Evaluation of perioperative antibiotics and indomethacin with cerclage for short cervix: a retrospective cohort study with the International Collaborative for Cerclage Longitudinal Evaluation and Research.

BACKGROUND: There was a randomized trial that suggested a benefit with indomethacin and antibiotics in the setting of an examination-indicated cerclage. However, there is little evidence to guide the use of perioperative indomethacin and/or antibiotics in the setting of an ultrasound-indicated cerclage.

OBJECTIVE: This study aimed to determine whether perioperative antibiotics and/or indomethacin at the time of ultrasound-indicated cerclage placement reduces the rate of spontaneous preterm birth at <37 weeks of gestation.

STUDY DESIGN: This was a multicenter retrospective cohort study of women with singleton pregnancies who received a transvaginal cervical cerclage from June 2016 to July 2021. This study aimed to evaluate whether perioperative antibiotics and/or indomethacin at the time of cerclage was superior to no antibiotics/indomethacin in the prevention of spontaneous preterm birth. Of note, 10 sites were involved, 8 in the United States and 2 in Colombia. Because this was an observational cohort, a few propensity score-based analyses were performed to adjust for potential confounding or assignment bias. First, the propensity score for each treatment group comparison (indomethacin vs none, perioperative antibiotics vs none, and indomethacin and perioperative antibiotics vs neither) was determined using multivariate logistic regression taking into consideration study country (United States or Colombia), previous preterm birth history (yes or no), body mass index, cervical length before placement, cervical dilation, gestational age at placement, use of postoperative progestogen (yes vs no), and use of other perioperative interventions (indomethacin or perioperative antibiotics). This propensity score was used for a weighted analysis (1/propensity score). The primary outcome was spontaneous preterm birth at <37 weeks of gestation. The secondary outcomes include rates of spontaneous preterm birth at <34 weeks of gestation and <28 weeks of gestation and latency (weeks) from randomization to delivery for the outcome of spontaneous preterm birth at <37 weeks. Data were weighted using the propensity score for the primary and secondary outcomes, with the respective predictors being indomethacin vs none, perioperative antibiotics vs none, or perioperative indomethacin and antibiotics vs neither in bivariate regression analysis. A 2-sided alpha level of 0.05 was considered statistically significant for all analyses.

RESULTS: The database included cerclages placed in women with singleton pregnancies from March 2016 to July 2021. Overall, 340 cases of ultrasound-indicated cerclage were included in this study. Of note, 29.4% of cases had documented cervical dilation at the time of surgery, 28.5% of cases did not have documented cervical dilation at the time of surgery, and 42.1% of cases did not have examination findings recorded. There were significant baseline differences between the groups. In weighted regression analyses, there was a reduced risk of spontaneous preterm birth at <37 weeks of gestation associated with perioperative antibiotics (adjusted odds ratio, 0.68; 95% confidence interval, 0.49-0.94), and an increased risk of spontaneous preterm birth at <28 weeks of gestation associated with perioperative indomethacin (adjusted odds ratio, 2.38; 95% confidence interval, 1.31-4.36). No intervention or combination was associated with an increased latency to delivery.

CONCLUSION: Our data suggest a possible benefit associated with perioperative antibiotics at the time of ultrasound-indicated cerclage. The potential benefit or harm of indomethacin is less clear due to collinearity and the low number of cases of very early preterm birth. Given the potential risks of antibiotic use, including antibiotic resistance, and indomethacin use, randomized trial data are needed to support the use of perioperative antibiotics and/or indomethacin in the setting of ultrasound-indicated cerclage.