Sexually Transmitted Diseases:
Letter to the Editor
From the *Research Unit for General Practice, Aarhus, Denmark; the †Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; ‡Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark; the §Department of Clinical Microbiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
To the Editor:
Recently, Bakken et al1 concluded from a Norwegian register-based study that a diagnosis of Chlamydia trachomatis (CT) infection was associated with a 2-fold increased risk of ectopic pregnancy. The study compared the prevalence of positive CT test results among 2 groups of tested women, namely one with ectopic pregnancy and one without. In 2005, we published a Danish study based on a similar data set,2 but we came to the opposite conclusion that women with positive CT test results had a low risk of ectopic pregnancy compared with women with only negative results. Bakken et al suggest that the explanation for the discrepant results is a number of limitations in the Danish study.
First, Bakken et al argue that exclusion of women who did not become pregnant during the follow-up period underestimated the risk of ectopic pregnancy. However, it is essential to exclude women who are not certainly at risk when using the Cox regression model. Exclusion of women who did not become pregnant during the follow-up period most likely increased the overall incidence rates of ectopic pregnancy. The hazard ratio associated with positive CT tests may either have been increased or decreased depending on how test results influenced tested women's risk of subsequently becoming pregnant. Second, Bakken et al claim that the CT test history was incomplete. We acknowledge this limitation, but it applies to the Norwegian study as well because both were based on data from one laboratory. Finally, Bakken et al give a critical comment to the observation period. Usually CT infections occur in younger women, whereas fertility complications are seen many years later. Therefore, the long-term follow up should be counted in favor of the Danish study.
Other factors than those considered by Bakken et al may also explain the results. First, the Norwegian population is screened, whereas the Danish is more sporadically tested. Second, the 2-fold increased risk of ectopic pregnancy in the Norwegian was solely based on a subgroup analysis of the youngest third of the population on average being 26 years at the time of ectopic pregnancy. By contrast, and in agreement with our study, the risk estimates were <1 in older age groups. Third, in neither of the studies was adjustment done for confounders such as sexual behavior and contraceptive use associated with positive CT test results. Such confounders might have played a substantial role, particularly in the youngest age group examined by Bakken et al.
The use of molecular diagnostic tests in Norway is in favor of Bakken et al's study, and despite the differing results, we want to compliment Bakken et al for the publication of an interesting study. A Swedish register-based study has also been published recently by Low et al.3 Their conclusion that the incidence of severe CT-associated complications is lower than expected might apply to all 3 Scandinavian studies. This provides some reassurance to patients with a diagnosis of CT infection, but it also suggests that benefits of screening programs may be lower than previously expected.
1. Bakken IJ, Skjeldestad FE, Nordbo SA. Chlamydia trachomatis
infections increase the risk for ectopic pregnancy: A population-based, nested case–control study. Sex Transm Dis 2006; July (e-pub ahead of print).
2. Andersen B, Østergaard L, Puho E, et al. Ectopic pregnancies and reproductive capacity after Chlamydia trachomatis
positive and negative test results: A historical follow-up study. Sex Transm Dis 2005; 32:377–381.
3. Low N, Egger M, Sterne JA, et al. Incidence of severe reproductive tract complications associated with diagnosed genital chlamydial infection: The Uppsala Women's Cohort Study. Sex Transm Infect 2006; 82:212–218.