Chlamydia and pregnancy

Background
Chlamydia trachomatis (Chlamydia) is the commonest bacterial sexually transmitted infection in the UK. It is an obligate intracellular parasite and can only survive by a replicative cycle that results in death of the infected host cells.Up to 10% of sexually active women aged less than twenty four years and men aged between twenty to twenty-four years may be currently infected with Chlamydia. Chlamydia prevalence is generally greater in women with ectropion than in those without (the organisms require columnar type epithelial cells in which replicate and such cells are more readily exposed to infection in the presence of ectropion) which may drive the infection in young females.

From the Health Protection Agency statistics In the UK in 2008 over 79% of diagnosed Chlamydia infection in females attending genitourinary medicine clinics in the UK was in those under twenty five years of age. Chlamydia is thus likely to be a very relevant consideration in many pregnant women!

Complications of Chlamydia infection in the female genital tract are responsible for significant morbidity but this article addresses Chlamydia in women who have already achieved a pregnancy.

Chlamydia may be a coincidental, often asymptomatic, finding in pregnancy (a risk of pregnancy means a risk of acquiring sexually transmitted infections has occurred!) or it may be implicated in pregnancy- related complications.

Symptoms and signs
The majority of Chlamydia-infected pregnant and non-pregnant women are asymptomatic. A proportion of women may present with very mild or non-specific symptoms such as increased/altered vaginal discharge, dysuria, abdominal pain, arthritis, post coital bleeding or pregnancy related complications

Vaginal discharge
Chlamydia cervicitis may cause increased/altered vaginal discharge and post coital or intermenstrual bleeding, although the majority of infected females are totally asymptomatic.

Cervicitis may be apparent in up to 30% of infected women. Examination of the ectocervix may show mucopurulent discharge, oedema, inflammation and contact bleeding may be elicited. Visual examination alone cannot exclude a diagnosis of Chlamydia. A cervical cytology smear is not a test for Chlamydia, although Chlamydia may cause inflammatory or other cytological changes.

Urethral symptoms
Most of the women attending clinics for sexually transmitted infections, who have Chlamydia, have no urethral symptoms.

Studies in clinics suggest that for females tested for Chlamydia from both the cervix and urethra, the majority of the positive women yield Chlamydia from both sites while a significant number may test positive from either site alone.

The diagnosis should be considered in women presenting with urethral symptoms where dysuria is present for more than a week, especially if there is lack of suprapubic tenderness and absence of haematuria.

Non-genital symptoms
Conjunctivitis, urethritis, sero-negative reactive arthritis (rare in females) and perihepatitis (occurring in about 10 per cent of laparoscopically diagnosed pelvic inflammatory disease) are all possible presenting complications of Chlamydia infection.

They are in the context of this article, primarily important, as markers of probable concomitant genital infection.

Pregnant women are at risk of pelvic inflammatory disease, ectopic pregnancy in the first trimester, miscarriage, premature rupture of membranes and pre-term labour as well as post-partum or post miscarriage endometritis.

Lower abdominal pain
Chlamydia-associated salpingitis or PID in early pregnancy rarely causes mild to severe, acute or chronic pelvic pain and deep dyspareunia, abnormal vaginal discharge, bleeding, systemic upset or pyrexia.

Invasive gynaecological procedures such as suction termination of pregnancy, increases the risk of Chlamydia causing PID.

An ultrasound scan of the pelvis may help confirm a clinical suspicion of PID. An obstetrician should always be involved if there is a clinical suspicion of PID in pregnancy.

Some other possible complication
A substantial number of studies suggest that Chlamydia trachomatis infection in pregnancy is associated with premature delivery.

So far, there appears to be no proven link between Chlamydia and chorioamnionitis.

DNA amplification has however found Chlamydia trachomatis in the amniotic fluid of 6.7 per cent of women with pre-labour rupture of membranes.

Laboratory diagnosis
Nucleic Acid Amplification tests (NAAT) are the tests of choice for urethral and endo-cervical or self-taken vaginal sampling in women in the UK because of their high level of sensitivity (around 90 to 95%) and specificity and should be available to all clinicians. The old enzyme immunoassay (EIA) tests were much less sensitive and specific for Chlamydia. Culture is not generally available. No test is 100% sensitive or specific and NAAT, Culture or EIA tests from the cervix can be negative in endometritis.

Specific kits for obtaining samples should be available for your local laboratory.

The attending physician considering the possibility of Chlamydia infection in a baby, or non genital sites in an adult, should discuss with the laboratory what test samples to obtain to exclude or make a diagnosis.

Neonatal infection
If Chlamydia is diagnosed in a neonate then it is essential that the mother and her partner(s) are also tested and treated for Chlamydia. Indeed, this may be the first indication of a missed or un-suspected maternal infection!

Conjunctivitis occurs in about 20-50 per cent of neonates whose mother had Chlamydia at the time of delivery. Although the infection is derived from the mother’s genital tract at birth, there have been cases reports where neonatal Chlamydia trachomatis infection was found in infants delivered by caesarean section in the presence of intact membranes, suggesting the possibility of trans-placental or trans-membranous infection.

Neonatal Chlamydia conjunctivitis has an incubation period of 10-12 days and therefore presents after midwifery involvement has generally been withdrawn. The eyelids are usually swollen, and there may be a sticky discharge which is purulent with conjunctival injection. The infection may be severe in pre-term babies. The cause of the relatively late presentation of this type of opthalmia neonatorum may be missed if it is not actively considered. The standard treatment for conjunctivitis will not clear the infection.

The onset of the atypical Chlamydia pneumonia is often insidious, becoming apparent at some 3 to 12 weeks of age. The infants may become very unwell or develop a chronic cough with no clinical signs except possible tachypnoea with or without marked chest X-ray changes. In order to make the diagnosis and treat the baby with effective antibiotics, it helps if the Neonatal Physician is furnished with the mother’s profile which indicates the possibility of Chlamydial pneumonia.

Management
An integrated approach to care management following diagnosis begins with taking a sexual history, a history of reproductive health, past STIs and clinical assessment. The four C’s approach encapsulates the factors required to ensure effective care management (Contact tracing (to reduce the risk of re-infection), Compliance (with medication), Condoms (to use after completion of therapy and partner treatment to prevent re-infection) and Counselling.)

Other sexually transmitted infections should be excluded.

Rarely in pregnancy, PID is associated with an increase in both maternal morbidity and an obstetrician should be involved in management. The advice of a Genito-Urinary Medicine Consultant, as well as a Consultant Microbiologist, is important.

The early diagnosis and treatment of Chlamydial infection of the female genital tract is essential to protect the reproductive health of women. Antibiotic therapy is the cornerstone of management.

The optimal antibiotic treatment for Chlamydia (UK British Association for Sexual Health and HIV (BASHH) National Guideline) is that treatment should be effective with a microbiological cure rate of more than 95 per cent, easy to take (not more than twice daily) with a low side effect profile and cause minimal interference with daily life.

Azithromycin 1gm stat in pregnancy is recommended by the World Health Organisation but unlicensed in the UK. However, it is suggested in the British National Formulary only if no alternative is available.

Erythromycin is thought to have a high rate of intolerance manifested by gastrointestinal upset, although this side effect has not been universally demonstrated. There are no trials of erythromycin 500mg twice a day for 14 days, which is generally better tolerated than four times a day, but it probably has good efficacy.

Azithromycin, although chemically related to erythromycin, has unique pharmacokinetics. The drug is rapidly absorbed from the gastrointestinal tract and widely distributed to body tissues, the safety of azithromycin in pregnancy and lactating mothers has not been fully assessed, although available data indicate that it is safe. Its efficacy in pregnancy has not been studied (although it has probably has less than 95% efficacy in pregnancy).

Amoxicillin has similar cure rate to Erythromycin and a better side effect profile, although it may induce bacterial latency and possible re-emergence of infection at a later date, causing some concerns about its regular use in pregnancy.

Recommended regimes in pregnancy and breast feeding:
Preparation Dose Duration
Erythromycin caps Erythromycin caps 500mg QDS (or 500mg BD) 7 days (or 14)days
Amoxicillin caps 500mg TDS 7 days
*Azithromycin tabs 1gm stat

Test of cure
A test of cure is essential in all pregnant women, including those treated with Azithromycin. It must be performed at least 5 weeks after the end of treatment (6 weeks if Azithromycin is used) or the NAAT may give a false positive result.

References

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  10. Horner P. J. et al British Association for Sexual Health and HIV UK National Guideline for the Management of Genital Tract Infection with Chlamydia trachomatis. 2006.
  11. Moumita Sarkar1, , Cindy Woodland C1,3 , Gideon Koren1,2,3 and Adrienne RN Einarson Pregnancy outcome following gestational exposure to azithromycin; BMC Pregnancy and Childbirth, 6:18 2006
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