Surgical techniques for caesarean section

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

U N I V E R S I T Y O F C O P E N H A G E N

PhD thesis

Anna J. M. Aabakke

Surgical techniques for caesarean section

Short- and long-term consequences

F A C U L T Y O F H E A L T H A N D M E D I C A L S C I E N C E S

U N I V E R S I T Y O F C O P E N H A G E N

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 Jørgen 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, Holbæk Hospital on the 19. September 2014.

Author

Anna J. M. Aabakke, MD

Department of Obstetrics and Gynaecology

University of Copenhagen, Holbæk Hospital

Institute for Gynaecology, Obstetrics and Paediatrics

Faculty of Health and Medical Sciences

University of Copenhagen

Academic advisors

Associate Professor Lone Krebs, MD, DMSC


University of Copenhagen, Holbæk Hospital, Denmark

Honorary Professor Niels Jørgen Secher, MD

Faculty of Health

Aarhus University, Denmark

The Research Unit Women’s and Children’s Health

The Juliane Marie Center

Copenhagen University Hospital, Denmark

Assessment Committee

Associate Professor Thomas Bergholt, MD, PhD (Chairperson)


University of Copenhagen, Hillerød Hospital, Denmark

Department Clinical Medicine

University of Copenhagen, Denmark

Professor Per Olofsson, MD, PhD, BSc


Skåne University Hospital, Sweden

Professor Philip J. Steer, BSc, MD, FRCOG


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 woman’s

obstetrical future is prejudice by the uterine

scar be forgotten.”

Dyre Trolle, 19821

I

Contents

PREFACE ........................................................................................................................... III

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

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

DANSK RESUMÉ (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

II

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

Preface

III

Preface

This PhD thesis was conducted during my employment at the Department of Obstetrics and

Gynaecology, University of Copenhagen, Holbæk 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.

English Summary

IV

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.

English Summary

V

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.

Dansk Resumé (Summary in Danish)

VI


Kejsersnit er et hyppigt kirurgisk indgreb som udføres på unge, i øvrigt raske kvinder. Kejsersnit

kan dog have konsekvenser for moderen både på kort og langt sigt, hvilket til dels afhænger 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 på 3 studier om kejsersnit, som undersøger kirurgiske teknikker

til åbning af muskel-fascien og lukning af huden, og estimerer risikoen for senere at udvikle et brok,

der kræver operation.

I afhandlingen indgår 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 undersøgt (teknik A til højre og teknik B til venstre, eller teknik B til højre og teknik A til

venstre). Et sådan design har den fordel, at det reducerer betydningen af forskelle blandt deltagerne

og dermed nedsætter det nødvendige deltagerantal.

I det første studie sammenlignede vi klips med intrakutan selvabsorberende sutur til lukning af

huden efter kejsersnit. Det primære effektmål var patientens foretrukne side af arret 6 måneder efter

operationen. Øvrige effektmål var forskellen mellem de objektive kosmetiske vurderinger af de to

sider af arret, som blev udført 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 både 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.

Både 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 højere ved brug af klips.

Der mangler fortsat viden om, hvorledes tidspunktet for fjernelse af klips påvirker forekomsten af

spaltning, infektion og det langsigtede kosmetiske resultat. Desuden bør fremtidlige studier

klassificere graden af spaltning og vurdere den langsigtede konsekvens af spaltning, samt omfatte

kvinder med højt BMI.


VII

I det andet studie sammenlignede vi to metoder til åbning af fascien ved kejsersnit - skarp incision

med saks og stump spaltning med fingrene. Det primære effektmål var patientens overordnet

foretrukne side af arret 3 måneder efter operationen. Det sekundære effektmål var forskelle i

oplevelsen af smerte imellem de to sider af arret. Studiet viste ingen forskel imellem de to

operationsmetoder postoperativt eller ved opfølning efter 3 måneder.

Et studiedesign, hvor patienten fungerer som sin egen kontrol, anvendes sjældent. Vi viste i studie I,

at designet signifikant reducerede variansen i de objektive kosmetiske scores og således at designet

reducerede betydningen af confoundere. Designet er velegnet til randomiserede studier af kirurgiske

teknikker, og især til studier med kosmetiske effektmål.

Det tredje studie er et register-baseret kohorte studie, hvor vi estimerede forekomsten af brok i

kejsersnitar, som krævede operation indenfor 10 år efter kejsersnitet. Vi fandt en kumuleret risiko i

vores studiepopulation på 2 pr. 1000 kejsersnit. De fleste af de kvinder, der udviklede

operationskrævende brok, havde fået foretaget kejsersnit gennem en midtlinjeincision i en periode,

hvor det var almindelig procedure at foretage kejsernit gennem tværsnit. Vi konkludererde derfor, at

risikoen for at udvikle et brok efter kejsersnit er uhyre lav, når kejsersnit udføres i henhold til

aktuelle anbefalinger.

Abbreviations

VIII

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

Introduction

1

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 Rousset’s 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

prevent overuse of caesarean sections.17

In Figure 1. Caesarean section rates in Denmark 1997–

2012.16

CS: Caesarean section.

Introduction

2

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.

Skin

Preperitoneal fat

Parietal peritoneum

Visceral peritoneum

Myometrium

Amniotic fluid

Fetus

Subcutaneous fat

Fascia

Rectus muscle

Figure 2. Transverse

section of the abdomen at

the level where the

caesarean section is done,

illustrating the anatomical

layers of the abdomen.

Drawing by Randi Iversen.

Adapted from Figure 17.1

in: Sørensen JL, Ottesen B,

Weber T, editors. Ars

Pariendi - håndgreb og akut

behandling ved fødsler.

København: Munksgaard

Danmark, 2011: 195. With

permission from Jette Led

Sørensen.

Background

3

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 19

th 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

Sänger 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.

Background

4

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

mentioned in the current WHO

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

Figure 3. The advantages of the midline and transverse incisions

for caesarean section. Adapted from Figure 1 in Maaløe et al., Int

J Gynecol Obstet 2014.26

Background

5

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 0.3–3 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

Background

6

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

Background

7

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 ½–1 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 author’s knowledge, no studies had focused solely on

techniques to incise the fascia before the initiation of study II. Additionally, blunt opening of the

Background

8

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 0.1‒0.3%.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 (0.28–0.43%).80;81

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

A B

Background

9

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 0.3–0.6% (3.3–4%

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 1.0–1.5% 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 1.3–1.6).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

caesarean section and

Figure 5. Removal of a placenta percreta after the birth of the baby.

Picture courtesy of the Department of Obstetrics and Gynecology,

Copenhagen University Hospital.

Background

10

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, 4–18% have chronic pain 1 year after caesarean section, and 1–6% have

pain on a daily basis.91-93

The pain interferes with daily activities in 1.4–14%.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 1.7–1.9) 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 24‒46%, 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.

Background

11

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 6–12 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 1½–5 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

Background

12

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

only one intervention.112

In

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 4–10 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


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

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

was randomised to skin closure with staples on the right side and

subcuticular sutures on the left side of the skin incision.

Background

13

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.

Aims

14

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.

Methods

15

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 31–60] 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 women’s 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 women’s 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

Methods

16

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.

Methods

17

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.

Methods

18

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.

Results

19

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 1.18–5.52), 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 1.10–3.64)

(Figure 7). Objectively, the stapled side was cosmetically preferred more frequently (OR 2.8; 95%

CI 1.01–7.78) 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 0.97–9.30; 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 0.99–4.46). There were four (6.8%) cases of infection—

three on the sutured side and one bilaterally. There were four (6.8%) cases of separation—one on

the stapled side and three described as being in the middle of the scar—of 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.

Results

20

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 Ogilvie’s syndrome,

which was treated conservatively.

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.

B A

Results

21

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 29–46%]) in a

transverse incision, and in 16 cases (12% [95% CI 7–19%]) 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 0.164–0.234 %) (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

0.127–0.187 %) (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 0.79‒2.27

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

Discussion

22

Discussion


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.


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

0.92–2.17]; Mackeen et al.: Relative risk (RR) 0.85 [95% CI 0.43–1.71]; 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 2.16–8.34]; Mackeen et al.: RR 3.82 [95% CI 2.05–7.12]; Clay et al.: OR 4.01

[95% CI 2.09–8.00]). 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 0.62–23.00], and Clay et al.: OR 4.00 [95% CI

0.71–22.45]), although this might be due to a lack of power. After completion of study I, an

Discussion

23

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 1.6–9.1],

and OR 5.0 [95% CI 2.0–14.3]),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 2.0–14.3]), 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

Discussion

24

cosmetic outcomes of previous trials.63-

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

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

evident to the investigators that the healing

process was not complete even after 6 months

(Figure 10).

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

staples are more expensive and need to be

removed but take less operating time compared

to subcuticular sutures. Overall the cost is

probably similar. Additionally, the bother for

the patient of an extra appointment for staple

removal has to be considered. In study I, staple

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

Figure 10. Caesarean section scars 6 months

postoperatively from four participants in study I where

staples were compared with subcuticular suture for skin

closure. A) and B) Incisions after a primary caesarean

section. C) and D) Incisions after two previous

caesarean sections. The cosmetic difference between

participants was larger than the cosmetic difference

between the two methods of skin closure in one subject.

Additionally, the majority of the scars were still

erythematous and thus not completely healed after 6

months.

C

D

B

A

Discussion

25

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

Discussion

26

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

Discussion

27

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.


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

Discussion

28

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

the proportion preferring the other technique. If it is

considered clinically significant when more than 2/3 with

a preference prefer one technique, approximately 140

participants would be needed to reach a statistical power

of 80%, with a significance level of 0.05 (Figure 11).

Figure 11. Sample size estimation based

on the null hypothesis that the proportion

preferring one technique is equal to the

proportion preferring the other technique

when it is considered clinically significant

when more than 2/3 with a preference

prefer one technique, 50% of the

participants have no preference, and each

patient is her own control.

Discussion

29

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 56─84%] [95% CI 53─86%] preferred the stapled side

and 28% [90% CI 16─44%] [95% CI 14─47%]

preferred the sutured side), because the 90%

confidence intervals are not within the 33% and

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

confidence intervals include one of these limits,

a significant superiority of one technique over

the other cannot be established either according

to the stated equivalence bounds. However, this

is probably due to lack of power in accordance

with the previous sample size calculation. And,

according to the superiority theory, staples are

significantly superior because the 95%

confidence intervals do not include the 50%

limit and the confidence intervals of the two

preferences do not overlap. In study II,

equivalence cannot be established either (of the

patients with a preference 44% [90% CI 23–

67%] [95% CI 20–70%] preferred the blunt side

33% 66% 0% 50%

0%

0%

Preference for sutures

(95% CI)

Preference for staples

(95% CI)

Preference for sharp

side (95% CI)

Preference for blunt

side (95% CI)

33%

33%

50%

50%

66%

66%

100%

100%

100%

Figure 12. Proportions of participants preferring the

techniques tested in studies I & II. A) Illustration of

percentage axis, where brackets indicate the

equivalence bounds of 33% and 66%. B) Proportion of

participant preferring staples (red) and subcuticular

sutures (green) in study I. C) Proportion of

participants preferring sharp (red) and blunt (green)

opening of the fascia in study II. The coloured lines

indicate the proportion with 95% confidence intervals

(CI).

A

B

C

Discussion

30

and 56% [90% CI 33–77%] [95% CI 30–80%] 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. 11–13).

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.

Discussion

31

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

surgical techniques may predispose to

incisional hernia. As previously

mentioned, the risk of herniation is

higher in a midline compared to a lower

transverse abdominal incision.

Additionally, in midline incisions the

suture technique and material for closure

of the fascia have been shown to affect

the risk of incisional hernia, which

might also be the case in lower

transverse incisions.56;57

Unfortunately,

Emigration

Hernia repair

CS after 2000

Abdominal

surgery

Death

10 years

after last CS

1991 2000 CS

Inclusion period

10 years of

follow-up

Figure 13. Timeline illustrating the inclusion period, competing

events, censoring event, and follow-up time in study III. CS:

Caesarean section. Censoring event.

Competing event.

CS

Discussion

32

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 woman’s 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

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

would have given a higher risk estimate which is the

risk of hernia repair if nothing else happens to the

woman.151

That is, the Kaplan-Meier risk estimate

does not account for the fact that other events can

occur that need to be considered to give an actual

risk estimate. In the competing risk analysis in study

III, emigration caused censoring, and patients who

had emigrated were thus not counted at follow-up

time. Cases lost due to emigration are still at the

same risk of hernia repair as the remaining cases in

contrast to cases with competing events, but cannot

be included in the risk estimation due to lack of

information.

The risk of hernia repair was estimated for each

caesarean section as a result of the search strategy.

An estimation of the risk per woman would have

required a cohort of women included and followed

from their first caesarean section. This would have

Competing

event

Death

Time

Person 2

Person 1

Risk analysis A

Censorin

g event

Death

Person 2

Person 1

Risk analysis B

Time

Figure 14. An illustration of how competing

events and censoring events affect a risk

estimation. A) In a cohort of two people where

one person has a competing event during follow-

up and the other person dies, the death rate is

50%. Cases with competing events stay in the

risk set. B) In a cohort of two people where one

person is censored during follow-up and the

other person dies, the death rate at assessment is

100%. Censored cases are excluded from the

risk set.

Discussion

33

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.

1 year 3 years 10 years

Herniotomy 0.072 (0.052‒0.092) 0.157 (0.127‒0.187) 0.197 (0.164‒0.231)

Abdominal surgery 3.879 (3.734‒4.024) 9.593 (9.372‒9.814) 23.295 (22.976‒23.613)

Death 0.048 (0.032‒0.065) 0.113 (0.088‒0.138) 0.315 (0.273‒0.357)

Caesarean section 0.203 (0.169‒0.236) 11.250 (11.013‒11.488) 26.049 (25.718‒26.380)

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).

Conclusions

34

Conclusions


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.


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.

Clinical Recommendations

35

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.

References

36

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Acknowledgements

47

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 Jørgen 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 Jørgen 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, Holbæk Hospital 2006–2014. 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, Holbæk 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 Krøll 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.

Acknowledgements

48

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 Näslund

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, Holbæk Hospital.

Appendix

49

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.

Appendix

57

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.

Appendix

64

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).

Surgical techniques for caesarean section

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