Parity and gestational age are associated with vaginal microbiota composition in term and late term pregnancies

Kervinen, Kaisa; Holster, Tiina; Saqib, Schahzad; Virtanen, Seppo; Stefanović, Vedran; Rahkonen, Leena; Nieminen, Pekka; Salonen, Anne; Kalliala, Ilkka

doi:10.1016/j.ebiom.2022.104107

Cited by 24 publications

(20 citation statements)

References 68 publications

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“…At an ASV-level, higher maternal parity was significantly associated with an increase in 58 ASVs classified as typical vaginal CST IV bacteria (e.g., Gardnerella, Megasphaera, Prevotella, and Sneathia), while lower maternal parity was exclusively correlated with 7 Lactobacillus ASVs, 6 of which were classified as L. crispatus (q<0.1) (Supplemental Table 1). This finding is consistent with a recent report of increased vaginal microbiota diversity with higher parity during subsequent gestations (109). The ecological and clinical implications of the correlation between increased parity and vaginal microbiota diversity warrant further investigation.…”

Section: Effect Of Maternal Paritysupporting

confidence: 92%

The vaginal microbiota of pregnant women varies with gestational age, maternal age, and parity

Romero

Theis

Gomez‐Lopez

et al. 2023

Preprint

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The composition of the vaginal microbiota is heavily influenced by pregnancy and may factor into pregnancy complications, including spontaneous preterm birth. However, results among studies have been inconsistent, due in part to variation in sample sizes and ethnicity. Thus an association between the vaginal microbiota and preterm labor continues to be debated. Yet, before assessing associations between the composition of the vaginal microbiota and preterm labor, a robust and in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required. Herein, we report a large longitudinal study (N = 474 women, 1862 vaginal samples) of a primarily African-American cohort, which experiences a relatively high rate of pregnancy complications, evaluating associations between individual identity, gestational age, and other maternal characteristics with the composition of the vaginal microbiota throughout gestation resulting in term delivery. The primary factors influencing the composition of the vaginal microbiota in pregnancy are individual identity and gestational age at sampling. Secondary factors are maternal age, parity, obesity, and self-reported Cannabis use. The principal pattern across gestation is for the vaginal microbiota to remain or transition to a state of Lactobacillus dominance. This pattern can be mitigated by maternal parity and obesity. Regardless, network analyses reveal dynamic associations among specific bacterial taxa within the vaginal ecosystem, which shift throughout the course of pregnancy. This study provides a robust foundational understanding of the vaginal microbiota in pregnancy among African-Americans, in particular, and sets the stage for further investigation of this microbiota in obstetrical disease.

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Section: Effect Of Maternal Paritysupporting

confidence: 92%

The vaginal microbiota of pregnant women varies with gestational age, maternal age, and parity

Romero

Theis

Gomez‐Lopez

et al. 2023

Preprint

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“…Small sample size in some of the comparisons might limit the validity of findings. In In a recent article by our team ( 55 ) we show that L. crispatus is up to 3x more abundant in primipara than multipara. The same study also shows that advancing gestational age relates to the higher abundance of L. crispatus .…”

Section: Limitationsmentioning

confidence: 76%

Cervicovaginal Complement Activation and Microbiota During Pregnancy and in Parturition

et al. 2022

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BackgroundVaginal microbiome and the local innate immune defense, including the complement system, contribute to anti- and proinflammatory homeostasis during pregnancy and parturition. The relationship between commensal vaginal bacteria and complement activation during pregnancy and delivery is not known.ObjectiveTo study the association of the cervicovaginal microbiota composition to activation and regulation of the complement system during pregnancy and labor.Study designWe recruited women during late pregnancy (weeks 41 + 5 to 42 + 0, n=48) and women in active labor (weeks 38 + 4 to 42 + 2, n=25). Mucosal swabs were taken from the external cervix and lateral fornix of the vagina. From the same sampling site, microbiota was analyzed with 16S RNA gene amplicon sequencing. A Western blot technique was used to detect complement C3, C4 and factor B activation and presence of complement inhibitors. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and staining intensities were analyzed using ImageJ/Fiji win-64 software. Patient data was collected from medical records and questionnaires.ResultsThe vaginal microbiota was Lactobacillus-dominant in most of the samples (n=60), L. iners and L. crispatus being the dominant species. L. gasseri and L. jensenii were found to be more abundant during pregnancy than active labor. L. jensenii abundance correlated with C4 activation during pregnancy but not in labor. Gardnerella vaginalis was associated with C4 activation both during pregnancy and labor. The amount of L. gasseri correlated with factor B activation during pregnancy but not during labor. Atopobium vaginae was more abundant during pregnancy than labor and correlated with C4 activation during labor and with factor B activation during pregnancy. Activation of the alternative pathway factor B was significantly stronger during pregnancy compared to labor. During labor complement activation may be inhibited by the abundant presence of factor H and FHL1.ConclusionsThese results indicate that bacterial composition of the vaginal microbiota could have a role in the local activation and regulation of complement-mediated inflammation during pregnancy. At the time of parturition complement activation appears to be more strictly regulated than during pregnancy.

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“…As alluded to above 59,70 , a history of childbirth is associated with a persistent shift in host hormonal status 72–74 and immune responsiveness – the latter triggered by exposures to paternal antigen 75 . Regardless of underlying causes, one implication of these findings is that future studies should take reproductive history into account, e.g., controlling or matching for parity 70,71 . Another implication is that past studies might be reframed; for example, our SU and UAB cohorts, the latter exhibiting lower rates of nulliparity and L. crispatus dominance, were headlined as racially distinct 17 , while they were also distinct in terms of reproductive history.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported a reduced prevalence of L. crispatus dominance among pregnant women with a history of prior delivery compared to those with no such history 59,70,71 . All were cross-sectional studies of healthy subjects enrolled at urban clinics (Toronto, New York City, Helsinki).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal dynamics of the human vaginal ecosystem across the reproductive cycle

Costello

DiGiulio

Robaczewska

et al. 2022

Preprint

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The vaginal ecosystem is closely tied to human health and reproductive outcomes. However, its dynamics in the wake of childbirth remain poorly characterized. Here, we profiled the vaginal microbiota and cytokine milieu of subjects sampled throughout pregnancy (two cohorts; n = 196 pregnancies) and, in a subset, for one year postpartum (one cohort; n = 72 pregnancies). Delivery was associated with a vaginal pro-inflammatory cytokine response and the depletion of dominant taxa,typically,Lactobacillusspecies. By contrast, neither the progression of gestation nor the approach of labor strongly altered the vaginal ecosystem. At ~9.5 months postpartum (the latest timepoint at which cytokines were analyzed), elevated inflammation was associated with vaginal bacterial communities that had remained perturbed (i.e., highly diverse) from the time of delivery. Using time-to-event analysis, we found that the one-year postpartum probability of transitioning toLactobacillusdominance was 49.4% (95% confidence interval (CI) [33.6%, 61.5%]; n = 58 at-risk cases, 86.2% of whom experienced this state prior to delivery). As diversity and inflammation declined postpartum, dominance byL. crispatus, the quintessential health-associated state, failed to recover: its prevalence before, immediately after, and one year after delivery was 41%, 4%, and 9%, respectively. Over the same period, states quasi-dominated by non-Lactobacillusspecies grew more common. Prompted by these findings, we revisited our pre-delivery data, discovering that a history of prior live birth was associated with a lower odds ofL. crispatusdominance in pregnant subjects (odds ratio (OR) 0.14; 95% CI [0.06, 0.32]; P < 0.001), an outcome modestly tempered by a longer (>18-month) interpregnancy interval. Our results suggest that reproductive history and childbirth in particular remodel the vaginal ecosystem and that the timing and degree of recovery from delivery may help determine the subsequent health of the woman and of future pregnancies.

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Parity and gestational age are associated with vaginal microbiota composition in term and late term pregnancies

Cited by 24 publications

References 68 publications

The vaginal microbiota of pregnant women varies with gestational age, maternal age, and parity

The vaginal microbiota of pregnant women varies with gestational age, maternal age, and parity

Cervicovaginal Complement Activation and Microbiota During Pregnancy and in Parturition

Longitudinal dynamics of the human vaginal ecosystem across the reproductive cycle

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