Cesarea bjog

Caesarean section surgical techniques: a
randomised factorial trial (CAESAR)*
The CAESAR study collaborative group
Correspondence: Professor P Brocklehurst, National Perinatal Epidemiology Unit, University of Oxford, Headington, Oxford OX3 7LF, UK.
Email peter.brocklehurst@npeu.ox.ac.uk
Accepted 27 June 2010.
Objective In women undergoing delivery by caesarean section, do
the following alternative surgical techniques affect the risk of
adverse outcomes: single- versus double-layer closure of the
uterine incision; closure versus nonclosure of the pelvic
peritoneum; liberal versus restricted use of a subrectus sheath
drain?
Design Pragmatic, 2 · 2 · 2 factorial randomised controlled trial.
Setting Hospitals in the UK and Italy providing intrapartum care.
Population Women undergoing their first caesarean section.
Methods The interventions were alternative approaches to the
three aspects of the caesarean section operation. A telephone
randomisation service was used. Surgeons could not be masked
to allocation, but women were unaware of which allocations had
been used. The analysis was by intention-to-treat, with a
prespecified subgroup analysis for women ‘in labour’ or ‘not
in labour’ at the time of caesarean section.
Main outcome measures Maternal infectious morbidity.
Results A total of 3033 women were recruited. Overall, the risk of
maternal infectious morbidity was 17%. For each pair of
interventions, there were no differences between the arms of the
trial for the primary outcome: single- versus double-layer closure
of the uterine incision [relative risk (RR) = 1.00, 95% confidence
interval (95% CI) = 0.85–1.18]; closure versus nonclosure of the
pelvic peritoneum (RR = 0.92, 95% CI = 0.78–1.08); liberal
versus restricted use of a subrectus sheath drain (RR = 0.92,
95% CI = 0.78–1.09). There were no differences in any of the
secondary morbidity outcomes and no significant adverse effects
of any of the techniques used.
Conclusions These results have implications for clinical practice,
particularly in relation to current guidance on the closure of the
peritoneum, which suggests that nonclosure is preferable. The
potential effects of these different surgical techniques on longer
term outcomes, including the functional integrity of the uterine
scar during subsequent pregnancies, are now becoming
increasingly important for guiding clinical practice.
Keywords Caesarean section, randomised controlled trial.
Please cite this paper as: The CAESAR study collaborative group. Caesarean section surgical techniques: a randomised factorial trial (CAESAR).
BJOG 2010;117:1366–1376.
Introduction
Caesarean section is one of the most common operations
undertaken worldwide. In Latin America, the median rate
of caesarean delivery is 33%.1
The global rate of caesarean
section is not known, but, if it is 10%, 13 million caesarean
sections are performed each year, equivalent to 24 each
minute.
The surgical techniques used at caesarean section vary
between surgeons, and few of these techniques have been
evaluated in randomised controlled trials. The existing
trials have been reviewed and, of 44 technical aspects of the
operation, six had ‘good evidence’ and three had ‘fair
evidence’ to make clear recommendations about their use.2
A survey of practice in the UK in 1999 asked obstetri-
cians to nominate aspects of the caesarean section opera-
tion that they would like to see evaluated in a randomised
trial.3
This report contains the outcome of this trial.
Methods
The CAESAR study was a pragmatic, 2 · 2 · 2 factorial,
multicentre, randomised controlled trial, designed to evalu-
ate two alternative approaches to three aspects of the tech-
nique of caesarean section.
* Trial registration number: ISRCTN 11849611.
The Caesar study collaborative group are listed in the Acknowledgements
section.
1366 ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology
DOI: 10.1111/j.1471-0528.2010.02686.x
www.bjog.org
General obstetrics

The trial assessed the following null hypotheses. In
women undergoing delivery by caesarean section, no differ-
ences would be detected with respect to maternal infectious
morbidity when comparing the following three pairs of
alternative surgical techniques: single- versus double-layer
closure of the uterine incision; closure versus nonclosure
of the pelvic peritoneum; liberal versus restricted use of a
subrectus sheath drain.
Women were eligible if they were undergoing delivery by
their first caesarean section, this was planned to be per-
formed through the lower uterine segment and there was
no clear indication for any particular technique to be used.
The only contraindication to participation was an age of
<16 years.
All women provided written informed consent. A tele-
phone randomisation service was employed to allocate the
interventions using a minimisation algorithm to ensure
comparability between women with respect to three
prognostic factors: participating centre; ‘in labour’ or ‘not
in labour’; single or multiple pregnancy. Participants were
enrolled by the clinicians providing care for women about
to undergo their caesarean section. The allocation provided
by the randomisation service was made available to the
operating surgeon prior to the onset of surgery.
Details of the clinical management used are described
in the CAESAR study protocol (www.npeu.ox.ac.uk/trials/
CAESAR). In summary, the trial interventions were as
follows.
1 Single- versus double-layer uterine closure. Single-layer
closure involves bringing both edges of the uterine inci-
sion together with a single layer of sutures. In double-layer
closure, the uterine incision is closed with two layers of
sutures. The first layer opposes the endometrial aspect of
the uterine muscle layer and the second brings together
the serosal layer.
2 Closure of the peritoneum. This refers to closure of the
pelvic peritoneum (the layer of peritoneum overlying the
uterine incision).
3 Liberal versus restricted use of a subsheath drain. We
recognised that clinicians would feel uncomfortable
using a subsheath drain if the abdominal wound had
excellent haemostasis. Similarly, if the wound continued
to ooze following appropriate haemostatis procedures,
clinicians would use a drain. Hence, the intervention
was to liberal or restricted use of the drain.
All nonallocated surgical elements and all other aspects
of the caesarean section procedure were performed at the
discretion of the surgeon. In particular, there were no
restrictions on the type of suture material that could be
used, and standard measures to effect haemostasis were
employed regardless of the allocated intervention. Each
participating centre initiated and maintained a training and
accreditation programme which ensured that all personnel
involved in undertaking caesarean sections were competent
in the techniques being compared before they were able to
recruit women into the trial. During the training, it was
made clear that obstetricians should not vary other aspects
of their surgical approach depending on the allocation. For
example, regardless of whether the woman was allocated
single- or double-layer uterine closure, the suture material
used should be the same.
The following outcomes were collected from all women
participating in the trial up to the time of the 6-week
follow-up assessment after the caesarean section. The pri-
mary outcome was maternal infectious morbidity, defined
as having one or more of the following: (i) antibiotic use
for maternal febrile morbidity during the postnatal hospital
stay; (ii) endometritis; (iii) wound infection treated with
antibiotics. Although not all the trial interventions might be
expected to affect all components of the primary outcome
equally, factorial trials have largely used a single primary
outcome for all of the factorial components. It was antici-
pated that each of the trial interventions would be expected
to contribute to a substantial part of the composite primary
outcome, making it justifiable to have a composite consist-
ing of these aspects of infectious morbidity. For example,
the use of a subsheath drain may be expected to make a
greater difference than single- versus double-layer closure of
the uterus to the risk of wound infection, but single- versus
double-layer closure of the uterus may be expected to make
a greater difference to the risk of endometritis.
Secondary outcomes included the individual components
of the primary outcome, as well as further operative proce-
dures on the wound, pain, blood transfusion, breastfeeding
at hospital discharge and at 6 weeks, and other severe or
unexpected maternal morbidity.
Sample size
In a meta-analysis of 68 trials of antibiotic prophylaxis at
caesarean section involving over 10 000 women, the inci-
dence of febrile morbidity/endometritis in the antibiotic
prophylaxis group was 13%.4
Prior to the start of the trial,
we therefore anticipated that the incidence of antibiotic use
for febrile morbidity would be approximately 12%. This
combined primary outcome of febrile morbidity/endome-
tritis was defined as either any antibiotics prescribed as
treatment for maternal fever (temperature of >39°C on any
occasion or >38°C on two or more successive days. Anti-
biotics prescribed for prophylaxis, such as those given for
Group B streptococcus carriage, were not included), or any
clinical diagnosis of endometritis made in hospital, which
was treated with antibiotics within 6 weeks of the caesarean
section.
A sample size of 3500 women was therefore necessary
to demonstrate a change in the incidence of the primary
Caesarean section surgical techniques: a randomised factorial trial
ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology 1367

outcome between any pair of arms from 12% to 9%, with
80% power and a two-sided significance level of 5%. The
sample size estimation was based on the detection of differ-
ences in the main effects of the interventions and not the
interactions between them.
Data analysis
Data were collected from the hospital notes up to the time
of hospital discharge. Women were then sent a question-
naire to complete 6 weeks after the date of caesarean sec-
tion. In this questionnaire, they were asked to record
whether antibiotics or additional painkillers had been pre-
scribed during the postnatal period and, if so, to give the
reason. Responses were coded by two clinicians (PB and
EA), independently, without knowledge of the trial alloca-
tion.
Patients were analysed in the groups to which they were
assigned, regardless of deviation from the protocol or treat-
ment received. Comparative statistical analysis entailed the
calculation of the relative risk (RR) plus the 95% confi-
dence interval (95% CI) for the primary outcome and 99%
CI for the secondary outcomes to take account of multiple
comparisons. Pairwise interactions between the different
interventions were examined. Most of the results are pre-
sented using the numbers allocated to each pair of inter-
ventions including all those allocated, irrespective of
allocation to the other pairs of interventions (i.e. the six
margins of the 2 · 2 · 2 table).5,6
In addition, three pre-
specified subgroup analyses were intended, based on the
primary and key secondary outcomes, stratified by ‘in
labour’ or ‘not in labour’ caesarean section, single and
multiple pregnancy and compliance with the subsheath
drain comparison by quartile of compliance.
An independent Data Monitoring and Ethics Committee
(DMEC) monitored the effectiveness and safety on a regular
basis (at least annually). DMEC employed the Haybittle–Peto
approach for interim analyses using three standard errors as
the cut-off for early cessation, preserving the type I error rate
across the trial.7
Research ethics committee approval
The trial sponsor was the University of Oxford. Multicentre
Research Ethics Committee approval for the trial was given
by the Eastern MREC (99/5/62), and all participants gave
informed consent to participate. The trial was registered
(ISRCTN number 11849611).
Role of the funding source
The trial was funded by the NHS South East Region
Research and Development Office. The funding source had
Figure 1. Randomisation and follow-up of study participants. CS, caesarean section; IQR, interquartile range.
CAESAR study collaborative group

no role in the study design, the collection and interpreta-
tion of the data, writing of the report, or decision to sub-
mit the paper for publication.
Results
Between November 2000 and June 2006, 3033 women were
randomised into the study in 45 UK and two Italian cen-
tres. Two centres elected to participate in two rather than
all three of the pairs of alternative interventions; hence, the
denominator for the pairs of interventions varies slightly.
The total population recruited was less than originally
anticipated. The recruitment period lasted for 5 years and
7 months. This lower than anticipated recruitment rate was
a consequence of the training and accreditation pro-
gramme. The recruitment period was 32 months longer
than planned and the combination of a lack of funding
and trial fatigue led the Trial Steering Committee (TSC) to
recommend premature closure at approximately 3000
women. Assuming that the primary outcome would be
observed in 12% of women, a trial of 3000 women would
allow us to detect an RR reduction of 27% with 80%
Table 1. Description of women at trial entry*
Uterine closure Closure of pelvic peritoneum Subrectus sheath drain
Single layer
n (%)
1483 (100)
Double layer
n (%)
1496 (100)
Closed
n (%)
1496 (100)
Not closed
n (%)
1499 (100)
Liberal
n (%)
1398 (100)
Restricted
n (%)
1398 (100)
Mean age [SD] 30.6 [5.9] 30.6 [5.9] 30.7 [5.9] 30.6 [6.0] 30.7 [6.0] 30.5 [5.8]
Single/multiple pregnancy
Singleton 1404 (95) 1420 (95) 1420 (95) 1420 (95) 1326 (95) 1325 (95)
Twin 78 (5) 75 (5) 75 (5) 78 (5) 71 (5) 73 (5)
Triplet or higher order 1 (0) 1 (0) 1 (0) 1 (0) 1 (0) 0 (0)
Gestation at entry
‡37 weeks 1334 (90) 1364 (91) 1355 (91) 1358 (91) 1279 (91) 1259 (90)
‡35 to <37 weeks 100 (7) 88 (6) 92 (6) 97 (6) 83 (6) 96 (7)
<34 weeks 35 (2) 29 (2) 36 (2) 28 (2) 27 (2) 27 (2)
Mean [SD] 39.0 [2.0] 39.1 [1.9] 39.0 [2.0] 39.1 [1.9] 39.1 [1.9] 39.0 [1.9]
Median {IQR} 39.0 {38.3–40.1} 39.0 {38.3–40.4} 39.0 {38.3–40.3} 39.0 {38.3–40.4} 39.0 {38.3–40.3} 39.0 {38.3–40.3}
Parity
Primiparous 989 (67) 1027 (69) 1005 (67) 1026 (68) 957 (68) 939 (67)
Multiparous 480 (32) 460 (31) 480 (32) 461 (31) 435 (31) 446 (32)
Caesarean section carried out
In labour 490 (33) 511 (34) 496 (33) 506 (34) 455 (33) 452 (32)
Not in labour 993 (67) 985 (66) 1000 (67) 993 (66) 943 (68) 946 (68)
Ruptured membranes 495 (33) 514 (34) 510 (34) 502 (33) 456 (33) 464 (33)
Unsure 3 (0) 8 (1) 5 (0) 6 (0) 4 (0) 7 (1)
Duration of labour
<6 hours 149 (10) 166 (11) 153 (10) 162 (11) 133 (10) 151 (11)
6–12 hours 152 (10) 175 (12) 160 (11) 169 (11) 139 (10) 157 (11)
>12 hours 163 (11) 160 (11) 166 (11) 156 (10) 169 (12) 129 (9)
No labour 993 (67) 985 (66) 1000 (67) 993 (66) 943 (67) 939 (67)
Indication for caesarean section
Breech 538 (36) 554 (37) 543 (36) 561 (37) 511 (37) 521 (37)
Failure to progress 236 (16) 250 (17) 240 (16) 246 (16) 235 (17) 200 (14)
AN or IP compromise 196 (13) 193 (13) 203 (14) 188 (13) 172 (12) 185 (13)
AN complications 142 (10) 135 (9) 160 (11) 117 (8) 135 (10) 128 (9)
Past obstetric history 100 (7) 105 (7) 102 (7) 103 (7) 101 (7) 96 (7)
Past medical history 54 (4) 52 (3) 45 (3) 61 (4) 52 (4) 49 (4)
Maternal request 77 (5) 79 (5) 72 (5) 85 (6) 73 (5) 79 (6)
Abnormal presentation 7 (0) 10 (1) 9 (1) 8 (1) 10 (1) 6 (0)
Other 118 (8) 108 (7) 112 (7) 115 (8) 102 (7) 119 (9)
AN, Antenatal; IP, Intrapartum.
*Less than 1% of data missing for each item.

power (rather than an RR reduction of 25% as originally
planned).
Following the ﬁrst meeting of DMEC when data from 600
women were reviewed, DMEC informed TSC that, instead
of a primary event rate of around 12%, the event rate was
closer to 1%. TSC recommended changing the primary
outcome from the original composite of febrile morbidity/
endometritis to include all infectious morbidity into a com-
bined primary outcome, i.e. the original primary outcome
of febrile morbidity/endometritis plus wound infection.
This would produce a revised event rate of approximately
12%. This amendment to the trial protocol was agreed by
the funding source, the sponsor and the research ethics
committee.
After randomisation, but prior to caesarean section, two
women withdrew consent and 30 women had a vaginal
delivery. These women were evenly distributed amongst the
trial arms, and these 32 women (1%) were excluded from
the analysis. Trial entry and discharge data were available
on over 99% of women and 6-week data on up to 90% of
women (Figure 1).8
The characteristics of the women at trial entry are
broadly similar (Table 1). The mean age of the women was
31 years, two-thirds were primiparous, about one-third
underwent an ‘in labour’ caesarean section and about 95%
had a singleton pregnancy.
Compliance with the single- versus double-layer uterine
closure and closure versus nonclosure of the pelvic perito-
neum was high (at least 93%). Compliance was poorer for
the liberal use of a subrectus sheath drain, for which a
drain was used in 63% of women allocated to liberal use
(Table 2). The main reasons for noncompliance with the
liberal use of a subrectus sheath drain were clinical, mainly
because there was good haemostasis (n = 374, 75% of those
noncompliant).
The nonallocated clinical aspects of the caesarean section
were compared between the arms of the study in order to
assess whether the allocated interventions had an effect on
other aspects of the surgical procedures used. There was a
difference in relation to closure of the parietal peritoneum
within the pelvic peritoneum comparison. For women allo-
cated to closure of the pelvic peritoneum, more operators
also closed the parietal peritoneum (23%) than if they were
allocated to nonclosure of the pelvic peritoneum (7%)
(Table 3).
The risk of maternal infectious morbidity varied only
slightly (between 16% and 18%) according to the trial arm.
For each pair of interventions, there were no differences
between the arms of the trial for the primary outcome or any
of the secondary outcomes (Table 4). There was evidence of
a strong positive (multiplicative) interaction (P = 0.006)
between closure of the peritoneum and use of a subrectus
sheath drain on the primary outcome, such that, in women
allocated liberal use of a subsheath drain, there was a higher
risk of the primary outcome associated with nonclosure of
the pelvic peritoneum (20.8% versus 14.8%), whereas, in
women allocated to restricted use of a subsheath drain, there
was a lower risk of the primary outcome associated with
nonclosure of the pelvic peritoneum (15.6% versus 17.7%).
This interaction was also apparent for the outcome of wound
infection treated with antibiotics (P = 0.01) and duration of
the caesarean section (P = 0.005) (see Tables S1 and S2).
When the effect of varying levels of compliance with the allo-
cation of subsheath drain between centres was explored,
Table 2. Compliance with allocated treatment*
Procedure allocated
Uterine closure Closure of pelvic peritoneum Subrectus sheath drain
Single layer
n (%)
1483 (100)
Double layer
n (%)
1496 (100)
Closed
n (%)
1496 (100)
Not closed
n (%)
1499 (100)
Liberal
n (%)
1398 (100)
Restricted
n (%)
1398 (100)
Option received
Single layer 1377 (93) 11 (1)
Double layer 96 (6) 1477 (99)
Option received
Closed 1398 (93) 23 (2)
Not closed 88 (6) 1459 (97)
Option received
Drain used 883 (63) 82 (6)
Drain not used 502 (36) 1302 (93)
*Less than 1% of data missing for each item.

Table 3. Clinical details of caesarean section*
Uterine closure Closure of pelvic
peritoneum
Subrectus sheath drain
Single layer
n (%)
1483 (100)
Double layer
n (%)
1496 100)
Closed
n (%)
1496 (100)
Not closed
n (%)
1499 (100)
Liberal
n (%)
1398 (100)
Restricted
n (%)
1398 (100)
Abdominal entry
Pfannenstiel 1103 (74) 1147 (77) 1148 (77) 1111 (74) 1053 (75) 1062 (76)
Joel–Cohen 355 (24) 321 (21) 320 (21) 357 (24) 317 (23) 309 (22)
Abdominal packs
Used 118 (8) 111 (7) 109 (7) 121 (8) 99 (7) 101 (7)
Not used 1347 (91) 1370 (92) 1375 (92) 1357 (91) 1289 (92) 1277 (91)
Uterine entry
Blunt dissection 1265 (85) 1304 (87) 1291 (86) 1289 (86) 1208 (86) 1183 (85)
Sharp dissection 191 (13) 168 (11) 183 (12) 182 (12) 172 (12) 185 (13)
Removal of placenta
CCT 1227 (83) 1250 (84) 1238 (83) 1251 (83) 1174 (84) 1153 (82)
Manual 242 (16) 236 (16) 248 (17) 234 (16) 219 (16) 229 (16)
Uterine repair
Single 1377 (93) 1477 (99) 700 (47) 686 (46) 649 (46) 645 (46)
Double 96 (6) 11 (1) 788 (53) 803 (54) 744 (53) 743 (53)
Uterine suture material
Vicryl 1369 (92) 1373 (92) 1375 (92) 1383 (92) 1284 (92) 1281 (92)
Dexon 24 (2) 21 (1) 25 (2) 20 (1) 18 (1) 27 (2)
Other 77 (5) 92 (6) 86 (6) 83 (6) 86 (6) 80 (6)
First-layer uterine suturing technique
Continuous nonlocking 446 (30) 464 (31) 468 (31) 442 (29) 443 (32) 435 (31)
Continuous locking 1002 (68) 1007 (67) 997 (67) 1028 (69) 930 (67) 931 (67)
Interrupted 2 (0) 2 (0) 3 (0) 1 (0) 3 (0) 1 (0)
Second-layer uterine suturing technique n = 96 n = 1477 n = 788 n = 803 n = 744 n = 743
Interrupted 6 (6) 5 (0) 7 (1) 4 (0) 6 (1) 4 (1)
Pelvic peritoneum
Closed 699 (47) 712 (48) 1398 (93) 23 (2) 668 (48) 654 (47)
Not closed 767 (52) 772 (52) 88 (6) 1459 (97) 720 (52) 728 (52)
Pelvic peritoneum suture material n = 699 n = 712 n = 1398 n = 23 n = 668 n = 654
Vicryl 649 (93) 657 (92) 1296 (93) 20 (87) 613 (92) 604 (92)
Dexon 10 (1) 12 (2) 22 (2) 0 (0) 6 (1) 16 (2)
Other 38 (5) 39 (5) 75 (5) 2 (9) 45 (7) 32 (5)
Pelvic peritoneum suture technique n = 699 n = 712 n = 1398 n = 23 n = 668 n = 654
Interrupted 5 (1) 5 (1) 10 (1) 0 (0) 5 (1) 5 (1)
Parietal peritoneum
Closed 211 (14) 228 (15) 343 (23) 99 (7) 201 (14) 208 (15)
Not closed 1252 (84) 1249 (83) 1134 (76) 1381 (92) 1181 (84) 1170 (84)
Parietal peritoneum suture material n = 211 n = 228 n = 343 n = 99 n = 201 n = 208
Vicryl 175 (83) 194 (85) 299 (87) 73 (74) 165 (82) 176 (85)
Plain catgut 0 (0) 1 (0) 0 (0) 1 (1) 0 (0) 1 (0)
Dexon 1 (0) 1 (0) 2 (1) 0 (0) 0 (0) 2 (1)
Other 31 (15) 30 (13) 37 (11) 24 (24) 32 (16) 29 (14)
Parietal peritoneum suturing technique n = 211 n = 228 n = 343 n = 99 n = 201 n = 208
Interrupted 2 (1) 4 (2) 4 (1) 2 (2) 1 (0) 3 (1)

there was no evidence that increasing compliance increased
the difference between the two groups.
For the pelvic peritoneum comparison, the effect of differ-
ential closure of the parietal peritoneum on the outcomes
was adjusted for in the analysis, and the Mantel–Haensel
risk ratio for the primary outcome was 0.95 (95% CI = 0.78–
1.15), which is similar to the crude risk ratio of 0.92 (95%
CI = 0.76–1.10). Similarly, this adjusted analysis produced
no differences in the estimate of effect for any of the second-
ary outcomes (Table 4).
Twelve serious adverse events were reported, and these
occurred equally in all arms. These included three women
who required hysterectomy to control bleeding and three
additional women who required blood transfusions of >4
units.
When the study outcomes were analysed according to the
eight randomised groups, there were no significant differ-
ences between the groups for any outcomes (data not
shown). A prespecified subgroup analysis was performed for
the comparison of liberal versus restricted use of a subsheath
drain. In this analysis, centres were divided into quartiles of
compliance (0–65.5%, >65.5% to <83.3%, 83.3% to <94.4%,
>94.4%). There was no evidence of any effect on the primary
outcome or the secondary outcomes by compliance. Finally,
the effect of each intervention on the study outcomes did not
vary according to whether the caesarean was ‘in labour’ or
‘not in labour’, and there was no evidence of an interaction.
A prespecified subgroup analysis by singleton versus multiple
pregnancy was not performed owing to the small number of
multiple pregnancies (155, 5%).
Discussion
CAESAR is the largest randomised trial of caesarean section
surgical techniques undertaken to date, and provides
important evidence to guide clinical practice. Mounting
such a large surgical trial presented a number of challenges,
including the need to ensure adequate competency of the
operators in surgical techniques which may have been
unfamiliar, particularly single-layer uterine closure. This
step was important to limit concerns that the comparisons
between groups may have been affected by operator experi-
ence or competence,9
but it did introduce a substantial
delay in the recruitment of operators, and therefore the
recruitment of women.
Despite lower than anticipated recruitment, the event
rate for the primary outcome was higher than that used in
the estimation of the sample size, and so the power for
Table 3. (Continued)
peritoneum
Single layer
n (%)
1483 (100)
Double layer
n (%)
1496 100)
Closed
n (%)
1496 (100)
Not closed
n (%)
1499 (100)
Liberal
n(%)
1398 (100)
Restricted
n (%)
1398 (100)
Superficial fat layer
Closed 507 (34) 549 (37) 517 (35) 537 (36) 457 (33) 475 (34)
Not closed 960 (65) 931 (62) 965 (65) 943 (63) 928 (66) 907 (65)
Fat layer suture material n = 506 n = 549 n = 516 n = 537 n = 457 n = 474
Vicryl 382 (75) 417 (76) 396 (77) 401 (75) 328 (72) 353 (74)
Plain catgut 4 (1) 2 (0) 5 (1) 1 (0) 3 (1) 3 (1)
Dexon 59 (12) 68 (12) 55 (11) 72 (13) 60 (13) 66 (14)
Other 57 (11) 57 (10) 55 (11) 59 (11) 62 (14) 47 (10)
Fat layer suturing technique n = 506 n = 549 n = 516 n = 537 n = 457 n = 474
Interrupted 171 (34) 175 (32) 149 (29) 196 (36) 147 (32) 144 (30)
Skin closure
Subcuticular 1266 (85) 1272 (85) 1277 (85) 1279 (85) 1200 (86) 1194 (85)
Interrupted 144 (10) 152 (10) 147 (10) 149 (10) 130 (9) 130 (9)
Clips/staples 57 (4) 55 (4) 59 (4) 52 (3) 57 (4) 55 (4)
Other 1 (0) 1 (0) 1 (0) 1 (0) 1 (0) 1 (0)
CCT, Controlled cord traction.
*Less than 2% of data missing for each item, except parietal peritoneum suturing technique (3–4% of data missing) and fat layer suturing tech-
nique (3% of data missing).

Table 4. Outcome measures by three comparisons*
peritoneum
Single layer
n (%)
1483 (100)
Double layer
n (%)
1496 (100)
Closed
n (%)
1496 (100)
Not closed
n (%)
1499 (100)
Liberal
n (%)
1398 (100)
Restricted
n (%)
1398 (100)
Primary outcome**
Maternal infectious morbidity 247 (16.9) 249 (16.9) 240 (16.3) 262 (17.7) 247 (17.9) 228 (16.6)
RR (95% CI)
RR (95% CI) adjusted for parietal peritoneum
1.00 (0.85–1.17) 0.92 (0.78–1.08)
0.95 (0.80–1.12)
1.08 (0.92–1.27)
Secondary outcomes
Temperature ‡39°C on any occasion 5 (0.3) 5 (0.3) 8 (0.5) 2 (0.1) 3 (0.2) 4 (0.3)
RR (99% CI)
1.01 (0.20–5.13) 4.02 (0.85–18.9)
3.03 (0.78–12.0)
0.75 (0.10–5.33)
Temperature ‡38°C on ‡2 days 12 (0.8) 10 (0.7) 13 (0.9) 9 (0.6) 11 (0.8) 10 (0.7)
RR (99% CI)
1.21 (0.40–3.64) 1.45 (0.62–3.39)
1.36 (0.54–3.46)
1.10 (0.36–3.36)
Antibiotics given for febrile morbidity 12 (0.8) 11 (0.7) 14 (1.0) 9 (0.6) 10 (0.7) 10 (0.7)
RR (99% CI)
1.09 (0.38–3.19) 1.56 (0.68–3.60)
1.39 (0.58–3.30)
0.99 (0.32–3.13)
Known to have had endometritis 63 (4.3) 62 (4.2) 59 (4.0) 66 (4.5) 65 (4.7) 53 (3.9)
RR (99% CI)
1.02 (0.65–1.61) 0.90 (0.64–1.27)
0.92 (0.65–1.30)
1.21 (0.76–1.94)
Known to have had wound infection
treated with antibiotics
188 (12.8) 188 (12.7) 182 (12.3) 200 (13.5) 186 (13.4) 178 (12.9)
RR (99% CI)
1.01 (0.79–1.29) 0.92 (0.76–1.10)
0.95 (0.78–1.15)
1.04 (0.81–1.33)
Known to have had operative procedures on wound 9 (0.6) 9 (0.6) 9 (0.6) 9 (0.6) 12 (0.9) 5 (0.4)
RR (99% CI)
1.01 (0.30–3.39) 1.01 (0.40–2.53)
1.05 (0.45–2.44)
2.40 (0.61–9.42)
Additional analgesia on day 3 526 (38) 493 (35) 506 (36) 514 (37) 483 (37) 501 (38)
RR (99% CI)
1.08 (0.95–1.23) 0.99 (0.87–1.13)
1.00 (0.91–1.11)
0.96 (0.85–1.10)
Pain VAS at hospital discharge
Median {IQR} 20 {8–35} 20 {9–36} 20 {9–36} 19 {8–35} 20 {9–37} 19 {8–34}
P value for rank sum test 0.2 0.08 0.2
Pain VAS at 6 weeks post-partum
Median {IQR} 2 {0–10} 2 {0–11} 2 {0–11} 2 {0–11} 3 {0–11} 2 {0–10}
P value for rank sum test 0.7 0.3 0.1
Blood transfusion 54 (3.7) 59 (4.0) 61 (4.1) 52 (3.5) 53 (3.8) 52 (3.7)
RR (99% CI)
0.93 (0.57–1.49) 1.15 (0.80–1.66)
1.12 (0.77–1.63)
1.02 (0.62–1.66)
Severe maternal morbidity 7 (0.5) 11 (0.7) 12 (0.8) 6 (0.4) 13 (0.9) 3 (0.2)
RR (99% CI)
0.65 (0.19–2.23) 2.00 (0.75–5.32)
1.96 (0.76–5.06)
4.32 (0.83–22.4)
Readmitted to hospital within
6 weeks of caesarean section
34 (2.6) 37 (2.7) 39 (2.9) 32 (2.4) 33 (2.6) 34 (2.7)
RR (99% CI)
0.93 (0.51–1.71) 1.22 (0.77–1.93)
1.31 (0.81–2.12)
0.98 (0.52–1.82)
Breastfeeding at hospital discharge 857 (62.5) 920 (65.4) 894 (64.2) 896 (64.0) 816 (62.8) 836 (64.2)
RR (99% CI)
1.05 (0.89–1.03) 1.00 (0.95–1.06)
0.99 (0.93–1.05)
0.98 (0.91–1.06)
Duration of caesarean (minutes)
Mean [SD] 36.2 [11.6] 38.3 [11.8] 38.5 [12.0] 36.1 [11.5] 37.7 [11.4] 37.3 [12.5]

detecting the main effects of the arms of the trial should
not have been adversely affected. For most of the compari-
sons, there was no statistically signiﬁcant interaction
between the trial arms, although it should be noted that
the trial had relatively low power to detect interactions.
Although there were no differences detected between the
randomised interventions, the results of CAESAR do have
implications for clinical practice, particularly in relation to
current guidance about closure of the peritoneum at the
time of caesarean section repair. Guidance in the UK10
rec-
ommends that both layers of the peritoneum should not be
closed, as this is associated with a lower risk of morbidity
based on existing evidence.11
The data from CAESAR dem-
onstrate that there are no differences in any of the short-
term morbidity outcomes associated with closure versus
nonclosure of the pelvic peritoneum at caesarean section,
although there is a difference in the duration of surgery
(mean difference, 2.4 minutes; 95% CI, 1.3–3.6 minutes),
favouring nonclosure. However, the duration of surgery is
a poor surrogate for morbidity, as there will be a lower
threshold below which duration is associated with greater
morbidity.
As there were no apparent differences in any of the
short-term outcomes, the potential effects of these surgical
techniques on longer term outcomes, such as the functional
integrity of the uterine scar during subsequent pregnancies
and effects such as chronic pelvic pain, infertility, perito-
neal adhesions and obstruction, become of increasing
importance for guiding clinical practice. Long-term out-
comes, even if uncommon, are likely to have a substantial
impact on morbidity, and can occasionally result in life-
threatening events or even death. There have been three
follow-up studies of existing trials of caesarean section
techniques.12–14
The sample sizes of these studies are small,
and included only 18% of the women randomised into the
original trials for two studies,12,13
and 51% for the third.14
In the only study comparing single- versus double-layer
uterine closure, no differences were found in interpregnan-
cy interval, vaginal delivery, length of hospital stay, preterm
delivery, amnionitis, postpartum endometritis, placental
abruption, postpartum haemorrhage, blood transfusion or
uterine dehiscence. This was based on a sample size of 145
women of the 906 randomised in the original trial.13
From
the two follow-up studies of trials comparing closure versus
nonclosure of the peritoneum (209 women in total), no
differences were observed in terms of intra-abdominal
adhesions, abdominal pain, dyspareunia, constipation, uri-
nary symptoms and infertility.14
Given the relatively low incidence of uterine rupture
(0.4–0.6% for women undergoing a trial of labour versus
0.2% for those having elective repeat caesarean) and dehis-
cence (1.1%),15–17
attempts to detect differences in these
outcomes between different surgical techniques with ade-
quate power is challenging. One large observational study
has looked at this outcome and found an association with
previous single-layer uterine closure.18
Table 4. (Continued)
peritoneum
Single layer
n (%)
1483 (100)
Double layer
n (%)
1496 (100)
Closed
n (%)
1496 (100)
Not closed
n (%)
1499 (100)
Liberal
n (%)
1398 (100)
Restricted
n (%)
1398 (100)
Difference in means (99% CI)
Difference in means (99% CI) adjusted
for parietal peritoneum
2.1 (1.0, 3.2) )2.4 ()3.6, )1.3)
)2.3 ()3.4, )1.2)
0.3 (–0.8, 1.5)
Duration of postnatal hospital stay (days)
Mean [SD]
Median {IQR}
4.7 [2.0]
4.0 {4–5}
4.7 [2.0]
4.0 {4–5}
4.8 [1.9]
4.0 {4–5}
4.7 [2.0]
4.0 {4–5}
4.8 [1.9]
4.0 {4–5}
4.7 [1.8]
4.0 {4–5}
Difference in means (99% CI)
Difference in means (99% CI) adjusted
for parietal peritoneum
0.0 (–0.2, 0.2) )0.1 ()0.3, 0.1)
)0.1 ()0.3, 0.1)
0.1 (–0.1, 0.3)
CI, conﬁdence interval; IQR, interquartile range; RR, relative risk; VAS, visual analogue scale.
*Data missing for <2% of items, except for whether the woman was readmitted to hospital within 6 weeks of caesarean section (missing for
10% of women), additional analgesia on day 3 after caesarean section (missing for 7% of women) and breastfeeding at hospital discharge (miss-
ing for 7% of women).
**Primary outcome comprises antibiotics given for pyrexia (temperature of >39°C on any occasion or >38°C on two or more successive days)
prior to discharge from hospital, or wound infection treated with antibiotics within 6 weeks or endometritis treated with antibiotics within
6 weeks of caesarean section.

This lack of adequate long-term follow-up and the
absence of short-term effects of these techniques raise
important issues about current clinical guidance. The lack
of differences between the interventions in the short term
may suggest that any one of the three pairs of approaches is
acceptable. However, there have been suggestions that non-
closure of the peritoneum may be harmful in the longer
term. It is possible, therefore, that clinical guidance may
dictate19
a course of action, such as continued recommen-
dation for nonclosure of the peritoneum, which may be
harmful in the longer term, and this information will not
be available until follow-up of trials, such as CAESAR, are
completed. In the meantime, there are difficult decisions to
be made if clinical guidance is to be provided to clinicians
about the surgical techniques used at caesarean section.
Conclusions
These results have implications for clinical practice, particu-
larly in relation to current guidance about closure of the
peritoneum, which suggests that nonclosure is preferable.
The potential effects of these different surgical techniques on
longer term outcomes, including the functional integrity of
the uterine scar during subsequent pregnancies, are becom-
ing increasingly important for guiding clinical practice.
Disclosure of interests
All authors declare that they have no relevant interests to
declare.
Contribution to authorship
PB designed the study and wrote the proposal with contri-
butions from SA. MQ and SA analysed the data, with input
from EJ and PB. PB wrote the final report, with all of the
writing committee contributing to the editing.
Details of ethics approval
Multicentre Research Ethics Committee approval for the
trial was given by the Eastern MREC (99/5/62), and all par-
ticipants gave informed consent to participate.
Funding
The trial was funded by the NHS South East Region
Research and Development Office. The funding source had
no role in the study design, the collection and interpreta-
tion of the data, writing of the report or decision to submit
the paper for publication.
Acknowledgements
Writing Committee: Peter Brocklehurst, Maria Quigley, Sarah
Ayers, Ed Juszczak, National Perinatal Epidemiology Unit.
CAESAR Co-ordinating Centre at the National Perinatal
Epidemiology Unit: Elizabeth Anderson, Sarah Ayers, Ursula
Bowler, Peter Brocklehurst, Ruth Davis, Madalena Gallagher,
Lucy Tully, Simon Gates, Juan Manuel Nardin, Maria
Quigley, Sally Tyndel. CAESAR Trial Steering Committee:
Jo Anthony (Northampton NHS Trust), Felicity Ashworth
(Chair) (Buckinghamshire NHS Trust), Ursula Bowler
(National Perinatal Epidemiology Unit), Peter Brocklehurst
(National Perinatal Epidemiology Unit), Ali Chevassut
(Oxford Radcliffe Hospital Trust), Debbie Chippington
Derrick (National Childbirth Trust), Simon Gates (until
April 2005) (National Perinatal Epidemiology Unit), Pauline
Hurley (Oxford Radcliffe Hospital Trust), Maria Quigley
(from April 2006) (National Perinatal Epidemiology Unit).
CAESAR Data Monitoring and Ethics Committee: Zarko
Alfirevic, Susan Bewley, Janet Darbyshire (Chair), Jon Deeks,
Ed Juszczak. CAESAR Trial Participating Hospitals: See
Appendix S1 for a full list of participating hospitals.
Supporting information
The following supplementary materials are available for this
article:
Table S1. P values for test for pairwise interactions
between trial arms.
Table S2. Stratum-specific results where there is evidence
of interaction between trial arms.
Appendix S1. CAESAR trial participating hospitals.
Additional Supporting Information may be found in the
online version of this article.
Please note: Wiley-Blackwell are not responsible for the
content or functionality of any supporting information
supplied by the authors. Any queries (other than missing
material) should be directed to the corresponding
author. j
References
1 Villar J, Valladares E, Wojdyla D, Zavaleta N, Carroli G, Vela A, et al.
Caesarean delivery rates and pregnancy outcomes: the 2005 WHO
global survey on maternal and perinatal health in Latin America.
Lancet 2006;367:1819–29.
2 Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for
cesarean delivery. Am J Obstet Gynecol 2005;193:1607–17.
3 Tully L, Gates S, Brocklehurst P, McKenzie-McHarg K, Ayers S. Surgi-
cal techniques used during caesarean section operations: results of a
national survey of practice in the UK. Eur J Obstet Gynecol Reprod
Biol 2002;102:120–6.
4 Smaill F. Prophylactic antibiotics in Caesarean section (all trials). In:
Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP, editors. Pregnancy
and Childbirth Module. Cochrane Database of Systematic Reviews,
Review No. 03690. Oxford: Update Software; 1994. Disk Issue 1.
5 McAlister FA, Straus SE, Sackett DL, Altman DG. Analysis and
reporting of factorial trials: a systematic review. J Am Med Assoc
2003;289:2545–53.
6 Montgomery AA, Peters TJ, Little P. Design, analysis and presenta-
tion of factorial randomised controlled trials. BMC Med Res Meth-
odol 2003;3:26.

7 Schulz KF, Grimes DA. Multiplicity in randomised trials II: subgroup
and interim analyses. Lancet 2005;365:1657–61.
8 Bourton I, Moher D, Altman D, Schulz K, Ravaud P.; for the CONSORT
group. Extending the CONSORT statement to randomized trials of
nonpharmacologic treatment: explanation and elaboration. Ann Intern
Med 2008;148:295–309.
9 Devereaux PJ, Bhandari M, Clarke M, Montori VM, Cook DJ,
Yusuf S, et al. Need for expertise based randomised controlled trials.
Br Med J 2005;330:88.
10 National Institute for Health and Clinical Excellence (NICE). Caesar-
ean Section Guideline CG13. London: NICE; 2004.
11 Bamigboye AA, Hofmeyr GJ. Closure versus non-closure of the perito-
neum at caesarean section. Cochrane Database Syst Rev 2003;4:
CD000163.
12 Weerawetwat W, Buranawanich S, Kanawong M. Closure vs non-
closure of the visceral and parietal peritoneum at cesarean delivery:
16 year study. J Med Assoc Thai 2004;87:1007–11.
13 Chapman SJ, Owen J, Hauth JC. One versus two layer closure of a
low transverse cesarean: the next pregnancy. Obstet Gynecol 1997;
89:16–8.
14 Roset E, Boulvain M, Irion O. Nonclosure of the peritoneum during
caesarean section: long-term follow-up of a randomised controlled
trial. Eur J Obstet Gynaecol Reprod Biol 2002;108:40–4.
15 Mozurkewich EL, Hutton EK. Elective repeat cesarean delivery versus
trial of labor: a meta-analysis of the literature from 1989 to 1999.
Am J Obstet Gynecol 2000;183:1187–97.
16 Chauhan SP, Martin JN Jr, Henrichs CE, Morrison JC, Magann EF.
Maternal and perinatal complications with uterine rupture in
142,075 patients who attempted vaginal birth after cesarean deliv-
ery: a review of the literature. Am J Obstet Gynecol 2003;189:
408–17.
17 Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP. Risk of uterine
rupture during labor among women with a prior cesarean delivery.
N Engl J Med 2001;345:3–8.
18 Bujold E, Bujold C, Hamilton EF, Harel F, Gauthier RJ. The impact of
a single-layer or double-layer closure on uterine rupture. Am J
Obstet Gynecol 2002;186:1326–30.
19 Lyell D, Caughey A, Hu E, Daniels K. Peritoneal closure at primary
caesarean delivery and adhesions. Obstet Gynecol 2005;106:
275–80.
Journal Club
Discussion points
1. Background: Discuss the existing recommendations with regard to the surgical techniques for caesarean sections,
for example by the National Institute for Clinical Excellence (NICE).1
Debate with your colleagues aspects of the
technique that you prefer, and discuss why.
2. Methods: Compare the methods in this study with those used by a previous study on a similar subject.2
Comment
on the advantages and disadvantages of the two different approaches. Debate the choice, definition and ascertain-
ment of the outcome measures used in this study. Discuss the strengths and weaknesses of factorial (e.g. 2 · 2)
designs for randomised controlled trials. Discuss the practical, ethical, clinical governance and scientific issues
around premature trial discontinuation. Illustrate with examples from this study as well as others of which you
might be aware.
3. Results and implications: Discuss the event rates for the individual outcomes in this study. Are you surprised by
the low rate (1%) of infection at the interim analysis/first meeting of the steering committee? Explain how the
results of this study, combined with other recent ones, may affect your current practice. Which outcome measures
would you want follow-up studies to address? j
D Siassakos
University of Bristol & Southmead Hospital, Bristol, UK
Email jsiasakos@gmail.com
References
1 National Collaborating Centre for Women’s and Children’s Health. Caesarean Section. London: National Institute for Clinical Excellence
(NICE), 2004.
2 Blumenfeld Y, Caughey A, El-Sayed Y, Daniels K, Lyell D. Single- versus double-layer hysterotomy closure at primary caesarean delivery and
bladder adhesions. BJOG 2010;117:690–4.

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