The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.

Despite extensive studies into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effect of maternal infection on the neonate is unclear. To investigate this, we characterized the immunology of neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Here we show that maternal SARS-CoV-2 infection affects the neonatal immune system. Despite similar proportions of B cells, CD4 + T cells and CD8 + T cells, increased percentages of natural killer cells, Vδ2 + γδ T cells and regulatory T cells were detected in neonates born to mothers with recent or ongoing infection compared with those born to recovered or uninfected mothers. Increased plasma cytokine levels were also evident in neonates and mothers within the recent or ongoing infection group. Cytokine functionality was enhanced in neonates born to SARS-CoV-2-exposed mothers, compared to those born to uninfected mothers. In most neonates, this immune imprinting was nonspecific, suggesting vertical transmission of SARS-CoV-2 is limited, a finding supported by a lack of SARS-CoV-2-specific IgM in neonates despite maternal IgG transfer.

In high-risk asymptomatic women, fFN may be used as a primary screening tool with CL measurement being reserved for those with a positive fFN result. Further prospective studies are needed to confirm our findings.

ObjectiveTo determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship.MethodsThis prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks’ gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks’ gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay.ResultsAll 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks’ gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8–147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0–23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0–17.7; p<0.001].ConclusionsAlthough GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length.

BACKGROUND: Vaginal cerclage (a suture around the cervix) commonly is placed in women with recurrent pregnancy loss. These women may experience late miscarriage or extreme preterm delivery, despite being treated with cerclage. Transabdominal cerclage has been advocated after failed cerclage, although its efficacy is unproved by randomized controlled trial. OBJECTIVE: The objective of this study was to compare transabdominal cerclage or high vaginal cerclage with low vaginal cerclage in women with a history of failed cerclage. Our primary outcome was delivery at <32 completed weeks of pregnancy. STUDY DESIGN: This was a multicenter randomized controlled trial. Women were assigned randomly (1:1:1) to receive transabdominal cerclage, high vaginal cerclage, or low vaginal cerclage either before conception or at <14 weeks of gestation. RESULTS: The data for 111 of 139 women who were recruited and who conceived were analyzed: 39 had transabdominal cerclage; 39 had high vaginal cerclage, and 33 had low vaginal cerclage. Rates of preterm birth at <32 weeks of gestation were significantly lower in women who received transabdominal cerclage compared with low vaginal cerclage (8% [3/39] vs 33% [11/33]; relative risk, 0.23; 95% confidence interval, 0.07e0.76; P¼.0157). The number needed to treat to prevent 1 preterm birth was 3.9 (95% confidence interval, 2.32e12.1). There was no difference in preterm birth rates between high and low vaginal cerclage (38% [15/39] vs 33% [11/33]; relative risk, 1.15; 95% confidence interval, 0.62e2.16; P¼.81). No neonatal deaths occurred. In an exploratory analysis, women with transabdominal cerclage had fewer fetal losses compared with low vaginal cerclage (3% [1/39] vs 21% [7/33]; relative risk, 0.12; 95% confidence interval, 0.016e0.93; P¼.02). The number needed to treat to prevent 1 fetal loss was 5.3 (95% confidence interval, 2.9e26). CONCLUSION: Transabdominal cerclage is the treatment of choice for women with failed vaginal cerclage. It is superior to low vaginal cerclage in the reduction of risk of early preterm birth and fetal loss in women with previous failed vaginal cerclage. High vaginal cerclage does not confer this benefit. The numbers needed to treat are sufficiently low to justify transabdominal surgery and cesarean delivery required in this select cohort.

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IntroductionThe aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (fFN) concentration, in combination with clinical risk factors.Methods and analysisThe study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts, USA) which quantifies fFN in a vaginal swab. In QUIDS part 2, we will perform a prospective cohort study in at least eight UK consultant-led maternity units, in women with symptoms of preterm labour at 22+0 to 34+6 weeks gestation to externally validate a prognostic model developed in QUIDS part 1. The effects of quantitative fFN on anxiety will be assessed, and acceptability of the test and prognostic model will be evaluated in a subgroup of women and clinicians (n=30). The sample size is 1600 women (with estimated 96–192 events of preterm delivery within 7 days of testing). Clinicians will be informed of the qualitative fFN result (positive/negative) but be blinded to quantitative fFN result. Research midwives will collect outcome data from the maternal and neonatal clinical records. The final validated prognostic model will be presented as a mobile or web-based application.Ethics and disseminationThe study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068).VersionProtocol V.2, Date 1 November 2016.Trial registration numberISRCTN41598423 and CPMS: 31277.