Abstract
Objective To assess the association between vaginal microbiome (VMB)
composition and recurrent early spontaneous preterm birth (sPTB)/preterm
prelabour rupture of membranes (PPROM). Design Nested case-control
study. Setting UK tertiary referral hospital. Sample High-risk women
with previous sPTB/PPROM <34(+0) weeks' gestation who had a recurrence
(n = 22) or delivered at >= 37(+0) weeks without PPROM (n = 87). Methods
Vaginal swabs collected between 15 and 22 weeks' gestation were analysed
by 16S rRNA gene sequencing and 16S quantitative PCR. Main outcome
measure Recurrent early sPTB/PPROM. Results Of the 109 high-risk women,
28 had anaerobic vaginal dysbiosis, with the remainder dominated by
lactobacilli (Lactobacillus iners 36/109, Lactobacillus crispatus
23/109, or other 22/109). VMB type and diversity were not associated
with recurrence. Women with a recurrence, compared to those without, had
a higher median vaginal bacterial load (8.64 versus 7.89 log(10)
cells/mcl, adjusted odds ratio [aOR] 1.90, 95% CI 1.01-3.56, P = 0.047)
and estimated Lactobacillus concentration (8.59 versus 7.48 log(10)
cells/mcl, aOR 2.35, (95% CI 1.20-4.61, P = 0.013). A higher recurrence
risk was associated with higher median bacterial loads for each VMB type
after stratification, although statistical significance was reached only
for L. iners domination (aOR 3.44, 95% CI 1.06-11.15, P = 0.040). Women
with anaerobic dysbiosis or L. iners domination had a higher median
vaginal bacterial load than women with a VMB dominated by L. crispatus
or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log(10) cells/mcl,
respectively). Conclusions Vaginal bacterial load is associated with
early sPTB/PPROM recurrence. Domination by lactobacilli other than L.
iners may protect women from developing high bacterial loads. Future PTB
studies should quantify vaginal bacteria and yeasts. Tweetable abstract
Increased vaginal bacterial load in the second trimester may be
associated with recurrent early spontaneous preterm birth.
