Discussion
In our cohort of 607 pregnant individuals who were at high risk for preterm birth, we found that those who had a positive Ureaplasma culture but did not receive treatment had comparable gestational age at delivery compared to those who have negative Ureaplasma culture as well as those who had a positive Ureaplasma culture and received treatment. Further, the rate of treatment failure after the initial treatment was very high (78.6%). We also found that cerclage was associated with lower odds of recurrence compared to a history of preterm birth.
We found that treatment failure of Ureaplasma was very high even after treatment of pregnant individuals and their sexual partners. This finding was consistent with a previous study that showed that treatment of pregnant individuals with preterm labor or PPROM with Azithromycin resulted in a 93.3% treatment failure rate. Interestingly, studies of intra-amniotic Ureaplasma infection showed that treatment of infection resulted in a high rate of clearance of infection (79%). Given that Ureaplasma species are normal genital flora, eradication of Ureaplasma might be challenging. We found that pregnant individuals who had a cervical culture due to cerclage had lower odds of recurrence compared to those who had a cervical culture due to a history of preterm births. We speculate that these lower odds could be due to abstinence from intercourse after cerclage placement. In non-pregnant individuals, sexual intercourse permits the spread of the various Ureaplasma species with their different resistance profiles. In pregnant individuals, those who had sexual intercourse 3 times or greater per week had a Ureaplasma positive rate of 37%, which was much higher than 18% for those who had intercourse less than 3 times per week (P=0.02). It is noteworthy that even though our institution treated all sexual partners with Doxycycline, the treatment failure rate remained high.
We found that giving appropriate antibiotics was not associated with an improvement in gestational age at delivery. Despite the use of different antibiotics, our finding was consistent with previous studies that showed treatment of Ureaplasma was not associated with improvement of adverse pregnancy outcomes compared to no treatment. For example, a double-blind randomized control trial that randomized pregnant individuals who tested positive for Ureaplasma Urealyticum to either erythromycin treatment or placebo did not show significant differences in gestational age at delivery, PPROM, or neonatal outcomes. Our study is unique, however, since our protocol adopts an Azithromycin regimen and treats their sexual partners.
It is important to note that giving antibiotics to pregnant individuals could change bacterial flora and could have unknown consequences. Even though Azithromycin is not associated with short-term neonatal adverse outcomes, little is known regarding the long-term outcomes. A previous study has indicated that antibiotics may be associated with an infant gut microbiota imbalance during the first year of life. Future studies that examine long-term neonatal and infants’ outcomes associated with prenatal Azithromycin exposure would be useful.
Our study has many strengths. In 2014, our institution started a quality improvement project that tests and treats pregnant individuals with a positive Ureaplasma cervical culture as well as their sexual partners. Our protocol was to repeat Ureaplasma cervical culture after the initial treatment and treat again if treatment failure is noted. Though previous studies treated pregnant individuals only once, we thought repeating Ureaplasma cervical culture was important due to the high treatment failure rate. We believe the quality of our data is high: data were obtained from a chart review of outpatient, inpatient, and anesthesia records. We think that this study sets a good example of a quality improvement project; given the high rate of treatment failure despite treatment of pregnant individuals and sexual partners, our institution decided to stop routine Ureaplasma cervical culture for pregnant individuals who were at high risk for preterm birth. Our study underscores the importance of assessing the effects of a quality improvement project and changing our practice based on study findings.
Our study is not without limitations. Given the retrospective nature of the study, we were not able to assess the compliance rates of treatment for pregnant individuals and their sexual partners. We tried to adjust for covariates using cox or multivariable logistic regression models. However, there could be residual confounding. Since this was a retrospective cohort study, we were only able to assess association but not causation. Our study was from a single academic center. Therefore, our findings may not be generalizable in other clinical settings. Unfortunately, due to our protocol of treating all pregnant individuals who had positive Ureaplasma culture, the sample size of pregnant individuals who had a positive Ureaplasma culture and did not receive treatment was low. Since our study was powered to examine gestational age at delivery, other analyses were exploratory. Lastly, we did not differentiate the Ureaplasma species. It is possible that some species of Ureaplasma such as Ureaplasma parvum but not Ureaplasma Urealyticum are associated with spontaneous preterm birth.