have primarily been within the fields of oto-rhino-laryngology, plastic surgery,
deontology, ophthalmology, local anaesthesia, and dermatology. However, surgical techniques in
gynaecological surgery have been compared in a few studies with each patient as her own control.
A Nordic trial studied women who were infertile due to bilateral tubal disease with adhesions.114
They received laparoscopic bilateral adhesiolysis, and an adjuvant therapy applied only unilaterally.
The extent of postoperative adhesions was assessed laparoscopically after 410 weeks. This study is
an example of how longer-term outcomes of surgical techniques can be evaluated in a study design
where each patient serves as her own control. A Finnish trial studied the pain reducing effect of a
local anaesthetic applied only unilaterally in the fallopian tubes after postpartum sterilisation and
found that patients were able to differentiate pain from the two sides.115 Skin closure techniques
have also been compared in studies with each patient as their own control.116-118 A skin adhesive has
been compared with sutures at bilateral mammaplasty;116 staples have been compared with
intradermal sutures in sternal and leg wounds at coronary bypass surgery, where all wounds were
closed with both techniques;117 and nylon sutures, subcuticular polyglactin sutures, and adhesive
strips have been compared in laparoscopy wounds.118

12
Background

In conclusion, the study design in which each participant serves as her own control, which was
applied in studies I & II, has previously only rarely been used but is suitable for trials of surgical
techniques. To the knowledge of the authors, the design has never been applied in obstetric surgery.

13
Aims

Aims
Study I
The aim of the study was to compare subcuticular sutures with staples for skin closure after
caesarean section in a study design in which each woman was her own control. Follow-up time was
6 months, and patient preference the primary outcome. We hypothesised that women would have a
side preference.

Study II
The aim of the study was to compare blunt opening of the fascia with manual traction and sharp
incision of the fascia with scissors at caesarean section in a study design in which each woman was
her own control. Follow-up time was 3 months, and patient preference the primary outcome. We
hypothesised that women would have a side preference.

Study III
The aim of the study was to estimate the incidence of incisional hernia requiring surgical repair
within 10 years after caesarean section in a large cohort.

14
Methods

Methods

Study I & II

Design: Randomised controlled trial in which each participant is her own control

Studies I and II were single-centre, prospective, randomised, controlled trials with each case as her
own control. Randomisation was computer generated by a third party not otherwise involved in the
trial. Patients were randomised to side distribution of the two techniques being investigated (A right
and B left or B right and A left). The allocation list was stored in a locked room by third parties not
involved in the trial. At the end of the trial, the list was passed on in exchange for a copy of the
locked data before the allocation was broken.

Participants

Eligible participants were woman having scheduled primary caesarean section and no history of
lower abdominal surgery. In study I, women with multiple caesarean sections were also eligible.

Procedures

The women gave written informed consent and were consecutively numbered (primary [numbers 1
30]; multiple (study I) [numbers 3160] caesarean sections). Women were included when surgery
had been performed according to protocol. Recruited women were replaced if procedures did not
follow protocol.
In study I, staples were removed 3 days postoperatively and Steri-Strips applied. The level of pain
and/or the type of discomfort during removal of staples was recorded. Patients were followed for 6
months with regular in-person and telephone follow-up visits. At the 6-month in-person visit with
the primary investigator, the scar was photographed under standardised conditions. The
photographs were evaluated by two blinded plastic surgeons. In study II, women were followed for
3 months with regular telephone follow-up visits.

Outcomes

The primary study outcome was womens overall preferred side (right/left/no difference) 6 and 3
months postoperatively in study I and study II, respectively.
In study I, secondary 6-month outcomes were womens preferred closure technique
(sutures/staples/no difference), cosmetically preferred side of the scar (right/ left/no difference), and
difference in objective cosmetic scores between the two sides of the scar as assessed by two plastic

15
Methods

surgeons. The objective cosmetic evaluation included the cosmetic side preference (right/left/no
difference), the Singer Scar Evaluation Scale score,119 and a 100 mm cosmetic visual analogue scale
(VAS) score.120;121 Additional outcomes were rate and side distribution of separation and infection
and difference in pain scores between the two sides of the scar measured 1 and 3 days and 3 and 6
months postoperatively.
In study II, secondary outcomes were (a) side with more pain (right/left/no difference) and (b)
difference in pain scores (absolute and relative) between the two sides 1, 3, and 7 days and 1 and 3
months postoperatively, and (c) the occurrence and side distribution of infection assessed after 1
and 3 months.
Pain was in both studies measured on a numerical rating scale from 0.0 (no pain) to 10.0 (worst
pain imaginable)122 on each side of the scar, in study II both at rest and during mobilisation. The
absolute difference was calculated by subtraction of the scores. In study II, the relative difference in
pain scores was calculated as: absolute difference/maximum pain score at the time x 100%.

Outcome assessors as well as the participants (in study I only for the first 24 postoperative hours)
were blinded to the allocation.

For further details about the caesarean section techniques utilised in the trials, follow-up
procedures, and additional outcomes, please see the respective papers.

Study III

Register data

Study III was a population-based cohort study with data obtained from the Danish National Patient
Register and the Danish Medical Birth Register. The main inclusion criterion was a caesarean
section between January 1, 1991 and December 31, 2000 in women with no history of previous
abdominal surgery. The cohort was followed from their first caesarean section until 10 years after
their last caesarean section in the inclusion period for an event of hernia repair. We also registered
events of death, emigration, abdominal surgery, and caesarean sections during the follow-up period.
For women with a hernia repair, hospital records of the primary examination, description of
surgery, and the discharge letter were retrieved as were the descriptions of the previous caesarean
sections, and the records were manually analysed for validation. For further details, please see the
paper.

16
Methods

Ethics
RCTs have to be approved by a research ethics committee before trial start to ensure that the trials
are carried out in a responsible manner from a research ethical point of view, and that the rights,
safety, and wellbeing of the participating trial subjects are protected, while at the same time
possibilities are being created for the development of new, valuable knowledge.123 Study I and
Study II were registered with the regional ethics committee (reg.nos. SJ-162, and H-2-2010-129).
In Denmark, research projects handling data about individuals that directly or indirectly can be
identified have to be authorised by the Danish data protection agency.124 All three studies were
registered (reg. numbers 2010-41-4302, 2010-41-5540 and 2013-41-2155).
Additionally, researchers are encouraged to register RCTs in a database of clinical trials to ensure
public access to the trials. Study I and Study II were registered with ClinicalTrials.gov (reg.
numbers NCT01217567 and NCT01297725).

CONSORT stands for the CONsolidated Standards Of Reporting Trials. The CONSORT statement
provides recommendations on how to report RCTs,125 and an extension to the CONSORT statement
exists for the reporting of non-pharmacological treatments.126 These recommendations were
followed in the reporting of studies I and II. STROBE stands for STrengthening the Reporting of
OBservational studies in Epidemiology and comprises recommendations for reporting observational
studies.127 We followed the STROBE recommendations in the manuscript of study III.

Statistics

Studies I & II

The sample size for the primary effect variable was based on the following reasoning. If the
probability of having a preference is 0.062, the probability of detecting at least one woman with a
side preference out of 25 women is 0.80. Due to the risk of dropouts, 30 women were included in
study I, and 30 women were included in each of the two groups, primary caesarean section or
multiple caesarean sections, in study II. No interim analyses were performed.
Categorical variables including the primary outcome were presented as counts with percentages and
modelled by polytomous logistic regression, which in study I was adjusted for caesarean section
status (primary or multiple). ORs were reported with 95% CI calculated on a log scale and back-
transformed. Differences in pain scores were analysed with a Wilcoxon signed-rank test for
robustness, and the CIs were obtained by a t-test. P < .05 was considered statistically significant.

17
Methods

For the repeated pain measures, the significance level was adjusted with a post hoc Bonferroni
correction equivalent to the number of time points investigated.
In study I, a formal likelihood ratio test for the significance of interpersonal variation in the
objective VAS scoring was conducted in a mixed linear model that included method as a fixed
factor and observer and person as random effects.

Study III

The cumulative risk of a hernia repair after caesarean section was estimated by a competing risk
analysis.128 Each caesarean section during the inclusion period was analysed individually. The
competing endpoints that mutually excluded each other were hernia repair, death, abdominal
surgery, and a consecutive caesarean section. Emigration during the follow-up period caused
censoring. Right censoring also occurred after 10 years if the woman did not meet any of the
endpoints mentioned above.

The statistical methods are described in further detail in each of the three articles.

18
Results

Results

Study I
Sixty-three women undergoing caesarean section were randomised, and 59 were included in the
analysis. At 6 months, significantly more women preferred the stapled side of the scar overall (OR
2.55; 95% CI 1.185.52), regarded the stapled side superior in appearance (OR 2.67; 95% CI 1.24
5.74), and reported staples as their preferred skin closure technique (OR 2.00; 95% CI 1.103.64)
(Figure 7). Objectively, the stapled side was cosmetically preferred more frequently (OR 2.8; 95%
CI 1.017.78) and scored significantly higher on a cosmetic VAS scale (P5.031) but not on the
Singer Scar Evaluation Scale (P5.391) in the evaluation by one plastic surgeon, whereas the other
found no significant cosmetic difference between the two methods (preferred side: OR 3.00; 95%
CI 0.979.30; VAS score: P = 5.098; Singer Scar Evaluation Score: P = 5.279). Cosmetically, the
women evaluated the width, protrusion, and visibility of the scar to be significantly less satisfactory
on the sutured side, whereas the plastic surgeons found no significant differences in scar
characteristics. There were no significant differences in number of women reporting pain or pain
scores at any time. During removal of the staples 16 women (27.1%) reported pain and 17 (28.8%)
reported discomfort. Three months postoperatively, the women had no significant side preference in
regard to appearance (OR 2.10; 95% CI 0.994.46). There were four (6.8%) cases of infection
three on the sutured side and one bilaterally. There were four (6.8%) cases of separationone on
the stapled side and three described as being in the middle of the scarof which three women had a

Figure 7. Patient and overall objective preference 6 months postoperatively in study I. Odds ratios were estimated
by multinomial logistic regression.

19
Results

repeat caesarean section and one had a primary caesarean section. All cases of separation were
treated with the application of Steri-Strips. None of the cases with infection or separation required
treatment in hospital. None of the outcome measures differed significantly between women
undergoing primary or repeat caesarean section; however, the study was underpowered to detect a
difference in this subgroup analysis. The sample variance of the differences between the cosmetic
VAS scores on the stapled side and on the sutured side (359.7) was significantly reduced by a factor
of 7.9 compared with the sum of variances of the two VAS scores (2,833.4; P = .001). No serious
adverse events were registered during the trial period.

Study II
Thirty-four women undergoing primary caesarean section were randomised and 28 included in the
analysis. Three months postoperatively, there was no significant difference in preference of
technique, with 9 women preferring the sharp side (32.1%) and 7 the blunt side (25.0%), (OR 1.29
[0.48; 3.45], P = .618). Twelve women (42.9%) had no side preference. There was no significant
difference with regard to which technique caused more pain at any time during follow-up. Nor was
there a significant absolute or relative difference in pain scores at any time (Figure 8). Infection was
registered in two women (7.1%). One woman had infection on the side of the sharp technique,
while the other had bilateral infection. The incidence was too low to be statistically analysed. No
side-specific serious adverse events were registered. One woman developed Ogilvies syndrome,
which was treated conservatively.

A B

Figure 8. Absolute differences in pain scores during A) mobilization and B) at rest in study II. Data are expressed as mean
absolute differences with 95% confidence intervals and significance levels at 1, 3, and 7 days and 1 and 3 months
postoperatively. Positive differences express more pain on the sharp side and negative differences more pain on the blunt side.
The blue dotted lines indicate the minimal clinically relevant difference of 2.

20
Results

Study III
Between January 1991 and December 2000, 57,564 unique women, with no history of previous
abdominal surgery, had a total of 68,271 caesarean sections. Of these, 158 were identified as having
a subsequent hernia repair performed within 10 years after their caesarean section within the
inclusion period. Analysis of the hospital records excluded 24 cases. Of these, four women had a
history of previous abdominal surgery, four had abdominal surgery after the caesarean section but
before the hernia repair, one had the hernia repair done coincidently with the including caesarean
section, nine hernias were not in the caesarean incision, five had diastasis recti without hernia, and
one had no hernia. A total of 134 cases of hernia repair were included in the analysis. In 20 patients,
hospital records from the hernia repair surgery were not available, primarily due to local policies
requiring destruction of medical records after 10 years of inactivity. In 68 cases (51% [95% CI 42
59%]) the hernias treated were in a midline incision, in 50 cases (37% [95% CI 2946%]) in a
transverse incision, and in 16 cases (12% [95% CI 719%]) in an incision of unknown type due to
missing caesarean section records. There was no change over time in either the frequency of
caesarean sections resulting in hernia repairs or the distribution of transverse and midline incisions
among the hernias requiring hernia repair.
The cumulated incidence of a hernia repair within 10 years after a caesarean section was 0.197%
(95% CI 0.1640.234 %) (Figure 9). The risk of a hernia repair was higher within the first 3 years
after a caesarean section, with a cumulated
incidence at 3 years of 0.157% (95% CI
0.1270.187 %) (Figure 9 and Table 1 [Pg.
33]). Among women who developed an
incisional hernia requiring surgical repair, the
median time from caesarean section to repair
was 1.36 years (interquartile range 0.792.27
years).

Figure 9. Cumulative incidence of incisional hernia


requiring surgical repair after caesarean section
estimated by a competing risk analysis in study III. CS:
Caesarean section

21
Discussion

Discussion
The studies on which this thesis is based explore surgical techniques to open the fascia and close the
skin at caesarean section as well as the long-term risk of incisional hernia requiring surgical repair
after caesarean section. The two randomised trials used a study design in which each patient served
as her own control.

Skin closure techniques


Study I showed that women undergoing caesarean section preferred staples for skin closure
cosmetically, overall, and as a technique after 6 months. Additionally, on objective evaluation, one
plastic surgeon preferred staples cosmetically, whereas another plastic surgeon found no significant
difference.

The ideal technique for skin closure should be quick, cost-effective, and simple, while maximising
wound cosmesis and patient satisfaction.62 Thus, both objective and subjective measures are of
importance and need to be evaluated in trials of skin closure techniques. We evaluated patient
preference, and found an overall preference of staples, which is in contrast with other studies,
which, in the main, have found no difference.

During the course of study I, an additional two studies67;68 and three meta-analyses69-71 comparing
subcuticular suture and staples for skin closure at caesarean section were published. The three meta-
analyses analysed the same five studies,63-65;67;68 and two of them included an additional study
each.19 The primary outcome of the Cochrane review was infection, while it was a composite
wound complication rate including infection and separation in the two other meta-analyses. The risk
of infection did not differ between the two skin closure methods (Tuuli et al.: OR 1.41 [95% CI
0.922.17]; Mackeen et al.: Relative risk (RR) 0.85 [95% CI 0.431.71]; Clay et al.: Not analysed
separately). But all studies found an increased risk of separation in the stabled group (Tuuli et al.:
OR 4.24 [95% CI 2.168.34]; Mackeen et al.: RR 3.82 [95% CI 2.057.12]; Clay et al.: OR 4.01
[95% CI 2.098.00]). Mackeen et al. and Clay et al. additionally did a sensitivity analysis of the risk
of separation where the largest trial was excluded,67 because it was a potential source of bias due to
higher complication rates and preterm trial end. The risk of separation then became statistically
insignificant (Mackeen et al.: RR 3.78 [95% CI 0.6223.00], and Clay et al.: OR 4.00 [95% CI
0.7122.45]), although this might be due to a lack of power. After completion of study I, an

22
Discussion

additional four studies129-132 have been published. The two largest of these (n = 350 and n = 746)
also found an increased risk of separation after skin closure with staples (RR 3.8 [95% CI 1.69.1],
and OR 5.0 [95% CI 2.014.3]),129;132 while the other trials had too few cases to be analysed. Thus,
there seems to be a higher risk of wound separation associated with skin closure with staples.
Unfortunately, the level of separation and its consequences has not been evaluated in previous
studies, except in the most recent by Mackeen et al. Wound separation and its consequences should
be graded. For example, all cases of separation in study I were mild and treated with application of
Steri-Strips alone, and it is unknown if such mild cases of separation have any long-term
consequences. Likewise, in the most recent study by Mackeen et al., which found a profoundly
increased risk of separation after skin closure with staples (OR 5.0 [95% CI 2.014.3]), the vast
majority of cases with separation either healed spontaneously or had Steri-Strips placed.132 Only
five of the 34 cases of separation were major complications and it is unclear from the publication
whether these were in the sutured or stapled group. Thus, an evaluation of the consequences of
separation in relation to skin closure method is warranted.
The timing of staple removal has also been suggested to influence the rate of separation.71;133;134 We
removed staples 3 full days after the caesarean section, which is relatively early but comparable
with other studies.63;65;67;129 One recent trial compared the risk of separation after staple removal on
postoperative day 3 with removal on postoperative day 7 to 10.135 Unfortunately, the trial was
halted preterm before inclusion of the entire scheduled sample size due to financial limitations and
the results are inconclusive. But the previously mentioned Cochrane review concluded that if
staples are removed on postoperative day 3, the risk of skin separation is increased compared to
absorbable sutures.71

Pain, patient satisfaction, and cosmetic results have in previous trials been evaluated by varying
outcome measures, thus comparisons have not been quantitatively possible in meta-analyses.69-71 In
study I, it was statistically shown that the objective cosmetic difference between women was much
larger than the cosmetic difference between the two methods of skin closure in one subject (Figure
10). The greater interpersonal variation probably explains the diverging conclusions regarding the
cosmetic result of various skin closure techniques compared in other trials. Cosmetic results may
not be an applicable outcome measure if a classical randomised design is utilised rather than a
design in which both techniques are compared in the same patient. Additionally, cosmetic follow-
up times have varied from 6 weeks to 1 year postoperatively, preventing the comparison of the

23
Discussion

cosmetic outcomes of previous trials.63- A


65;68;130;131
Wound healing is an ongoing process
and cosmetic evaluation requires at least 6
months follow-up.66 In study I, the patients
had no significant side preference after 3
B
months, whereas they preferred the stapled side
after 6 months, which could be explained by
wound healing being an ongoing process. And
during the course of the study, it became
C
evident to the investigators that the healing
process was not complete even after 6 months
(Figure 10).

D
The financial aspects of the two skin closure
techniques have been compared in several
publications, but these rely on
estimations.64;67;129 It has been considered that Figure 10. Caesarean section scars 6 months
staples are more expensive and need to be postoperatively from four participants in study I where
staples were compared with subcuticular suture for skin
removed but take less operating time compared closure. A) and B) Incisions after a primary caesarean
section. C) and D) Incisions after two previous
to subcuticular sutures. Overall the cost is caesarean sections. The cosmetic difference between
participants was larger than the cosmetic difference
probably similar. Additionally, the bother for between the two methods of skin closure in one subject.
Additionally, the majority of the scars were still
the patient of an extra appointment for staple erythematous and thus not completely healed after 6
removal has to be considered. In study I, staple months.

removal was done before discharge from hospital or during the appointment for hearing screening
to save the patient an extra appointment. Additionally, the secondary outcome of preferred skin
closure technique comprised an overall assessment of the two techniques. It showed that
significantly more women preferred staples as closure method, although the outcome could have
been be affected by recall bias.

The prevalence of obesity among fertile women is high, and there is an increasing interest in this
group of patients, which have a higher risk of wound complication.133;136 In study I, patients with
BMIs more than 35 were excluded because of the increased risk of wound complications, and the

24
Discussion

results may not be applicable for morbidly obese women. To date, only the study on the timing of
staple removal (with inconclusive results) has focused specifically on obese women in relation to
skin closure techniques at caesarean section.135 Further studies are warranted.

A limitation of study I is that more than half the patients assessed as eligible declined to participate.
At the time of the study, the standard procedure for skin closure at caesarean section in the
department was subcuticular absorbable suture. If the women who declined participation in study I
more frequently disliked staples, this would have caused inclusion bias. However, the effect would
have been reduced by the study design in which each patient served as her own control.

Other methods of skin closure at caesarean section have been compared in randomised trials. They
include barbed suture versus PDS suture,137 metallic versus non-absorbable staples,138 absorbable
versus non-absorbable sutures,139 and non-absorbable sutures versus Leukosan SkinLink.140 Three
of these studies have been mentioned in the Cochrane review of skin closure techniques and the
risk of infection, but the analysis only included the results of one study.71;137;139;140 The studies
found no cosmetic difference between barbed wire versus PDS suture and non-absorbable suture
versus absorbable suture or Leukosan SkinLink.137;139;140 The study of staples did not evaluate
cosmetic outcome, but it found no difference in postoperative pain.138 The studies are of varying
quality, and their power is too low to evaluate the risk of infection. Additionally, as previously
mentioned, interpersonal variation might make classic RCTs of skin-closure techniques useless in
the evaluation of cosmetic outcomes. Thus, it is currently not possible to make any conclusions
regarding these other skin closure techniques.

In conclusion, both objective and subjective measures have to be considered in the evaluation of
skin closure techniques for caesarean section. We found subjective and cosmetic outcomes in
favour of staples, whereas meta-analyses of previous studies found the use of staples increased the
rate of separation. More studies and meta-analyses of skin closure techniques for caesarean section
will doubtlessly be published in the future. Until further evidence is available, both staples and
sutures can be recommended for skin closure at caesarean section at the discretion of the surgeon.

Methods to incise the fascia


In study II, sharp incision of the fascia with scissors was compared to blunt opening by manual
traction. The study found no difference in patient preference for the blunt or sharp technique. Nor

25
Discussion

were there any significant differences in pain scores after either technique up to 3 months
postoperatively.

The experience of pain was the most frequently reported reason for technique preference after 3
months in study II. Pain intensity is the most clinically relevant dimension of the pain experience
and should be assessed by unidimensional scales based on self-reporting.122 In this study, pain
intensity was measured on a numerical rating scale from 0.0 to 10.0. Pain intensity was measured
both at rest and during mobilisation. Pain scores were generally higher during mobilisation,
independent of the fascial opening technique. Under what circumstances pain intensity scores are
more precise is unknown, and therefore it was reasonable to measure pain both at rest and during
mobilisation.
It may be argued that pain would have been a more appropriate primary outcome of study II, since
it was the most frequently reported reason for technique preference. A different method of sample
size determination would then have been required. Techniques for fascial incision have previously
only been compared in studies where several surgical steps and techniques were investigated at the
same time. Thus, it is unknown whether one technique for fascial incision is superior to the other.
We hypothesised that the blunt technique would cause less pain (stated in the protocol but not the
published article). A classic two-sided superiority sample size estimation would then be appropriate.
A study of postoperative pain and reproducibility of pain scores on a VAS scale during a 3-minute
interval found that 95% of the repeat ratings were between 2.0 cm.141 Thus, in a two-sided
sample size estimation, the minimal relevant difference in absolute pain scores should be 2. With a
power of 80% and a two-sided significance level of 5%, a trial with each patient as her own control
would then require 11 participants. The power of study II was thus adequate if pain had been the
primary outcome. This is confirmed by the confidence intervals of the absolute pain differences,
which did not pass the 2.0 limits (Figure 8, pg. 20).
Assuming that the purpose of the study had been to test whether there was equivalence of pain
scores caused by the two techniques, we can conclude that the two methods of fascial incision are
equivalent. According to the previously mentioned study, the equivalence margin should be 2.
Thus the confidence interval of the differences in pain scores should be within this level to be
considered equivalent. Differences in pain scores have to be not only statistically significant but
also clinically significant.142 And the equivalence margin corresponds to the clinically relevant
difference in absolute pain scores. At all times, the confidence intervals of the absolute pain scores

26
Discussion

at rest were within the 2.0 margins. And during mobilisation, the confidence interval only
exceeded 2.0 at 7 days after surgery (Figure 8, pg. 20). Thus only at that one time was non-
equivalence shown. However, since pain was measured repeatedly and non-equivalence was only
shown once for the absolute pain scores, the finding is not relevant. Additionally, the confidence
intervals of the pain differences at the other time points were so far from the equivalence margins
that it is doubtful that a larger sample size would have changed the results.
Postoperative pain is due to nerves traumatised by perioperative injury or compression, constricting
sutures, or postoperative fibrotic tissue.143;144 In study II, pain from other steps of the caesarean
section may have overshadowed the pain caused by the fascial opening. For example, the fascia is
closed with a tight suture, which may cause pain. The clear lack of pain differences between the two
techniques could be because the pain from the fascial incision is overshadowed by pain from other
surgical steps. And therefore pain would probably not have been the appropriate primary outcome
in a study comparing fascial incision techniques after all.
Pain is a multifactorial experience associated with previous pain, acute postoperative pain, the
individual perception of pain, and preoperative anxiety.145 However, the study design in which each
patient served as her own control should control for these confounders.

Apart from pain, the long-term consequences of the two techniques to incise the fascia were not
explored in study II. However, an interesting long-term consequence of the two techniques would
be the extent of scar tissue evaluated during a consecutive caesarean section.

In conclusion, we found no difference in patient preference for blunt opening by manual traction or
sharp incision with scissors or any differences in pain scores after either technique up to 3 months
postoperatively.
Several studies have compared groups of caesarean procedures for abdominal incision without
differentiating between the individual steps. We recommend that studies be performed that evaluate
the individual surgical steps and their long-term consequences.

Randomised controlled trial in which each participant is his/her own control


The study design in which each case serves as her own control was statistically tested in study I.
The significance of interpersonal variation in the objective VAS scoring was analysed by
comparing the sample variance of the differences between the cosmetic VAS scores on the two

27
Discussion

sides with the sum of variances of the two VAS scores. The sample variance was significantly
reduced, thus showing that matching substantially reduces the influence of confounders. We
concluded that the design is suitable for trials of surgical techniques. Especially trials with cosmetic
outcomes could benefit from the trial design due to the elimination of interpersonal variation
confounding the outcome measure.
The study design has further advantages that need mentioning. Both study I and study II had a large
proportion of screened participants who declined to participate (inclusion bias) (study I: 50%, study
II: 62%) as well as a number of different surgeons performing the procedures (study I: n = 15; study
II: n = 14). However, the effect of these factors on the study outcome is limited by the study design
in which each patient is her own control.

There are some statistical limitations in study I and study II that should be addressed. The sample
size calculation was not directly related to the analysis of the primary outcome. The sample size
calculation was performed during the planning of the study to get an estimate of the number of
participants needed to find one participant with a side
preference. When the results were analysed, we found a
significant difference regarding preference of method in
the initial study (study I), showing that more patients had
a preference than first expected. Had an alternative
power calculation matching the analysis of the primary
outcome been reported in the final manuscripts (different
from the one described in the protocol) it would have
been fraudulent. Additionally, it would not have changed
the results of the trials.
A sample size estimation matching the final analysis of
the results would have been based on the null hypothesis
that the proportion preferring one technique is equal to Figure 11. Sample size estimation based
on the null hypothesis that the proportion
the proportion preferring the other technique. If it is preferring one technique is equal to the
proportion preferring the other technique
considered clinically significant when more than 2/3 with when it is considered clinically significant
a preference prefer one technique, approximately 140 when more than 2/3 with a preference
prefer one technique, 50% of the
participants would be needed to reach a statistical power participants have no preference, and each
patient is her own control.
of 80%, with a significance level of 0.05 (Figure 11).

28
Discussion

The estimate is for a study in which 50% of the participants have no preference (as was the case for
the primary and cosmetic outcomes in study I), and in which each patient is her own control. This
sample size estimation is suitable when the objective of the study is to show superiority of one
technique over the other, as was the case in both study I and study II (stated in the respective
protocols). If the purpose of the trials had been to show whether the techniques were equal or not,
the sample size for testing equivalence should have been estimated. With an equivalent proportion
of 50%, 160 participants would be needed to show equivalence if the lower and upper equivalence
bounds are 33% and 66% respectively, the statistical power 80%, the significance level 0.05, and
50% of the participants have no preference.
The objective of both study I and study II was to show superiority of patient preference of one
technique over the other rather than equality or non-equality. However, if the primary outcomes of
studies I and II are analysed according to a hypothesis of testing equivalence post-hoc, both studies
show non-equivalence. In study I, equivalence cannot be established for the primary outcome (of
the patients with a preference 72% [90% CI 5684%] [95% CI 5386%] preferred the stapled side
and 28% [90% CI 1644%] [95% CI 1447%]
A
preferred the sutured side), because the 90%
confidence intervals are not within the 33% and 0% 33% 50% 66% 100%

66% limits (Figure 12B). And since the 95%


confidence intervals include one of these limits, Preference for sutures Preference for staples
(95% CI) (95% CI)
a significant superiority of one technique over B

the other cannot be established either according


0% 33% 50% 66% 100%
to the stated equivalence bounds. However, this
is probably due to lack of power in accordance
Preference for blunt Preference for sharp
with the previous sample size calculation. And, C side (95% CI) side (95% CI)

according to the superiority theory, staples are


0% 33% 50% 66% 100%
significantly superior because the 95%
confidence intervals do not include the 50%
Figure 12. Proportions of participants preferring the
limit and the confidence intervals of the two techniques tested in studies I & II. A) Illustration of
percentage axis, where brackets indicate the
preferences do not overlap. In study II, equivalence bounds of 33% and 66%. B) Proportion of
participant preferring staples (red) and subcuticular
equivalence cannot be established either (of the sutures (green) in study I. C) Proportion of
patients with a preference 44% [90% CI 23 participants preferring sharp (red) and blunt (green)
opening of the fascia in study II. The coloured lines
67%] [95% CI 2070%] preferred the blunt side indicate the proportion with 95% confidence intervals
(CI).

29
Discussion

and 56% [90% CI 3377%] [95% CI 3080%] preferred the sharp side) (Figure 12C). Neither can a
significant difference be established, since the 95% confidence intervals overlap each other and the
50% limit. However, the confidence intervals are extremely large because of a lack of power.

It may be questioned whether study I and study II were randomised trials or cohort studies. Since
the studies compare two surgical techniques in a randomised design where the patients were
randomised to side distribution of the two techniques (technique 1 right and technique 2 left, or
technique 2 right and technique 1 left) the authors contend that the studies were randomised. (Please
refer to the description of randomised controlled trials on pg. 1113).

Incisional hernia
The cumulated risk of developing an incisional hernia requiring repair within 10 years after a
caesarean section was 0.197% in study III. Most hernias were in midline incisions in a population in
which the transverse incision was the primary approach at caesarean section.

The data for study III were obtained from the Danish National Patient Register and the Danish
Medical Birth Register, and hernia repairs were identified by their surgical codes. Neither the
surgical repair codes nor the diagnostic hernia codes include the anatomical location of the hernia,
and we therefore had to validate the cases of hernia repair. We did not use the diagnostic hernia
codes because the validity of the diagnostic codes in the registries have been shown to be
poor.146;147 And since the codes do not include information about the anatomical location of the
hernia, rigorous validation would be needed and the risk of a false estimate would be great. For the
same reason we planned to exclude women with previous abdominal surgery from our cohort. The
risk of incisional hernia is known to be higher among midline incisions, which are commonly used
in major abdominal surgery. A search of all hernia repairs without exclusion of women with
previous abdominal surgery would have given a high rate of repairs unrelated to a previous
caesarean section and thus a risk of false risk estimation because many records were not available
and missing records caused the case to be maintained in the cohort. However, it is unlikely the
incidence of hernia repairs of caesarean section hernias is different in the excluded group compared
with our cohort, and thus exclusion of these women should not have affected our results.

30
Discussion

Through validation, we found that the hernia repairs identified in this study were of hernias in both
midline and transverse incisions and that more than half of them were of hernias in midline
incisions. Unfortunately, the distribution of the two types of incisions in Denmark in the 1990s is
unknown, although the transverse incision was the incision of choice. This is the primary limitation
of our study, which prevented us from estimating the risk of hernia repair in the two types of
incisions separately. Instead, we gave an estimate of the risk in a population where the transverse
incision was the primary approach. As an alternative approach, the study could have been set up as
a case-control study, where the number of herniotomies in each type of incision was related to the
distribution of the incisions in a matched control group. The control group would consist of women
who had had a caesarean section during the same period, and in whom the number of previous
caesarean sections and the hospital where the caesarean section was done matched that of the hernia
repair group. The control group would have a size 3 to 4 times that of the population with a
confirmed hernia repair. A case-control study would have given an odds ratio of the risk of
herniation in the two types of incisions. However, it is known that the risk of developing a hernia in
a midline compared with a transverse incision is increased, with ORs of 1.68 to 3.33.148;149 Ideally, a
case-control study could also provide information about possible risk factors such as BMI and post-
operative infection. Unfortunately, during the validation of this study we learned that records were
not of a quality to provide this information. Therefore a case-control study would probably only add
information about risk differences due to incision type.

Several different caesarean section Inclusion period

surgical techniques may predispose to


1991 CS CS 2000
incisional hernia. As previously 10 years of
follow-up Emigration
mentioned, the risk of herniation is
10 years
higher in a midline compared to a lower after last CS
Hernia repair

transverse abdominal incision. CS after 2000

Additionally, in midline incisions the Abdominal


surgery
suture technique and material for closure
Death
of the fascia have been shown to affect
the risk of incisional hernia, which Figure 13. Timeline illustrating the inclusion period, competing
events, censoring event, and follow-up time in study III. CS:
might also be the case in lower Caesarean section. Censoring event.
Competing event.
transverse incisions.56;57 Unfortunately,

31
Discussion

this study could not provide data about fascial closure techniques due to missing registration in the
available caesarean section records.

The risk of hernia repair after a caesarean section was estimated with a competing risk analysis. A
competing risk analysis is suitable for prognostic research questions of probability over time.150 The
risk of hernitomy was 0.20%, accounting for the fact that other risks may modify a womans risk of
hernia repair related to a previous caesarean section. These competing risks were death, abdominal
surgery, and a consecutive caesarean section (Figure 13). Thus, the risk of hernia repair was 0.20%,
accounting for the fact that 0.32% die, 26.05% have a consecutive caesarean section, and 23.30%
have abdominal surgery within 10 years of the last caesarean section in the inclusion period (Table
1). Cases with competing events stay in the risk set. (Figure 14A). Had the risk been estimated with
a classic Kaplan-Meier survival analysis, then the competing events would have been censored,
causing the cases to be completely excluded from the

A risk set at the time of the event (Figure 14B) This


Risk analysis

Competing would have given a higher risk estimate which is the


Person 2 event
risk of hernia repair if nothing else happens to the
Person 1 woman.151 That is, the Kaplan-Meier risk estimate
Death

does not account for the fact that other events can

Time
occur that need to be considered to give an actual
risk estimate. In the competing risk analysis in study
B Risk analysis
III, emigration caused censoring, and patients who
Censorin
Person 2 g event had emigrated were thus not counted at follow-up
time. Cases lost due to emigration are still at the
Person 1
Death
same risk of hernia repair as the remaining cases in
contrast to cases with competing events, but cannot
Time
be included in the risk estimation due to lack of
Figure 14. An illustration of how competing information.
events and censoring events affect a risk
estimation. A) In a cohort of two people where The risk of hernia repair was estimated for each
one person has a competing event during follow-
up and the other person dies, the death rate is caesarean section as a result of the search strategy.
50%. Cases with competing events stay in the
risk set. B) In a cohort of two people where one An estimation of the risk per woman would have
person is censored during follow-up and the required a cohort of women included and followed
other person dies, the death rate at assessment is
100%. Censored cases are excluded from the from their first caesarean section. This would have
risk set.

32
Discussion

given us a smaller cohort if the inclusion period had been the same and thus even fewer cases of
the rare outcome. The risk per woman cannot be estimated post-hoc either since our dataset did not
include information about previous caesarean sections before the inclusion period or the number of
the caesarean sections performed during the inclusion period.

In conclusion, we found an overall risk of incisional hernia requiring surgical repair within 10 years
after a caesarean section of 2 per 1000 caesarean sections in a population in which the transverse
incision was the primary approach at caesarean section.

Table 1. Cumulative incidence of incisional hernias requiring herniotomy as well as the competing events 1, 3, and
10 years after a caesarean section in study III. Data are expressed as % (95% confidence interval).

1 year 3 years 10 years


Herniotomy 0.072 (0.0520.092) 0.157 (0.1270.187) 0.197 (0.1640.231)
Abdominal surgery 3.879 (3.7344.024) 9.593 (9.3729.814) 23.295 (22.97623.613)
Death 0.048 (0.0320.065) 0.113 (0.0880.138) 0.315 (0.2730.357)
Caesarean section 0.203 (0.1690.236) 11.250 (11.01311.488) 26.049 (25.71826.380)

33
Conclusions

Conclusions
The studies on which this thesis is based explore surgical techniques to open the fascia and close the
skin at caesarean section as well as the long-term risk of incisional hernia requiring surgical repair
after caesarean section. The two randomised trials used a study design in which each patient was
her own control.

Several studies have compared groups of caesarean procedures for abdominal incision without
differentiating between the individual steps. We recommend future studies of the individual surgical
steps in order to optimise the techniques.

In the evaluation of skin closure techniques for caesarean section, both objective and subjective
measures have to be considered. We found subjective and cosmetic outcomes in favour of staples,
whereas meta-analyses of previous studies found the rate of separation increased by the use of
staples. Future studies need to explore the influence of removal time of staples on separation,
infection, and long-term cosmetic outcomes; to grade the severity of separation and explore the
various consequences; and to study outcomes in women with higher BMIs.

In the evaluation of techniques to incise the fascia, we found no difference in patient preference for
blunt opening by manual traction or sharp incision with scissors, or any differences in pain scores
after either technique up to 3 months postoperatively. Increasing the power of the study by
including more women would probably not have changed this outcome.

In the evaluation of the study design in which each patient served as her own control, we showed
that the design substantially reduces the influence of confounders. The design is rarely implemented
but suitable for trials of surgical techniques.

Caesarean section may have several long-term consequences for the mother. We found that the risk
of having an incisional hernia requiring repair within 10 years of a caesarean section was 2 per 1000
caesarean sections. Most hernias were in midline incisions in a population in which the transverse
incision was the primary approach at caesarean section. Consequently, the risk of developing a
hernia in a transverse caesarean section incision requiring repair following current surgical
recommendations is very low.

34
Clinical Recommendations

Clinical Recommendations
For skin closure at caesarean section both staples and sutures can be recommended at the discretion
of the surgeon and the patient. Other skin closure techniques have been proposed and may be used.

For fascial opening, both sharp opening with scissors and blunt opening with manual traction can be
recommended at the discretion of the surgeon.

The risk of incisional hernia after caesarean section is low. However, a continuous suture with a
suture material that is slowly absorbable reduces the risk of incisional hernia in midline incisions
and might be used for closure of the fascia in lower transverse incisions.

35
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46
Acknowledgements

Acknowledgements
The work of this PhD thesis has only been possible thanks to the support from numerous people.

First I would like to thank my academic advisors Lone Krebs and Niels Jrgen Secher for their
continuous support and prompt replies in every matter. They introduced me to research, believed in
me and the projects, and have challenged me professionally:
Niels Jrgen Secher, the man of the many ideas, fostered the ideas of the trials and the study
design in which each patient is her own control. It has been very inspiring working with you, and I
hope we can continue our collaboration.
Lone Krebs has been my daily, dependable advisor next door. Thank you for your continuous,
steady, and thorough support all through the years. You have led me into the world of Danish
obstetrics and fostered many ideas beyond this thesis. I hope we will continue collaborating both
clinically and in future research.

Torben Larsen, head of the Department of Obstetrics and Gynaecology, University of


Copenhagen, Holbk Hospital 20062014. Thank you for giving me the opportunity to do research
in the department, and for believing in me and the projects from the very beginning.

I wish to extend a great thank you to the doctors, midwives, and secretaries at the Department of
Obstetrics and Gynaecology, University of Copenhagen, Holbk Hospital, for their assistance
with the surgeries, outcome assessment, and practical management in study I. The study had not
been possible without your help.

A special thank you to Christian Kragh, MD, DMSc, and Camilla Asklund, MD, PhD,
Department of Plastic Surgery, Herlev University Hospital, for their thorough and excellent
evaluation of the scars in study I.

Thank you to the doctors at Hvidovre University Hospital, who operated the included patients in
study II according to randomization. And to secretary Mette Krll for her dependable assistance in
the study.

Statisticians Christian Pipper, the department of Biostatistics, University of Copenhagen, and


Steen Ladelund, Clinical Research Center, Hvidovre University Hospital, assisted in the statistical
analyses. Thank you for illustrating the statistical problems, making statistics make sense to me.

47
Acknowledgements

Steen Rasmussen, Hvidovre University Hospital, assisted in the data management of study III.
Thank you for your patience and good humour.

Thank you to all the employees at the hospitals across Denmark who assisted with retrieving
hospital records for study III.

The companionship of all the trainees with whom I have shared the office during the past four years
has been invaluable. A special thanks to my colleagues Dorthe Thisted and Ida Nslund
Thagaard, who I have been able to share and discuss ideas with.

Last but not least, a great sincere thank you to my family, who have supported me through good and
bad times and have always been there for me.

Funding

The research of this PhD thesis was possible thanks to grants from the following institutions:
- Faculty of Health and Medical Sciences, University of Copenhagen.
- The Region Zealand Health Sciences Research Foundation.
- Department Obstetrics and Gynaecology, University of Copenhagen, Holbk Hospital.

48
Appendix

Appendix

Article I
Aabakke AJM, Krebs L, Pipper CB, Secher NJ. Subcuticular Suture Compared with Staples for
Skin Closure After Cesarean Delivery: A Randomized Controlled Trial. Obstet Gynecol
2013;122:878-84.

49
Appendix

Article II
Aabakke AJM, Hare KJ, Krebs L, Secher NJ. Sharp Compared with Blunt Fascial Incision at
Cesarean Delivery: A Randomized Controlled Trial with Each Case as her Own Control. Eur J
Obstet Gynecol Reprod Biol 2014; 172:40-45.

57
Appendix

Article III
Aabakke AJM, Krebs L, Ladelund S, Secher NJ. The Incidence of Incisional Hernia after Cesarean
Delivery: A Register-based Cohort Study. Plos One 2014. (In press).

64

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