Reproductive tract complication risks following Chlamydia trachomatis infections: a long-term prospective cohort study from 2008 to 2022

Abstract

Background: The clinical and public health relevance of widespread testing for asymptomatic Chlamydia trachomatis (chlamydia) infections is under debate. To address uncertainties in screening programs, we estimate reproductive tract complication risks following asymptomatic and symptomatic chlamydia infections in a long-term prospective cohort.

Methods: A cohort of 5704 reproductive-age women recruited from a chlamydia screening study was followed for up to 14 years. Chlamydia positivity was determined using screening polymerase chain reaction test results, self-reported diagnoses (with/without symptoms), and chlamydia Immunoglobulin G antibodies. Outcome data (pregnancies, pelvic inflammatory disease (PID), ectopic pregnancy, and tubal factor infertility) were collected through self-completed questionnaires. Cox regression calculated adjusted hazard ratios (aHR) with confidence intervals (CI) to compare outcomes between time-updated chlamydia groups since sexual debut.

Findings: During 104,612 person-years, 2103 (36.9%) women were chlamydia-positive and 3692 women (64.7%) had been pregnant at least once. Risks for PID, ectopic pregnancy and tubal factor infertility were 1.62 (95% CI 1.20-2.17), 1.84 (95% CI 1.14-2.95) and 2.75 (95% CI 1.53-4.94), compared to chlamydia-negatives. aHRs for PID after symptomatic and asymptomatic infections were 2.29 (95% CI 1.62-3.25) and 1.06 (95% CI 0.66-1.69), respectively. Incidence of PID, ectopic pregnancy and tubal factor infertility after symptomatic chlamydia infection remained low with rates per 1000 person-years of 5.8, 1.9, and 1.8, respectively.

Interpretation: We found a significantly higher risk of PID, ectopic pregnancy and tubal factor infertility in chlamydia-positive women compared to chlamydia-negative women, although the overall incidence rates of complications remained low. Symptomatic, but not asymptomatic, chlamydia infections were associated with PID risk, suggesting the largest disease burden of complications is in this group.

Funding: The Netherlands Organisation for Health Research and Development (ZonMW Netherlands) and Research Funding from the Ministry of Health, Welfare and Sports.

Keywords: Asymptomatic chlamydia infections; Chlamydia control; Chlamydia trachomatis; Prospective cohort study; Reproductive tract complications.

Fig. 1

Methodology for classification of chlamydia groups based on time-varying chlamydia status. Circles represent chlamydia infections (t1–t2). Dotted lines represent hypothetical follow-up period for an individual (Δt0–Δt2). Follow-up always starts at sexual debut (t0) with chlamydia-negative status. Screening (+) = having a positive PCR-test outcome in the screening study; self-reported (+) = a self-reported chlamydia infection; serology (+) = presence of chlamydia IgG antibodies in serum. ^# serology (+) only applies if no other known chlamydia diagnoses (screening-PCR (+) or self-reported (+)). ^$ remains classified as symptomatic even after subsequent asymptomatic infection. CT, Chlamydia trachomatis; PCR, polymerase chain reaction; IgG, Immunoglobulin G.

Fig. 2

Kaplan–Meier plots of time (years since sexual debut) to complications by chlamydia status. (a) Pelvic inflammatory disease, (b) Ectopic pregnancy, (c) Tubal factor infertility. Chlamydia-positive was defined as a positive PCR-test outcome in the CSI study (screening-PCR+), and/or a self-reported chlamydia infection (self-reported+) and/or presence of chlamydia IgG antibodies in serum (serology+)∗. Shaded areas represent corresponding 95% confidence intervals. Time was censored at a sample size reduction of less than 15 participants per stratum. ∗Median serology+ cases of 15 multiple imputation. PCR, polymerase chain reaction; IgG, Immunoglobulin G.

Fig. 3

Complication risks for chlamydia subgroups, reference is chlamydia-negative. (a) Chlamydia diagnosis: asymptomatic, symptomatic, and serology+ only, (b) Repeat chlamydia infection: single infection (self-reported + or screening-PCR+), multiple infections (≥2 or more) (self-reported+ and/or screening-PCR+), and serology+ only. Error bars represent 95% confidence intervals. Number of events per group and unadjusted hazard ratios can be found in Table S8. CT, Chlamydia trachomatis; PCR, polymerase chain reaction.

Fig. 4

Kaplan–Meier plots of time (years or months) to pregnancy by chlamydia status. (a) Pregnancy, (b) Planned pregnancies. Chlamydia-positive was defined as a positive PCR-test outcome in the CSI study (screening-PCR+), and/or a self-reported chlamydia infection (self-reported+) and/or presence of chlamydia IgG antibodies in serum (serology+)∗. Shaded areas represent corresponding 95% confidence intervals. Time was censored at a sample size reduction of less than 15 participants per stratum.∗Median serology+ cases of 15 multiple imputation. PCR, polymerase chain reaction; IgG, immunoglobulin G.