Effectiveness of Prophylactic Cervical Cerclage in Prolonging Higher-Order Multiple Pregnancies *

OBJECTIVES
This study aimed to assess the value of prophylactic cervical cerclage in prolonging higher-order multiple pregnancies.


METHODS
This retrospective study included all women with higher-order multiple pregnancies beyond 24 gestational weeks treated at the King Abdullah University Hospital in Irbid, Jordan, and King Fahad Medical City in Riyadh, Saudi Arabia, between February 2014 and January 2015. Selected maternal characteristics and obstetric outcomes were compared between women who received prophylactic cervical cerclage and those who did not.


RESULTS
A total of 146 women with higher-order multiple pregnancies were included in the study; of these, 94 (64.4%) underwent a prophylactic cervical cerclage insertion procedure and 52 (35.6%) women did not. No significant difference was found between the two groups with regards to maternal age, parity or number of fetuses. However, the mean gestational age at delivery was significantly higher for women without compared to those with prophylactic cervical cerclage (32.9 weeks versus 31.7 weeks) according to both univariate and multivariate analyses (P = 0.013 and 0.046, respectively). Additionally, 40.4% of women without and 14.9% of women with prophylactic cervical cerclage gave birth after 34 gestational weeks (P = 0.003).


CONCLUSION
Overall, prophylactic cervical cerclage was not associated with prolongation of the pregnancy among women with higher-order multiple pregnancies in the current study.

][8][9][10] The rate of higherorder multiple pregnancies is especially high in certain countries, particularly those in the developing world where there are no legal restrictions on the number of embryos transferred at in vitro fertilisation centres.[8][9][10] The approximate mean gestational age at delivery is 36, 33, 29 and 28 weeks for twin, triplet, quadruplet and quintuplet pregnancies, respectively. 5,8,11While the pathophysiology of preterm birth in higher-order multiple pregnancies remains unclear, the most likely cause is overdistension of the uterus. 12Although routine prophylactic cervical cerclage has been suggested as a strategy for prolonging gestation and some evidence exists suggesting that its routine use in twin pregnancies is beneficial, its role or advantage in higher-order multiple pregnancies is unclear. 8,9,13his study therefore aimed to determine the effect of prophylactic cervical cerclage in the prolongation of higher-order multiple pregnancies.

Methods
All women with triplet or higher-order pregnancies beyond 24 gestational weeks seen between February 2014 and January 2015 at the King Abdullah University Hospital in Irbid, Jordan, or the King Fahad Medical City in Riyadh, Saudi Arabia, were included in this retrospective study.A review was conducted of the electronic patient databases at each tertiary institution.For maternal characteristics, the following variables were reviewed: age, parity and body mass index (BMI); history of previous cervical insufficiency, cervical surgery, preterm labour or premature rupture of membranes (PPROM); and number of fetuses and method of conception.Obstetric outcome measures included the incidence of preterm labour, PPROM and neonatal or intrauterine fetal death; admission to the neonatal intensive care unit (NICU); gestational age at delivery; and the mode and indications for delivery.
All patients were under the direct supervision of consultant obstetricians during their care.For women who received prophylactic cervical cerclage, the suture was placed into and around the cervix at between 11-16 gestational weeks, regardless of past obstetric history or the state of the cervix.All cerclage sutures were of the McDonald type, using 5 mm MERSILENE ® polyester tape (Ethicon Inc., Somerville, New Jersey, USA), and were inserted under general anaesthesia with no specific instructions for suture placement.Following the procedure, patients received an ultrasound to check fetal wellbeing before being discharged on the same day, with instructions to seek attention at the emergency room if they experienced any symptomatic abnormalities.Patients were also advised to refrain from demanding physical activities but were not assigned complete bed rest.A follow-up visit to the antenatal clinic was arranged two weeks later to assess the state of the cervix.Patients were then seen regularly until the elective removal of the suture, or earlier in the case of an emergency.Most cervical cerclage sutures were removed during the 36 th gestational week without sedatives or any form of anaesthesia.No antimicrobial or tocolytic medications were administered.For patients in both groups, decisions regarding the timing and mode of delivery and pain relief options offered during labour were made according to the policies and protocols for higher-order multiple pregnancies at each institution.
The women were categorised into two groups for statistical analysis according to whether they had received prophylactic cervical cerclage or not.The sample size yielded a power of >80% to detect a 5% difference in outcomes between the two groups.The Statistical Package for the Social Sciences (SPSS), Version 20.0 (IBM Corp., Armonk, New York, USA), was used to analyse the data.Chi-squared and Student's t-tests were used to compare percentages and means.A general linear model was used to conduct the regression analysis to determine statistical differences in gestational age at birth.The level of statistical significance was set at P ≤0.050.This retrospective study received ethical approval from the institutional review boards at both the King Abdullah University Hospital and the King Fahad Medical City.

Results
A total of 146 women with higher-order multiple pregnancies were seen at the two tertiary institutions during the study period.Of these, 94 (64.4%) underwent a prophylactic cervical cerclage insertion procedure and 52 (35.6%) did not.The majority of the pregnancies (94.5%) were the result of assisted reproductive techniques (ART), mainly intracytoplasmic sperm injection and embryo transfers; 98.9% of women with versus 86.5% of women without prophylactic cervical cerclage had used ART (P = 0.002).None of the women had a history of cervical insufficiency, prior cervical surgery, preterm labour or PPROM or had undergone fetal reduction.There was no statistically significant difference between the two groups in relation to maternal age (P = 0.674), parity (P = 0.177) or number of fetuses (P = 0.563) [Table 1].In addition, no statistically significant differences were noted between the two groups with regards to BMI.
All of the women delivered by Caesarean section after 24 gestational weeks, with the majority of cases (92.5%) considered emergency or urgent procedures.There was no statistically significant difference between the two groups in relation to the mode of delivery (P = 0.139), the occurrence of stillbirths or neonatal deaths (P = 0.406) or admission to the NICU (P = 0.682).However, 14.9% and 40.4% of women with and without prophylactic cervical cerclage, respectively, gave birth after 34 gestational weeks (P = 0.003).Moreover, the mean gestational age at delivery was significantly higher among women without compared to those with prophylactic cervical cerclage (32.9 versus 31.7 weeks; P = 0.013) [Table 2].This difference remained significant during the multivariate analysis after adjusting for ART, number of fetuses, parity and maternal age (P = 0.046).
Among those who received prophylactic cervical cerclage, there was no statistically significant difference in studied outcomes according to the time of cerclage insertion.The mean gestational age at delivery was 31.6 and 32.0 weeks for women who underwent the cerclage procedure at 11-13 and 14-16 gestational weeks, respectively (P = 0.542).One miscarriage occurred in the prophylactic cervical cerclage group.Of the women who had not initially received prophylactic cervical cerclage, none required subsequent emergency or rescue cerclage.

Discussion
Theoretically, there may be a higher pressure burden on the uterine cervix, particularly the internal opening of the cervix, in cases of higher-order multiple pregnancies in comparison to singleton pregnancies. 12,13Intuitively, a routine prophylactic cervical cerclage procedure for women with higher-order multiple pregnancies should automatically decrease the chances of preterm birth by preventing undue cervical shortening and dilatation.However, the role of the cervix in the aetiology of preterm birth in multiple pregnancies is not clear.Furthermore, the function of the cervix in higherorder multiple pregnancies might differ from that of singleton pregnancies. 12,14The anatomical status of the cervix and the likelihood of preterm birth can be evaluated by reviewing past obstetric history and carrying out a speculum or digital vaginal examination or reviewing abdominal and vaginal ultrasound findings in the second trimester.[17]   The insertion of cervical cerclage sutures for patients with ultrasonographically-documented cervical shortening has been proposed so as to avoid unnecessary surgery. 18On the other hand, its effectiveness and safety in higher-order multiple pregnancy remains unclear. 8,13,190][21] Some studies have demonstrated that prophylactic cerclage is of no value in prolonging gestation in high-order multiple pregnancies. 10,14,19,221][22] Nevertheless, routine prophylactic cervical cerclage is not recommended for every woman with a multiple pregnancy and the safety and efficacy of the procedure as a form of preterm birth prevention should be appraised on a case-by-case basis according to obstetric history and cervical assessment. 12,14In a study of current practices to prevent preterm births, Baker et al. found that the majority of Canadian specialists (82%) recommended routine cervical length assessment at 16-21 gestational weeks, with none supporting routine cerclage insertion; however, 71% stated that they would perform cerclage based on the patient's history or an ultrasound. 23rophylactic cerclage procedures in the current study were performed at between 11-16 gestational weeks, irrespective of obstetric history or cervical assessment.It is likely that this gestational age is somewhat early for cerclage, even in cases of multiple pregnancies in which there may yet be further physiological shortening of the uterine cervix. 23owever, the timing of the prophylactic cervical cerclage insertion in the current study did not prolong pregnancy or have a significant difference on pregnancy outcomes.Limitations of the present study include its retrospective nature and the lack of randomisation in the selection of the patients.Furthermore, the incidence of immediate adverse effects of prophylactic cervical cerclage, such as rupture of the membranes, infection and pregnancy loss, between the date of the cerclage insertion and the beginning of the study when the women were at ≥24 gestational weeks was not evaluated.

Conclusion
The current study found that the routine use of prophylactic cervical cerclage to prolong gestation among women with higher-order multiple pregnancies was not effective.

Table 1 :
Maternal characteristics of women with higherorder multiple pregnancies treated at the King Abdullah University Hospital in Irbid, Jordan, and King Fahad Medical City in Riyadh, Saudi Arabia (N = 146)

Table 2 :
Pregnancy outcomes among women with higher-order multiple pregnancies treated at the King Abdullah University Hospital in Irbid, Jordan, and King Fahad Medical City in Riyadh, Saudi Arabia (N = 146)