The association between vaginal microbiota composition and miscarriage: a nested case-control study

ObjectiveTo characterise vaginal microbiota composition in early pregnancy and investigate its relationship with first and second trimester miscarriages.DesignNested case-control study.SettingQueen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London.PopulationOne hundred and sixty-one pregnancies of which 64 resulted in first trimester miscarriage, 14 in second trimester miscarriage and 83 term pregnancies.Methods Miseq sequencing of 16S rRNA gene amplicons was used to prospectively profile and compare vaginal bacteria composition from as early as five weeks gestation in pregnancies that ended in miscarriage or uncomplicated term delivery pregnancies matched for age, gestation and body mass index.Main outcome measuresRelative abundance of vaginal bacteria characterised by culture-independent next generation bacterial DNA sequencing and assessment of bacterial diversity and richness.Pregnancy outcomes defined as first trimester miscarriage, second trimester miscarriage or uncomplicated term delivery.ResultsFirst trimester miscarriage (but not second trimester miscarriage (P=0·893), was associated with reduced Lactobacillus spp. abundance (65.6% vs. 87·7%; P=0·003) and increased alpha diversity (P=0·003) and richness (P=0·017), when compared to viable pregnancies. The association of Lactobacillus spp. depletion and miscarriage was independent of vaginal bleeding and was observed prior to the diagnosis of first trimester miscarriage (when the pregnancy appeared to be viable on ultrasound) (P=0·015), Incomplete/complete miscarriage was associated with a higher proportion of Lactobacillus spp. deplete communities compared to missed miscarriage. Early pregnancy vaginal microbial stability in women experiencing miscarriage is similar to those who have healthy viable pregnancies at term.ConclusionsCollectively these findings suggest that vaginal microbiota composition is a risk factor for first trimester miscarriage and indicate that suboptimal community composition is established very early in pregnancy. While further studies are required to elucidate the mechanism by which vaginal microbial composition increases risk, it represents a potentially modifiable risk factor for first trimester miscarriage.