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Chlamydial infections in pregnancyPre-term labourPrematurity is one of the leading causes of perinatal mortality. Uterine contractions may be induced by cytokines, proteolytic enzymes or prostaglandins released or induced by microorganisms. Asymptomatic bacteriuria, gonococcal cervicitis and bacterial vaginosis are strongly associated with preterm delivery, but the role of C. trachomatis, Trichomonas vaginalis and Ureaplasma urealyticum is less clear [Cram et al., 2002; Locksmith & Duff, 2001]. However, a substantial number of studies suggest that maternal C. trachomatis infection in pregnancy is associated with premature delivery. Andrews et al., 2000] looked at the prevalence of genitourinary C. trachomatis infection in 190 women [cases] who spontaneously delivered after less than 37 weeks of gestation [early for dates] versus 190 control women [normal dates]. Both groups were selected after matching for race, number of previous children and the clinical centre attended from 2,929 women enrolled in a study of the National Institute of Child Health and Human Development in the US . Infection with C. trachomatis was determined by detection of chlamydial nucleic acid in urine by the ligase chain reaction at both 24 weeks and 28 weeks gestation . After adjustment for various known risk factors, women with C. trachomatis infection at 24 weeks' gestation were twice as likely as uninfected women to have a spontaneous preterm birth [odds ratio, 2.2; 95% confidence interval, 1.03-4.78] and three times as likely to have a spontaneous preterm birth at <35 weeks' gestation [odds ratio, 3.2; 95% confidence interval, 1.08-9.57]; [Andrews et al., 2000]. C. trachomatis has also been associated with intrauterine growth retardation [Anon, 1989] and has been shown experimentally to induce pre-term birth in intravaginally infected BalbC mice [Blanco et al., 1997; Pal et al., 1997]. A similar multicentre study in Hungary of 6,156 pregnant women with an overall chlamydial infection rate of 5.9% [GenProbe Pace 2 hybridization test] found that chlamydial infection [Odds ratio 1.9; 95% confidence interval 1.1 - 3.3], high unemployment rate [OR 1.5; 1.2 - 2.2] and low birth weight [OR 1.7; 1.1 - 2.7] were significant predictors of perinatal mortality [Nyari et al., 2001]. This is broadly in agreement with earlier studies [Anon, 1989; Gencay et al., 1995; Kovacs et al., 1998; Nishimura et al., 1990; Rastogi et al., 1999], although some other studies found no significant association [ French et al., 1999; Ville et al., 1999]. Infections with other pathogenic microorganisms may also cause premature birth, including Ureaplasma urealyticum [Lamont et al., 1987], Mycoplasma hominis [Anon, 1989; Lamont et al., 1987], bacterial vaginosis [French et al., 1999] and Trichomonas vaginalis [French et al., 1999]. These results suggest that, as a part of antenatal care, it is important to assess pregnant women for diseases that can be transmitted perinatally [Nyari et al., 2001]. This is particularly the case for sexually active women under the age of 24 years who are likely in many countries to have rates of chlamydial carriage in excess of 5%. Of course the costs of screening for genital infection have to be balanced against the overall risk factors for premature birth. Of greatest relevance here are the population attributable risks, which take into account the frequencies of defined risk factors in the study population. These have been little investigated but the table below from a study by Mittendorf et al., 1994 show estimates of population attributable risk for low birth weight for one particular sample:
Table 1. The population attributable risk percentage of various known risk factors for low birth weight in the United States. Data of: Mittendorf et al., 1994. The above table cannot be taken too literally because many of the risk factors are not mutually exclusive. Overall, it was estimated for this particular population that the prevalence of low birth weight, a significant cause of infant mortality, could be reduced from only 6.9 to 6.3% of births based on known risk factors [Mittendorf et al., 1994]. Other populations are quite different. In India, for example, C. trachomatis was isolated from the genital tract of 21.3% of 122 pregnant women [Rastogi et al., 1999] whereas in the UK a figure of between 2 - 5% is more likely. Management and treatment of chlamydial infections in pregnancyThe CDC STI Guidelines 2002 suggest that a test for C. trachomatis should be performed at the first prenatal visit. Women aged <25 years and those at increased risk for chlamydiae (i.e., women who have a new sexual partner of multiple sexual partners) should subsequently be tested during the third trimester to prevent maternal postnatal complications and chlamydial infection in the infant. Screening during the first trimester might help prevent the adverse effects of chlamydiae during pregnancy, although direct evidence for this is lacking. The disadvantage of screening only during the first trimester is that a longer period exists for acquiring infection before delivery. For treatment, doxycycline, ofloxacin and erythromycin estolate are contraindicated in pregnant women [CDC STI Guidelines 2002], but preliminary data suggest that azithromycin is reasonably safe and effective. The CDC recommended regimes are as follows:
The use of amoxycillin has been criticised on the grounds, among others, that it may induce persistent chlamydial infection. However a metanalysis of 11 studies by the Cochrane collaboration [Brocklehurst & Rooney, 2002] concluded that amoxycillin was as effective as erythromycin in achieving microbiological cure and was better tolerated. Azithromycin also appeared to be effective, though the relevant trials were small. In a comparison of 19 pregnant women before 33 weeks gestation who received 500 mg amoxycillin three times a day for 7 days versus 20 who received a single 1 g dose of azithromycin gastrointestinal side effects occurred in 40% of the women taking azithromycin and in 17% of the amoxycillin group, though this difference was not significant. Nevertheless compliance and cure rates with both regimens was high [Kacmar et al., 2001]. Similar findings were reported by Jacobson et al., 2001. A separate Cochrane metanalysis of 13 trials of antibiotics for the prevention of pre-term labour, randomised over 6,000 women and their babies and not restricted to chlamydiae, found that there is sufficient evidence of better maternal and foetal outcome to justify the routine administration of antibiotics after preterm, prelabour rupture of the membranes [Kenyon et al., 2002]. However a macrolide antibiotic (erythromycin) was recommended rather than a beta lactam (augmentin) because the latter was associated in 2 trials with a highly significant increase in neonatal necrotising enterocolitis. Termination of pregnancyTermination of pregnancy (i.e. induced abortion) is one of the most commonly performed gynaecological procedures. A large number of studies have shown that there is a high prevalence of C. trachomatis genital tract infection among women seeking termination of pregnancy. Moreover post-abortal pelvic inflammatory disease is a well recognised complication of termination of pregnancy, with its attendant risks of tubal dysfunction and either infertility or subsequent ectopic pregnancy. Blackwell et al., 1999 working in Swansea, Wales reported substantial savings to their health authority from a combined screening and treatment strategy for C. trachomatis, bacterial vaginosis and Trichomonas vaginalis. There is however controversy as to whether one should screen and treat (in which case for which pathogens does one screen ?). Alternatively, should one blindly give prophylactic antibiotic or a combination of both strategies? Cameron & Sutherland, 2002 reviewed these options with respect to the UK. They considered C. trachomatis to be the main target organism because, at least in the UK, gonorrhoea is relatively uncommon except in certain focal groups, the role of bacterial vaginosis in post-abortal infection was considered uncertain whereas the role of C. trachomatis is clearly established and the organism is potentially easily treated with no compliance problems by giving patients a single dose of 1g of azithromycin. In their view, universal prophylaxis had obvious advantages for those clinics that do not yet have good diagnostic laboratory services available for C. trachomatis. It would be expected to reduce post-abortal infection in the woman herself, particularly if a drug-induced rather than surgical abortion was chosen. However, non-treatment of sexual partners perpetuates the risk to the individual of re-infection and does not diminish the pool of chlamydial infection in the community, leading to possible long term clinical and financial costs. Combined screen and treat with prophylaxis is a more 'belt and braces' approach demanding a screening strategy with treatment of partners, prophylaxis in the woman herself in case infection is missed, and regular audit to identify any deficiencies in the screening system. If properly done it should lead to reduction of infection in the community. However, in the (UK) national health service, this was viewed as a luxury which possibly could not be afforded [ Cameron & Sutherland, 2002]! Thomas & Simms, 2002 point out that it is important to ensure that all at risk women undergoing uterine instrumentation receive proper screening and treatment for any genital C. trachomatis infection prior to their operation. [MEW] November 2002 NEXT: Infection of the new born ReferencesAndrews, W. W., Goldenberg, R. L., Mercer, B., Iams, J., Meis, P., Moawad, A., Das, A., Vandorsten, J. P., Caritis, S. N., Thurnau, G., Miodovnik, M., Roberts, J. & McNellis, D. (2000). The Preterm Prediction Study: association of second-trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth. American Journal of Obstetrics & Gynecology 183, 662 - 868. Anonymous (1989). Association of Chlamydia trachomatis and Mycoplasma hominis with intrauterine growth retardation and preterm delivery. The John Hopkins Study of Cervicitis and Adverse Pregnancy Outcome. American Journal of Epidemiology 129, 1247 - 1257. Blackwell, A. L., Emery, S. J., Thomas, P. D. & Wareham, K. (1999). Universal prophylaxis for Chlamydia trachomatis and anaerobic vaginosis in women attending for suction termination of pregnancy: an audit of short-term health gains. International Journal of STD & AIDS 10, 508 - 513. [See also discussion in: Int J STD AIDS. 2000 Jan;11(1):69-70. ; Int J STD AIDS. 2000 Jan;11(1):70. ; Int J STD AIDS. 2000 Mar;11(3):203-4.] Blanco, J. D., Wen, T. S. Bishop, K. (1997). Prolonged prior infection with Chlamydia prevents adverse pregnancy outcome in a murine model. American Journal of Obstetrics & Gynecology 176, 745 - 748. [Also a Discussion pp 748 - 750.] Brocklehurst, P. & Rooney, G. (2002). Interventions for treating genital Chlamydia trachomatis infection in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 3 2002. Oxford: Update Software. Cameron S. T. & Sutherland, S. (2002). Controversy: Universal prophylaxis compared with screen-and-treat for Chlamydia trachomatis prior to termination of pregnancy. British Journal of Obstetrics and Gynaecology 109, 606 - 609. Cram, L. F., Zapata, M. I,, Toy, E. C. & Baker, B. 3rd. (2002). Genitourinary infections and their association with preterm labor. American Family Physician 65, 241 - 248. [Review]. French, J. I., McGregor, J. A., Draper, D., Parker, R. & McFee, J. (1999). Gestational bleeding, bacterial vaginosis, and common reproductive tract infections: risk for preterm birth and benefit of treatment. Obstetrics & Gynecology 93, 715 - 724. Gencay, M., Koskiniemi, M., Saikku, P., Puolakkainen, M., Raivio, K., Koskela, P. & Vaheri, A. (1995). Chlamydia trachomatis seropositivity during pregnancy is associated with perinatal complications. Clinical Infectious Diseases 21, 424 - 426. Jacobson, G. F., Autry, A. M., Kirby, R. S, Liverman, E. M, & Motley, R. U. (2001). A randomized controlled trial comparing amoxicillin and azithromycin for the treatment of Chlamydia trachomatis in pregnancy. American Journal of Obstetrics and Gynecology 184, 1352 - 1354; discussion 1354 - 1356. Kacmar, J., Cheh, E., Montagno, A., Peipert, J. F. (20021). A randomized trial of azithromycin versus amoxicillin for the treatment of Chlamydia trachomatis in pregnancy. Infectious Disease in Obstetrics and Gynecology 9, 197 - 202. Kenyon, S., Boulvain, M. & Neilson, J (2002). Antibiotics for preterm premature rupture of membranes (Cochrane Review). In: The Cochrane Library, Issue 3 2002. Oxford: Update Software. Kovacs, L., Nagy, E., Berbik, I., Meszaros, G., Deak, J. & Nyari T. (1998). The frequency and the role of Chlamydia trachomatis infection in premature labor. International Journal of Gynaecology and Obstetrics 62, 47 - 54. Lamont, R. F., Taylor-Robinson, D., Wigglesworth, J. S., Furr, P. M., Evans, R. T. & Elder, M. G. (1987). The role of mycoplasmas, ureaplasmas and chlamydiae in the genital tract of women presenting in spontaneous early preterm labour. Journal of Medical Microbiology 24, 253 - 257. Locksmith, G. & Duff, P. (2001). Infection, antibiotics and preterm delivery. Seminars in Perinatology 25, 295 - 309. Mittendorf, R., Herschel, M., Williams, M. A., Hibbard, J. U., Moawad, A. H. & Lee, K. S. (1994). Reducing the frequency of low birth weight in the United States. Obstetrics and Gynecology 83, 1056 - 1059. Nishimura, M., Kumamoto, Y., Koroku, M., Tsunekawa, T., Hiroe, T., Hayashi, K., Matsukawa, M., Nishijima, N., Minami, K., Yoshio, H. et al. (1990). Epidemiological study on Chlamydia trachomatis infection in pregnant housewives and investigation on its influence on outcome of pregnancy and on their newborns. Kansenshogaku Zasshi 64, 179 - 187. [In Japanese.] Nugent, R. P. & Hillier, S. L. (1992). Mucopurulent cervicitis as a predictor of chlamydial infection and adverse pregnancy outcome. The Investigators of the Johns Hopkins Study of Cervicitis and Adverse Pregnancy Outcome. Sexually Transmitted Diseases 19, 198 - 202. Nyari, T., Woodward, M., Meszaros, G., Karsai, J. & Kovacs, L. (2001). Chlamydia trachomatis infection and the risk of perinatal mortality in Hungary. Journal of Perinatal Medicine 29, 55 - 59. Pal, S., Peterson, E. M. & De La Maza, L. M. (1999). A murine model for the study of Chlamydia trachomatis genital infections during pregnancy. Infection and Immunity 67, 2607 - 2610. Full article Rastogi, S., Kapur, S., Salhan, S., Mittal, A. (1999). Chlamydia trachomatis infection in pregnancy: risk factor for an adverse outcome. British Journal of Biomedical Science 56, 94 - 98. Thomas, K. & Simms, I. (2002). Chlamydia trachomatis in subfertile women undergoing uterine instrumentation: How we can help in the avoidance of iatrogenic pelvic inflammatory disease? Human Reproduction 17, 1431 - 1432. Ville, Y., Carroll, S. G., Watt, P., Ward, M. E. & Nicolaides, K. H. (1997). Chlamydia trachomatis infection in prelabour amniorrhexis. British Journal of Obstetrics and Gynaecology 104, 1091 - 1093. [MEW] November 2002 |
