We assessed randomised controlled trial evidence on the effects of cervical stitch in combination with other treatments for prolonging pregnancy in women who were at high risk of pregnancy loss and were carrying a single baby. Additional treatments were used in the same time period as when the cervical stitch was surgically inserted.
What is the issue?
The cervix is a cylinder-shaped neck of tissue connecting the vagina and uterus (womb). The cervix should stayed closed during pregnancy, but some pregnant women have cervical weakness resulting in pain-free opening of the cervix. This may lead to a late miscarriage or preterm birth before 37 weeks of pregnancy. A cervical stitch is a surgical procedure performed in the second trimester to place a stitch around the cervical neck with the intention of helping the woman carry the pregnancy until around 37 weeks. Other treatments that can be combined with cervical stitch include antibiotics, vaginal support inserts (pessaries), placement of a second cervical stitch, uterine relaxants (tocolytics), progesterone (hormonal drugs), omega-3 long chain polyunsaturated fatty acids and bed rest.
Why is this important?
Cervical weakness is diagnosed through a woman’s history of pregnancy losses or premature births in the second trimester, ultrasound examination or physical examination. Preventing preterm birth is a healthcare priority because it is the leading cause of infant ill health and death worldwide. A cervical stitch in combination with other treatments could help prevent preterm birth in women carrying a single baby as a single stitch may not be sufficient for pregnant women with prior premature births and short cervical length or weakness.
What was studied in the review?
We wanted to know whether a cervical stitch, in addition to one of a range of treatments (antibiotics administration, a vaginal pessary, reinforcing or second cervical stitch placement, a uterine relaxant or progesterone) can prolong pregnancy for women carrying a single baby who are at high risk of pregnancy loss.
What evidence did we find?
We searched the literature for evidence from randomised controlled trials up until 26 September 2019. We identified two trials involving a total of 73 women. Only one trial with 50 mother-baby pairs had results that could be included in this review. The trial compared cervical cerclage in combination with indomethacin (tocolytic) and the antibiotics cefazolin or clindamycin with cervical cerclage alone. Women were not blinded to the treatment they received.
We are unclear about the effects of the intervention because we identified very low-certainty evidence for the main outcomes in this review: serious complications; loss of the baby (data for miscarriage and stillbirth only - data were not available for the numbers of babies who died within 28 days of being born), or preterm birth before 34 completed weeks of pregnancy. There were no stillbirths (death within the womb at 24 or more weeks).
Data for death of the newborn baby at discharge, or the number of babies discharged home healthy were not available.
What does this mean?
We found insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with inserting a cervical stitch compared with inserting a cervical stitch alone for preventing spontaneous preterm labour in women with singleton pregnancies.
We did not identify any studies looking at other treatments in combination with inserting a cervical stitch. Additional research needs to focus on the role of other interventions such as a vaginal support pessary (device), reinforcing or second cervical stitch placement, 17-alpha-hydroxyprogesterone caproate, dydrogesterone or vaginal micronised progesterone, omega-3 long chain polyunsaturated fatty acid supplementation and bed rest.
Future studies should recruit sufficient numbers of women to provide meaningful results and should investigate the risk of death of the baby shortly after birth and the numbers of babies discharged home healthy.
Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies.
Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review.
We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17-alpha-hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega-3 long chain polyunsaturated fatty acid supplementation and bed rest.
Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments.
To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of ’short cervix’ and/or physical examination.
History-indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation.
Physical exam-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination.
We searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies.
We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster-RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi-RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross-over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies.
Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout.
We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary).
One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone - this study did provide useable data for this review (and the study authors also provided additional data on request) but meta-analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals).
Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies)
We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low-certainty evidence); perinatal loss (data for miscarriage and stillbirth only - data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low-certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low-certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks).
The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death.