Indomethacin and Cefazolin for Physical Exam-Indicated Cerclage to Improve Latency: A Protocol Validation Study.

Abstract

Objective:  A single-center randomized trial showed improved latency with use of indomethacin and cefazolin (I/C) during and following exam-indicated cerclage (EIC). The same center recently published a pre/post comparison demonstrating similar results. This research aimed to validate the protocol in a different setting.

Study design:  Retrospective cohort study of singleton pregnancies undergoing EIC at a single center between 2013 and 2022. EIC was performed for painless cervical dilation between 16 and 23 weeks' gestation with dilation ≥1 cm. Exposure was defined as receipt of I/C during and following EIC. The primary outcome was latency ≥ 28 days after cerclage placement. Secondary outcomes included latency; gestational age at delivery; delivery ≤ 28 weeks; preterm premature rupture of membranes; intra-amniotic infection (IAI); and median birth weight. Bivariate statistics were used to analyze data; multivariable regression analyses were used to control for confounders (progesterone use, cervical dilation at time of cerclage placement, history of preterm birth, and prolapsing membranes).

Results:  EIC was placed in 81 pregnancies and 48 (59%) received I/C. Baseline characteristics did not differ between groups, except that prolapsing membranes were significantly less likely in patients receiving I/C (6.2 vs. 21.2%; p = 0.04). Latency ≥ 28 days occurred in 90% of I/C recipients and 82% of the controls (p = 0.32); this difference remained nonsignificant after controlling for confounders (adjusted relative risk: 1.02 [95% confidence interval: 0.85, 1.21]). I/C recipients had lower rates of IAI (4.2 vs. 24.2%, p = 0.007), even after adjustment (adjusted relative risk: 0.18 [95% confidence interval: 0.04, 0.74]). Other secondary outcomes did not differ.

Conclusion:  Use of I/C at the time of EIC at this center was not associated with increased latency to delivery (albeit in a small cohort) but was associated with lower rates of intra-amniotic infection. Larger-scale validation studies would be helpful to confirm the value of this intervention.

Key points: · Indomethacin/cefazolin (I/C) increased latency for exam-indicated cerclage in a trial.. · We performed an observational comparison to validate these findings.. · I/C use for exam-indicated cerclages was associated with decreased intra-amniotic infection.. · I/C was not associated with change in latency.. · Larger-scale validation studies needed to confirm the value of intervention..