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

Zoïe W Alexiou; Bernice M Hoenderboom; Christian J P A Hoebe; Nicole H T M Dukers-Muijrers; Hannelore M Götz; Marianne A B van der Sande; Henry J C de Vries; Janneke E den Hartog; Servaas A Morré; Birgit H B van Benthem

doi:10.1016/j.lanepe.2024.101027

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

Lancet Reg Health Eur. 2024 Aug 17:45:101027. doi: 10.1016/j.lanepe.2024.101027. eCollection 2024 Oct.

Authors

Zoïe W Alexiou^{1

2

3}, Bernice M Hoenderboom^{1

2}, Christian J P A Hoebe^{3

4}, Nicole H T M Dukers-Muijrers^{4

5}, Hannelore M Götz^{6

7}, Marianne A B van der Sande⁸, Henry J C de Vries^{9

10

11

12}, Janneke E den Hartog^{13

14}, Servaas A Morré^{2

15

16}, Birgit H B van Benthem¹

Affiliations

¹ Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
² Institute for Public Health Genomics (IPHG), GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
³ Department of Social Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.
⁴ Department of Sexual Health, Infectious Diseases, and Environmental Health, Living Lab Public Health Mosa, Public Health Service South Limburg, the Netherlands.
⁵ Department of Health Promotion, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.
⁶ Department of Public Health, Municipal Public Health Service Rotterdam-Rijnmond, Rotterdam, the Netherlands.
⁷ Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁸ Department Global Public Health, Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁹ Amsterdam UMC Location University of Amsterdam, Department of Dermatology, Amsterdam, the Netherlands.
¹⁰ Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
¹¹ Center for Sexual Health, Department of Infectious Diseases, Public Health Service Amsterdam, the Netherlands.
¹² Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.
¹³ GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
¹⁴ Department of Obstetrics and Gynecology, Maastricht University Medical Center +, Maastricht, the Netherlands.
¹⁵ Dutch Chlamydia Trachomatis Reference Laboratory, Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands.
¹⁶ Department of Molecular and Cellular Engineering, Jacob Institute of Biotechnology and Bioengineering, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, India.

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.