A prospective cohort study examining the association between the periconceptual vaginal microbiota and first‐trimester miscarriage in Kenyan women

Author:

McClelland R. Scott1234,Lokken Erica M.3ORCID,Kinuthia John56,Srinivasan Sujatha7ORCID,Richardson Barbra A.378,Jaoko Walter4,Lannon Sophia9,Pulei Anne5610,Fiedler Tina L.7,Munch Matthew M.7,Proll Sean7,John‐Stewart Grace12311,Fredricks David N.17

Affiliation:

1. Department of Medicine University of Washington Seattle Washington USA

2. Department of Epidemiology University of Washington Seattle Washington USA

3. Department of Global Health University of Washington Seattle Washington USA

4. Department of Medical Microbiology and Immunology University of Nairobi Nairobi Kenya

5. Department of Obstetrics and Gynaecology University of Nairobi Nairobi Kenya

6. Department of Research and Programs Kenyatta National Hospital Nairobi Kenya

7. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle Washington USA

8. Department of Biostatistics University of Washington Seattle Washington USA

9. Northwest Perinatal, Women's Healthcare Associates Portland Oregon USA

10. Department of Human Anatomy and Medical Physiology University of Nairobi Nairobi Kenya

11. Department of Pediatrics University of Washington Seattle Washington USA

Abstract

AbstractBackgroundStudies evaluating the association between the vaginal microbiota and miscarriage have produced variable results.ObjectiveThis study evaluated the association between periconceptual and first‐trimester vaginal microbiota and women's risk for miscarriage.MethodsAt monthly preconception visits and at 9–12 weeks gestation, women collected vaginal swabs for molecular characterisation of the vaginal microbiota. Participants who became pregnant were followed to identify miscarriage versus pregnancy continuing to at least 20 weeks gestation.ResultsForty‐five women experienced miscarriage and 144 had pregnancies continuing to ≥20 weeks. A principal component analysis of periconceptual and first‐trimester vaginal bacteria identified by 16S rRNA gene PCR with next‐generation sequencing did not identify distinct bacterial communities with miscarriage versus continuing pregnancy. Using taxon‐directed quantitative PCR assays, increasing concentrations of Megasphaera hutchinsoni, Mageeibacillus indolicus, Mobiluncus mulieris and Sneathia sanguinegens/vaginalis were not associated with miscarriage. In exploratory analyses, these data were examined as a binary exposure to allow for multivariable modelling. Detection of Mobiluncus mulieris in first‐trimester samples was associated with miscarriage (adjusted relative risk [aRR] 2.14, 95% confidence interval [CI] 1.08, 4.22). Additional analyses compared women with early first‐trimester miscarriage (range 4.7–7.3 weeks) to women with continuing pregnancies. Mobiluncus mulieris was detected in all eight (100%) first‐trimester samples from women with early first‐trimester miscarriage compared to 101/192 (52.6%) samples from women with continuing pregnancy (model did not converge). Detection of Mageeibacillus indolicus in first‐trimester samples was also associated with early first‐trimester miscarriage (aRR 4.10, 95% CI 1.17, 14.31).ConclusionsThe primary analyses in this study demonstrated no association between periconceptual or first‐trimester vaginal microbiota and miscarriage. Exploratory analyses showing strong associations between first‐trimester detection of Mobiluncus mulieris and Mageeibacillus indolicus and early first‐trimester miscarriage suggest the need for future studies to determine if these findings are reproducible.

Funder

National Institute of Allergy and Infectious Diseases

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Publisher

Wiley

Reference36 articles.

1. Trends in the incidence, rate and treatment of miscarriage‐nationwide register‐study in Finland, 1998‐2016;Linnakaari R;Hum Reprod,2019

2. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss;Quenby S;Lancet,2021

3. Connecting links between genetic factors defining ovarian reserve and recurrent miscarriages;Dean DD;J Assist Reprod Genet,2018

4. Alteration of vaginal microbiota in patients with unexplained recurrent miscarriage;Zhang F;Exp Ther Med,2019

5. Alteration of vaginal microbiota in patients with recurrent miscarriage;Jiao X;J Obstet Gynaecol,2022

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