Elective caesarean section at 38 weeks versus

39 weeks: neonatal and maternal outcomes in a

randomised controlled trial*
J Glavind,
a
SF Kindberg,
a
N Uldbjerg,
a
M Khalil,
b
AM Mller,
c
BB Mortensen,
d
OB Rasmussen,
e
JT Christensen,
f
JS Jrgensen,
g
TB Henriksen
h
a
Department of Obstetrics and Gynaecology, Aarhus University Hospital, Aarhus N, Denmark
b
Department of Obstetrics and Gynaecology,
Kolding Hospital, Kolding, Denmark
c
Department of Obstetrics and Gynaecology, Aalborg University Hospital, Aalborg, Denmark
d
Department of Obstetrics and Gynaecology, Regional Hospital of Viborg, Viborg, Denmark
e
Department of Obstetrics and Gynaecology,
Regional Hospital of Randers, Randers, Denmark
f
Department of Obstetrics and Gynaecology, Regional Hospital of Herning, Herning,
Denmark
g
Department of Obstetrics and Gynaecology, Odense University Hospital, Odense, Denmark
h
Department of Paediatrics, Aarhus
University Hospital, Aarhus N, Denmark
Correspondence: Dr J Glavind, Department of Obstetrics and Gynaecology, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-8200
Aarhus N, Denmark. Email julie.glavind@dadlnet.dk
Accepted 14 April 2013. Published Online 20 May 2013.
Objectives To investigate whether elective caesarean section before
39 completed weeks of gestation increases the risk of adverse
neonatal or maternal outcomes.
Design Randomised controlled multicentre open-label trial.
Setting Seven Danish tertiary hospitals from March 2009 to June
2011.
Population Women with uncomplicated pregnancies, a single
fetus, and a date of delivery estimated by ultrasound scheduled for
delivery by elective caesarean section.
Methods Perinatal outcomes after elective caesarean section
scheduled at a gestational age of 38 weeks and 3 days versus
39 weeks and 3 days (in both groups 2 days).
Main outcome measures The primary outcome was neonatal
intensive care unit (NICU) admission within 48 hours of birth.
Secondary outcomes were neonatal depression, NICU admission
within 7 days, NICU length of stay, neonatal treatment, and
maternal surgical or postpartum adverse events.
Results Among women scheduled for elective caesarean section at
38
+3
weeks 88/635 neonates (13.9%) were admitted to the NICU,
whereas in the 39
+3
weeks group 76/637 neonates (11.9%) were
admitted (relative risk [RR] 0.86, 95% condence interval [95%
CI] 0.651.15). Neonatal treatment with continuous oxygen for
more than 1 day (RR 0.31; 95% CI 0.100.94) and maternal
bleeding of more than 500 ml (RR 0.79; 95% CI 0.630.99) were
less frequent in the 39 weeks group, but these ndings were
insignicant after adjustment for multiple comparisons. The risk
of adverse neonatal or maternal outcomes, or a maternal
composite outcome (RR 1.1; 95% CI 0.791.53) was similar in the
two intervention groups.
Conclusions This study found no signicant reduction in neonatal
admission rate after ECS scheduled at 39 weeks compared with
38 weeks of gestation.
Keywords Elective caesarean section, maternal outcomes, neonatal
intensive care unit admission, neonatal outcomes, timing.
Please cite this paper as: Glavind J, Kindberg S, Uldbjerg N, Khalil M, Mller A, Mortensen B, Rasmussen O, Christensen J, Jrgensen J, Henriksen T.
Elective caesarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial. BJOG 2013;120:11231132.
Introduction
British and American societies in obstetrics recommend
elective caesarean section to be scheduled after 39 com-
pleted weeks of gestation.
1,2
This recommendation is based
on a subset of several observational studies suggesting a
strong association between earlier gestational age at elective
caesarean section delivery and risk of respiratory morbid-
ity.
37
In addition, two recent, large cohort studies investi-
gated timing of elective caesarean section and the incidence
of a composite adverse neonatal outcome including neona-
tal death or any of a series of adverse events. Both showed
a decreasing incidence of the composite outcome with
increasing gestational age from 37 to 39 completed weeks
of gestation.
8,9
In contrast, any maternal benet of post-
poning elective caesarean section to 39 completed weeks *Trial registration: www.clinicaltrials.gov, number NCT00835003
2013 RCOG 1123
DOI: 10.1111/1471-0528.12278
www.bjog.org
General obstetrics
has not been shown, but knowledge is sparse when it
comes to maternal consequences of elective caesarean sec-
tion timing.
10,11
However, confounding by indication may impair results
from observational studies. In this case, neonates with a
higher risk of an adverse outcome may be over-represented
in caesarean sections undertaken before 39 weeks for rea-
sons other than the caesarean section per se. This method-
ological problem would only be solved in a randomised
controlled trial. Furthermore, to fully investigate the neona-
tal and maternal benets or adverse events associated with
a certain elective caesarean section timing, outcomes from
women with unscheduled procedures who intended to deli-
ver by elective caesarean section should be included in the
assessment.
We therefore conducted a randomised controlled trial of
neonatal and maternal morbidity after elective caesarean
section scheduled at 38
+3
weeks compared with 39
+3
weeks
of gestation. The primary study objective was to investigate
the risk of neonatal intensive care unit (NICU) admission
associated with elective caesarean delivery scheduled before
versus after 39
+0
weeks of gestation.
Methods
We conducted a multicentre, open-label randomised con-
trolled trial in seven Danish hospitals, all with an NICU
within the hospital. Approvals were obtained from The
Central Denmark Region Committees on Biomedical
Research (ID M-20080142) and the Danish Data Protection
Agency (ID 2008-41-2522). Registration at www.Clinical-
trials.gov was ensured with identication number
NCT00835003. An independent trial steering committee
was appointed for data monitoring, safety and advice dur-
ing the trial.
Clinical management and data collection
Participants were randomly assigned in a 1:1 ratio to an
elective caesarean section scheduled 11 days before the esti-
mated due date (38
+3
weeks; referred to as 38-week group)
or to an elective caesarean section scheduled 4 days before
the estimated due date (39
+3
weeks; referred to as 39-week
group). In both groups, the scheduled date was allowed to
deviate 2 days from this specic date.
Hospital staff and participants were all aware of the esti-
mated gestational age at the elective caesarean section sched-
uled date. During antenatal consultations, participants and
nonparticipants had a case report form assessing inclusion
and exclusion criteria lled out by the responsible physician,
and after written consent had been obtained, elective caesar-
ean section was booked according to the randomisation. To
limit the inuence of subjective timing preferences, the
responsible staff members were asked to book the elective
caesarean section according to a prioritised gestational
age sequence (38
+3
> 38
+2
> 38
+4
> 38
+5
> 38
+1
versus
39
+3
> 39
+4
> 39
+2
> 39
+1
> 39
+5
).
Neonatal outcomes were assessed 30 days after delivery
or at nal discharge (with NICU length of stay >30 days)
by a designated physician, research nurse, or midwife.
Maternal outcomes were assessed 30 days postpartum. Data
from all the participating hospitals were collected and
checked for accuracy by the rst author, before they were
entered into a database (EPIDATA software version 3.1).
12
Study population and setting
Singleton pregnant women with a gestational age deter-
mined by ultrasound before 15 weeks of gestation were eli-
gible for inclusion, when a decision of delivery by elective
caesarean section was made. Exclusion criteria were multi-
ple gestations, age <18 years, language difculties requiring
an interpreter, or an estimated risk of the caesarean section
being undertaken before 39
+5
weeks of gestation. Accord-
ingly, women with conditions such as placenta praevia,
high blood pressure, or elevated levels of liver enzymes
were not included. Women with type 1 diabetes or gesta-
tional diabetes, veried at the time of randomisation by an
oral glucose tolerance test, were also excluded from partici-
pation. Any fetal condition warranting delivery before
39
+5
weeks or necessitating NICU admission also excluded
participation in the study.
In Denmark, elective caesarean section is only performed
at public hospitals; hence, women assessed for eligibility in
this study represented the entire population of the partici-
pating councils. All participating hospitals had one neona-
tal department (in our facilities named the neonatal
intensive care unit/NICU) and in-house obstetrician, paedi-
atrician and anaesthesiologists available day and night, with
physicians typically working in 8-, 16- or 24-hour shifts.
The participating units complied with the Danish National
Obstetrics Guidelines for elective caesarean section includ-
ing spinal anaesthesia as the preferred analgesia and admin-
istration of prophylactic intravenous antibiotics during the
procedure. A midwife handled the neonate immediately
after the birth.
Paediatricians were not routinely present in the operat-
ing theatre and were only called in if the neonate presented
with clinical signs warranting paediatric assistance. At all
the participating hospitals, NICU admission and separation
of the mother and child were avoided if possible, and all
decisions related to NICU admission were on a case-to-case
basis. Although the paediatricians responsible for the deci-
sion to admit the neonate to the NICU were not blinded
to gestational age at delivery, only neonates with a gesta-
tional age <35 weeks were routinely admitted to the NICU.
If paediatricians were called to assess the newborn, they
were unaware that a trial was being conducted.
1124 2013 RCOG
Glavind et al.
Randomisation
Participants were randomised using a computer-generated
voice response telephone randomisation system in a per-
muted block design with block sizes of two, four and six in
random order, stratied by previous caesarean and site.
Study outcomes
The primary outcome was admission to the NICU, regard-
less of cause, within 48 hours of birth, which was assessed
by information from individual hospital records. Secondary
short-term neonatal outcomes were admission to the NICU
within 7 days of birth, NICU length of stay, type and dura-
tion of treatment (mechanical ventilation, continuous oxy-
gen supplementation, continuous positive airway pressure
[CPAP], intravenous antibiotics, treated hypoglycaemia),
Apgar score, umbilical artery pH and standard base excess
values. We dened any respiratory morbidity as mechanical
ventilation, continuous oxygen supplementation, or CPAP
during NICU admission. Serious respiratory morbidity was
dened as mechanical ventilation, or three or more initi-
ated days of treatment with oxygen or CPAP during NICU
admission. Furthermore, birthweight and gender were reg-
istered. If a neonate was transferred to another NICU, data
were registered continuously throughout the entire admis-
sions, and the total admission period was registered until
discharge from the nal NICU.
The following maternal outcomes were registered: mater-
nal death, hysterectomy, or serious thromboembolic compli-
cations (deep venous thrombosis or pulmonary embolism).
Surgical adverse outcomes such as injury to bowel or bladder
or a uterine lateral tear were registered if they were speci-
cally mentioned in the procedure description. Likewise, pro-
cedural complications such as adherences, difculties in
delivery (prolonged, described as difcult, use of forceps or
vacuum), or the presence of total uterine rupture or a noted
dehiscence (intact serosa) were registered if mentioned in the
operation description. Anaesthetic complications included
serious cases of hypotension or hypertension, spinal head-
ache, or the need for general anaesthesia. A re-operation was
registered if any of the following procedures were performed
after delivery: evacuation, wound opened because of sus-
pected infection or bleeding in the abdomen, or other opera-
tions such as the placement of a JJ-catheter. Treatment for
excessive postoperative bleeding was registered if a blood
transfusion was administered, or if uterotonic medication in
addition to prophylactic treatment was instituted at the
operating theatre. Total blood loss volume was dened as the
volume registered in the operating theatre during the caesar-
ean section procedure, or in vaginal deliveries until transfer
from the delivery room occurred. Any antibiotic treatment
and the suspected source of infection (endometritis, wound
infection, mastitis, or any other infection attributed to the
delivery) were registered from the patient record. The diag-
nosis of endometritis was based on clinical criteria with fever,
elevated biochemical inammatory markers and vaginal dis-
charge. Finally, we constructed a composite outcome with
inclusion of at least one of the following adverse outcomes:
maternal death, hysterectomy, pulmonary embolism or deep
venous thrombosis, uterine incision lateral tear, injury to
bowel or bladder, procedural or anaesthesia complications,
rupture or dehiscence, bleeding requiring treatment, addi-
tional operations, or antibiotic treatment within 30 days of
delivery.
Sample size
With an a (two-sided) of 0.05 and a power of 0.80, an
estimated sample size of 1010 participants was calculated
based on primary outcome proportions of 8% (39-week
group) and 14% (38-week group), which were numbers
available from a large cohort (women with diabetes and
fetal malformations excluded) at the beginning of the
trial in 2008.
6
After delivery of 750 participants, approxi-
mately 9% of the participants had not been delivered
within the two 5-day randomisation group intervals for
reasons such as the mothers request for another delivery
date, miscalculations of the gestational age, or postponing
of the procedure for logistic problems in the operating
theatre. To account for the higher than expected non-
compliance, the steering committee recalculated the sam-
ple size, without knowledge of the results until then, and
decided to increase the sample size to a total of 1270
participants.
Statistical analyses
Basic demographic data are presented with counts and per-
centages for categorical variables, with mean and standard
deviation for continuous Gaussian variables and with med-
ian and interquartile range (IQR) for continuous non-
Gaussian variables. We analysed all data according to the
intention-to-treat principle.
In the outcome analyses, relative risks and absolute risk
differences with 95% condence intervals (95% CI) were
calculated for dichotomous outcomes using Fishers exact
test. Non-Gaussian continuous variables were compared
using the Wilcoxon rank-sum test, and birthweight was
compared using Students t test. For the primary outcome
and the maternal composite outcome a potential centre
effect was evaluated by testing the hypothesis of no treat-
ment by centre interaction in a multiple logistic regression
model. Adjustment for multiple comparisons (Bonferroni)
was made in evaluating the secondary outcomes.
All data analyses were performed using the statistical
software program STATA v.11 (2009).
13
2013 RCOG 1125
Timing of elective caesarean section: RCT
Results
Participants
From March 2009 to June 2011, a total of 1274 pregnant
women were enrolled in this study (Figure 1). Seven study
sites recruited between 119 and 329 participants each, rep-
resenting approximately 2034% of all eligible women.
Baseline characteristics (Table 1) were similar in the two
intervention groups at trial entry; however, slightly more
women with two or more previous caesarean sections were
randomised to the 38-week group whereas more women in
the 39-week group had a maternal request caesarean. Four
women who were randomised did not full the inclusion
criteria: two of these had no ultrasound-validated
gestational age, one woman was only 17 years old, and one
fetus had a planned NICU stay after delivery (39-week
group). One neonate (39-week group) died from congenital
pulmonary lymphangiectasia 11 days postpartum. The
intention-to-treat analysis included these participants. Only
data from two participants (one in each group) were not
included in the analyses of neonatal outcomes. Both had
induced vaginal delivery because of stillbirth.
A total of 1097 participants (571 in 38-week group ver-
sus 526 in 39-week group) had an elective caesarean deliv-
ery and 156 participants (59 in 38-week group versus 97 in
39-week group) had an unscheduled caesarean (within
8 hours of the decision). Among these, 49 women in 38-
week group (7.7%) and 82 women in 39-week group
(12.9%) had spontaneous onset of labour. Twenty-one par-
ticipants delivered vaginally (ve in 38-week group versus
16 in 39-week group). Apart from one vaginal stillbirth in
each group, ve out of 16 vaginal deliveries among women
in 39-week group occurred because of imminent delivery,
whereas the remaining ten women in 39-week group and
Elective CS assessed for
eligibility (n = 4048)
Excluded (n = 2774)*
Did not meet study criteria (n = 1380)
No validated due date (n = 69)
Below 18 years of age (n = 11)
Needs interpreter (n = 152)
Multiple pregnancy (n = 269)
Likely to have CS before 39
+5
weeks (n = 935)
Diabetes (n = 218)
Previously participated or too close to due date to
participate (n = 147)
Met study criteria (n = 1394)
Refused to participate (n = 849)
Logistics (n = 133)
Not asked (n = 165)
Information not available (n = 247)
1274 women randomised
Allocated to elective CS at 38
+3
weeks
(n = 636)
Received allocated intervention (n = 591)
Did not receive allocated intervention (n = 45)
Logistics (n = 20)
Mothers wish (n = 7)
Unspecified (n = 18)
Allocated to elective CS at 39
+3
weeks
(n = 638)
Received allocated intervention (n = 567)
Did not receive allocated intervention (n = 71)
Logistics (n = 16)
Mothers wish (n = 35)
Unspecified (n = 20)
All participants available to follow-up All participants available to follow-up
Included in the intention-to-treat analyses
635 neonates (one stillbirth excluded)
636 mothers
Included in the intention-to-treat analyses
637 neonates (one stillbirth excluded)
638 mothers
Figure 1. CONSORT Flow diagram. CS, caesarean section. *One woman can have more than one reason for not participating.
1126 2013 RCOG
Glavind et al.
four women in 38-week group decided to deliver vaginally
because of spontaneous reversion to an occipital presenta-
tion or change of preferred mode of delivery after inclu-
sion.
Systematic registration of nonparticipants during the
inclusion period showed baseline characteristics similar to
participants in terms of age, body mass index, smoking
habits and previous vaginal births. Eligible nonparticipants
were more likely than participants to be nulliparous (27%
versus 19%), with no previous caesarean section (49% ver-
sus 40%), and to have a breech or transverse lie presenta-
tion (24% versus 16%).
Primary and secondary outcomes
The median difference in gestational age at delivery was
6 days (38
+3
; IQR 38
+1
38
+5
versus 39
+2
; IQR 38
+6
39
+5
).
Gestational ages at delivery in the two groups are illus-
trated in Figures 2 and 3. There was no signicant differ-
ence in the primary outcome proportion as 88 of 635
neonates (13.9%) randomised to elective caesarean section
at 38 weeks of gestation were admitted to the NICU com-
pared with 76 of 637 neonates (11.9%) at 39 weeks of ges-
tation (Table 2). The relative risk (RR) of NICU admission
was 0.86 (95% CI 0.651.15) for elective caesarean section
at 39 weeks compared with 38 weeks, and the risk differ-
ence was 1.9% (95% CI 5.6 to 1.8). No signicant
treatment by centre interaction was found for the primary
outcome (P = 0.57).
With respect to secondary neonatal outcomes (Table 2),
duration of treatment with continuous oxygen for more
than 1 day was signicantly less frequent in the 39-week
group, with an RR of 0.31 (95% CI 0.100.94) and a risk
difference of 1.4% (95% CI 2.7 to 0.2). After adjust-
ment for multiple comparisons, this association was no
0
50
100
150
200
<
3
8
+
0
3
8
+
0
3
8
+
1
3
8
+
2
3
8
+
3
3
8
+
4
3
8
+
5
3
8
+
6
3
9
+
0
3
9
+
1
3
9
+
2
3
9
+
3
3
9
+
4
3
9
+
5
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9
+
6
>
3
9
+
6
N
u
m
b
e
r

o
f

d
e
l
i
v
e
r
i
e
s
Group 38
+3
weeks: gestational age at delivery
Elective delivery
Unscheduled delivery
Figure 2. Gestational age at caesarean section in the 38-week group
in number of weeks + days (n = 630).
Table 1. Baseline characteristics of the study population
Elective
caesarean
section at
38
+3
weeks
Elective
caesarean
section at
39
+3
weeks
Maternal age in
years, mean (SD)
32.1 (4.4) 31.6 (4.6)
Maternal height in
cm, mean (SD)
167.7 (6.5) 167.6 (6.5)
Maternal pre-pregnant weight
in kg, median (IQR)
68 (5086) 68 (4987)
Body mass index 30 107 (16.8) 111 (17.4)
Maternal smoking 65 (10) 83 (13)
Gestational age
validated by ultrasound
before 15 weeks
636 (100) 636 (99.7)
Nulliparous 126 (19.8) 117 (18.3)
Previous caesarean
section births
0 253 (39.8) 255 (40.0)
1 383 (60.2) 383 (60.0)
Previous vaginal births
0 426 (67.0) 421 (66.0)
1 210 (33.0) 217 (34.0)
Gestational age at
randomisation
<32
+0
weeks of gestation 279 (43.9) 290 (45.5)
32
+0
weeks of gestation 357 (56.1) 348 (54.5)
Skin closure type*
Suture 63/628 (10.0) 64/621 (10.3)
Staples 565/628
(90.0)
557/621 (89.7)
Indication for
caesarean section**
Two or more previous
caesarean sections
128 (20.1) 102 (16.0)
Maternal disease/caesarean
section advised by
the physician
54 (8.5) 57 (8.9)
Breech or transverse
lie presentation
114 (17.9) 90 (14.1)
Previously complicated birth 78 (12.3) 83 (13.0)
Maternal request 262 (41.2) 306 (48.0)
Data are presented as number (*) unless indicated with mean (SD)
or median (IQR).
*Information missing for four women (two in each group) and not
applicable in 21 vaginal deliveries (six in 38-week group and 15 in
39-week group).
**Categorised according to most weighty indication for caesarean
section.
2013 RCOG 1127
Timing of elective caesarean section: RCT
longer signicant (adjusted level of signicance 0.003).
There were no signicant differences in the frequency of
NICU admission within 7 days of birth, respiratory mor-
bidity, or treatment with intravenous antibiotics. Similar
proportions were found in the two groups with respect to
NICU length of stay of 2 days (Figure 4).
Among the neonates who did not receive respiratory
support (e.g. mechanical ventilation, nasal CPAP, oxygen
supplementation, or intravenous antibiotics), 12 neonates
in the 38-week group versus 11 in the 39-week group had
transitory tachypnoea or respiratory distress as their pri-
mary diagnosis. Apart from prematurity (ve neonates in
the 38-week group versus three in the 39-week group), the
remaining reasons for NICU admission comprised a broad
range of categories in both groups, such as asphyxia (one
versus two), hypoglycaemia (three versus none), or various
suspected endocrine or haematological disorders. Two
neonates in the 39-week group compared with none in the
38-week group were admitted because of congenital malfor-
mations detected at birth.
Participants were dened as compliant if elective caesar-
ean section was performed within the randomisation group
dates or at any other date because of labour or complica-
tions in pregnancy, as any rescheduling among the last-
mentioned groups of women would be based strictly on
professional criteria. Accordingly, we performed a per pro-
tocol analysis with exclusion of 117 non-compliant and
four not eligible participants and found an RR of the pri-
mary outcome of 0.90 (95% CI 0.671.21). Finally, if
vaginal deliveries were excluded from the analysis, the RR
was 0.92 (95% CI 0.681.23).
With respect to secondary maternal outcomes no cases
of maternal death, hysterectomy, or serious thromboembo-
lic events were registered (Table 3). The risk of maternal
bleeding >500 ml was signicantly lower in the 39-week
group (17.1%) compared with the 38-week group (21.7%)
with an RR of 0.79 (95% CI 0.630.99), but this nding
was insignicant after Bonferroni adjustment. The median
bleeding volume was 300 ml in each group. The number of
maternal adverse events was low in the majority of the
complications evaluated. We registered three versus one
case of uterine rupture or dehiscence (RR 3.04, 95% CI
0.3129.13) and one versus four cases of injury to the
bowel or bladder (RR 0.25; 95% CI 0.032.26) in the 39-
week group versus the 38-week group, respectively. We also
found a similar risk of uterine incision lateral tear, proce-
dural difculties, and bleeding needing further treatment in
the two groups. The risk of a composite maternal outcome
was similar in the two groups with proportions of 66/638
women (10.3%) in the 39-week group and 60/636 women
(9.4%) in the 38-week group (RR 1.1; 95% CI 0.791.53).
No signicant treatment by centre interaction was found
for the maternal composite outcome (P = 0.81).
Discussion
Main ndings
In this randomised controlled trial including 1274 pregnant
women, scheduling elective caesarean section at 39
+3
weeks
compared with 38
+3
weeks did not result in a signicant
decrease in neonatal admission within 2 days of birth. In
addition, no secondary neonatal or maternal outcomes
improved signicantly with late scheduling.
Strengths and weaknesses of the study
The major strength of this trial was the randomised design,
which has, to the best of our knowledge, not previously
been used for investigating the association between gesta-
tional age at elective caesarean section and adverse perina-
tal outcomes. With an intention-to-treat analysis, the data
presented reect the whole spectrum of consequences of
timing of elective caesarean from booking of the procedure
to birth of the child. The trial population was homoge-
neous, with approximately 95% being of white European
descent which in this case should be considered a strength,
as neonates delivered by White women in particular may
be vulnerable to performing the elective caesarean section
before rather than after 39 completed weeks of gestation.
14
We had a 100% short-term follow-up rate, which among
other circumstances was related to the fact that if a neonate
required admission within 7 days postpartum, the neonate
was admitted to the NICU in the same hospital as the
delivery. Furthermore, a major advantage compared with
0
50
100
150
200
<
3
8
+
0
3
8
+
0
3
8
+
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3
8
+
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3
8
+
3
3
8
+
4
3
8
+
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3
8
+
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3
9
+
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9
+
1
3
9
+
2
3
9
+
3
3
9
+
4
3
9
+
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3
9
+
6
>
3
9
+
6
N
u
m
b
e
r

o
f

d
e
l
i
v
e
r
i
e
s
Group 39
+3
weeks: gestational age at delivery
Elective delivery
Unscheduled delivery
Figure 3. Gestational age at caesarean section in the 39-week group
in number of weeks + days (n = 623).
1128 2013 RCOG
Glavind et al.
previous studies was a due date validated by ultrasound in
99.8% of the participants.
With this trial we wanted to be able to assess the bal-
ance of potential adverse events or benets of elective
caesarean section timing to the neonate and mother
according to the two timing interventions.
3
Hence, NICU
admission that reects a composite outcome as the pri-
mary outcome should be considered an advantage over
more specic measures. Although the decision to admit
a neonate relies on the physician, this decision is taken
on the basis of objective symptoms or signs necessitating
further observation or treatment, and no neonate would
be hospitalised without a clear indication. At the same
time, admission has implications for the families
involved, because it may lead to separation of mother
and child, anxiety and worries.
Some limitations to this study may apply. In terms of
serious events such as stillbirth, hysterectomy, thrombo
embolism, or death, the study was not powered to evaluate
the inuence of elective caesarean section timing. In a
recent study, Rosenstein et al.
15
found a similar risk of fetal
and neonatal death associated with delivery and expectant
management at 38 weeks, whereas at 39 weeks, delivery
carried a lower risk of neonatal death than expectant man-
agement. Hence, large observational studies would be of
value in this eld. Another limitation to the current study
may be that the outcomes evaluated were all short-term. In
fact, delivery at 38 weeks may lead to increased healthcare
use in early childhood or increased risk of special educa-
tional school needs compared with delivery at 39 weeks of
gestation, but this association has not been investigated in
elective deliveries only.
16,17
Interpretation
Before applying the results to other populations and set-
tings, several factors have to be considered. Overall, the
Table 2. Neonatal outcomes by intervention group: elective caesarean section (ECS) at 38 or 39 weeks of gestation*
ECS 38 weeks
(n = 635)
ECS 39 weeks (n = 637) Relative risk (95% CI) Unadjusted P value
Primary outcome
NICU admission within 48 hours 88 (13.9) 76 (11.9) 0.86 (0.651.15) 0.3136
Secondary outcomes
NICU admission within 7 days of delivery 101 (15.9) 89 (14.0) 0.88 (0.681.14) 0.3460
NICU length of stay 2 days 39 (6.1) 38 (6.0) 0.97 (0.631.50) 0.9070
NICU length of stay in hours, median (IQR) 44.5 (42.246.8) 47.9 (45.650.2) NA 0.6995
Birth weight in g, mean (SD) 3369 (449) 3509 (511) NA <0.0001
Neonate male gender 324 (51.0) 329 (51.6) NA 0.8237
Apgar score at 1 minutes 7 20 (3.1) 24 (3.8) 1.20 (0.672.14) 0.6458
Apgar score at 5 minutes 7 6 (1.0) 12 (1.9) 1.99 (0.755.28) 0.2345
Umbilical artery pH at birth <7.10 5 (1.0) 6 (1.2) 1.24 (0.384.03) 0.7700
Standard base excess 10 3 (0.6) 2 (0.4) 0.69 (0.124.13) 1.0000
Mechanical ventilator treatment** 1 (0.2) 4 (0.6) 3.99 (0.4535.6) 0.3740
CPAP treatment 55 (8.7) 42 (6.6) 0.76 (0.521.12) 0.1711
CPAP treatment 1 day 17 (2.7) 9 (1.4) 0.53 (0.241.18) 0.1178
Continuous oxygen supplementation 23 (3.6) 14 (2.2) 0.61 (0.321.17) 0.1307
Continuous oxygen supplementation 1 day 13 (2.0) 4 (0.6) 0.31 (0.100.94) 0.0296***
Any respiratory morbidity**** 57 (9.0) 43 (6.8) 0.75 (0.511.10) 0.1459
Serious respiratory morbidity***** 11 (1.7) 9 (1.4) 0.82 (0.341.95) 0.6607
Intravenous antibiotic treatment 17 (2.7) 14 (2.2) 0.82 (0.411.65) 0.5916
Intravenous antibiotic treatment 5 days 7 (1.1) 5 (0.8) 0.71 (0.232.23) 0.5788
Treated hypoglycaemia 5 (0.8) 5 (0.8) 1.0 (0.293.43) 1.0000
NA, not applicable.
Data are presented as number (%) unless otherwise indicated. Data were missing for neonates in the following categories: birthweight, one in
38-week group, base excess, 137 in 38-week group and 158 in 39-week group; pH, 135 in 38-week group and 152 in 39-week group,
hypoglycaemia, one in 38-week group and three in 39-week group.
*Two cases of stillbirth were not included in the intention-to-treat analysis.
**Duration was more than 1 day in all neonates treated with mechanical ventilation.
**
*
Bonferroni signicance level 0.05/18 = 0.003.
**
**
Mechanical ventilation, continuous oxygen supplementation or CPAP during the NICU stay.
**
***
Mechanical ventilation, or three or more initiated days of treatment with continuous oxygen supplementation or CPAP during the NICU stay.
2013 RCOG 1129
Timing of elective caesarean section: RCT
study population had a low body mass index and was very
homogeneous, and the study aimed to only include healthy
women with no a priori risks related to the neonate. In
addition, the eligible non-participating women may have
had a lower risk of an adverse neonatal outcome, because
they were probably booked closer to their due date (more
breech presentations) and fewer women were to have
repeat procedures.
The NICU admission rate was quite high compared with
those of other studies.
8,9
This may be a consequence of all
neonatal admissions being included, whereas studies con-
ducted in facilities with differentiated levels of neonatal
care may have excluded neonatal admissions that were not
to the NICU. Comparing the incidence of a composite
adverse neonatal outcome after caesarean delivery at 38
and 39 weeks of gestation, Tita et al.
8,9
found an odds
ratio of 0.67 and Wilmink et al. found an odds ratio of
0.71 in favour of delivery at 39 weeks of gestation, which
are both estimates that lie within our calculated 95% CI of
0.651.15. Our primary outcome may compare with these
composites, which in our setting in each case would proba-
bly translate into NICU admission. Some of the excess
morbidity in our trial may be explained by prematurity or
unscheduled procedures because of complications or
labour. Still, these studies reported signicant benet of
elective caesarean section at 39
+06
weeks compared with
1 week earlier, in opposition to the smaller (insignicant)
differences observed in our trial.
8,9
In terms of maternal morbidity, the most interesting
aspect before the trial was whether more women with
spontaneous onset of labour in the late ECS group would
result in an increase in the number of women with infec-
tion or intraoperative complications because of the urgency
of the procedure. Apart from maternal intensive care
admission not being evaluated in our sample, the individ-
ual adverse outcomes otherwise assessed were comparable
P
e
r
c
e
n
t
a
g
e

i
n

g
r
o
u
p
15
10
5
0
38
+3
weeks group 39
+3
weeks group
<1 day 12 days
27 days 7 days
Figure 4. NICU length of stay in days in neonates admitted within
48 hours of delivery. NICU length of stay proportion in 38-week group
versus 39-week group was 1 day: 5.5% versus 4.4%; 12 days:
2.2% versus 1.6%; 27 days: 3.0% versus 3.1%; and 7 days:
3.1% versus 2.8%, respectively.
Table 3. Maternal individual and composite outcomes by intervention group: elective caesarean section (ECS) at 38 or 39 weeks of gestation
ECS 38 weeks
(n = 636)
ECS 39 weeks (n = 638) Relative risk (95% CI) Unadjusted P value
Uterine incision lateral tear 17 (2.7) 16 (2.5) 0.94 (0.481.84) 0.8622
Bowel or bladder injury 4 (0.6) 1 (0.2) 0.25 (0.032.22) 0.2173
Adherences, procedural or delivery complications 14 (2.2) 16 (2.5) 1.14 (0.562.31) 0.8538
Anaesthesia complications 2 (0.3) 7 (1.1) 3.49 (0.7316.7) 0.1781
Rupture or dehiscence 1 (0.2) 3 (0.5) 3.0 (0.31 28.7) 0.6244
Bleeding needing treatment or transfusion 9 (1.4) 12 (1.9) 1.33 (0.563.13) 0.6610
Reoperation* 10 (1.6) 6 (0.9) 0.60 (0.221.64) 0.3286
Antibiotic treatment within 30 days of delivery** 15 (2.4) 14 (2.2) 0.93 (0.451.91) 0.8537
Blood loss at delivery >500 ml 138 (21.7) 109 (17.1) 0.79 (0.630.99) 0.0399***
Composite maternal outcome**** 60 (9.4) 66 (10.3) 1.1 (0.791.53) 0.6391
Data are presented as number (%). Data were missing in the following outcomes: surgical outcomes: one case in 38-week group, two in 39-
week group; bleeding: nine cases in 38-week group, 11 cases in 39-week group; uterotonic perioperative medications: three cases in each group.
*Included in 38-week versus 39-week group: Evacuation (three versus two), wound revision (two versus two), and other operations (ve versus
two).
**Included in 38-week group versus 39-week group: Endometritis (four versus one), wound infection (six versus ve), and other procedure-related
infection (ve versus eight).
***Bonferroni adjusted level of signicance 0.05/9 = 0.006.
****Dened by any of the following events: uterine incision lateral tear, injury to bowel or bladder, procedural or anaesthesia complications,
rupture or dehiscence, bleeding needing additional treatment, re-operation, or antibiotic treatment.
1130 2013 RCOG
Glavind et al.
with the composite outcome of Tita et al.
10
We found a
higher proportion of composite maternal outcome in both
groups (9.4% versus Tita et al.
10
7.5% at 38 weeks and
10.3% versus Tita et al. 6.6% at 39 weeks), but similarly,
no difference was found between the 2 weeks of gestation.
This may reect the fact that unscheduled caesarean sec-
tions were included in our population.
When this study was initiated, a substantial number of
elective caesarean sections in Denmark were scheduled
before 39 weeks of gestation. Recently published literature
on the timing of elective caesarean section almost uniformly
advises against elective caesarean section before 39 com-
pleted weeks.
4,8,9,1822
The risk estimates from this trial are
currently the only estimates available from a randomised
trial, and they could be interpreted in different ways. If the
power calculations overestimated the difference in NICU
admission between the two groups, this study would be
underpowered to detect a statistically signicant difference.
Assuming a valid power calculation, our study has an 80%
chance that the ndings were correct. We predicted (and
found) that 14% of the 38-week group neonates would be
admitted to the NICU, whereas the risk of NICU admission
in the 39-week group was almost 50% higher than expected.
This difference could be explained by an increased risk of an
adverse outcome in women who were delivered before their
scheduled date because of complications or labour. Interest-
ingly, the proportion of neonates with an NICU length of
stay >2 days was almost identical in the two groups. This
may indicate that even if more neonates were admitted with
elective caesarean section at 38 weeks, there was a similar
risk of severe neonatal morbidity in the two groups.
Our results could suggest that scheduling elective caesar-
ean section after the prevailing cut-off at 39
+0
weeks of gesta-
tion may have less impact on short-term neonatal morbidity
than previously anticipated. In the mothers, timing of elec-
tive caesarean section at 38 or 39 weeks seems to carry a sim-
ilar risk of adverse events. Accordingly, scheduling of elective
caesarean section 35 days before 39
+0
completed weeks may
be an acceptable option in women in whom an acute caesar-
ean section delivery should be avoided. Otherwise, schedul-
ing after 39 completed weeks may continue to be the best
option, until further trials support the evidence from this
study, and possible long-term consequences of elective cae-
sarean section timing are claried.
Conclusions
In conclusion, elective caesarean section scheduled after
39 weeks of gestation versus before 39 weeks carried a
similar risk of neonatal special care admission. The inci-
dence of other adverse neonatal and maternal outcomes
was similar in the two groups. Any long-term consequences
to the neonate or mother of elective caesarean timing at
term are uncertain and need further investigation.
Disclosure of interests
The authors have no conicts of interest.
Contribution to authorship
JG, SFK, NU and TBH had the idea for the study and were
responsible for the data analysis. JG was the principle inves-
tigator and wrote the rst draft of the protocol and the
manuscript. JG, SFK, NU and TBH contributed to the gath-
ering of data from the University Hospital of Aarhus and
were responsible for the overall supervision of the trial man-
agement. MK was the responsible investigator at the Hospi-
tal in Kolding. AMM was the responsible investigator at
Aalborg University Hospital. BBM was the responsible
investigator at the Regional Hospital of Viborg. OBR was
the responsible investigator at the Regional Hospital of Ran-
ders. JTC was the responsible investigator at the Regional
Hospital of Herning. JSJ was the responsible investigator at
Odense University Hospital. Guarantors for the study were
JG, NU and TBH. All authors had full access to the data in
the study and take responsibility for the integrity of the data
and the accuracy of the data analysis. All authors reviewed
and approved the nal version of the paper.
Details of ethics approval
The study was approved by The Central Denmark Region
Committees on Biomedical Research (ID M-20080142).
Funding
The study was supported by grants from The Danish
Council for Independent Research Medical sciences, Health
Research Fund of Central Denmark Region, The Philan-
thropic Foundation TrygFonden, Aase and Ejnar Daniel-
sens Foundation, Sophus Jacobsens Foundation, Dagmar
Marshalls Foundation, Marie Dorthea and Holger From,
Haderslevs Foundation. The funders of the study had no
role in study design, data collection and analysis, or prepa-
ration of the manuscript.
Acknowledgements
We wish to thank all the families who participated in this
trial, the dedicated staff from all participating departments,
and our trial steering committee members.
&
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