Adjunct Therapy at Time of Examination-Indicated Cervical Cerclage in Singleton Pregnancies: A Systematic Review and Meta-analysis

Abstract

Objective: Physical examination-indicated cerclage for cervical insufficiency prolongs gestation, but evidence on the addition of adjuncts to further prolong latency is limited. The aim of this systematic review and meta-analysis was to compare gestational latency between those who did and did not receive adjunct antibiotic or tocolytic therapy at the time of examination-indicated cerclage.

Study design: Electronic databases (1966-2020) were searched for randomized controlled trials (RCTs) and cohort studies comparing adjunct antibiotic or tocolytic use versus nonuse at time of examination-indicated cerclage, defined as placement for cervical dilation ≥1 cm, in a current singleton pregnancy. Studies including individuals with intra-amniotic infection, cerclage in place, nonviable gestation, or ruptured membranes were excluded. The primary outcome was latency from cerclage placement to delivery. Secondary outcomes included preterm birth, preterm premature rupture of membranes, birth weight, and neonatal survival. Risk of bias was assessed using standardized tools. Heterogeneity was assessed using χ ² and I ² tests. Results were pooled and analyzed using a random-effects model. This study is registered with The International Prospective Register of Systematic Reviews (PROSPERO) with registration no.: CRD42021216370.

Results: Of 923 unique records, 163 were reviewed in full. Three met inclusion criteria: one RCT and two retrospective cohorts. The included RCT (n = 50) and one cohort (n = 142) compared outcomes with and without adjunct use of antibiotic and tocolytic, while the second cohort (n = 150) compared outcomes with and without adjunct tocolytic, with a subpopulation also receiving antibiotics. The RCT was nested within one of the cohorts, and therefore only one of these two studies was utilized for any given outcome to eliminate counting individuals twice. Risk of bias was "critical" for one cohort study, "moderate" for the other cohort study, and "some concerns" for the RCT. Gestational latency could not be pooled and meta-analyzed. Adjunct tocolytic-antibiotic therapy was not associated with a decrease in risk of preterm delivery <28 weeks (relative risk [RR] = 0.90, 95% confidence interval [CI]: 0.65-1.26; χ ² = 0.0, I ² = 0.0%) or neonatal survival to discharge (RR = 1.11, 95% CI: 0.91-1.35; χ ² = 0.05, I ² = 0.0%).

Conclusion: There is not enough evidence to robustly evaluate the use of adjunct tocolytics or antibiotics at time of examination-indicated cerclage to prolong latency.

Key points: · Limited data on adjunct antibiotic tocolytics at cerclage.. · Widely variable practices at time of cerclage identified.. · Role of adjunct therapies at time of examination-indicated cerclage remains unclear..

Figure 1.

PRISMA flow diagram of study inclusion

Figure 2.

Forest plot of preterm birth at less than 28 weeks’ gestation in selected studies comparing adjunct use of tocolytics/antibiotics to non-use

Figure 3.

Forest plot of neonatal survival to hospital discharge in selected studies comparing adjunct use of tocolytics/antibiotics to non-use