The prevalence of chlamydial infection in pregnancy is between 2% to 30% depending on the patient's age and risk factors (Berggren 2011; Much 1991). It is particularly common in women younger than 25 years of age (Walker 2012). Genital Chlamydia trachomatis (C.trachomatis) infection has been shown to be associated with pregnancy complications such as miscarriage (Nigro 2011), preterm labour (Pararas 2006; Rours 2011), low birthweight (Attenburrow 1985) and increased perinatal mortality (Silva 2012). There may also be an association with preterm rupture of membranes (Blas 2007) and postpartum endometritis (Ismail 1987). If the mother is untreated, 20% to 50% of newborn babies may develop chlamydial conjunctivitis (Kakar 2010), and another 10% to 20% may develop C.trachomatis pneumonia (Rours 2009). Vaginal birth is associated with the highest risk of transmission of chlamydial infection, however, there is a small risk of acquiring the infection even in infants born by caesarean section with premature rupture of membranes and intact membranes (Pammi 2012; Yu 2009).
Genital C.trachomatis infection is detected by nucleic acid amplification test (NAAT) on the specimens of genital secretions or urine. This test has replaced tissue culture of C.trachomatis (Jespersen 2005).
Description of the condition
Genital C.trachomatis infection is a common bacterial sexually transmitted infection. The majority of women infected with this bacteria are asymptomatic and, therefore, may be more likely to transmit the infection because they do not seek treatment for the infection, which may result in a longer duration of the infection. The sequelae of C.trachomatis genital infection range from cervicitis to pelvic inflammatory disease, perihepatitis, ectopic pregnancy and infertility (Zenilman 2012). We have described complications of pregnancy and diseases of newborn related to genital chlamydia infection in the Background section above.
C.trachomatis is a small gram-negative intracellular bacterium with a two-phased life-cycle, which includes the form that infects new cells, (e.g. the small elementary body) and the active form (e.g. the reticulate body). The life-cycle is about two to three days, and, therefore, sustained high serum minimum inhibitory concentration of antimicrobial agents is needed to achieve eradication of the infection, which can be achieved by long-acting antimicrobials treatment or prolonged treatment. The incubation period of C.trachomatis infection varies between seven and 14 days (Zenilman 2012).
Description of the intervention
There are various treatment regimens for the management of chlamydial infection during pregnancy, however, there is no consensus on the most effective and safest option.
According to the Centers for Disease Control and Prevention (CDC) guideline followed by many countries around the world, the recommended regimens for treatment of genital chlamydial infection in pregnancy are azithromycin (1 g orally given as a single dose) or amoxicillin (500 mg orally three times daily for seven days) (Workowski 2010). The alternative regimen according to the CDC guideline is erythromycin (500 mg or 250 mg orally four times daily for seven days) or erythromycin ethylsuccinate (800 mg orally four times daily for seven days or 400 mg orally four times daily for 14 days) (Workowski 2010). Erythromycin is associated with a high degree of gastrointestinal side-effects (primarily nausea) and the compliance may an issue in such cases Workowski 2010.
Women who present in labour but were not treated for a prior positive chlamydial test are advised to be treated immediately with one of the above regimens. However, such late treatment is unlikely to substantially decrease the risk of transmission of chlamydia to the newborn.
Clindamycin is another alternative drug for treatment of genital C.trachomatis infection. Despite it being safe in pregnancy, clindamycin is not used widely due to its cost (Miller 2000).
Other antibiotics (e.g. doxycycline, levofloxacin, ofloxacin, and erythromycin estolate) used for treatment of genital C.trachomatis are contraindicated in pregnancy and lactation (Workowski 2010).
Azithromycin is believed to be the superior agent in comparison to other antibiotics for treatment of chlamydial infection. New research has emerged suggesting that there is a higher failure rate with azithromycin treatment of chlamydial infection than previously believed Schwebke 2011. One of the explanations for this recent finding is a higher sensitivity of NAAT in comparison to that previously used in the tissue culture as a test of cure (Handsfield 2011), although it does not explain the similar cure rates reported after doxycycline treatment with both of these tests. Another explanation for treatment failure is heterotopic resistance with high chlamydia loads which leads to treatment failures (Horner 2006). Re-infection is also a cause of treatment failure (Horner 2006).
Cure rates of C.trachomatis in women who are pregnant are lower than in non-pregnant women. The reasons behind this is a generally higher failure rate of treatment with amoxicillin, which has been traditionally used for treatment of C.trachomatis infection during pregnancy. A test of cure has always been recommended for all pregnant women and is performed no earlier than three weeks after treatment is initiated (Workowski 2010).
The previous Cochrane review on interventions for treating genital C.trachomatis infection in pregnancy found that amoxycillin was as effective as erythromycin (odds ratio 0.54, 95% confidence interval 0.28 to 1.02) (Brocklehurst 1998). Amoxycillin was found to be better tolerated than erythromycin (odds ratio 0.16, 95% confidence interval 0.09 to 0.30). Clindamycin and azithromycin were reported to be effective, however, the numbers of women included in trials were small (Brocklehurst 1998). There are new studies published in this area that are awaiting classification, therefore, it is important to update this review, which will be done under new authorship.
How the intervention might work
Irradicating genital chlamydial infection during pregnancy with antibacterial drugs will lead to following:
treatment of symptoms and sequelae of genital chlamydial infection such as discharge, cervicitis, pelvic inflammatory disease, tubal disease and infertility;
a decrease in perinatal complications such as preterm labour and early pregnancy loss, preterm rupture of membranes;
a decrease in transmission of the infection to the fetus or newborn and, therefore, prevention of intrauterine infection, neonatal conjunctivitis and pneumonia during pregnancy;
prevention of postpartum infection such as endometritis.
Why it is important to do this review
It is important to assess the different interventions for treating genital C.trachomatis in order to establish whether effective treatment of this infection improves perinatal outcomes and decreases maternal complications.