Preterm premature rupture of membranes in the presence of cerclage: isthe risk for intra-uterine infection and adverse neonatal outcomeincreased?

MATTHEW D. LASKIN, YOAV YINON, & WENDY L. WHITTLE

Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

AbstractObjective. To determine whether preterm premature rupture of membranes (PPROM) in the presence of a cerclage is associatedwith an increased incidence of intrauterine infection and/or adverse neonatal outcome compared to PPROM in the absence ofcerclage.Study design. Patients diagnosed with PPROM with a cerclage (cases) between 24–34 weeks were matched (1:2.6) for gestationalage at PPROM, gestational number, and chorionicity with patients diagnosed with PPROM without a cerclage (controls).Results. Pregnancy latency period was not different but the rates of chorioamnionitis [clinical (26.6% versus 13.5%) andhistological (92.6% versus 65.4%)] and the rates of adverse perinatal outcome were higher following PPROM in the presence of acerclage compared with no cerclage.Conclusion. The presence of a cerclage in patients with PPROM appears to increase the risk of intra-uterine infection and affectneonatal outcome; it may not be justified to leave a cerclage in place in patients with PPROM.

Keywords: Cerclage, PPROM, chorioamnionitis

Introduction

Spontaneous preterm delivery (PTD) occurs in 5–8% of all

pregnancies, one-third of which is attributed to preterm

premature rupture of membranes (PPROM) [1]. In patients

with a cervical cerclage, regardless of the indication for the

suture, the rate of PPROM is estimated to be as high as 30%.

Routine care of patients with PPROM in the absence of labor

and/or fetal distress, since the publication of the ORACLE

trial in 2002, includes fetal and maternal surveillance for signs

of chorioamnionitis and/or fetal distress with the initiation of a

7-day course of erythromycin therapy to reduce the composite

risk of neonatal morbidity [2]. However, the management of

PPROM in the presence of a cerclage has not been well

defined. Studies by Ludmir et al. [3], Kuhn and Pepperell [4],

and O’Connor et al. [5] each found an increase in pregnancy

latency (time from diagnosis of PPROM to delivery) but a

concomitant increase in perinatal morbidity and mortality

when a cerclage remained in situ after PPROM. In contrast,

studies by Yeast and Garite [6] and Kominiarek and Kemp

[7] detected no difference in obstetrical outcome with cerclage

removal or retention following PPROM. Jenkins et al. [8] and

McElrath et al. [9,10] compared patients with and without a

cerclage following PPROM and found no difference in

obstetrical and neonatal outcomes. Taken as a whole, the

data suggest that PPROM is not an absolute indication for

removal of the cerclage and that expectant management

following PPROM with a cerclage in situ may be appropriate.

However, each of these studies predates the ORACLE trial

finds supporting the use of erythromycin after the diagnosis of

PPROM. Therefore, the current study was undertaken to test

the hypothesis that PPROM in the presence of a cervical

cerclage is not associated with an increased incidence of

intrauterine infection and/or adverse neonatal outcome in the

current era of clinical practice. Our study objectives were to

determine whether there was a difference in latency, rates of

clinical and histological chorioamnionitis, and rates of adverse

intrauterine and neonatal outcomes in patients following

PPROM in the presence and absence of a cervical cerclage.

Materials and methods

A retrospective observational cohort study with matched

controls was conducted at Mount Sinai Hospital (Toronto,

Ontario, Canada) between January 2002 and December 2008

with institutional ethics board approval (REB08-0128-C).

Cases were identified by chart review as patients diagnosed

with preterm premature ruptured fetal membranes (PPROM)

between 24 and 34 completed weeks gestation in the presence

of a cervical cerclage. At our institution it is conventional

obstetrical practice to leave the cerclage in place following the

diagnosis of PPROM; in all of the cases, the cerclage was only

removed once the decision for delivery was made by the

attending physician. The types of cervical cerclage were

(Received 27 October 2010; revised 3 March 2011; accepted 4 March 2011)

Correspondence: Wendy L. Whittle, Department of Obstetrics and Gynaecology, Room 3157, Mount Sinai Hospital, 700 University Avenue, Toronto,

Ontario, Canada M5G 1Z5. Tel: þ1-416-586-4800, 2452. Fax: þ1-416-586-8718. E-mail: wwhittle@mtsinai.on.ca

These findings were presented at the Society for Maternal Fetal Medicine Annual Clinical Meeting, Chicago, USA; January 2010 (abstract no. 0443).

The Journal of Maternal-Fetal and Neonatal Medicine, 2012; 25(4): 424–428

� 2012 Informa UK, Ltd.

ISSN 1476-7058 print/ISSN 1476-4954 online

DOI: 10.3109/14767058.2011.569800

categorized based on history as: (1) elective – placed

prophylactically based on obstetrical history or in the presence

of a transvaginal ultrasound cervical length less than or equal

to 2.5 cm; (2) rescue – placed when the cervix was dilated and

the fetal membranes visible at or beyond the internal cervical

os; and/or (3) repeat – a rescue cerclage (as previously

defined) done in the presence of a previous cerclage placed

anytime in the current pregnancy. Controls were defined as

patients diagnosed with PPROM between 24 and 34

completed weeks gestation in the absence of a cerclage. The

cases were randomly matched 1:2.6 to controls for gestational

age at diagnosis of PPROM +2 days and year of delivery (to

account for subtle year-to-year changes in practice). The

clinical management of the case and control patients was at

the discretion of the attending physician.

The outcomes measured were: (1) latency – defined as the

time (in weeks) from diagnosis of PPROM to delivery; (2)

clinical chorioamnionitis – any of the following clinical events

that triggered delivery based on the discretion of the attending

physician: elevated maternal temperature (437.88C), mater-

nal leukocytosis (414 6 109/l), and/or fetal tachycardia

(4160 bpm); (3) histological chorioamnionitis – any of the

following identified on placental pathology: acute chorioam-

nionitis (grade I–III), acute deciduitis and/or funisitis; and (4)

adverse fetal and neonatal events including intrauterine fetal

demise, neonatal death (NND), neonatal sepsis, respiratory

distress syndrome (RDS), neonatal anemia, necrotizing

enterocolitis, and grade III and IV intraventricular hemor-

rhage (IVH). Each neonatal diagnosis was taken from the

coding diagnoses on the neonatal discharge summary and was

at the discretion of the attending neonatologist.

A significance value of p 5 0.05 was used in all statistical

analyses. Continuous variables were analyzed using an

unpaired t-test and categorical variables with a Fisher’s exact

test.

Results

A total of 668 patients were diagnosed with preterm

premature ruptured fetal membranes (PPROM) between 24

and 34 completed weeks gestation during the observation

period. Of these 76 (11.4%) were diagnosed with PPROM in

the presence of a cervical cerclage (cases) and 592 patients

(88.6%) had PPROM in the absence of a cerclage (controls).

From this cohort, 170 controls were matched to the 64 cases

upon eliminating all multiple gestational pregnancies. Table I

summarizes the demographics of the two matched groups.

There was no significant difference in maternal age, gravidy,

parity, or Celestone use. All cases and controls were planned

to initiate erythromycin treatment (250 mg QID for 7 days) at

the time of diagnosis; however, almost an equal number of

patients in both groups delivered prior to the initiation of

antibiotic therapy. As expected, there was a significantly

higher rate of prior spontaneous preterm birth and prior

PPROM in the case group (35.9% and 9.4%, respectively)

compared to controls (17.2% and 1.8%, respectively). As

well, there was a higher rate of cesarean section in the cerclage

group compared to the control group (46.8% versus 26.2%).

To account for the potential effect of gestational age at

diagnosis of PPROM on latency and obstetrical outcome the

gestational age at PPROM was categorized as either (1)

extreme prematurity with PPROM prior to 28 weeks gestation

or (2) mild–moderate prematurity with PPROM between 28

and 34 completed weeks gestation. When classified by

gestational age at PPROM, there were no significant

differences with respect to the mean gestational age at

diagnosis of PPROM, mean gestational age at delivery, and

mean latency interval (Table II).

The incidence of both clinical and histological chorioam-

nionitis in the study cohort as a whole is illustrated in Figure

1. As expected, the rate of histological chorioamnionitis was

greater than that of clinical chorioamnionitis for both the cases

and controls. Overall, there was a significantly higher rate of

both clinical and histological chorioamnionitis in the cases

versus controls (26.6% versus 13.5%; p¼ 0.03; and 92.6%

versus 65.4%; p¼ 0.02). The rates of both clinical and

histological chorioamnionitis were greatest in patients with

cerclage who were diagnosed with PPROM prior to 28 weeks

gestation as illustrated in Figure 2. If delivery occurred prior

to 28 weeks gestation, 35.9% of patients with cerclage were

diagnosed with clinical chorioamnionitis and delivered as

compared with only 15.1% of patients without a cerclage

(p¼ 0.03). The overall incidence of histological chorioamnio-

nitis in patients who delivered prior to 28 weeks gestation was

greater than 90%; in the presence of a cerclage the rate was

modestly increased (97.1% versus 90.2%; p¼ 0.39). The

incidence of clinical and histological chorioamnionitis was

lower if delivery occurred after 28 weeks gestation in the

presence or absence of a cerclage. If delivery occurred after 28

weeks gestation there was no difference in the rate of clinical

chorioamnionitis triggering delivery between the cases and

controls (12.0% versus 12.8%; p¼ 1.00); however, the rate of

histological chorioamnionitis was greater in the presence of a

cerclage (85.0% versus 53.7%; p¼ 0.01). A history of preterm

birth did not influence the rate of clinical or histological

chorioamnionitis in either group of patients.

Table I. Patient demographics of both the cases and control groups.

Cases (n¼ 64) Control (n¼ 170) p-value

Maternal age (yrs) 31.6 þ 5.6 (18-43) 31.2 þ 6.2 (16-43) 1.00

Mean gravidy 3þ2 (0-13) 3þ2 (1-8) 1.00

Mean parity 1þ1 (0-6) 1þ1 (0-6) 1.00

Mean abortus 1þ1 (0-6) 1þ1 (0-5) 1.00

History PTB 35.9% (23) 9.4% (16) 0.0001

History PPROM 17.2% (11) 1.8% (3) 0.0001

Erythromycin use 71.9% (46) 60.6% (103) 0.13

Celestone use 78.1% (50) 77.7% (132) 1.00

Previous cerclage 17.2% (11) 0.0% (0) 0.0001

Mode of delivery Vaginal C. section 53.1% (34) 46.9% (30) 71.8% (122) 28.2% (48) 0.008

Italic values: p � 0.05.

Perinatal outcome after PPROM with cerclage 425

To determine any effect of cerclage type on the incidence

of infectious pathology, the cases were evaluated based on

cerclage classification. With respect to the cases, 28.1%

received an elective cerclage, 71.9% had a rescue cerclage

and of those 12.5% had a repeat cerclage. Overall, there were

no significant differences in the incidence of clinical chor-

ioamnionitis triggering delivery when cases were compared by

cerclage type; however, the incidence of clinical chorioamnio-

nitis in the cases was always greater than that of the control

group regardless of cerclage type. As well, there was a

significantly higher rate of histological chorioamnionitis

compared with controls (Figure 3).

Perinatal outcome data are presented in Figure 4. There

was a significantly greater incidence of sepsis (p¼ 0.05),

neonatal respiratory distress (p¼ 0.003), and neonatal anemia

(p¼ 0.002) in the neonates delivered after PPROM in the

presence of a cerclage compared to neonates delivered

following PPROM in the absence of a cerclage. As well, there

was a trend to higher rates of rates intrauterine demise

(p¼ 0.3), NND (p¼ 0.14), and IVH (p¼ 0.25) for neonates

delivered after PPROM in the presence of a cerclage but these

were not statistically significant values.

Discussion

Preterm premature rupture of the fetal membranes (PPROM)

accounts for approximately one-third of all spontaneous

preterm births and often is complicated by the presence of a

cervical cerclage. Traditional acute management of PPROM

in the absence of indications for delivery including chorioam-

nionitis, preterm labor, maternal and/or fetal distress is

expectant with the recent introduction of erythromycin

treatment to reduce neonatal morbidity based on the findings

of the ORACLE study [2]. However, there is a paucity of

information to guide the acute management of PPROM in the

presence of a cerclage as all studies predate the use of

erythromycin. In our study, the cerclage was only removed at

the time the patient went into spontaneous labor or a decision

was made for delivery (based on clinical chorioamnionitis,

fetal distress) as is the standard obstetrical practice at our

institution. The objective of our study was to determine

whether pregnancy latency, the rates of chorioamnionitis, and

adverse intrauterine and neonatal outcomes in patients

following PPROM differed in the presence and absence of a

cervical cerclage in the current era of clinical practice. We

determined that when compared with patients without a

cerclage, the latency period is not affected by the presence of

the cerclage but the rates of chorioamnionitis (both clinical

and histological) and the rates of adverse perinatal outcome

are higher following PPROM in the presence of a cervical

cerclage. The higher rate of chorioamnionitis is especially

pronounced when the patient is diagnosed with PPROM prior

to 28 weeks of gestation.

Latency was no different for patients diagnosed with

PPROM before and after 28 weeks of gestation both in the

presence and absence of a cerclage. The average time to

delivery was 7–10 days regardless of the cerclage and/or

gestational age at diagnosis. These findings are contrary to

several previous reports [3–5]. Kuhn and Pepperall (1977)

reported that regardless of the gestational age at diagnosis of

PPROM, latency was increased when the cerclage was left in

situ. This study was not a randomized control trial to

determine the effect of cerclage retention on latency, the

indications for cerclage retention or removal were not

specified and the sample size was limited to 31 patients with

cerclage removal retrospectively compared with 38 patients

with cerclage retention [4]. Ludmir et al. (1994) also reported

an increase in pregnancy latency with cerclage retention when

27 patients diagnosed with PPROM in the presence of a

cerclage were compared with 33 patients diagnosed with

PPROM without a cerclage; the cerclage was removed in 20

patients following PPROM with no specific protocol or

indication regarding cerclage removal versus retention [3].

However, Ludmir did determine that a greater portion of

patients whose cerclage was immediately removed delivered

within the first 24 h compared with those who retained the

Table II. Mean gestational age at PPROM, delivery and latency for

both cases and controls.

Extreme prematurity

(delivery 528 weeks)

Case

(n¼39)

Control

(n¼ 53) p-values

Mean GA at PPROM (wks) 24.8 þ 1.7 25.4 þ 1.4 0.78

Mean GA at delivery (wks) 25.8 þ 1.7 27.0 þ 2.0 0.66

Mean latency (wks) 1.0 þ 1.7 1.6 þ 2.1 0.83

Prematurity

(delivery 428 weeks)

Case

(n¼25)

Control

(n¼ 117)

p-values

Mean GA at PPROM (wks) 31.5 þ 2.3 31.7 þ 2.1 0.96

Mean GA at delivery (wks) 32.1 þ 2.0 32.2 þ 1.9 0.98

Mean latency (wks) 0.6 þ 0.6 0.5 þ 0.7 0.95

Figure 1. Incidence of clinical and histological chorioamnionitis.

(*p 5 0.05).

Figure 2. Incidence of clinical and histological chorioamnionitis

divided into gestational age at PPROM. (* and ap 5 0.05).

426 M. D. Laskin et al.

cerclage suggesting that cerclage retention at least prolongs the

pregnancy by 48 h. Jenkins et al. (2000) retrospectively in a non-

randomized fashion compared immediate cerclage removal with

delayed removal at the time of delivery and found that the

delayed removal group had on average a greater than 5 day

increase in latency [8]. In contrast, and in keeping with our own

study design and findings, McElrath et al. (2000) presented a

case–control study with matching based on year of presentation;

51 patients had the cerclage retained until delivery, 30 patients

who had their cerclage removed immediately and both of these

groups were compared with women diagnosed with PPROM in

the absence of a cerclage [9]. There was no significant difference

in latency between the retained, removed, or control groups [9].

Similar findings were reported by Yeast et al. (1988). Taken as a

whole, there is very limited data in support of cerclage removal

or retention at the time of PPROM diagnosis on the sole basis of

latency alone. However, we speculate that latency is not affected

by the presence of the cerclage because the main trigger for

delivery is no longer cervical competence but appears to be

infectious pathology [6].

As expected, chorioamnionitis was the main outcome

associated with PPROM regardless of gestational age or

presence of cerclage. With a cerclage in situ and the diagnosis

of PPROM prior to 28 weeks gestation, over one-third of

these patients were delivered due to clinical chorioamnionitis

and over 90% of patients had histological chorioamnionitis at

the time of delivery. The rate of clinical chorioamnionitis was

three times greater in these patients compared with patients

diagnosed with PPROM at the same gestational age without a

cerclage. These findings support the hypothesis that chor-

ioamnionitis is a key etiologic factor associated with extreme

prematurity. After 28 weeks gestation, the rate of clinical

chorioamnionitis was similar between the two groups but still

accounted for 12% of deliveries and subacute chorioamnio-

nitis was present in over 2/3 of patients regardless of cerclage

likely reflecting the co-incidence and/or the effect of sub-

clinical chorioamnionitis on spontaneous PTD after PPROM.

The type of cerclage did not affect that rates subacute or acute

infection significantly and therefore should not be considered

in the algorithm of clinical management after PPROM.

Our data suggest that the presence of cerclage is associated

with an increased rate of intrauterine infection especially with

PPROM diagnosed prior to 28 weeks gestation. Our sugges-

tion is echoed by Kuhn and Pepperall [4] and Ludmir et al.

[3] who determined that the rate of chorioamnionitis was

lower in the patients whose cerclage was removed at the time

of PPROM diagnosis. But our results are in contrast to those

reported by several authors. In the largest case–control study,

McElrath et al. (2002) did not detect any difference in the rate

of clinical chorioamnionitis or maternal postpartum fever in

women with PPROM with and without a cerclage [9]. The

same author also detected no difference in the rate of

chorioamnionitis when comparing cerclage removal or reten-

tion after PPROM [10]; these findings were confirmed by

Jenkins et al. (2000). Given that our study was conducted in a

different era of clinical practice as these previous studies it is

difficult to make direct comparisons regarding rates of

infection in the presence or absence or early removal of a

cerclage after PPROM [8]. Although, the majority of the

previous studies did not detect differences in neonatal

mortality or morbidity, our study, despite not being suffi-

ciently powered to examine neonatal outcome, did detect a

higher rate of intrauterine demise, neonatal respiratory

distress, and neonatal anemia. Again, given that our study

was conducted in an era of erythromycin use post-PPROM

which has been shown to improve neonatal outcome, it is valid

to compare with previous studies but should be evaluated in

the context of today’s clinical practice. What has become

apparent is there is limited data in support of cerclage

retention at the time of PPROM diagnosis on the basis of

Figure 3. Incidence of clinical and histological chorioamnionitis based on cerclage type. (*, a and bp 5 0.05).

Figure 4. Incidence of adverse fetal and neonatal outcomes. (*p 50.05).

Perinatal outcome after PPROM with cerclage 427

perinatal outcome; the potential for increased rates of acute

and subacute chorioamnionitis and adverse neonatal outcome

infection with no difference in latency would suggest that

cerclage removal at the diagnosis of PPROM may be a

prudent clinical decision.

Our study had three salient points of conclusion. When

compared patients diagnosed with PPROM, the patients with

PPROM in the presence of cerclage had: (1) no change in

pregnancy latency, (2) a greater rate of subacute and acute

chorioamnionitis, and (3) a higher rate of adverse neonatal

outcome, especially sepsis, RDS and anemia. We acknowl-

edge that our study is limited by its retrospective design and

power analysis. The rate of prior PPROM and prior preterm

birth was higher in the patients with a cerclage but the rate of

chorioamnionitis in this pregnancy were not affected by

obstetrical history; however, the differences in the rates of

chorioamnionitis and adverse neonatal outcome could be

explained by obstetrical history and not related to the cerclage.

However, taken as an isolated cohort of patients, women with

a cerclage in place and the diagnosis of PPROM may be at

significant risk of developing clinical and histological chor-

ioamnionitis regardless of their obstetrical history. However,

given the aforementioned limitation, the findings in this study

provide a rationale for removal of the cerclage at the time of

PPROM. More importantly, our study provides a rationale for

a randomized control trial to address the clinical question:

retention versus removal of a cerclage in the presence of the

diagnosis of PPROM.

Declaration of interest: The authors report no conflicts of

interest. The authors alone are responsible for the content and

writing of the paper.

References

1. Berghella V, Baxter JK, Hendrix NW. Cervical assessment by

ultrasound for preventing preterm delivery. Cochrane Database

Syst Rev 2009;(3):CD007235.

2. Kenyon S, Taylor D, Tarnow-Mordi WO. ORACLE –

antibiotics for preterm prelabour rupture of the membranes:

short-term and long-term outcomes. Acta Paediatr

2002;91(437):12–15.

3. Ludmir J, Bader T, Chen L, Lindenbaum C, Wong G. Poor

perinatal outcome associated with retained cerclage in patients

with premature rupture of membranes. Obstet Gynecol

1994;84:823.

4. Kuhn RPJ, Pepperell RJ. Cervical ligation: a review of 242

pregnancies. Aust N Z J Obstet Gynecol 1977;17:79.

5. O’Connor S, Kuller JA, McMahon MJ. Management of cervical

cerclage after preterm premature rupture of membranes. Obstet

Gynecol Surv 1999;54:391–394.

6. Yeast JD, Garite TR. The role of cervical cerclage in the

management of preterm premature rupture of the membranes.

Am J Obstet Gynecol 1988;158:106.

7. Kominiarek MA, Kemp A. Perinatal outcome in preterm

premature rupture of membranes at � 32 weeks with retained

cerclage. J Reprod Med 2006;51:533.

8. Jenkins TM, Berghella V, Shlossman PA, McIntyre CJ, Maas BD,

Pollock MA, Wapner RJ. Timing of cerclage removal after

preterm premature rupture of membranes: maternal and neonatal

outcomes. Am J Obstet Gynecol 2000;183:847.

9. McElrath TF, Norwitz ER, Lieberman ES, Heffner LJ. Manage-

ment of cervical cerclage and preterm premature rupture of the

membranes: should the stitch be removed? Am J Obstet Gynecol

2000;183:840.

10. McElrath TF, Norwitz ER, Lieberman ES, Heffner LJ.

Perinatal outcome after preterm premature rupture of mem-

branes with in situ cervical cerclage. Am J Obstet Gynecol

2002;187:1147.

428 M. D. Laskin et al.

Copyright of Journal of Maternal-Fetal & Neonatal Medicine is the property of Taylor & Francis Ltd and its

content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's

express written permission. However, users may print, download, or email articles for individual use.