• 
• 

Three Part Question

In [pregnant women presenting with chlamydia infection] is [antibiotic treatment] effective in [reducing the incidence of miscarriage or preterm labor]?

Clinical Scenario

A patient presents to the Emergency Department with complaints of abdominal pain and vaginal discharge. You find out she is pregnant and has chlamydia; will antibiotic treatment help decrease the incidence of miscarriage and/or preterm labor?

Search Strategy

MEDLINE 1950 to September 2008 using OVID interface, Cochrane Library (2008)
[(exp chlamydia and exp chlamydia infections and chlamydia.mp) AND (exp obstetric labor, premature or exp abortion, spontaneous)] LIMIT to human AND English language

Search Outcome

165 papers found, 161 were irrelevant to the question or insufficient quality for inclusion, leaving 4 papers that were relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Andrews et. al, 2006, USA	2470 women that had asymptomatic bacterial vaginosis or Trichomonas vaginalis that were between 16 and 30 weeks gestation were subsequently screened for chlamydia via a ligase chain reaction assay of their urine. These women were also enrolled in another study that elected to treat or give placebo for the b. vaginosis or t. vaginalis infections, however, the results of the chlamydia screens were not available to the other primary study team for evaluation and/or treatment.	Prospective observational Study	Estimate whether midpregnancy genitourinary tract infection with Chlamydia trachomatis is associated with an increased risk of subsequent preterm delivery.	Chlamydia infection was more common among women with trichomonas vaginalis infection at the randomization visit, but no difference was observed in the percentage of positive Chlamydia tests among women with and without bacterial vaginosis or trichomonas at the follow-up visit. The presence of Chlamydia was not associated with an increased risk of spontaneous preterm delivery prior to 37 or 35 weeks’ gestational age among women positive at the randomization, follow-up, either or both visits (14.1 vs. 12.8 p= 0.579; 13.0 vs. 10.8 p= 0.330; 13.3 vs. 10.9 p= 0.442; 12.7 vs. 10.8 p= 0.340 respectively). Compared to women without Chlamydia infection at the randomization visit, infected women had similar frequencies of preterm delivery regardless of whether they were enrolled in the BV (12.2 vs. 13.0 p= 0.785) or trichomonas (14.9 vs. 16.7 p= 0.689) trials. The authors concluded that mid-trimester Chlamydia infection was not associated with an increased risk of preterm birth and the treatment of Chlamydia was not associated with a decreased frequency of preterm birth.	Approximately 10% of the women that were successfully screened for chlamydia tested positive at both screening periods (randomized visit #1 and follow-up visit #2). The women that tested positive for chlamydia had, at some point, received antibiotics that were either effective against chlamydia (azithromycin, erythromycin) or potentially effective against chlamydia (ampicillin, amoxicillin, penicillin) for various DIFFERENT reasons (URI, UTI, GBS prophylaxis, suspected preterm labor, dental disease etc.) but it was not specifically known if they were given therapy directed at other symptoms of chlamydia.
French et. al, 2006, USA	1038 African American women at <29 weeks of gestation were evaluated for their risks of preterm complications from infection(s) with bacterial vaginosis, chlamydia, Trichomonas vaginalis, Mycoplasma hominis, gonorrhea or Group B Strep.	A secondary analysis of combined data from a prospective cohort study and 3 clinical trials was conducted and evaluated.	Rates of preterm birth, preterm labor and preterm premature rupture of membranes were the primary outcomes that were examined.	Preliminary studies found that preterm birth occurred among approximately 10% of the described population yearly. Prevalence of specific infections and other variables were compared between infected and non-infected black women. 66% of women with trichomonas, 45% of women with bacterial vaginosis and 65% of women with Chlamydia received appropriate antimicrobial treatment. The intervening use of antibiotics was controlled by limiting the dataset to untreated women for analyses to examine the risks for preterm birth that were associated with infection. The results demonstrated that preterm birth was increased among untreated black women with a previous preterm birth and those having their first child compared with untreated comparator women with similar pregnancy histories. Also, untreated multiparous black women without a previous preterm birth demonstrated risks for preterm birth that were similar to untreated multiparous comparator women. Overall, preterm birth occurred among 34.6% of untreated black women who were infected with combinations of BV, trichomonas and Chlamydia compared with 9.5% of uninfected black women.	The study population included low-income, urban women living in Denver Colorado. Behavioral, cultural and medical differences between this studied population and those living in other regions or socioeconomic levels are likely.
McGregor et. al, 1990, USA	229 women between 26 and 30 weeks gestation selected between October 1985-August 1988 from publicly supported antenatal clinics in Denver Colorado.	Prospective double-blind placebo-controlled study	Attempted to determine/evaluate the relationship of microbial factors or conditions with obstetric and neonatal outcomes including premature rupture of membranes, preterm premature rupture of membranes (<37 weeks), gestational length, birth weight and newborn infection.	Signs and symptoms of vaginitis and characteristics of vaginal discharge were similar between study groups. Follow-up evaluation was performed ~1 month after study enrollment in 63% of the women enrolled in the erythromycin group and 74% of the women enrolled in the placebo group. Spontaneous vaginal delivery occurred among 80% of the patients in the erythromycin group and 71% of placebo patients. Rupture of membranes before labor occurred significantly more often among women who received placebo (16%) compared with those who received erythromycin (6%). Preterm premature rupture of membranes occurred less frequently in those who received erythromycin (2%) vs. placebo (5%), though not statistically significant. Cervical infection with C. trachomatis accounted for 20% of preterm birth. Overall, treatment with erythromycin significantly decreased to occurrence of premature ROM among women initially positive for Chlamydia trachomatis. The findings of bacterial vaginosis, mycoplasma homiis, ureaplasma urealyticum were not significantly associated with increased risk of preterm birth or premature ROM.	Needs larger controlled treatment trials of specific infections and/or conditions associated with preterm birth. Only 73% of the erythromycin and 84% of the placebo group completed at least 4 days of medication.
Rastogi et al, 2003, India	328 women in their first through third trimester of pregnancy were evaluated for chlamydia and it's potential negative impacts in India. Of the 328 women enrolled in the study, 164 were able to be treated and evaluated through to completion of the study.	Prospective Observational Trial	To treat infected women for Chlamydia in order to assess the effects of therapeutic intervention on the outcome of Chlmaydia-infected pregnancies.	These women were divided into three groups: Group I consisted of women that tested positive for chlamydia and were in the treatment group, Group II consisted of infected women	small numbers evaluated

Comment(s)

Three of the articles cited associated preterm birth complications ranging from premature rupture of membranes to increased rates of stillbirths in those women found to have chlamydial infections (some polymicrobial) that did not receive treatment. One article (Andrews et al.) found no correlation between chlamydial infection and an increased risk of preterm birth.

Clinical Bottom Line

Treatment of chlamydial infections during pregnancy can prevent early potential complications.

References

1. Andrews WW, Klebanoff MA, Thom EA, et al. Midpregnancy genitourinary tract infection with Chlamydia trachomatis: Association with subsequent preterm delivery in women with bacterial vaginosis and Trichomonas vaginalis American Journal of Obstertrics and Gynecology 2006;194:493-500.
2. French JI, McGregor JA, Parker R. Readily treatable reproductive tract infections and preterm birth among black women American Journal of Obstetrics and Gynecology 2006;194:1717-27.
3. McGregor JA, French JI, Richter R, et al. Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment American Journal of Obstetrics & Gynecology 1990;163:1580-91.
4. Rastogi S, Das B, Salhan S, Mittal A. Effect of treatment for chlamydia trachomatis during pregnancy International Journal of Gynecology and Obstetrics 2003;80:129-137.