Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes

Brown, Richard; Al‐Memar, M.; Marchesi, Julian R.; Lee, Yun Sok; Smith, Ann; Chan, Derek J; Lewis, H.; Kindinger, Lindsay; Terzidou, Vasso; Bourne, T.; Bennett, Phillip R.; MacIntyre, David A.

doi:10.1016/j.trsl.2018.12.005

Cited by 132 publications

(111 citation statements)

References 36 publications

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“…In contrast, adverse pregnancy outcomes such as preterm pre‐labour rupture of membranes and preterm birth are associated with reduced Lactobacillus spp. dominance and a shift towards high bacterial diversity community compositions . However, vaginal microbial composition is poorly described prior to 8 weeks of gestation, a crucial time period of pregnancy given that most miscarriages occur early in the first trimester …”

Section: Introductionmentioning

confidence: 99%

The association between vaginal bacterial composition and miscarriage: a nested case–control study

Al‐Memar

Bobdiwala

Fourie

et al. 2019

BJOG

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109

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Objective To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages.Design Nested case-control study.Setting Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London.Population 161 pregnancies: 64 resulting in first trimester miscarriage, 14 in second trimester miscarriage and 83 term pregnancies.Methods Prospective profiling and comparison of vaginal bacteria composition using 16S rRNA gene-based metataxonomics from 5 weeks' gestation in pregnancies ending in miscarriage or uncomplicated term deliveries matched for age, gestation and body mass index.Main outcome measures Relative vaginal bacteria abundance, diversity and richness. Pregnancy outcomes defined as first or second trimester miscarriage, or uncomplicated term delivery.Results First trimester miscarriage associated with reduced prevalence of Lactobacillus spp.-dominated vaginal microbiota classified using hierarchical clustering analysis (65.6 versus 87.7%; P = 0.005), higher alpha diversity (mean Inverse Simpson Index 2.5 [95% confidence interval 1.8-3.0] versus 1.5 [1.3-1.7], P = 0.003) and higher richness 25.1 (18.5-31.7) versus 16.7 (13.4-20), P = 0.017), compared with viable pregnancies. This was independent of vaginal bleeding and observable before first trimester miscarriage diagnosis (P = 0.015). Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.-depleted communities compared with missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies.Conclusions These findings associate the bacterial component of vaginal microbiota with first trimester miscarriage and indicate suboptimal community composition is established in early pregnancy. While further studies are required to elucidate the mechanism, vaginal bacterial composition may represent a modifiable risk factor for first trimester miscarriage.Keywords First trimester miscarriage, second trimester miscarriage, vaginal bacteria, vaginal microbiome.Tweetable abstract Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding.

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Section: Introductionmentioning

confidence: 99%

The association between vaginal bacterial composition and miscarriage: a nested case–control study

Al‐Memar

Bobdiwala

Fourie

et al. 2019

BJOG

Self Cite

109

110

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“…state type) rather than a "type" which implies it is static over time. The dimensionality reduction provided by the CST approach has allowed epidemiologists to link variation in the vaginal microbiota with vaginal inflammation [25], STI occurrence [21,26,27], Candida detection [28], as well as increased risk of preterm birth [29].…”

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confidence: 99%

VALENCIA: A nearest centroid classification method for vaginal microbial communities based on composition

France

Gajer

et al. 2020

Preprint

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Background: Taxonomic profiles of vaginal microbial communities can be sorted into a discrete number of categories termed Community State Types (CSTs). This approach is advantageous because collapsing a hyper dimensional taxonomic profile into a single categorical variable enables efforts such as data exploration, epidemiological studies and statistical modeling. Vaginal communities are typically assigned to CSTs based on the results of hierarchical clustering of the pairwise distances between samples. However, this approach is problematic because it complicates between-study comparisons and because the results are entirely dependent on the particular set of samples that were analyzed. We sought to standardize and advance the assignment of samples to CSTs.Results: We developed VALENCIA (VAginaL community state typE Nearest CentroId clAssifier), a nearest centroid based tool which classifies samples based on their similarity to a set of reference centroids. The references were defined using a comprehensive set of 13,160 taxonomic profiles from 1,975 women in the United States. This large dataset allowed us to comprehensively identify, define, and characterize vaginal CSTs common to reproductive age women, and expand upon the CSTs that had been defined in previous studies. We validated the broad applicability of VALENCIA for the classification of vaginal microbial communities by using it to classify three test datasets which included reproductive age African women, adolescent girls, and menopausal women. VALENCIA performed well on all three datasets despite the substantial variations in sequencing strategies and bioinformatics pipelines, indicating its broad application to vaginal microbiota. We further describe the relationships between community characteristics (vaginal pH, Nugent score) and participant demographics (race, age) and the CSTs defined by VALENCIA. Conclusion: VALENCIA provides a much-needed solution for the robust and reproducible assignment of vaginal community state types. This will allow unbiased analysis of both small and large vaginal microbiota datasets, comparisons between datasets and meta-analyses that combine multiple datasets.

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“…Another study implicated the abnormal vaginal microbiome that is less dominated by Lactobaccilli sp. as a risk for PPROM [25].…”

Section: Discussionmentioning

confidence: 99%

Preterm prelabour rupture of membranes (PPROM) and pregnancy outcomes in association with HIV-1 infection in KwaZulu-Natal, South Africa

Onwughara

Moodley

Valashiya

et al. 2020

BMC Pregnancy Childbirth

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Background: SubSaharan Africa has a disproportionate burden of HIV and preterm births (PTB). We hypothesized that PTB in HIV-1 infected women are more likely a result of prelabour rupture of membranes (PROM) and could lead to worse birth outcomes than HIV-uninfected women. We also hypothesized that PPROM increased the risk of mother-to-child transmission (MTCT) of HIV-1. Current clinical management protocols for PPROM do not include a differential treatment plan for HIV-infected women. Methods: The maternity register at a regional hospital in a high HIV-burden district in South Africa was reviewed to identify all preterm births over a 3 month-period in 2018. We determined the incidence of PPROM using predefined criteria. Maternal age, parity, previous pregnancy complications, antenatal care, body mass index, history of smoking or alcohol, HIV infection and syphilis were computed on chi-square contingency tables to determine risk of PPROM. Overall pregnancy outcomes that included mode of delivery, fetal survival, birth weight, gestational age and newborn apgar scores were compared between HIV-infected and HIV-uninfected women whose pregnancies were complicated by PPROM. HIV-exposed newborns are routinely tested at birth for HIV by PCR. Results: A total of 1758 deliveries were recorded for Jan-Mar, 2018, and 295 (16.8%) were preterm. Maternity charts were retrieved for 236 (80.0%) PTB; 47 of PTB (19.9%; 95%CI 15.0-25.6) were further complicated by PROM which translates to 2.7% (95%CI 1.9-3.4) of all deliveries. None of the risk variables including HIV-positive status (48.9% vs 47.6%) were different between PPROM and non-PPROM groups and the majority of women were receiving cART (94.7 and 92.0%). There were no differences in the proportion of low birth weight (RR 1.2 95%CI 0.6-2.1) or severe preterm birth (RR 1.6; 95%CI 0.9-2.9) between HIV-infected and HIV-uninfected women whose pregnancies were complicated by PPROM. None of the 22 HIV-exposed newborns in the PPROM group were HIV-infected at birth. Conclusion: The PPROM incidence is not higher among HIV-infected women and our findings suggest that HIVinfected women who are virally suppressed on cART and presenting with PPROM are less likely to transmit HIV to their infants and do not have worse birth outcomes than HIV-uninfected women.

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Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes

Cited by 132 publications

References 36 publications

The association between vaginal bacterial composition and miscarriage: a nested case–control study

The association between vaginal bacterial composition and miscarriage: a nested case–control study

VALENCIA: A nearest centroid classification method for vaginal microbial communities based on composition

Preterm prelabour rupture of membranes (PPROM) and pregnancy outcomes in association with HIV-1 infection in KwaZulu-Natal, South Africa

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