The role of the vaginal microbiota, sexually transmitted infections, ureaplasmas, and Mycoplasma hominis in pregnancy loss: a prospective study in pregnant women in Denmark

Background
The microbiota of the reproductive tract can affect human reproduction and has been associated with adverse pregnancy outcomes. We aimed to examine associations between pregnancy loss and the vaginal microbiota, sexually transmitted infections (STIs), and colonisation with ureaplasmas and Mycoplasma hominis.
Methods
We did a prospective cohort study at Aarhus University Hospital, Denmark. We included pregnant women aged 18 years or older either who attended the hospital for a nuchal translucency scan scheduled at 11–14 weeks or who were admitted for suspected involuntary pregnancy loss. Term birth was defined as birth after 36 weeks and 6 days of gestation; pregnancy loss was defined as involuntary loss of pregnancy before 22 weeks of gestation. All women self-collected a high vaginal swab at this hospital visit, which was analysed retrospectively using 16S rRNA gene sequencing and specific real-time PCR assays for STIs, ureaplasmas, and Mycoplasma hominis.
Findings
Between Jan 5, 2015, and Jan 15, 2019, 2472 women were enrolled, of whom 1984 were included in the study, 173 (9%) women had pregnancy loss and 1811 (91%) had term birth. In our cohort, Lactobacillus spp were dominant both in women with pregnancy loss and in those with term birth. Linear discriminant analysis effect size suggested enrichment of Lactobacillus crispatus in women with term birth and Lactobacillus iners and several other taxa in women with pregnancy loss. Among the other taxa, Prevotella spp (mean 4·1 [SD 11·4] vs 3·6 [9·3]; p=0·015) and Sneathia spp (2·4 [8·9] vs 0·8 [4·3]; p=0·014) showed significantly higher relative abundances in women with pregnancy loss versus those with term birth, STIs were rarely identified by quantitative PCR and showed no association with pregnancy loss in our cohort. The presence of Ureaplasma spp or Mycoplasma hominis, similarly, was also not associated with pregnancy loss in our cohort.
Interpretation
In this cohort study, evaluation of the vaginal microbiota highlighted differences in Lactobacillus spp between women with ongoing pregnancy and those experiencing pregnancy loss. Bacterial vaginosis-associated genera might play a part in pregnancy loss, and targeted microbiota assessment could potentially help identify at-risk women. However, further research is necessary to confirm the effect of the vaginal microbiota on pregnancy loss and whether these findings apply to pregnant women from diverse ethnic backgrounds.