The Role of Chlamydiales in adverse pregnancy outcome: a community-based nested case-control study

Objectives: Over the last decades, the Chlamydiales order has expanded and a new group of Chlamydia-related bacteria has emerged, covering species such as Waddlia chondrophila associated with bovine abortion. However, it is unknown whether they compromise human reproduction such as Chlamydia trachomatis. We therefore aimed to investigate the association between vaginal colonization of selected species of the Chlamydiales order with spontaneous abortion, preterm birth, and animal exposure. Methods: Pregnant women were enrolled at the nuchal translucency scan or when admitted for suspected miscarriage at Aarhus University Hospital, Denmark. Cases were defined as spontaneous abortion <22 weeks and preterm birth <37 weeks. Controls were defined as term birth ≥37 weeks. Vaginal samples from 1203 women were assessed using C. trachomatis, W. chondrophila, and pan-Chlamydiales–specific real-time PCRs targeting the 16S rRNA gene. Results: A total of 1120 women of primarily Caucasian ancestry were enrolled, including 193 spontaneous abortions, 88 preterm births, and 839 term births. After sequencing for verification, the prevalence of Chlamydiales was 3 of 193 (1.6%; 95% CI, 0.5–4.8) in women experiencing spontaneous abortion, 2 of 88 (2.3%; 95% CI, 0.6–8.9) in women with preterm birth, and 20 of 839 (2.4%; 95% CI, 1.6–3.7) in women giving birth at term. Thus, Chlamydiales infection was neither significantly associated with spontaneous abortion (OR, 0.68; 95% CI, 0.15–2.01) nor preterm birth (OR, 1.02; 95% CI, 0.15–3.60) compared with women giving birth at term. Amplicons from the pan-Chlamydiales assay revealed close sequence homology and were primarily identified as uncultured Chlamydiales bacteria. Discussion: : Among Danish pregnant women, the prevalence of Chlamydiales was low and not associated with adverse pregnancy outcomes.