Antibiotic Prophylaxis to Prevent Obesity-Related Induction Complications in Nulliparae at Term: a pilot randomized controlled trial

Abstract

Background: Women with obesity are at increased risk of complications during and after labor and delivery, including puerperal infection and cesarean delivery. As labor induction has become increasingly common, it is crucial to find ways to decrease complication rates in this high-risk population.

Objective: This study aimed to explore the effect of prophylactic antibiotics during labor induction of nulliparous women with obesity on the rates of cesarean delivery and puerperal infection and to estimate the parameters needed to calculate the sample size for a larger, multicenter trial.

Study design: In this randomized, placebo-controlled pilot trial, nulliparous patients with a body mass index of ≥30 kg/m² were randomized to either prophylactic antibiotics (500 mg azithromycin for 1 dose and 2 g cefazolin every 8 hours for up to 3 doses) or placebo, administered starting at the beginning of labor induction. The exclusion criteria were known fetal anomaly, fetal demise, multifetal gestation, ruptured membranes >12 hours, infection requiring antibiotics at the start of labor induction, and/or allergy to azithromycin or beta-lactam antibiotics. The co-primary outcomes were rates of puerperal infection (composite of chorioamnionitis, endometritis, and/or cesarean delivery wound infection) and cesarean delivery. Participants were followed up for 30 days after delivery, and maternal and neonatal demographic and outcome data were collected. Proportions and 95% confidence limits were calculated for each of these outcomes.

Results: From January 2019 to May 2021, 101 patients were randomized in the class III stratum (1 patient who was randomized ultimately did not undergo labor induction). From February 2020 to May 2021, 38 and 47 patients were randomized to class I and II strata, respectively (to assess the effect of obesity class on the outcomes expected to be influenced by antibiotic prophylaxis). In the antibiotics and placebo groups, the rates of cesarean delivery were 29.0% (95% confidence interval, 19.8-38.3) and 39.8% (95% confidence interval, 29.8-49.7), respectively, and puerperal infection occurred in 8.6% (95% confidence interval, 2.9-14.3) and 9.7% (95% confidence interval, 3.7-15.7), respectively. In the subgroup with class III obesity, in the antibiotics and placebo groups, the rates of cesarean delivery were 33.3% (95% confidence interval, 20.4-47.9) and 46.0% (95% confidence interval, 32.2-59.8), respectively, and puerperal infection occurred in 7.8% (95% confidence interval, 0.5-15.2) and 10.0% (95% confidence interval, 1.7-18.3), respectively. Note that this pilot study was not powered to detect differences of this magnitude but rather to estimate parameters.

Conclusion: The administration of prophylactic antibiotics during labor induction of nulliparous patients with obesity resulted in a 27% lower cesarean delivery rate overall and a 28% lower rate in patients with class III obesity. A larger trial is warranted to evaluate these differences.

Trial registration: ClinicalTrials.gov NCT03801252.

Keywords: cesarean; cesarean delivery rate; chorioamnionitis; endometritis; labor induction; obese; obesity; pilot study; puerperal infection; wound infection.

Figure.

CONSORT (Consolidated Standards of Reporting Trials) enrollment flow diagram. This diagram shows the number of patients approached for the study, the number who declined, the number who were enrolled and randomized, and the number of women in each treatment group. ^a30 had an allergy to one or more of the study medications, 8 underwent pre-labor cesarean delivery, 6 had a major fetal anomaly, 5 were minor patients without parent consent, 5 had infection requiring antibiotic therapy, 3 had ruptured membranes >12 hours, 3 were preterm, and 1 was incarcerated ^bOne participant presented for induction of labor and received study drug, but over the course of her admission was found to be in spontaneous labor and did not undergo labor induction ^cTwo participants allocated to the placebo group did not receive the placebo: One participant was randomized but ultimately did not undergo labor induction (delivered via primary cesarean due to concern for fetal macrosomia); one participant was excluded after randomization due to discovery of an infection requiring antibiotic treatment (chlamydia) prior to the start of her labor induction