Article
Association of the vaginal microbiota with pregnancy outcomes in Chinese women after cervical cerclage

https://doi.org/10.1016/j.rbmo.2020.06.016Get rights and content

Abstract

Research question

The study aimed to investigate the relationship between risk factors associated with vaginal microbiota and outcomes of cervical cerclage.

Design

A retrospective cohort study of singleton pregnancies with cervical cerclage was conducted. Before cerclage, participants underwent a vaginal microbiota assay, including morphological examination and functional vaginal microecological analysis using a vaginitis multi-test kit. The chi-squared test and logistic and linear regression analyses were performed to evaluate the associations of various risk factors with maternal and neonatal outcomes.

Results

Eighty-five participants were included. The mean interval between cerclage and delivery was 69.4 ± 36.7 days, and 12 (14.1%) of newborns died. A higher grade of vaginal cleanliness, a higher pH, a lower abundance of Lactobacillus spp., a higher sialidase-positive percentage, a higher positive percentage of clue cells, a higher lactobacillary grade, a higher Nugent score and a higher rate of microecological dysbiosis were significantly associated with a poor neonatal outcome and shorter cerclage to delivery intervals (P < 0.001–0.041). Furthermore, sialidase positivity was associated with the highest risk of cervical cerclage failure (odds ratio [OR] 10.469; 95% confidence interval [CI] 1.096–36.087), followed by the presence of bulging membranes (OR 6.400; 95% CI 0.428–15.641) and vaginal microbiota dysbiosis (OR 6.038; 95% CI 0.173–17.072).

Conclusions

An absence of Lactobacillus spp. and some functional factors of vaginal microbiota are potential risk factors that predict subsequent cerclage failure. These findings indicate the potential clinical utility of these factors to predict cervical cerclage failure for managing patient expectations and providing improved postoperative surveillance.

Introduction

Globally, approximately 15 million pregnancies each year end in preterm birth (PTB) (WHO, 2014). PTB is the leading cause of death among children under the age of 5 years, with many survivors suffering significant morbidity (Liu et al., 2015), causing a series of problems for families and society. Although PTB has multiple aetiologies, cervical insufficiency is a risk factor with an incidence of up to 2.0%, and the treatment is not optimum (Frey and Klebanof, 2016). Several interventions have been used to improve the prognosis of PTB, such as progesterone, cervical cerclage and cervical pessaries (Butler, 2007).

According to guidelines for the National Institute for Health and Care Excellence, cervical cerclage can be considered in women who are diagnosed with or without exposed membranes between 16 and 27+6 weeks of gestation to reduce the risk of preterm delivery and to prolong gestation to delivery (NICE, 2015). Cervical cerclage is a widely used clinical strategy to prolong gestation and prevent PTB that reduces the risk of PTB by approximately 20% in pregnant women with cervical insufficiency (Alfirevic et al., 2017; Berghella et al., 2011), and this procedure is recommended by both the American and the UK colleges of obstetricians and gynaecologists (American College of Obstetricians and Gynecologists, 2014; Shennan and To, 2011). Approximately 2 million cerclage procedures are performed annually (Israfil-Bayli et al., 2013). Its mechanisms are uncertain, but it is postulated to strengthen the weakened cervix (Hein et al., 2002) and support the cervical mucosal plug as a barrier to ascending infection (Ethicon et al., 2007). However, some adverse outcomes, such as preterm premature rupture of membranes (PPROM) and chorioamnionitis, have been identified (Kassanos et al., 2001; Kurup et al., 1999).

Cervical cerclage significantly improves pregnancy outcomes and neonatal outcomes by prolonging gestational age (Gluck et al., 2016; Khan et al., 2012). Many factors modulate its effect. The outcomes of overall gestational age at delivery, delivery interval and neonatal outcomes for women with visible membranes at the time of cerclage insertion have been reported to be considerably worse than for women with no visible membranes (Groom et al., 2002). Additionally, greater cervical dilation and potential infection are factors contributing to a poor prognosis. The microbiota may spread haematogenously or ascend from the vagina along mucosal surfaces (Aagaard et al., 2014). According to recent studies, vaginal dysbiosis increases the risk of PTB and late miscarriage (Daniel et al., 2015;Leitich et al., 2007). Based on accumulating evidence, the dominance of the vaginal microbiome by Lactobacillus spp. is related to healthy reproductive outcomes. However, a reduction in the abundance of Lactobacillus spp. is associated with subsequent PTB and PPROM (Brown et al., 2018; Kindinger al., 2016; Kindinger et al., 2017).

Methods to predict which women will benefit from cervical cerclage are lacking. Fortunately, elevated concentrations of acute phase proteins, such as C-reactive protein, appear to have some capacity to predict poor outcomes (Gundabattula et al., 2013; Gupta et al., 2010), and a positive aerobic culture of vaginal bacteria identified using next-generation sequencing techniques at the time of cerclage was recently reported to potentially predict subsequent preterm delivery (Brown et al., 2019; Kanbayashi et al., 2018). However, these studies only analysed the relationship between the composition of the vaginal flora and delivery time in a small sample. A detailed examination of the relationship between composition of vaginal bacterial and outcomes of cervical cerclage has not been performed. More convenient, fast and effective indicators are needed to identify those women in whom cerclage is more likely to fail.

The aims of this study were to analyse the relationship between the morphological and functional indicators of the vaginal microbiota and the maternal and neonatal outcomes in the clinic, and to test the hypothesis that vaginal dysbiosis is associated with failure of cervical cerclage.

Section snippets

Participants

This retrospective observational study was performed at Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University (FMCH), from 1 January 2018 to 31 December 2019. Women of singleton pregnancies were recruited to participate in the study if they were undergoing cervical cerclage based on the following indications for cervical cerclage: (i) a prior history of one or more second-trimester pregnancy losses related to painless cervical dilation in the absence of

The maternal data and neonatal outcomes

Eighty-five patients were included during the study period. The maternal data and neonatal outcomes are presented in Table 1. The mean gestational age at the time of cerclage was 23.9 ± 2.2 weeks, the mean gestational age at PPROM was 29.8 ± 6.3 weeks, and the mean gestational age at delivery was 34.0 ± 5.6 weeks. The mean interval between cerclage and delivery was 69.4 ± 36.7 days. No severe maternal complications, such as maternal death, hysterorrhexis or pulmonary oedema, were observed in

Discussion

The neonatal mortality rate in the present study was 14.1%, consistent with recent studies reporting rates ranging from 12.7% to 47.5% (Aguin et al., 2014; Galyean et al., 2014). The results of the current study also indicate that women with a non-Lactobacillus spp.-dominant microbiome and a Lactobacillus spp.-depleted microbiome are more likely to experience failure of cervical cerclage, consistent with recent studies (Brown et al., 2019; Kanbayashi et al., 2018). Interestingly, this article

Acknowledgements

This study was supported by grants from the Fujian Provincial Maternity and Children's Hospital Technology Innovation Project (grant no. YCXZ 18-21). The authors would like to thank all the patients for their agreement to participate in follow-up, and the all staff of the Department of Obstetrics for providing excellent assistance during this study.

Mian Pan has developed his career as a Clinical Obstetrician since 1996 at Fujian Provincial Maternity and Child Health Hospital, affiliated to Fujian Medical University, China, and subsequently as a tutor. His major interests are treatment for high-risk pregnancy and cervical cerclage. He has published 10 papers and been invited to lecture on several university courses.

Key message

An absence of Lactobacillus spp. and some functional factors of vaginal microbiota can be potential

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    Key message

    An absence of Lactobacillus spp. and some functional factors of vaginal microbiota can be potential risk factors for failure of cervical cerclage. Identification of women with risk factors for cerclage failure would be useful to manage patient expectations and provide improved postoperative surveillance.

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    These authors contributed equally to this work.

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