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\begin{document}

\title{Cesarean section in the second delivery to prevent anal incontinence
after asymptomatic obstetrical anal sphincter injury: the EPIC
multicenter randomized trial}



\author[1]{laurent abramowitz}%
\author[2]{Laurent Mandelbrot}%
\author[3]{Agnes Bourgeois-Moine}%
\author[4]{Arnaud Le Tohic}%
\author[3]{Celine De Carné Carnavalet}%
\author[5]{Olivier Poujade}%
\author[3]{Carine Roy}%
\author[3]{Florence Tubach}%
\affil[1]{APHP}%
\affil[2]{Hopital Louis-Mourier}%
\affil[3]{AP-HP}%
\affil[4]{Centre Hospitalier de Versailles Service de Gynecologie et Obstetrique}%
\affil[5]{Beaujon Hospital, AP-HP}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: To determine whether planned cesarean section (CS) for a
second delivery protects anal continence in women with obstetrical anal
sphincter lesions. Design: Randomized trial. Setting: 6 maternity units
in the Paris area. Sample : Women at high risk of sphincter lesions
(first delivery with 3d degree laceration and/or forceps) but no
symptomatic anal incontinence. Methods : Endoanal ultrasound was
performed in the third trimester of the second pregnancy. Women with
sphincter lesions were randomized to planned CS or vaginal delivery
(VD). Main outcome measures : Anal continence at 6 months post-partum.
Secondary outcomes were urinary continence, sexual morbidity, maternal
and neonatal morbidities and worsening of external sphincter lesions.
Results : Anal sphincter lesions were detected by ultrasound in 264/434
women enrolled (60.8\%) ; 112 were randomized to planned VD and 110 to
planned CS. At 6-8 weeks after delivery, there was no significant
difference in anal continence between the 2 groups. At 6 months after
delivery, median Vaizey scores of anal continence were 1 {[}IQR 0-4{]}
in the CS group and 1 {[}IQR 0-3{]} in the VD group (p = 0.34). There
were no significant differences for urinary continence, sexual functions
or for other maternal and neonatal morbidities. Conclusions : In women
with asymptomatic obstetrical anal sphincter lesions diagnosed by
ultrasound, planning a CS had no significant impact on anal continence 6
months after the second delivery. These results do not support advising
systematic CS for this indication.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Anal incontinence is a source of distress for patients, with a major
impact on sexual health \textsuperscript{1} and quality of
life\textsuperscript{2,3}. It is a frequent symptom \textsuperscript{4},
with a prevalence 14.8\% among women in a population-based study in the
United States \textsuperscript{5}. Obstetrical anal sphincter injuries
(OASIS) are visible third or fourth-degree perineal lacerations,
reported in 2 to 12\% of vaginal deliveries \textsuperscript{6,7}.
Occult anal sphincter lesions, which are not noticed at the time of
delivery, can be detected by systematic endoanal ultrasonography in up
to 27\% of women after their first vaginal delivery\textsuperscript{8}.
Anal sphincter lesions may result in anal incontinence in 9\% of
women\textsuperscript{7,8}. Instrumental delivery is the most important
risk factor for anal incontinence, with anal sphincter lesions reported
in up to 63\% to 82 \% of forceps deliveries \textsuperscript{8} and
anal incontinence in 23 \% \textsuperscript{8}. Post-delivery anal
incontinence decreases over time, but it contributes to anal
incontinence in the long term \textsuperscript{9}.

In case of anal sphincter lesions at the first delivery, cesarean
section (CS) is often discussed for subsequent deliveries, with the
purpose of protecting anal function. However, recommendations differ
between countries and centers. \textsuperscript{10}
\textsuperscript{1112}. Current ACOG guidelines state that women with a
history of OASIS who are asymptomatic and without any evidence of
sphincter compromise may be allowed to have a vaginal delivery, however
it is reasonable to perform a cesarean delivery based on patient
request\textsuperscript{13}. To date there is no high-level evidence
from a randomized trial to inform the decision\textsuperscript{13} . The
potential benefit needs to be proven, since CS is a major surgical
procedure with risks for the mother and infant \textsuperscript{14},
including maternal morbidities and mortality at the time of the surgery
and during subsequent pregnancies\textsuperscript{15}. In recent
retrospective cohort studies comparing CS versus repeat VD in women with
a history of anal sphincter lesions, no significant difference was found
in the incidence of anal incontinence \textsuperscript{9,16}. However,
the limitations were the potential indication bias inherent to
observational studies and the retrospective design. The potential
benefit of prophylactic CS on urinary incontinence, quality of life and
sexual functions also must be addressed, as they deeply impact quality
of life \textsuperscript{2,17}. Our main purpose was to evaluate whether
anal incontinence could be prevented by planned CS for the second
delivery, in women with asymptomatic anal sphincter disruption after the
first delivery.

\textbf{Methods}

\emph{Study design}

The multicenter, prospective, randomized, open EPIC (Etude de Pr\selectlanguage{ngerman}évention
de l'Incontinence par Césarienne) trial compared planned CS to planned
VD for the second delivery in women with a history of a traumatic first
delivery with anal sphincter lesions on endosonography and no
self-reported anal incontinence at baseline.

Women were recruited in 6 maternity units in the Paris area (5 academic
centers and 1 general hospital), between 01/04/2008 and 29/12/2014, with
their written, informed consent for each of the 2 steps of the study.
The study was approved by an ethics committee (Comité de Protection des
Personnes Ile de France V, Paris, France).

\emph{Participants}

Women having a history of a traumatic first delivery were first assessed
for eligibility for anal ultrasonographic examination by the
obstetrician at clinic visits in the third trimester of their second
pregnancy. Women were eligible if they had a first vaginal instrumental
delivery with forceps (vacuum extractions were not considered) and/or
with a diagnosis of a third-degree perineal tear, had no self-reported
anal incontinence at inclusion, were 18 years old or over, and signed
informed consent to participate. The main exclusion criteria were a
history of anal surgery, a fourth-degree perineal tear at the first
delivery, self-reported AI, defined as involuntary leakage of gas or
stools and any other indication for planned CS for non-proctologic
reasons. After inclusion, women had a proctological evaluation including
the Vaizey score \textsuperscript{18} and anal endosonography with the
same expert operator (LA).The Vaizey score was chosen for its
sensitivity by accounting for 24 components of AI, including the loss of
flatus with or without the loss of liquid and solid stool, pad use,
stool urgency, medication use and quality of life. Endosonography was
performed with an ultrasound scanner with a rotating rectal probe, a
multifrequency of 7-10 MHz,and a hard sonolucent plastic cone (Bruel and
Kjaer,Naemm, Denmark). Three anal canal levels (upper,middle, and lower)
were studied and recorded (videorecorder, Sony, Tokyo, Japan). External
anal sphincter lesions, as well as any internal sphincter lesions, were
characterized as defined by Law et al. \textsuperscript{19}, according
to defect angle and defined as severe if more than 90°. In case of anal
sphincter lesions at endosonography, the patient was eligible for the
randomized part of the trial.

\emph{Trial procedures}

Women with external anal sphincter lesions at ultrasound were offered to
participate in the randomized trial, and if they consented were assigned
(1:1 ratio) to planned CS at 39 weeks' gestation or vaginal delivery.
Concealment was obtained by use of a computer-generated randomization
scheme, in various-sized blocks, stratified by center, and by use of
separate serialized sealed and opaque envelopes prepared by the sponsor.
Investigator or participant blinding to group assignment was not
feasible, but investigators were unaware of aggregate outcomes during
the study, since the analysis was performed only after the follow-up
period was completed and the database was frozen. In the vaginal
delivery group, the management of the delivery, including episiotomy,
forceps or vacuum, was left to the appreciation of the clinician. In
case of an emergent indication for CS unrelated to the issue of anal
sphincter protection, according to the obstetrician, cross-over was
allowed.

\emph{Outcomes}

Standard obstetrical and perinatal outcomes were recorded at delivery
and the post-partum period. Study visits were planned with the
proctologist and the obstetrician at 6-8 weeks post-partum and 6 months
(up to 24 months). The 6-8 weeks and 6 months follow-up visit included
the Vaizey, Wexner, FSFI, physical and mental SF12 and MUH scores. In
addition, the 6-months visit included an anal ultrasound examination.
The primary outcome was anal incontinence at 6 months after delivery
(M6), as measured by the Vaizey score \textsuperscript{18}. Secondary
endpoints were anal incontinence (Vaizey score) at 6 to 8 weeks after
delivery (W6-8); post-partum transient anal incontinence (at least 1
stool and/or at least 2 gas leakages after delivery, which has
disappeared at W6-8), maternal morbidities (hemorrhage, uterine rupture,
placenta accreta, hematomas, cervico-vaginal lacerations, hemoperiteum,
organ wounds, anesthesic complications, infections, deep vein
thrombosis), fetal/neonatal morbidities (respiratory distress,
infection, acidosis, trauma, neonatal intensive care), urinary
continence meaured with the Measurement of Urinary Handicap (MUH) score,
quality of life with the 12-Item Short-Form Health Survey (SF12)
score\textsuperscript{20}, women's sexuality with the Female Sexual
Function Index (FSFI) \textsuperscript{21}~and worsening of external
sphincter lesions (defined as increase of angulation from baseline of
more than 10 degrees) measured 6 months after delivery.

\emph{Statistical analysis}

Assuming a mean (SD) Vaizey score at M6 of 5 (6) in the control
group\textsuperscript{8,18}, 86 women/group would provide 90\% power at
a 2-sided \selectlanguage{greek}α-\selectlanguage{english}level of 0.05 to detect a clinically meaningful difference
of mean Vaizey score of 3 between groups. The target for enrollment was
increased to account for potential loss to follow-up..

Baseline characteristics are reported by trial group (CS and VD) as
numbers (\%) for categorical variables and means (\selectlanguage{ngerman}± standard deviations,
SD) or medians {[}interquartile range, IQR{]} for continuous variables,
as appropriate.

All analyses were performed according to the intention-to-treat (ITT)
principle. Missing data were handled using multiple imputations (5
datasets) on principal and secondary endpoints except maternal and
neonatal outcomes. The Vaizey score at M6 post-partum was compared
between CS and VD groups using a permutation test, as this variable was
not normally distributed and showed a floor effect. A post-hoc subgroup
analysis of the primary outcome was conducted in the 27 women with
Vaizey scores \selectlanguage{english}[?]5 (a cut-off usually defining anal
incontinence\textsuperscript{22}) at the prenatal visit, after testing
positive for interaction with trial arm. Secondary outcomes were
compared between VD and CS groups using Chi-square or Fisher exact test,
Student, Wilcoxon or permutation test as appropriate.

All statistical analyses were performed using SAS V.9.4 (SAS Institute
Inc., Cary, North Carolina, USA).

\textbf{Results}

A total of 549 women were included, of whom 434 had anal endosonography,
which showed that 264 (60.8\%) had anal sphincter lesions. Of these, 222
(84.1\%) accepted to be randomized, 112 were assigned to planned VD and
110 to planned CS (Figure 1, Flowchart). Among the 222 randomized women,
20 (9.0\%) had third-degree perineal tears during spontaneous VD at the
first delivery and 202 (91.0\%) had forceps delivery including 140
(71.1\%) without perineal tears and 29 (14.7\%) with third-degree
perineal lacerations (table 1). Although according to the eligibility
criteria, none of the women self-reported any anal incontinence symptom
at inclusion, the Vaizey score was calculated during the data analysis
as being \selectlanguage{english}[?]5 in 27 women before the second delivery, corresponding to the
definition of symptomatic anal incontinence. The flow chart is reported
in figure 1. Women who did not complete the M6 visit did not differ from
those who completed this visit except for age (see supplementary
appendix).

\emph{Trial procedures}

For the second delivery, 17 (15.6\%) women in the VD arm had CS for
obstetrical indications, whereas 18 (16.5\%) women in the CS arm
delivered vaginally (table 2). In the VD arm, 5 women had (5.5\%)
forceps delivery and 1 (1.9\%) 3d degree lacerations during spontaneous
VD. Description of the second deliveries is reported in table 2.

\emph{Outcomes}

Primary and secondary outcomes are reported in Table 3. At W6-8 after
delivery, anal incontinence was not statistically different between
trial arms, nor was post-partum transient anal incontinence (11.7\% in
the CS arm vs 25.0\% in the VD arm (absolute risk difference {[}95\%
CI{]}: -13.3 {[}-25.1 to 0.0{]}).

At M6, the median {[}IQR{]} Vaizey score for anal incontinence was 1/24
{[}0-4{]} in the CS arm vs 1/24 {[}0-3{]} in the VD arm (p=0.34) (figure
2). This primary outcome was actually measured at a median {[}IQR{]}
time of 8.0 {[}6.8 -- 11.2{]} months post-partum. When comparing Vaizey
scores at inclusion and at the M6 visit, the results did not differ
between the CS and VD groups (median (IQR) differences 0.0
{[}-1.5-2.0{]} and 0.0 {[}0.0-1.0{]}, respectively, p = 0.9825). The
effect of trial arm on Vaizey score at M6 differed between women with
Vaizey score at inclusion \textless{}5 and women with Vaizey score at
inclusion \selectlanguage{english}[?]5 (significant interaction, p=0.008). Post-hoc subgroup
analyses showed that in the subgroup of 27 women with a Vaizey score
before delivery \selectlanguage{english}[?]5, Vaizey score at M6 were significantly lower in the
CS than in the VD arm (median 3 IQR {[}0-7{]} vs 6 {[}3.5-8.5{]},
p=0.026).

At M6, there was no statistically significant difference between groups
for urinary incontinence (MUH score), sexual function (FSFI) and
physical and mental quality of life assessed with SF12.

Regarding maternal morbidity, 4 (4.9\%) patients had at least one minor
complication in the VD arm and 8 (8.8\%) in the CS arm, including 3
(3.3\%) anesthetic complications (headaches) in the CS arm and none in
the VD arm. For neonatal outcomes, 5 (6.1\%) had at least one
complication in the VD arm including 4 transfers to neonatal care units
(2 for respiratory distress and 2 for infection) versus none in the CS
arm.

Among the 222 randomized women, 125 (56.3\%) had post-partum
endosonography at the M6 visit, 61 (54.5\%) in the VD arm and 64
(58.2\%) in the CS arm. Baseline characteristics of these women did not
differ from those without endosonography (see supplementary appendix).
External sphincter lesions deteriorated more frequently in the VD arm
than in the CS arm (11 (22.4\%) women vs 1 (2.2\%), absolute risk
difference -20.2 {[}95\% CI: -31.7 to -7.6{]}), but no additional
internal sphincter lesions were observed.

\textbf{Discussion}

\textbf{Main Findings :} In this randomized trial of women with
asymptomatic anal sphincter lesions resulting from a first delivery,
planned cesarean section for the second delivery was not protective
against anal incontinence at 6 months post-partum. In addition, we
failed to show any benefit of cesarean section in this population on
quantitative evaluations of urinary incontinence, sexual functions or
quality of life. These results should be useful for clinicians and
women, avoiding numerous unnecessary cesarean
sections\textsuperscript{12}.

\textbf{Results vis-a-vis other studies :} Our findings are consistent
with those from recent observational studies, including longer
follow-up\textsuperscript{16,23}. In a recent observational cohort
study, CS for women with anal sphincter disruption at the first delivery
was associated with no benefit on anal incontinence 5 years after the
second delivery \textsuperscript{16}. However, most women who sustained
obstetric injuries develop anal incontinence later, after their 50s.
Nygaard et al \textsuperscript{24} found that anal sphincter disruption
following an index delivery was a risk factor for flatus incontinence 30
years later. Some large population-based cohort studies failed to show
any difference in the incidence of flatus incontinence in women above 50
years old, according to whether they delivered vaginally or by
CS\textsuperscript{17}, but a recent population-based study from Sweden
found that the risk of anal incontinence was lower after CS than after
VD \emph{\textsuperscript{25}} . In this study, AI also was higher among
women who delivered by CS compared with nulliparous and higher among
nulliparous compared with men. In another study, an association has been
found between ultrasound diagnosis of anal sphincter lesions and
long-term fecal incontinence after a first delivery\textsuperscript{26}.
Because anal incontinence is multifactorial, including neurological and
gastro-intestinal as well as mechanical causes, this symptom can occur
without sphincter lesions and vice versa. Anal sphincter lesions are
observed by ultrasound in less than half of women with postpartum anal
incontinence \textsuperscript{8}. In an unselected primiparous
population, anal sphincter disruption was detected by ultrasound
screening after delivery in 27 \% of women, most of whom had no symptoms
\textsuperscript{27}. Thus, although CS can be protective from anal
sphincter lesions \textsuperscript{8, 9}, ultrasound evidence is one of
many factors associated with anal continence. Besides, it has been shown
that the severity of the anal sphincter lesion is an important risk
factor for subsequent anal incontinence, particularly the depth of the
disruption of both the external and internal sphincter
\textsuperscript{28}. In our trial, we did not observe a protective
effect of CS in the subgroup with severe anal sphincter ruptures
(defined as \textgreater{}90deg)(data not shown). In another study, only
4th-degree tears were associated with an increased risk of anal
incontinence at 10 months postpartum\textsuperscript{29}, but this was
an exclusion criterion in our trial.

One important difference between our study and most retrospective
studies was the inclusion of women whose first delivery was by forceps,
even in the absence of a diagnosis of a third-degree perineal
laceration.

Some observational studies have shown that a subsequent vaginal delivery
following an obstetrical anal sphincter injury may result in additional
or recurrent lesions \textsuperscript{30}, which may be apparent or
occult, however without any significant change in the continence score
according to the mode of delivery. In our trial, the incidence of
repeated clinically apparent OASIS was low, since only one woman had a
repeated 3\textsuperscript{rd} degree tear.

Endosonographic aggravation of external sphincter lesions occurred
significantly more often in the VD group than the CS group. These
findings may indicate that CS avoids some occult sphincter disruptions,
but on the other hand they signify that ultrasound evidence of anal
sphincter lesions is not predictive of symptoms of anal incontinence.

\textbf{Clinical implications:} Our results do not support a policy of
systematic prophylactic CS in women with asymptomatic ultrasound anal
sphincter lesions resulting from a first delivery. However, we cannot
exclude a protective effect of prophylactic CS for women with
symptomatic anal sphincter lesions. In a subgroup analysis, we did find
a significant benefit of CS among women with mild clinical anal
incontinence detected before the second delivery at the proctological
visit. Since it is a post-hoc analysis, it must be interpreted with
caution. Our findings underline the importance of correct diagnosis of
anal incontinence.

Because of the taboos surrounding anal incontinence, it is difficult to
reveal without meticulous questioning. In our study, 27 women
self-reported no anal incontinence at inclusion, but had a Vaizey score
\selectlanguage{english}[?]5 at the visit with a proctologist. Comparatively to endosonography,
clinical-based diagnosis of anal incontinence is less expensive, more
accessible and appears to be more predictive of functional outcome, as
has been previously suggested in retrospective
studies\textsuperscript{16,23}. Thus, our findings do not support
performing anal endosonography for women with an overt OASI or forceps
instrumentation for their first delivery in order to decide on the mode
of delivery.

\textbf{Research Implications :} Further studies are needed to determine
whether CS may be useful in the long term, among women with mildly
symptomatic anal lesions, and if so whether women with third- or
fourth-degree perineal tears and/or forceps at their first delivery can
benefit from a proctological examination in order to make a decision
regarding their subsequent deliveries.\textsuperscript{8}

\textbf{Strengths/Limitations:} This trial has several strengths. To our
knowledge, it is the first randomized controlled trial addressing this
issue. Also, anal incontinence was assessed with a standardized,
validated and widely used score, the Vaizey score, and sphincter lesions
were defined by endosonography. Third, the external validity was
supported by the diversity of trial settings, including teaching
hospitals and general hospitals in diverse populations from
neighborhoods ranging from poor to affluent, with no center effect.

This trial also has limits. It was necessarily unblinded, and the main
outcomes were patient-reported, thus we cannot exclude patient reporting
bias. However, all investigators were unaware of aggregate outcomes
during the study. Also, crossovers were observed (cesareans in the
vaginal delivery group and vice versa), as expected in this pragmatic
trial comparing strategies (planned CS or planned VD). Lastly, one fifth
of the randomized women did not complete the 6 months post-partum
follow-up, which could lead to attrition bias; however their
characteristics did not differ between the two study groups, and
multiple imputations were performed for missing variables and
comparisons were based on all the patients randomized.

\textbf{Conclusion}

In this randomized trial of women with anal sphincter lesions resulting
from their first delivery, anal incontinence was rare 6 months after
second delivery and planned CS was not associated with a decrease of
this risk. These findings are not in favor of recommending CS for
subsequent deliveries in case of asymptomatic obstetrical anal sphincter
lesions. \textbf{Acknowledgmen} ts

We thank Coralie Gernez, Amandine Fauquembergue, Aline Dechanet and
Marion Schneider from the Unite de Recherche Clinique of Hopital
Bichat--Claude-Bernard for their efforts in project management,
enrollment, data collection, monitoring and data management of the
trial, all the staff members of the participating maternities, the women
who participated.

We also thank Drs Anabela RODRIGUES, Amelie BENBARA and Guillaume GIRARD
for strong motivation of womens inclusions.

\textbf{All the authors report no conflict of interest.}

\textbf{Contribution to authorship}

LA, FT and ABM contributed to the design of this study. LA, ALT, CCC, OP
included most of the patients. LA, LM, CR and FT conducted the analyses
and LA, LM, ABM, ALT, CCC, OP, CR and FT contributed to the
interpretation of data. LA, LM and FT drafted the manuscript and all the
authors critically revised the manuscript and approved the version to
published.

\textbf{Trial Registration} : EPIC trial. ClinicalTrials.gov number,
NCT00632567

This study (Ndeg ID-RCB 2006-A00518-43) was approved by the Comite de
Protection des Personnes (Ethical Human Subjects Protection Review)
Paris-Ile-de-France V of Saint Antoine Hospital PARIS 12 on the 02
October 2007 (ndeg07709) and French Health Authority on 22 October 2007
(Ref: DGS2007-0188).



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15. Ducarme G, Pizzoferrato AC, de Tayrac R, et al. Perineal prevention
and protection in obstetrics: CNGOF clinical practice guidelines.\emph{J
Gynecol Obstet Hum Reprod} 2019; \textbf{48} (7): 455-60.

16. Jango H, Langhoff-Roos J, Rosthoj S, Sakse A. Mode of delivery after
obstetric anal sphincter injury and the risk of long-term anal
incontinence. \emph{Am J Obstet Gynecol} 2016; \textbf{214} (6): 733 e1-
e13.

17. Fritel X, Ringa V, Varnoux N, Zins M, Breart G. Mode of delivery and
fecal incontinence at midlife: a study of 2,640 women in the Gazel
cohort. \emph{Obstet Gynecol} 2007; \textbf{110} (1): 31-8.

18. Vaizey CJ, Carapeti E, Cahill JA, Kamm MA. Prospective comparison of
faecal incontinence grading systems. \emph{Gut} 1999; \textbf{44} (1):
77-80.

19. Law PJ, Bartram CI. Anal endosonography: technique and normal
anatomy. \emph{Gastrointest Radiol} 1989; \textbf{14} (4): 349-53.

20. Ware J, Jr., Kosinski M, Keller SD. A 12-Item Short-Form Health
Survey: construction of scales and preliminary tests of reliability and
validity. \emph{Med Care} 1996; \textbf{34} (3): 220-33.

21. Rosen R, Brown C, Heiman J, et al. The Female Sexual Function Index
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female sexual function. \emph{J Sex Marital Ther} 2000; \textbf{26} (2):
191-208.

22. Perry S, Shaw C, McGrother C, et al. Prevalence of faecal
incontinence in adults aged 40 years or more living in the
community.\emph{Gut} 2002; \textbf{50} (4): 480-4.

23. Fradet-Menard C, Deparis J, Gachon B, et al. Obstetrical anal
sphincter injuries and symptoms after subsequent deliveries: A 60
patient study. \emph{Eur J Obstet Gynecol Reprod Biol} 2018;\textbf{226}
: 40-6.

24. Nygaard IE, Rao SS, Dawson JD. Anal incontinence after anal
sphincter disruption: a 30-year retrospective cohort study. \emph{Obstet
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25. Larsson C, Hedberg CL, Lundgren E, Soderstrom L, TunOn K, Nordin P.
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(10177): 1233-9.

26. Guzman Rojas RA, Salvesen KA, Volloyhaug I. Anal sphincter defects
and fecal incontinence 15-24 years after first delivery: a
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(5): 677-83.

27. Faltin DL, Boulvain M, Irion O, Bretones S, Stan C, Weil A.
Diagnosis of anal sphincter tears by postpartum endosonography to
predict fecal incontinence. \emph{Obstet Gynecol} 2000; \textbf{95} (5):
643-7.

28. Roos AM, Thakar R, Sultan AH. Outcome of primary repair of obstetric
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29. Laine K, Skjeldestad FE, Sanda B, Horne H, Spydslaug A, Staff AC.
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(4): 319-24.

30. Fitzpatrick M, Cassidy M, Barassaud ML, et al. Does anal sphincter
injury preclude subsequent vaginal delivery? \emph{Eur J Obstet Gynecol
Reprod Biol} 2016; \textbf{198} : 30-4.

\textbf{Figure: Enrollment, Randomization, and Follow-up of the Study
Participants}

\textbf{Table 1. Baseline characteristics of women randomized*}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& \textbf{Total} \textbf{(N=222)} & \textbf{Vaginal delivery group}
\textbf{(N=112)} & \textbf{Cesarean section group}
\textbf{(N=110)}\tabularnewline
\midrule
\endhead
Lost to follow-up & 4 & 3 & 1\tabularnewline
Presentation Cephalic, no. (\%) Breech, no. (\%) Transverse, no. (\%) &
208 (95.4) 6 (2.8) 4 (1.8) & 107 (98.2) 1 (0.9) 1 (0.9) & 101 (92.7) 5
(4.6) 3 (2.8)\tabularnewline
Actual mode of delivery Vaginal, no. (\%) Cesarean, no. (\%) & 110
(50.5) 108 (49.5) & 92 (84.4) 17 (15.6) & 18 (16.5) 91
(83.5)\tabularnewline
In case of vaginal delivery Vacuum, no. (\%) Forceps, no. (\%) Anterior
presentation, no. (\%) \emph{Missing data} Posterior presentation, no.
(\%) Episiotomy, no. (\%) Perineal laceration, no. (\%)
1\textsuperscript{st} degree 2\textsuperscript{nd} degree 3d degree
Shoulder dystocia, no. (\%) Birthweight (g), mean \selectlanguage{ngerman}± SD Duration of first
stage of labor (hours), median {[}IQR{]} Duration of active pushing
(min), median {[}IQR{]} & 4 (3.7) 5 (4.6) 100 (96.2) \emph{6 (5.5)} 2
(1.9) 34 (31.2) 57 (52.3) 47 (82.5) 9 (15.8) 1 (1.8) 2 (2.5) 3408 \selectlanguage{ngerman}± 450
4.0 {[}3.0 - 5.0{]} 11.0 {[}5.0 -15.0{]} & 3 (3.3) 5 (5.5) 84 (95.5)
\emph{4 (4.5)} 2 (2.3) 28 (30.4) 52 (56.5) 42 (80.8) 9 (17.3) 1 (1.9) 2
(2.8) 3420 \selectlanguage{ngerman}± 435 4.0 {[}3.0 - 5.0{]} 12.0 {[}5.0 - 16.0{]} & 1 (5.6) 0
(0.0) 16 (100.0) \emph{2 (11.1)} 0 (0.0) 6 (35.3) 5 (29.4) 5 (100.0) 0
(0.0) 0 (0.0) 0 (0.0) 3325 \selectlanguage{ngerman}± 559 3.0 {[}1.5 - 4.5{]} 9.5 {[}7.0 -
10.0{]}\tabularnewline
Treatments after 2nd delivery Iron supplements, no. (\%) Laxatives, no.
(\%) & 21 (13.8) 8 (5.3) & 14 (20.0) 4 (5.7) & 7 (8.5) 4
(4.9)\tabularnewline
\bottomrule
\end{longtable}

\begin{quote}
*There was no significant differences (p\textless{}0.05) between the
trial arms.
\end{quote}

\emph{} \textbf{Table 2. Description of the second deliveries*}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& \textbf{Total} \textbf{(N=222)} & \textbf{Vaginal delivery group}
\textbf{(N=112)} & \textbf{Cesarean section group}
\textbf{(N=110)}\tabularnewline
\midrule
\endhead
Lost to follow-up & 4 & 3 & 1\tabularnewline
Presentation Cephalic, no. (\%) Breech, no. (\%) Transverse, no. (\%) &
208 (95.4) 6 (2.8) 4 (1.8) & 107 (98.2) 1 (0.9) 1 (0.9) & 101 (92.7) 5
(4.6) 3 (2.8)\tabularnewline
Actual mode of delivery Vaginal, no. (\%) Cesarean, no. (\%) & 110
(50.5) 108 (49.5) & 92 (84.4) 17 (15.6) & 18 (16.5) 91
(83.5)\tabularnewline
In case of vaginal delivery Vacuum, no. (\%) Forceps, no. (\%) Anterior
presentation, no. (\%) \emph{Missing data} Posterior presentation, no.
(\%) Episiotomy, no. (\%) Perineal laceration, no. (\%)
1\textsuperscript{st} degree 2\textsuperscript{nd} degree 3d degree
Shoulder dystocia, no. (\%) Birthweight (g), mean \selectlanguage{ngerman}± SD Duration of first
stage of labor (hours), median {[}IQR{]} Duration of active pushing
(min), median {[}IQR{]} & 4 (3.7) 5 (4.6) 100 (96.2) \emph{6 (5.5)} 2
(1.9) 34 (31.2) 57 (52.3) 47 (82.5) 9 (15.8) 1 (1.8) 2 (2.5) 3408 \selectlanguage{ngerman}± 450
4.0 {[}3.0 - 5.0{]} 11.0 {[}5.0 -15.0{]} & 3 (3.3) 5 (5.5) 84 (95.5)
\emph{4 (4.5)} 2 (2.3) 28 (30.4) 52 (56.5) 42 (80.8) 9 (17.3) 1 (1.9) 2
(2.8) 3420 \selectlanguage{ngerman}± 435 4.0 {[}3.0 - 5.0{]} 12.0 {[}5.0 - 16.0{]} & 1 (5.6) 0
(0.0) 16 (100.0) \emph{2 (11.1)} 0 (0.0) 6 (35.3) 5 (29.4) 5 (100.0) 0
(0.0) 0 (0.0) 0 (0.0) 3325 \selectlanguage{ngerman}± 559 3.0 {[}1.5 - 4.5{]} 9.5 {[}7.0 -
10.0{]}\tabularnewline
Treatments after 2nd delivery Iron supplements, no. (\%) Laxatives, no.
(\%) & 21 (13.8) 8 (5.3) & 14 (20.0) 4 (5.7) & 7 (8.5) 4
(4.9)\tabularnewline
\bottomrule
\end{longtable}

Data are mean \selectlanguage{ngerman}± SD or median {[}inter-quartile range{]} or n (\%)

\begin{quote}
*There was no significant differences between the trial arms
(p\textless{}0.05), except for the occurrence of perineal laceration
among women having undergone vaginal delivery (absolute difference risk
{[}CI 95\%{]}: -27.1 {[}-49.7 to -1.4{]}).\textbf{Table 3 : Outcomes}
\end{quote}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Endpoint}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Vaginal delivery arm} \textbf{(N=112)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Cesarean section arm} \textbf{(N=110)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Median or mean difference or Absolute Risk Difference}
\textbf{(95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{P Value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Primary endpoint}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Vaizey score at M6, median {[}IQR{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.0 {[}0.0-3.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.0 {[}0.0-4.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.0 (0.0 to 2.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.34\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Secondary endpoints}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Vaizey score at W6-8, median {[}IQR{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.0 {[}0.0-3.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.0 {[}0.0-3.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.0 (-2.0 to 1.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Post-partum transient anal incontinence at W6-8, no. (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
18 (25.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
9 (11.7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-13.3 (-25.1 to 0.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
MUH score at M6, median {[}IQR{]}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.0 {[}0.0-4.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.0 {[}0.0-4.0{]}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.0 (-1.0 to 2.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
FSFI score at M6, median {[}IQR{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
28.1 {[}23.5-31.2{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
27.1 {[}22.1-31.4{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-1.0 (-4.0 to 1.9)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Physical SF12 score at M6, mean \selectlanguage{ngerman}± SD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
52.1 (6.7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
51.7 (7.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-0.4 (-2.5 to 1.6)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Mental SF12 score at M6, mean \selectlanguage{ngerman}± SD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
46.2 (9.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
46.6 (9.5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.4 (-2.3 to 3.2)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Maternal morbidities, no. (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
4 (4.9)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
8 (8.8)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3.9 (-2.7 to 11.2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Neonatal morbidities, no. (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
5 (6.1)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0 (0.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-6.1 (-11.7 to -1.3)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Worsening of external sphincter lesions at ultrasound, no. (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
11 (22.4)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1 (2.2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-20.2 (-31.7 to -7.6)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

All the analyses were conducted in the intent-to-treat population except
maternal and neonatal morbidities (completers), and are superiority
analyses. For secondary endpoints, the confidence intervals have not
been adjusted and inferences drawn from the intervals may not be
reproducible.

\textbf{Hosted file}

\verb`figure BJOG abramowitz.docx`  available at \url{https://authorea.com/users/302646/articles/432742-cesarean-section-in-the-second-delivery-to-prevent-anal-incontinence-after-asymptomatic-obstetrical-anal-sphincter-injury-the-epic-multicenter-randomized-trial}

\textbf{Hosted file}

\verb`CONSORT-2010-Checklist-MS-Word.doc`  available at \url{https://authorea.com/users/302646/articles/432742-cesarean-section-in-the-second-delivery-to-prevent-anal-incontinence-after-asymptomatic-obstetrical-anal-sphincter-injury-the-epic-multicenter-randomized-trial}

\selectlanguage{english}
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\end{document}

