Article

Leitich H, Kiss H.. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol 21: 375-390

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

We updated a previously published meta-analysis to evaluate bacterial vaginosis (BV) and intermediate vaginal flora as risk factors for adverse pregnancy outcome. Selection criteria were original, published, English-language reports of cohort studies or control groups of clinical trials including women <37 weeks' gestation with intact amniotic membranes. All women had to be screened for BV, diagnosed either by clinical criteria or by criteria based on Gram-stain findings. Outcomes were preterm delivery, late miscarriages, maternal or neonatal infections, and perinatal mortality. Fourteen new studies with results for 10,286 patients were included, so that results for 30,518 patients in 32 studies were available for this meta-analysis. BV more than doubled the risk of preterm delivery in asymptomatic patients (OR: 2.16, 95% CI: 1.56-3.00) and in patients with symptoms of preterm labor (OR: 2.38, 95% CI: 1.02-5.58). BV also significantly increased the risk of late miscarriages (OR: 6.32, 95% CI: 3.65-10.94) and maternal infection (OR: 2.53, 95% CI 1.26-5.08) in asymptomatic patients. No significant results were calculated for the outcomes of neonatal infection or perinatal mortality. Also, intermediate vaginal flora was not significantly associated with any outcome included. The results of this meta-analysis confirm that BV is a risk factor for preterm delivery and maternal infectious morbidity and a strong risk factor for late miscarriage.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... 9 In pregnant women, vaginal dysbiosis, and BV in particular, represents causative factors in the multifactorial event of PTB. [10][11][12][13][14] In addition to the association between BV and PTB, [15][16][17] certain groups have an increased risk of vaginal infections, which underlines the importance of screening women for vaginal dysbiosis and for colonization by potentially harmful pathogens, in order to prevent them from ascending and causing preterm contractions, cervical insufficiency, and PTB. 11,18,19 Among these risk groups are women receiving opioid-maintenance therapy, who have an increased risk of vaginal infections. ...
... Imbalances in the vaginal ecosystem can lead to PTB, [10][11][12][13][14] which is the main cause of neonatal morbidity and mortality worldwide. In our study, we found that HIV-positive women had an increased risk of developing dysbiosis, BV, and VVC during pregnancy, when being compared to the controls. ...
... Women who are HIV-positive have an increased risk of obstetric complications, including PTB, 4-6 which is a multifactorial event that is frequently caused by an overgrowth of anaerobic bacteria in the vaginal microbiota. [10][11][12][13][14]30 Of note, the risk of PTB was not increased in the cases of our study, which might be because infections were consequently treated and follow-up smears were performed. ...
Article
Full-text available
Background This study aimed to evaluate the vaginal microbiota of HIV‐positive pregnant women relative to HIV‐negative controls, and to compare their risk of vaginal dysbiosis, bacterial vaginosis, and vulvovaginal candidosis (VVC). Methods This is a nested matched case‐control study that analyzed data from women who received pregnancy care at our center from 2003 to 2014. Women routinely underwent screening for asymptomatic vaginal infections using phase microscopy on Gram‐stained smears. HIV‐positive women were assigned to the case group, and HIV‐negative women were assigned to the control group. Cases and controls were matched in a 1:4 ratio. Logistic regression was used to test whether HIV infection was associated with vaginal dysbiosis (Nugent score 4‐6), BV (Nugent score 7‐10), or VVC. Results One hundred and twenty‐seven women were assigned to the case group, and 4290 were assigned to the control group (including 508 matched controls). Dysbiosis or BV was found in 29.9% of the cases and 17.6% of the controls. Women in the case group had increased risk of vaginal dysbiosis or BV (odds ratio [OR] 2.09, 95% confidence interval [CI], 1.30‐3.32, P = .002). The risk of VVC was also higher in the case group (OR 2.14, 95% CI, 1.22‐3.77, P = .008). The incidence of preterm birth did not differ significantly between the groups (cases: 8.7%; controls: 10%, P = .887). Conclusions HIV‐positive women are at risk of vaginal dysbiosis, BV, and VVC during pregnancy. As imbalances of the vaginal microbiota can lead to preterm birth, screening and treatment of HIV‐positive pregnant women are warranted.
... and maternal infection (OR 2.53, 95% CI 1.26-5.08) [8]. Additionally, there is also evidence that intermediate flora (Nugent score between 4 and 6) may increase the risk of prematurity [9,10], and other endocervical germs have been associated with preterm birth, such as Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) [11][12][13]. ...
... Among the findings, we must highlight that more than one of every four screened pregnant women had a vaginal or endocervical infection, and therefore, an increased risk of perinatal adverse events according to previous studies [5][6][7][8][9][10][11][12][13][14][15], and especially of preterm delivery [8,9,28]. This finding notes that vaginal flora alteration is a condition that affects our pregnant women considerably more frequently than other infections for which systematic screening are established, such as toxoplasmosis infection (affecting 0.1% of pregnancies) [29], cytomegalovirus infection (1%) [30] or asymptomatic bacteriuria (2-10%) [31]. ...
... Among the findings, we must highlight that more than one of every four screened pregnant women had a vaginal or endocervical infection, and therefore, an increased risk of perinatal adverse events according to previous studies [5][6][7][8][9][10][11][12][13][14][15], and especially of preterm delivery [8,9,28]. This finding notes that vaginal flora alteration is a condition that affects our pregnant women considerably more frequently than other infections for which systematic screening are established, such as toxoplasmosis infection (affecting 0.1% of pregnancies) [29], cytomegalovirus infection (1%) [30] or asymptomatic bacteriuria (2-10%) [31]. ...
Article
Full-text available
Objectives: Vaginal and endocervical infections are considered a global health problem, especially after recent evidence of their association with preterm delivery and other adverse obstetric outcomes. Still, there is no consensus on the efficacy of a screening strategy for these infections in the first trimester of pregnancy. This study evaluated their prevalence and whether screening and treatment resulted as effective in reducing pregnancy and perinatal complications. Methods: A single-center prospective observational study was designed; a sample size of 400 first-trimester pregnant women was established and they were recruited between March 2016-October 2019 at the Puerta de Hierro University Hospital (Spain). They were screened for vaginal and endocervical infections and treated in case of abnormal flora. Pregnancy and delivery outcomes were compared between abnormal and normal flora groups by univariate analysis. Results: 109 patients had an abnormal flora result (27.2%). The most frequently detected infection was Ureaplasma urealyticum (12.3%), followed by Candida spp. (11.8%), bacterial vaginosis (5%), Mycoplasma hominis (1.2%) and Trichomonas vaginalis (0.8%). Patients with abnormal flora had a 5-fold increased risk of preterm premature rupture of membranes (5.3% vs. 1.1% of patients with normal flora, Odds Ratio 5.11, 95% Confidence Interval 1.20-21.71, p = 0.028). No significant differences were observed regarding preterm delivery or neonatal morbidity. Conclusions: Considering the morbimortality related to prematurity and that the results of our study suggest that the early treatment of abnormal flora could improve perinatal outcomes, the implementation of a screening program during the first trimester should be considered.
... BV is associated with increased risks of sexually transmitted infections (Wiesenfeld et al. 2003;Brotman et al. 2010), endometritis (Watts et al. 1990;Wiesenfeld et al. 2002) and pelvic inflammatory disease (Sweet 1995). In pregnancy, BV has been associated with complications such as preterm birth (Hillier et al. 1988;Holst et al. 1994;McGregor et al. 1994;Hillier et al. 1995;Leitich and Kiss 2007), late pregnancy loss (Leitich et al. 2003;Leitich and Kiss 2007), preterm premature rupture of membranes (McGregor et al. 1994), delivery of a low birth weight infant (Holst et al. 1994;Hillier et al. 1995;Svare et al. 2006) and infections of the placenta and amniotic fluid (Silver et al. 1989;Hitti et al. 2001;Svare et al. 2006;Leitich and Kiss 2007;Rezeberga et al. 2008). Importantly, many BV-associated bacterial species have been detected in invasive infections of the placenta and amniotic fluid (Berardi-Grassias et al. 1988;Hillier et al. 1988;Silver et al. 1989;Watts et al. 1990;Holst et al. 1994;DiGiulio et al. 2010;DiGiulio 2012). ...
... BV is associated with increased risks of sexually transmitted infections (Wiesenfeld et al. 2003;Brotman et al. 2010), endometritis (Watts et al. 1990;Wiesenfeld et al. 2002) and pelvic inflammatory disease (Sweet 1995). In pregnancy, BV has been associated with complications such as preterm birth (Hillier et al. 1988;Holst et al. 1994;McGregor et al. 1994;Hillier et al. 1995;Leitich and Kiss 2007), late pregnancy loss (Leitich et al. 2003;Leitich and Kiss 2007), preterm premature rupture of membranes (McGregor et al. 1994), delivery of a low birth weight infant (Holst et al. 1994;Hillier et al. 1995;Svare et al. 2006) and infections of the placenta and amniotic fluid (Silver et al. 1989;Hitti et al. 2001;Svare et al. 2006;Leitich and Kiss 2007;Rezeberga et al. 2008). Importantly, many BV-associated bacterial species have been detected in invasive infections of the placenta and amniotic fluid (Berardi-Grassias et al. 1988;Hillier et al. 1988;Silver et al. 1989;Watts et al. 1990;Holst et al. 1994;DiGiulio et al. 2010;DiGiulio 2012). ...
... BV is associated with increased risks of sexually transmitted infections (Wiesenfeld et al. 2003;Brotman et al. 2010), endometritis (Watts et al. 1990;Wiesenfeld et al. 2002) and pelvic inflammatory disease (Sweet 1995). In pregnancy, BV has been associated with complications such as preterm birth (Hillier et al. 1988;Holst et al. 1994;McGregor et al. 1994;Hillier et al. 1995;Leitich and Kiss 2007), late pregnancy loss (Leitich et al. 2003;Leitich and Kiss 2007), preterm premature rupture of membranes (McGregor et al. 1994), delivery of a low birth weight infant (Holst et al. 1994;Hillier et al. 1995;Svare et al. 2006) and infections of the placenta and amniotic fluid (Silver et al. 1989;Hitti et al. 2001;Svare et al. 2006;Leitich and Kiss 2007;Rezeberga et al. 2008). Importantly, many BV-associated bacterial species have been detected in invasive infections of the placenta and amniotic fluid (Berardi-Grassias et al. 1988;Hillier et al. 1988;Silver et al. 1989;Watts et al. 1990;Holst et al. 1994;DiGiulio et al. 2010;DiGiulio 2012). ...
Article
Bacterial vaginosis (BV) is a condition of the vaginal microbiome in which there are few lactobacilli and abundant anaerobic bacteria. Members of the genus Gardnerella are often one of the most abundant bacteria in BV. BV is associated with a wide variety of poor health outcomes for women. It has been recognized since the 1980s that women with BV have detectable and sometimes markedly elevated levels of sialidase activity in vaginal fluids and that bacteria associated with this condition produce this activity in culture. Mounting evidence collected using diverse methodologies points to the conclusion that BV is associated with a reduction in intact sialoglycans in cervico-vaginal secretions. Here we review evidence for the contributions of vaginal bacteria, especially Gardnerella, in the processes of mucosal sialoglycan degradation, uptake, metabolism, and depletion. Our understanding of the impacts of vaginal sialoglycan degradation is still limited. However, the potential implications of sialic acid depletion are discussed in light of our current understanding of the roles played by sialoglycans in vaginal physiology.
... BV is associated with adverse reproductive health outcomes, such as sexually transmitted infections (STIs) and pelvic inflammatory disease (PID) (Unemo et al., 2017;Ravel et al., 2021). Moreover, preterm birth (PTB) (Hillier et al., 1995), low birthweight (Svare et al., 2006), miscarriage (Leitich and Kiss, 2007), and other adverse obstetric outcomes are also linked to BV. ...
... PTB and other adverse obstetric outcomes have reportedly been associated with BV (Hillier et al., 1995). BV is verified in a meta-analysis to be powerful risk factor for late miscarriage and associated with maternity infectious incidence rate and preterm delivery (Leitich and Kiss, 2007). The BV in early pregnancy is linked to preterm delivery or delivery of an infant with a low birthweight (Svare et al., 2006). ...
Article
Full-text available
The vaginal microbiome is an intricate and dynamic microecosystem that constantly undergoes fluctuations during the female menstrual cycle and the woman’s entire life. A healthy vaginal microbiome is dominated by Lactobacillus which produce various antimicrobial compounds. Bacterial vaginosis (BV) is characterized by the loss or sharp decline in the total number of Lactobacillus and a corresponding marked increase in the concentration of anaerobic microbes. BV is a highly prevalent disorder of the vaginal microbiota among women of reproductive age globally. BV is confirmed to be associated with adverse gynecologic and obstetric outcomes, such as sexually transmitted infections, pelvic inflammatory disease, and preterm birth. Gardnerella vaginalis is the most common microorganism identified from BV. It is the predominant microbe in polymicrobial biofilms that could shelter G. vaginalis and other BV-associated microbes from adverse host environments. Many efforts have been made to increase our understanding of the vaginal microbiome in health and BV. Thus, improved novel and accurate diagnosis and therapeutic strategies for BV have been developed. This review covers the features of vaginal microbiome, BV, BV-associated diseases, and various strategies of diagnosis and treatment of BV, with an emphasis on recent research progresses.
... Meanwhile, non-lactobacillary flora is present, the type and rate of the microbiota being significantly influenced by race. Whenever the number of lactobacilli decrease, the risk of apparition of other microorganisms significantly increase, leading to the apparition of bacterial vaginosis (2,(7)(8)(9)(10). Furthermore, this condition seems to be directly correlated with the apparition of other significant disorders such as pelvic inflammatory disease, human immunodeficiency virus infection, human papilloma virus infection or adverse outcomes during pregnancy (3). ...
... Therefore, it should not be omitted the fact that human papilloma virus infection represents the leading cause of severe pathological conditions such as cervical intraepithelial neoplasia ann cervical cancer as well as vaginal and vulvar cancer. In this respect, attention should be focused on preventing the development of vaginosis (6)(7)(8). ...
Article
Full-text available
Vaginal microbiome is submitted to permanent changes accordingly to age, menopausal status or association of different pathological conditions such as inflammation or mucosal atrophy. The presence of these modifications is usually associated with local development of infectious, inflammatory or atrophic vulvovaginitis. These represent the most commonly complaints which affect women at all ages. Therefore, attention was focused on creating a topic product which is able to control the local process and to alleviate the symptoms. The aim of the current paper is to analyse the physiology, physiopathology and therapeutic strategies in such cases with special focus on Cerviron, a product which seems to provide multiple therapeutic benefits in such cases.
... A meta-analysis including over 30.000 women from 32 studies showed that BV approximately doubled the risk of preterm delivery in asymptomatic patients; OR 2.16, 95% CI: 1.56-3.00 [11]. The longitudinal study of Brotman et al. indicated that intravaginal douching, a practice of intravaginal cleaning that includes insertion of a liquid solution in the vagina through a tube, was practiced more often by women who had BV [12]. ...
... As for other vaginal practices, we found that vaginal washing with soap or water, both before and during pregnancy, was not associated with SPTB. There are a few studies that investigated the association between these vaginal hygiene practices and BV and sexual transmitted infections, which are known to be potential contributors to SPTB [11,23]. Joesoef et al. showed that the vaginal use of water did not increase the susceptibility for sexual transmitted infections in pregnant women [24]. ...
Article
Full-text available
Background Spontaneous preterm birth (SPTB) is a major cause of neonatal morbidity and mortality worldwide and defining its risk factors is necessary to reduce its prevalence. Recent studies have pointed out that bacterial vaginosis, a disturbance in the vaginal microbiome, is associated with SPTB. It is hypothesized that vaginal hygiene practices can alter the vaginal microbiome and are therefore associated with SPTB, but there are no studies investigating this matter. Methods and findings A case-control study was conducted between August 2018 and July 2021 in two affiliated university medical centers in Amsterdam, the Netherlands. We included a total of 79 women with a SPTB and compared them with 156 women with a term birth. Women with uterine anomalies, a history of cervical surgery or major congenital anomalies of the fetus were excluded. All participants filled in a questionnaire about vaginal washing with water, soap or gel, the use of intravaginal douches and vaginal steaming, both before and during pregnancy. Most women washed vaginally with water, 144 (61.3%) women before pregnancy and 135 (57.4%) women during pregnancy. A total of 43 (18.3%) washed with soap before and 36 (15.3%) during pregnancy. Before pregnancy, 40 (17.0%) women washed with vaginal gel and 27 (11.5%) during pregnancy. We found that the use of vaginal gel before pregnancy (aOR 2.29, 95% CI: 1.08–4.84) and even more during pregnancy, was associated with SPTB (aOR 3.45, 95% CI: 1.37–8.67). No association was found between washing with water or soap, intravaginal douching, or vaginal steaming and SPTB. Conclusions Our findings suggest that the use of vaginal gel is associated with SPTB. Women should be informed that vaginal use of gels might not be safe.
... Bacterial vaginosis in early pregnancy has been reported to be associated with preterm delivery in pregnant women without cervical surgery [44]. Therefore, screening and treatment for bacterial vaginosis should be performed in pregnant women after fertility-sparing surgery [21]. ...
... There is little data on intra-abdominal adhesions after RT. In our institution, one patient underwent a small bowel resection during CS due to severe intra-abdominal adhesions [44]. Anti-adhesive material was not used in this case at the time of RT; however, we have used it in all subsequent cases. ...
Article
Full-text available
Radical trachelectomy (RT) is a surgery for early-stage cervical cancer treatment that preserves the childbearing ability, and its use has become increasingly common worldwide. Thus, the rate of conception in women who have undergone RT is increasing. However, pregnancy after RT is associated with a higher risk of several obstetric complications such as preterm delivery, preterm premature membrane rupture, and abnormal bleeding from varices at the site of uterovaginal anastomosis. Furthermore, since RT have a residual prophylactic cerclage, it is difficult to manage first- and second-trimester miscarriages. There is little previous data on the management of pregnancy after RT. In this review article, we summarize various management methods and experiences to provide a guide to clinicians for perinatal management after RT.
... Bacterial vaginosis (BV) is a commonly observed non-optimal vaginal microbial community, characterized by a lower relative abundance of lactobacilli, and increased abundance of facultative or strict anaerobes [4]. BV has been linked to increased susceptibility to sexually transmitted infections including human immunodeficiency virus (HIV) infection, as well as pregnancy complications [5][6][7]. Despite its clinical importance, the exact etiology of BV remains enigmatic and current treatments show limited efficacy and high recurrence rates [8,9], hence the recent expansion in interest regarding the constitutive microbiome of the female genital tract. ...
... In the context of the vaginal microbiome, where diverse communities including those linked to BV and aerobic vaginitis have been linked to negative health outcomes [5][6][7]39], understanding how DNA extraction methods affect vaginal microbial patterns is imperative. When comparing extraction methods for cervicovaginal samples, the BT extractions resulted in higher species diversity and indicated the presence of gram-negative bacteria associated with BV, including P. timonensis, P. uenonis and D. microaerophilus [40]. ...
Article
Full-text available
Background The microbiota of the lower female genital tract plays an important role in women’s health. Microbial profiling using the chaperonin 60 ( cpn 60) universal target (UT) improves resolution of vaginal species associated with negative health outcomes compared to the more commonly used 16S ribosomal DNA target. However, the choice of DNA extraction and PCR product purification methods may bias sequencing-based microbial studies and should be optimized for the sample type and molecular target used. In this study, we compared two commercial DNA extraction kits and two commercial PCR product purification kits for the microbial profiling of cervicovaginal samples using the cpn 60 UT. Methods DNA from cervicovaginal secretions and vaginal lavage samples as well as mock community standards were extracted using either the specialized QIAamp DNA Microbiome Kit, or the standard DNeasy Blood & Tissue kit with enzymatic pre-treatment for enhanced lysis of gram-positive bacteria. Extracts were PCR amplified using well-established cpn 60 primer sets and conditions. Products were then purified using a column-based method (QIAquick PCR Purification Kit) or a gel-based PCR clean-up method using the QIAEX II Gel Extraction Kit. Purified amplicons were sequenced with the MiSeq platform using standard procedures. The overall quality of each method was evaluated by measuring DNA yield, alpha diversity, and microbial composition. Results DNA extracted from cervicovaginal samples using the DNeasy Blood and Tissue kit, pre-treated with lysozyme and mutanolysin, resulted in increased DNA yield, bacterial diversity, and species representation compared to the QIAamp DNA Microbiome kit. The column-based PCR product purification approach also resulted in greater average DNA yield and wider species representation compared to a gel-based clean-up method. In conclusion, this study presents a fast, effective sample preparation method for high resolution cpn 60 based microbial profiling of cervicovaginal samples.
... 17,18 An abnormal vaginal microbiota has been associated with a poor reproductive outcome in patients who undergo in vitro fertilization (IVF). [19][20][21][22][23][24][25] However, the existence and predominance of lactobacilli has been associated with a higher rate of pregnancy. 26,27 It has been reported that vaginal bacteria go up to the endometrium and generate bacterial contamination during transfer of embryos. ...
Article
History: Bacterial vaginosis has been seen to have a negative impact on the reproductive outcomes of in vitro fertilization (IVF). Aim: To determine its impact on the rates of biochemical pregnancy, clinical pregnancy, early spontaneous miscarriage and live newborns. Data source: Bibliographic search according to PRISMA guidelines in the MEDLINE, EMBASE, CINAHL and Cochrane Library databases. Eligibility criteria for the studies: The process for identifying and selecting studies is shown in the PRISMA flowchart. Evidence was evaluated according to the GRADE method. Subjects and interventions: Infertile women with IVF. Diagnosis of bacterial vaginosis according to Nugent or qPCR criteria. Evaluation of studies and summary methods: Forest plot, sensitivity analysis, funnel plots and evaluation of evidence according to GRADE. Results: A total of seven studies were included. We detected an overall statistically significant association with the rate of biochemical pregnancy (OR 0.55; 95%CI: 0.36-0.85; P=0.004) and rate of clinical pregnancy 0.43; 95%CI: 0.22-0.87; P=0.018). This was not the case for early spontaneous miscarriage (OR 1.13; 95%CI: 0.46-2.82; P=0.78) and rate of live newborns (OR 1.63; 95%CI: 0.61- 4.32; P=0.33). Limitations: Observational studies with a small sample and significant heterogeneity between them. Conclusions: Bacterial vaginosis appears to have some impact on the rate of clinical and biochemical pregnancy achieved with IVF.
... Its effectiveness and safety in mothers in reducing hepatitis B virus from mother to baby is not clearly understood. HBV is a risk factor for preterm delivery and maternal infectious complications such as late miscarriage [91]. HBV is a risk factor for preterm delivery. ...
Article
Full-text available
The pregnancy process involves many physiological changes, including weight gain, hormonal, metabolic and immune changes. One of the effective factors in this process is infection caused by microorganisms. Originally, before the advent of antibiotics, pregnancy was known as a risk factor for severe complications of pneumococcal pneumonia. Among viral infections, the 2009 flu pandemic issued a newer warning that some infections may disproportionately affect pregnant women and cause miscarriage and its complications during pregnancy. Generalization of pregnancy as a condition of suppression of the general immune system or increased risk is misleading and prevents the establishment of adequate guidelines for the treatment of pregnant women during epidemics. Viral infection has also become an important factor in pregnancy conditions. The recent outbreak of Ebola and other viral outbreaks and epidemics shows how pregnant women show worse outcomes (such as preterm delivery and fetal adverse outcomes) than the general population and non-pregnant women. The purpose of this article is studying pathogenesis of microorganisms and the risks which pose to the mother and the fetus. In order to investigate these factors, from 120 article prepared from google scholar and Pub med, Elsevier database. Knowing these factors can increase the ability to treat the infections in a timely manner and prevent their effects on the fetus and the patient.
... There is enough evidence through various studies that BV in pregnancy is associated with increased risk of severe complications including premature rupture of the membranes (PROM), preterm delivery, low-birthweight (LBW) infants, amniotic fluid infection, chorioamnionitis and post-cesarean and postpartum endometritis [5][6][7] . A meta-analysis by Leitich et al showed that BV significantly increases chances of preterm delivery in both asymptomatic women and those with preterm labour symptoms 8 . Another meta-analysis reported BV as an important risk factor for prematurity and pregnancy morbidity 9 . ...
Article
Full-text available
Bacterial Vaginosis (BV) has recently emerged as a global health issue especially in pregnant women because of its adverse outcomes. Various studies have shown the impact of BV on both mother and baby as well as overall reproductive health of women. The study intended to assess the prevalence of BV in pregnant women visiting our hospital and estimate the risk of associated complications. A retrospective study was done on pregnant women who underwent vaginal swab for BV during the period January 2018- July 2019. BV was diagnosed by Nugent score and obstetric details until delivery were noted for pregnancy outcomes. Out of 217 women included in the study, 44 were diagnosed as positive for BV. Variables were compared between BV positive and negative groups by Chi square and t- test and risk ratios calculated for adverse pregnancy outcomes. Statistical analysis was done using SPSS 20.0 version. Prevalence of BV was found to be 20.3%. BV was significantly associated with preterm labour, premature rupture of membranes, preterm delivery, miscarriage, birth asphyxia, low birth weight, and neonatal intensive care unit admission. The study substantiated the evidence from previous studies that pregnant women with BV are at much higher risk for adverse maternal and fetal outcomes. Early Screening and awareness amongst women may help to prevent this.
... Septic gardnerellosis is another form of the disease that has been associated with the isolation of G. vaginalis from the blood of women with postpartum endometriosis [18]. The incidence of preterm birth may also be affected by a bacterial vaginitis occurring in the early phase of pregnancy [19,20]. This pathogen may also be implicated in neonatal sepsis [21][22][23]. ...
Article
Full-text available
Gardnerella vaginalis is a bacterium that is found as the most common cause of bacterial vaginitis in women. In this paper, we describe a case report of a 22-years old woman infected with G. vaginalis, who was initially suspected to have Dengue fever. The similarity of clinical symptoms developed by this disease with the symptoms of some other tropical infectious diseases, as well as a travel history, complicated identification of the disease cause for this particular patient. Here, we present a detailed epidemiological and clinical description of this case, leading to a final diagnosis of a septic form of gardnerellosis.
... While this needs to be confirmed in a larger, prospective study, one explanation is that Treg regulate the inflammatory response to non-optimal, bacterial vaginosis (BV) associated bacteria like Sneathia, Gardnerella, and Prevotella, rather than their presence in the mucosa. This could be an important consideration, as bacterial vaginosis, a condition marked by depletion of vaginal health associated Lactobacillus, is associated with increased risk of STI acquisition [32][33][34][35] , reproductive complications [36][37][38] , and is highly recalcitrant to existing treatments 39 Lactobacillus crispatus induces an anti-inflammatory phenotype that included increased Tregs in the female reproductive tract (FRT) 41 . However, this could not be confirmed in this study due to the infrequency of these 'optimal' bacteria in our study population. ...
Preprint
Full-text available
Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FoxP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.
... Typically, a healthy vaginal ecosystem and term birth has been described as a Lactobacillus-dominated microbiome, with microbiota metabolites playing important roles in inhibition of bacterial and viral infections (14,20) -e.g., Lactobacillus crispatus contributes to low pH by secreting the metabolite D-lactate (21). In contrast, vaginal dysbiosis (with or without symptoms of BV), by disrupting the ecological equilibrium, has been proposed to induce local inflammation and risk of invasion by infectious agents potentially increasing sPTB risk (22,23). Low relative abundance of L. crispatus, with raised L. iners and acetatetogether with low levels of succinate and lactate -have been implicated in this (15). ...
Article
Full-text available
The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and management. Individual associations between sPTB, ethnicity, vaginal microbiota, metabolome and innate immune response are known, but not fully understood and knowledge has yet to impact clinical practice. Here we use multi-data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n=346 women; n=60 sPTB <37 weeks' gestation, including n=27 sPTB <34 weeks). Analysis of cervicovaginal samples (10-15+6 weeks) identified novel interactions between risk of sPTB and microbiota, metabolite, and maternal host defense molecules. Statistical modelling identified a composite of metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate and Ca2+) associated with risk of sPTB <37 weeks (Area Under the Curve - AUC 0.752). A combination of glucose, aspartate, Ca2+ and Lactobacillus crispatus and L. acidophilus relative abundance, identified risk of early sPTB <34 weeks, (AUC 0.758); improved by ethnicity stratification (AUC 0.835). Increased relative abundance of L. acidophilus appeared protective against sPTB <34 weeks. By using cervicovaginal fluid samples, we demonstrate the potential of multi-datatype integration for developing composite models towards understanding the contribution of the vaginal environment to risk of sPTB.
... This condition has been associated with increased risk of sexually transmitted infections (STIs) and pelvic inflammatory disease (PID), which in turn, are associated with ectopic pregnancy and tubal factor infertility (Taylor et al., 2013;Tsevat et al., 2017). During pregnancy, BV and vaginal microbiota disruption are associated with spontaneous abortion and preterm birth (Leitich and Kiss, 2007;Fettweis et al., 2019;Al-Memar et al., 2020). The effects of BV on fecundity are not well understood outside the context of medically assisted reproduction. ...
Article
Study question: Is bacterial vaginosis (BV) associated with fecundability? Summary answer: Women with BV may be at increased risk for sub-fecundity. What is known already: While BV has been associated with poor IVF outcomes, the association between vaginal microbiota disruption and non-medically assisted conception has not been thoroughly explored. Study design, size, duration: Kenyan women with fertility intent were enrolled in prospective cohort that included monthly preconception visits with vaginal fluid specimen collection and pregnancy testing. Four hundred fifty-eight women attempting pregnancy for ≤3 menstrual cycles at enrollment were eligible for this fecundability analysis. Participants/materials, setting, methods: At monthly preconception visits, participants reported the first day of last menstrual period and sexual behavior, underwent pregnancy testing and provided vaginal specimens. Discrete time proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% CI in menstrual cycles with and without BV (Nugent score ≥ 7) at the visit prior to each pregnancy test. We also assessed the association between persistent BV (BV at two consecutive visits) and fecundability. Main results and the role of chance: Participants contributed 1376 menstrual cycles; 18.5% (n = 255) resulted in pregnancy. After adjusting for age, frequency of condomless sex and study site, BV at the visit prior to pregnancy testing was associated with a 17% lower fecundability (adjusted FR (aFR) 0.83, 95% CI 0.6-1.1). Persistent BV was associated with a 43% reduction in fecundability compared to cycles characterized by optimal vaginal health (aFR 0.57, 95% CI 0.4-0.8). Limitations, reasons for caution: Detection of vaginal microbiota disruption using Gram stain and a point-of-care test for elevated sialidase identified a non-optimal vaginal environment, but these non-specific methods may miss important relationships that could be identified by characterizing individual vaginal bacteria and bacterial communities using molecular methods. In addition, results may be subject to residual confounding by condomless sex as this was reported for the prior month rather than for the fertile window during each cycle. Wider implications of the findings: Given the high global prevalence of BV and infertility, an association between BV and reduced fecundability could have important implications for a large number of women who wish to conceive. Multi-omics approaches to studying the vaginal microbiota may provide key insights into this association and identify potential targets for intervention. Study funding/competing interest(s): This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-R.S.M.). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were made possible using REDCap electronic data capture tools hosted at the University of Washington's Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for consulting from Lupin Pharmaceuticals. L.E.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for service on scientific advisory boards from Hologic and Nabriva Therapeutics. Trial registration number: N/A.
... Moreover, in pregnant women it has been linked to negative outcomes such as preterm birth and miscarriage. [6][7][8] The etiology of BV is not fully understood but detailed information of the microbiological state of healthy and infected women has been generated. Composition of the vaginal microbiota in healthy, intermediary and infected women has been described by Shipitsyna and Roos et.al. ...
Article
Full-text available
The effect of a novel treatment principle for bacterial vaginosis has been investigated in an open clinical study. 10 patients received a single dose while 20 patients received three applications every third day. The formulation is in the form of vaginal foam, containing lactic acid, hydrogen peroxide and an antimicrobial lipid. The intention of using the foam form for delivery is to avoid the creation of untreated areas, as is the case for other local formulations. Clinical signs, symptom and microbial effects have been studied using strict Amsel criteria and modified Hay/Ison for inclusion and modified Hay/Ison to monitor clinical efficacy pre- and post- menstruation. Therapeutic parameters as pH, malodor, abnormal discharge, itch and pain were monitored during the study. The microbiological was monitored by PCR being able to detect 6 pathogens and Lactobacilli.
... It is related to a chromosomal anomaly of conceptuses almost 50% of early pregnancy loss [23]. The other percent is associated with Anatomical anomaly [24], Hematological disease [25][26][27][28][29][30], microbial causes [31], Endocrinologic [23,[32][33][34] and Immunologic [1,[35][36][37] problems. It is indicated in literature that an important part of RPL may be related to Immune etiology and hematological. ...
Article
Spontaneous loss is seen 12-15 % in all pregnancies. More than %50 of those patients do not have a defined etiology, so they are named unexplained Recurrent Pregnancy Loss (URPL). Studies in recent years have made us think that Pregnancy Losses may be related to insufficient decidualization and undetected prothrombotic problems. Tyro3 receptor kinase (RTK) is a member of TAM receptors and has been reported to have an important role in migration, Epithelial-mesenchymal transition (EMT), and platelet aggregation. There is not sufficient knowledge about expression levels of Tyro3 RTK in human first-trimester URPL decidua (URPLD). By immunohistochemistry, immunoblotting, and qPCR, we investigated the expression of Tyro3 RTK in the decidua of human first-trimester termination healthy pregnancy (TPD)(n:6) and URPLD(n:6), and human endometrium (CE)(n:6). Our results suggest that Tyro3 RTK expression significantly decreases with pregnancy and then returns to levels of CE for URPLD. Considering the role of Tyro3 RTK in platelet activation and thrombus formation, it suggests that this decrease observed in TPD may prevent the formation of prothrombosis which can prevent placental flow, and thus, hemostasis could be regulated in pregnancy through Tyro3 RTK. Although Tyro3 RTK decrease in TPD, locally increase on TPD, and also decrease on URPLD of Tyro3 RTK on DSCs makes us think, which Tyro3 RTK has a regulating role for EMT formation on DSCs and may participate in implantation and survival processing of the embryo through DSCs. If those predictions are supported by further functional analyses, one of the causes of URPLD can be enlightened.
... It is related to a chromosomal anomaly of conceptuses almost 50% of early pregnancy loss [23]. The other percent is associated with Anatomical anomaly [24], Hematological disease [25][26][27][28][29][30], microbial causes [31], Endocrinologic [23,[32][33][34] and Immunologic [1,[35][36][37] problems. It is indicated in literature that an important part of RPL may be related to Immune etiology and hematological. ...
Article
Spontaneous loss is seen 12-15 % in all pregnancies. More than %50 of those patients do not have a defined etiology, so they are named unexplained Recurrent Pregnancy Loss (URPL). Studies in recent years have made us think that Pregnancy Losses may be related to insufficient decidualization and undetected prothrombotic problems. Tyro3 receptor kinase (RTK) is a member of TAM receptors and has been reported to have an important role in migration, Epithelial-mesenchymal transition (EMT), and platelet aggregation. There is not sufficient knowledge about expression levels of Tyro3 RTK in human first-trimester URPL decidua (URPLD). By immunohistochemistry, immunoblotting, and qPCR, we investigated the expression of Tyro3 RTK in the decidua of human first-trimester termination healthy pregnancy (TPD)(n:6) and URPLD(n:6), and human endometrium (CE)(n:6). Our results suggest that Tyro3 RTK expression significantly decreases with pregnancy and then returns to levels of CE for URPLD. Considering the role of Tyro3 RTK in platelet activation and thrombus formation, it suggests that this decrease observed in TPD may prevent the formation of prothrombosis which can prevent placental flow, and thus, hemostasis could be regulated in pregnancy through Tyro3 RTK. Although Tyro3 RTK decrease in TPD, locally increase on TPD, and also decrease on URPLD of Tyro3 RTK on DSCs makes us think, which Tyro3 RTK has a regulating role for EMT formation on DSCs and may participate in implantation and survival processing of the embryo through DSCs. If those predictions are supported by further functional analyses, one of the causes of URPLD can be enlightened.
... It is caused by an imbalance in the normal, healthy microbiome of the vagina that results mostly in discharge, odor, and irritation. BV is associated with an increased risk of preterm delivery and low birthweight [3,4], infertility and early spontaneous abortion [5][6][7], and it is also a high risk factor for contracting sexually transmitted diseases, including HIV [8,9]. Besides these potentially severe physiological consequences, frequently recurring and strongly symptomatic BV can have a huge negative impact on some women's quality of life and psychological wellbeing. ...
Article
Full-text available
Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.
... BV has been associated with pelvic inflammatory disease and adverse pregnancy outcomes such as late miscarriage and preterm birth, premature rupture of membranes, chorioamnionitis and post-partum endometritis [5][6][7]. ...
Article
Full-text available
Background Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is caused by an imbalance in the normal vaginal microbiota. Symptoms include an offensive odour. Standard oral or vaginal antimicrobial treatments have high immediate cure rates but almost as high recurrence rates. pHyph, a vaginal pessary, contains glucono-delta-lactone (GDL) and sodium gluconate (NaG) which restore normal pH and disrupt the associated biofilm. Aim To investigate the clinical performance of pHyph, for both treatment and recurrence prevention. Design An open-label, single arm, multi-centre first in women study. Setting Two private gynaecology clinics in Skåne County, Southern Sweden. Methods Twenty four adult women with confirmed bacterial vaginosis received the investigational product for self-administration on days 0, 2, 4, and 6 and were assessed on day 7. Clinical cure was defined as absence of three of four Amsel’s criteria (pH excluded) on day 7. Safety and tolerability were also recorded. Those not cured by day 7 received a prolonged treatment protocol. Results There were three withdrawals, two before the day 7 assessment. 18/22 (82 %) were clinically cured at day 7. The pessary was well tolerated. Recurrence rates at 14 days in patients cured at day 7 after receiving standard study treatment (n = 18) were 1/18 (5.6 %) with no additional recurrences reported at 35 days. Three of four patients not cured at 7 days received continued treatment (day 7, 9, 11, and 13), but none were cured at 14 days. Conclusion pHyph has the potential for both high cure rates and a reduction in recurrence.
... Bacterial vaginosis (BV) is a disorder of the vaginal microecosystem, which seems related to the increased the risk of abortion, [17] premature delivery, [18] and puerperal endometritis. [19] BV accounts for 50% of all types of vaginitis. ...
Article
Full-text available
The diagnosis and treatment of unexplained recurrent spontaneous abortion (URSA) is an important and hot topic in the field of obstetrics and gynecology. During our clinical investigation (observation), we have found that URSA patients usually experience recurrent vaginitis or vaginal dysbacteriosis during periods of non-pregnancy, pregnancy, and post-abortion. However, there is no research on vaginal dysbacteriosis's influence on URSA. Using women with normal induced abortion as a control group, and using 16S rRNA sequencing, which helps to screen differentially expressed flora, this study discusses the relevance between differential bacteria at the genus level and the incidence of URSA. Another aim of this study is to determine whether certain pathogenic genera can cause an imbalance in immune tolerance of the maternal and fetal interface through regulatory chemokines, which leads to recurrent spontaneous abortion. This article has explored URSA pathogenesis from the perspective of differentially expressed vaginal flora, which has great theoretical significance for the early diagnosis and treatment of URSA.
... It is generally known that vaginal microbiota disturbance is highly related to various gynecological diseases, especially BV, which is characterized by the alteration of vaginal microbiome from Lactobacillus dominance to anaerobic and facultative bacteria (Gardnerella, Atopobium, Prevotella, Megasphaera, Leptotrichia, Sneathia, etc.) dominance (Ling et al., 2010;Srinivasan et al., 2012;Nasioudis et al., 2017). BV has been shown to be associated with various other reproductive tract disorders, including infertility, preterm, cervical cancer, and HIV acquisition (Leitich and Kiss, 2007;van Oostrum et al., 2013;Torcia, 2019). It is also reported that many sextually transmitted infections (STI), such as infections of N. gonorrhoeae and C. trachomatis, are facilitated by vaginal microbiota dysbiosis and more prevalent in BV-positive women (Lewis et al., 2017). ...
Article
Full-text available
Vaginal microbiota dysbiosis, characterized by the loss of Lactobacillus dominance and increase of microbial diversity, is closely related to gynecological diseases; thus, intervention on microbiota composition is significant and promising in the treatment of gynecological diseases. Currently, antibiotics and/or probiotics are the mainstay of treatment, which show favorable therapeutic effects but also bring problems such as drug resistance and high recurrence. In this review, we discuss the role of vaginal microbiota dysbiosis in various gynecological infectious and non-infectious diseases, as well as the current and potential interventions.
... Two hypotheses put forward for bacterial vaginosis on preterm onset of labor, first; organisms that move ascending to the uterus and secondly, bacterial vaginosis is a marker of intrauterine colonization by similar organisms. 20 Bacterial vaginosis in most studies can increase interleukin-1 beta levels in women, which in turn can lead to activation of Matrix Metalloproteinases (MMP) such as MMP-1 and MMP-9. Metalloproteinase matrix will act as an enzyme that degrades the extracellular matrix in the cervix and causes cervical weakness due to inflammatory processes. ...
Article
Background: Research conducted at the Central General Hospital (RSUP) Dr. Kariadi Semarang in 2013 stated that out of 1,719 deliveries, 82 (5%) were preterm labor cases. Although there are many predictors for predicting imminent preterm labour, the complete prediction and prevention have not been established. Prevention of preterm labor through screening is the key to antenatal care. Good early prediction on a premature labor will provide adequate antenatal surveillance and special interventions.Objective: to analyze the relationship between cervical length, bacterial vaginosis, urinary tract infections, and premature rupture of membranes with the incidence of preterm labor.Methods: It is an observational analytic study in the form of the design of cross sectional with subject of pregnant women who experienced imminent preterm labour at gestational age 28-34 weeks and were treated at the ward of Obstetrics Gynecology Hospital Dr. Kariadi Semarang and network hospital during the study period (n=112). Subjects were assessed for the clinical risk (BV, premature rupture of the membrane, urinary tract infection) and sonography (cervical length). Statistical analysis was performed with paired t-test for normally distributed data and Mann Whitney if otherwise. Analysis of the relationship between variables and the incidence of preterm labor was carried out by the X 2 testResults: From 112 subjects, it was found that the Prevalence Ratio (PR) for cervical length, bacterial vaginosis, urinary tract infections and premature rupture of membranes to the incidence of imminent preterm labor was 2.2;2.32;1.99 and 2.36 respectively. From the multivariate analysis, it was found that bacterial vaginosis and premature rupture of membranes were the most influencing factors for the incidence of imminent premature labor with Odd Ratios of 6.497 and 21.362, respectively.Conclusion: There is a relationship between cervical length (≤25 mm ), bacterial vaginosis, urinary tract infections and premature rupture of membranes in the incidence of preterm labor.
... While this needs to be confirmed in a larger, prospective study, one explanation is that Treg regulate the inflammatory response to non-optimal, bacterial vaginosis (BV) associated bacteria like Sneathia, Gardnerella, and Prevotella, rather than their presence in the mucosa. This could be an important consideration, as bacterial vaginosis, a condition marked by depletion of vaginal health associated Lactobacillus, is associated with increased risk of STI acquisition (32)(33)(34)(35), reproductive complications (36)(37)(38), and is highly recalcitrant to existing treatments (39), so modulating the detrimental effects of bacteria could be an alternative or additional approach to minimize the impact of BV. Similar to what we have previously shown in a cohort of adolescent girls and young women in Mombasa, Kenya (40), our current data also indicates that involvement in sex work might be associated with non-optimal vaginal microbiomes. ...
Article
Full-text available
Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FOXP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.
... An association between bacterial vaginosis (BV) and PTB has been shown [34]. However, screening and treating of asymptomatic BV have not been shown to be useful [35]. ...
Article
Full-text available
Preterm births (PTBs), defined as births before 37 weeks of gestation account for the majority of deaths in the newborn period. Prediction and prevention of PTB is challenging. A history of preterm labour or second trimester losses and accurate measurement of cervical length help to identify women who would benefit from progesterone and cerclage. Fibronectin estimation in the cervicovaginal secretions of a symptomatic woman with an undilated cervix can predict PTB within 10 days of testing. Antibiotics should be given to women with preterm prelabour rupture of membranes but tocolysis has a limited role in the management of preterm labour. Antenatal corticosteroids to prevent complications in the neonate should be given only when gestational age assessment is accurate PTB is considered imminent, maternal infection and the preterm newborn can receive adequate care. Magnesium sulphate for fetal neuroprotection should be given when delivery is imminent. After birth, most babies respond to simple interventions essential newborn care, basic care for feeding support, infections and breathing difficulties. Newborns weighing 2000 g or less, benefit from KMC. Babies, who are clinically unstable or cannot be given KMC may be nursed in an incubator or under a radiant warmer. Treatment modalities include oxygen therapy, CPAP, surfactant and assisted ventilation.
... dominance by a wide array of other bacterial types (Nugent et al., 1991;Spiegel, 1991). The presence of BV was already associated with poor pregnancy outcomes and with increased risk for several sexually transmitted infections (STI), including the human immunodeficiency virus (HIV) (Leitich and Kiss, 2007;Gallo et al., 2012;Mitchell et al., 2013). The exact components of the vaginal microbiota were described utilizing sequencing hypervariable regions of the bacterial 16s rRNA gene (Ravel et al., 2011). ...
Article
Full-text available
Introduction Sialidase activity in the cervicovaginal fluid (CVF) is associated with microscopic findings of bacterial vaginosis (BV). Sequencing of bacterial 16S rRNA gene in vaginal samples has revealed that the majority of microscopic BV cases fit into vaginal community-state type IV (CST IV), which was recently named “molecular-BV.” Bacterial vaginosis-associated bacterial species, such as Gardnerella spp., may act as sources of CVF sialidases. These hydrolases lead to impairment of local immunity and enable bacterial adhesion to epithelial and biofilm formation. However, the impact of CVL sialidase on microbiota components and diversity remains unknown. Objective To assess if CVF sialidase activity is associated with changes in bacterial components of CST IV. Methods One hundred forty women were cross-sectionally enrolled. The presence of molecular-BV (CST IV) was assessed by V3–V4 16S rRNA sequencing (Illumina). Fluorometric assays were performed using 2-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUAN) for measuring sialidase activity in CVF samples. Linear discriminant analysis effect size (LEfSe) was performed to identify the differently enriched bacterial taxa in molecular-BV according to the status of CVF sialidase activity. Results Forty-four participants (31.4%) had molecular-BV, of which 30 (68.2%) had sialidase activity at detectable levels. A total of 24 bacterial taxa were enriched in the presence of sialidase activity, while just two taxa were enriched in sialidase-negative samples. Conclusion Sialidase activity in molecular-BV is associated with changes in bacterial components of the local microbiome. This association should be further investigated, since it may result in diminished local defenses against pathogens.
... However, a vast body of evidence shows that the pathogenic effects of BV are not confined to the lower genital tract. BV is strongly associated with reproductive failure, notably late foetal loss and preterm birth (Leitich and Kaider 2003;Leitich and Kiss 2007). In accordance with the results of published studies, our study showed that the rate of microbiota disruptions supporting AV and BV was higher in women with RM compared with normal women. ...
Article
Full-text available
Balanced vaginal microbiota and, as a continuum, cervical canal microbiota help prevent reproductive disorders, including recurrent miscarriage (RM). In a significant proportion of couples with RM, routine diagnostic workup cannot find any manageable cause, leading to a requirement for new diagnostic tools. In the present study, we determined the quantitative composition of the microbiota of the vagina and cervical canal, assessed by real-time polymerase chain reaction, in women with RM. It also evaluated their derangements related to the pathogenesis of RM, and thus the suitability of this test as a diagnostic tool for managing RM. Vaginal and cervical canal specimens of 25 women with RM and 25 healthy volunteers were collected. The test results revealed information about the total vaginal bacterial biomass by measuring the abundance of Lactobacillus spp.; other bacteria; and pathogens, including Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma (urealyticum + parvum), and Candida spp. Overall, the findings of this study implied the abundance of Lactobacillus spp. decreased in women with RM with an increase in the abundance of other microorganisms in accordance with the reduction in the abundance of Lactobacillus spp. due to aerobic vaginitis and bacterial vaginosis. Vaginal and cervical canal microbiota need to be considered during the diagnostic workup of women with RM. • IMPACT STATEMENT • What is already known on this subject? Recurrent miscarriage (RM) is a well-known reproductive disorder. Its diagnostic workup is not successful in determining the underlying problem in many cases. Hence, novel diagnostic tools based on real-time polymerase chain reaction (PCR) are needed for evaluating reproductive microbiota, which are considerably reliable, to satisfy the expectations of women with RM. • What do the results of this study add? Overall, the decrease in the abundance of Lactobacillus spp. was found to be related to RM, and the patterns of the presence of other microorganisms were in accordance with the reduction in the abundance of Lactobacillus spp. These findings suggested an important role of vaginal and cervical canal microbiota in the pathogenesis of RM. • What are the implications of these findings for clinical practice and/or further research? Additional research is warranted to elucidate the functional impact of altered components of the microbiota of vaginal and cervical canals on the physiology of the local cervical canal and its participation in the microbiota of the endometrial cavity, especially regarding unsuccessful pregnancies as a result of the disturbed physiology of the local endometrial microenvironment. However, possible applications of real-time PCR-based tests for the screening of subclinical infections in clinical practice require the performance of further investigations in patients with RM.
... Bacterial vaginosis (BV) is the worldwide leading vaginal bacterial infection identified in women of childbearing age, with a high prevalence in the general population, ranging from 23% to 29% across regions (Peebles et al., 2019). If left untreated, BV may cause serious obstetric and gynaecologic complications, including preterm delivery (Romero et al., 2004;Shimaoka et al., 2019), spontaneous abortion (Leitich and Kiss, 2007;Isik et al., 2016), low birth weight (Goldenberg and Culhane, 2003;Dingens et al., 2016), pelvic inflammatory disease (Ness et al., 2005;Gondwe et al., 2020), infertility (Salah et al., 2013), and may also lead to an increased risk of acquisition and transmission of several sexually transmitted infectious agents (Gillet et al., 2011;Haddad et al., 2018). Although the understanding of BV etiology is still limited, it is known that BV is characterized by a decrease of beneficial vaginal bacteria and by an increase of strict and facultative anaerobic bacteria (Chen et al., 2021) leading to the development of a polymicrobial biofilm (Swidsinski et al., 2005). ...
Article
Full-text available
Bacterial vaginosis (BV) is associated with serious gynaecologic and obstetric complications. The hallmark of BV is the presence of a polymicrobial biofilm on the vaginal epithelium, but BV aetiology is still a matter of debate. We have previously developed an in vitro biofilm model that included three BV-associated species, but, up to now, no studies are available whereby more bacterial species are grown together to better mimic the in vivo situation. Herein, we characterized the first polymicrobial BV biofilm consisting of six cultivable BV-associated species by using both in vitro and ex vivo vaginal tissue models. Both models revealed that the six species were able to incorporate the polymicrobial biofilm, at different bacterial concentrations. As it has been thought that this polymicrobial biofilm may increase the survival of BV-associated species when exposed to antibiotics, we also assessed if the Thymbra capitata essential oil (EO), which has recently been shown to be highly bactericidal against several Gardnerella species, could maintain its anti-biofilm activity against this polymicrobial biofilm. Under our experimental conditions, T. capitata EO exhibited a high antibacterial effect against polymicrobial biofilms, in both tested models, with a significant reduction in the biofilm biomass and the number of culturable cells. Overall, this study shows that six BV-associated species can grow together and form a biofilm both in vitro and when using an ex vivo model. Moreover, the data obtained herein should be considered in further applications of T. capitata EO as an antimicrobial agent fighting BV.
... A specific complication that may be related to BV is a 2-fold increased risk of spontaneous preterm birth (PTB) (2,3). However, screening for asymptomatic BV in pregnancy in low-risk groups has not aided preterm birth prediction, and evidence is insufficient or conflicting even in studies of higher-risk groups (4). ...
Article
Full-text available
Bacterial vaginosis (BV) is the most common vaginal infection for women of childbearing age. Although 50% of women with BV do not have any symptoms, it approximately doubles the risk of catching a sexually transmitted infection and also increases the risk of preterm delivery in pregnant women.
Article
While the benefits of human papillomavirus (HPV) vaccination relating to cervical cancer prevention have been widely documented, recent published evidence is suggestive of an impact on adverse pregnancy outcomes (APOs) in vaccinated mothers and their infants, including a reduction in rates of preterm births and small for gestational age infants. In this review, we examine this evidence and the possible mechanisms by which HPV vaccination may prevent these APOs. Large-scale studies linking HPV vaccination status with birth registries are needed to confirm these results. Potential confounding factors to consider in future analyses include other risk factors for APOs, and historical changes in both the management of cervical precancerous lesions and prevention of APOs. If confirmed, these additional benefits of HPV vaccination in reducing APO rates will be of global significance, due to the substantial health, social and economic costs associated with APOs, strengthening the case for worldwide HPV immunization.
Article
Full-text available
Antibiotics are the mainstay of therapy for bacterial vaginosis (BV). However, the rate of treatment failure in patients with recurrent BV is about 50%. Herein, we investigated potential mechanisms of therapy failure, including the propensity of resistance formation and biofilm activity of metronidazole (MDZ), clindamycin (CLI), and PM-477, a novel investigational candidate that is a genetically engineered endolysin with specificity for bacteria of the genus Gardnerella. Determination of the MIC indicated that 60% of a panel of 22 Gardnerella isolates of four different species were resistant to MDZ, while all strains were highly susceptible to CLI and to the endolysin PM-477. Six strains, all of which were initially susceptible to MDZ, were passaged with MDZ or its more potent hydroxy metabolite. All of them generated full resistance after 5 to 10 passages, resulting in MICs of >512 μg/mL. In contrast, only a mild increase in MIC was found for PM-477. There was also no cross-resistance formation, as MDZ-resistant Gardnerella strains remained highly susceptible to PM-477, both in suspension and in preformed biofilms. Strains that were resistant to MDZ in suspension were also tolerant to MDZ at >2,048 μg/mL when growing as biofilm. All strains were susceptible to PM-477 when grown as preformed biofilms, at minimum biofilm eradication concentrations (MBECs) in the range of 1 to 4 μg/mL. Surprisingly, the MBEC of CLI was >512 μg/mL for 7 out of 9 tested Gardnerella strains, all of which were susceptible to CLI when growing in suspension. The observed challenges of MDZ and CLI due to resistance formation and ineffectiveness on biofilm, respectively, could be one explanation for the frequent treatment failures in uncomplicated or recurrent BV. Therefore, the high efficacy of PM-477 in eliminating Gardnerella in in vitro biofilms, as well as its high resilience to resistance formation, makes PM-477 a promising potential alternative for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.
Article
Full-text available
Background Changes in microbial communities are a known characteristic of various inflammatory diseases and have been linked to adverse pregnancy outcomes, such as preterm birth. However, there is a paucity of information regarding the taxonomic composition and/or diversity of microbial communities in pre-eclampsia. The aim of this study was to determine the diversity of the gut, vaginal and oral microbiome in a cohort of South African pregnant women with and without pre-eclampsia. The diversity of the gut, vaginal and oral microbiome was determined by targeted next generation sequencing (NGS) of the V3 and V4 region of the 16S rRNA gene on the Illumina MiSeq platform. Results In this study population, pre-eclampsia was associated with a significantly higher alpha diversity ( P = 0.0472; indicated by the Shannon index) in the vaginal microbiome accompanied with a significant reduction in Lactobacillus spp. ( P = 0.0275), compared to normotensive pregnant women. Lactobacillus iners was identified as the predominant species of the vaginal microbiome in both cohorts. High inter-individual variation in alpha diversity was observed in the gut and oral microbiome in both cohorts. Although differences in the relative abundance of bacteria at all phylogenetic levels were observed, overall microbial composition of the gut, oral and vaginal microbiome was not significantly different in the pre-eclampsia cohort compared to the normotensive cohort. Conclusion Collectively, a reduction of Lactobacillus spp., and predominance of L. iners in pregnant women with pre-eclampsia could suggest an unstable vaginal microbiome that might predispose pregnant women to develop pre-eclampsia. The lack of significant structural changes in the gut, oral and vaginal microbiome does not suggest that the characterized communities play a role in pre-eclampsia, but could indicate a characteristic unique to the study population. The current study provided novel information on the diversity of the gut, oral and vaginal microbiome among pregnant women in South Africa with and without pre-eclampsia. The current study provides a baseline for further investigations on the potential role of microbial communities in pre-eclampsia.
Article
This study aimed to determine the prevalence of and risk factors associated with BV(bacterial vaginosis, BV), VVC (vulvovaginal candidiasis, VVC) and TV (trichomonal vaginitis, TV) among non-pregnant women. Among 770 women included in analyses, surveyed using a questionnaire and subsequently diagnosed with BV, VVC and TV via Gram staining and vaginal swab microscopy. Vaginal infections were prevalent in 31.30%, with BV being the most prevalent (21.35%). Single-variable analysis revealed that an age of 20–29 years (odds ratio [OR] = 2.31, 95% CI: 1.24–4.29; p = .007) and lack of education (OR = 0.50, 95% CI: 0.28-0.89; p = .018) were significantly associated with BV. However, an age of 30–39 years was significantly associated with VVC (OR = 2.12, 95% CI: 1.03–4.38; p = .038). Multivariable analysis confirmed that miscarriage was an independent predictor of BV and VVC. Miscarriage was significantly associated with the incidence of BV and VVC (OR = 1.680, 95% CI: 1.146–2.462; p = .011 and OR = 2.04, 95% CI: 1.30–3.20; p = .002, respectively). In conclusion, BV appears to be the predominant cause of vaginitis, risk factors for vaginitis include age and level of education and miscarriage. • IMPACT STATEMENT • What is already known on this subject? Inflammation of the vagina, or vaginitis, is caused by various infectious and non-infectious factors. The most common causes of infectious vaginitis are BV, VVC and TV. Kunming located at the southwestern border of China, However, there is still no systematic research investigating the status of vaginitis infection in Yunnan Province. Therefore, the present study aimed to determine the prevalence of these vaginal infections; BV, VVC, and TV, among women of childbearing age, and to assess the prevalence of vaginal infections and the associated risk factors. • What do the results of this study add? In our study we found that vaginal infections were prevalent in 31.30% of reproductive-age women, with BV being the most prevalent (21.35%). We believe that our study makes a significant contribution to the literature because we report that BV appears to be the predominant cause of vaginitis, followed by VVC and TV. Risk factors for vaginitis include age, miscarriage and level of education. • What are the implications of these findings for clinical practice and/or further research? This study aimed to determine the prevalence of these vaginal infections, BV, VVC and TV, and to assess the prevalence of vaginal infections and the associated risk factors. Health education interventions are recommended to raise women’s awareness of vaginitis and its prevention.
Article
Full-text available
A prospective cohort study was conducted on a convenience sample of 1370 pregnant women with a gestational age of 20 to 25 weeks in the city of Ribeirão Preto. Data on obstetrical history, maternal age, parity, smoking habit, and a history of preterm delivery was collected with the application of a sociodemographic questionnaire. Cervical length was determined by endovaginal ultrasound, and urine and vaginal content samples were obtained to determine urinary tract infection (UTI) and bacterial vaginosis (BV), respectively. The aim of this study was to verify the association of cervical length and genitourinary infections with preterm birth (PTB). Ultrasound showed no association of UTI or BV with short cervical length. PTB rate was 9.63%. Among the women with PTB, 15 showed UTI (RR: 1.55, 95%CI: 0.93–2.58), 19 had BV (RR: 1.22, 95%CI: 0.77–1.94), and one had both UTI and BV (RR: 0.85, 95%CI: 0.13–5.62). Nineteen (14.4%) PTB occurred in women with a cervical length ≤2.5 cm (RR: 2.89, 95%CI: 1.89–4.43). Among the 75 patients with PTB stratified as spontaneous, 10 showed UTI (RR: 2.02, 95%CI: 1.05–3.86) and 14 had a diagnosis of BV (RR: 1.72, 95%CI: 0.97–3.04). A short cervical length between 20 and 25 weeks of pregnancy was associated with PTB, whereas UTI and BV determined at this age were not associated with short cervical length or with PTB, although UTI, even if asymptomatic, was related to spontaneous PTB.
Article
Actualization. Non-gonococcal urethritis (NGU) in men may occur with little or no symptoms. The disease is often diagnosed only on the ba-sis of laboratory data. In more than 35% of cases, the etiology of NGU cannot be determined. These factors make it difficult to prescribe etio-tropic treatment in time, contributing to the chronicity of the disease with possible complications. Objective. To evaluate the clinical features of urethritis in men associated with bacterial vaginosis (BV) in their sexual partners. Materials and methods. The study involved 166 heterosexual men and 174 their sexual partners who sought out STIs. After excluding STIs, all men were divided into 2 clinical groups: Group 1 — with clinical and/or laboratory signs of urethritis, Group 2 (control) — without ure-thritis. Each group has 2 subgroups depending on the presence or absence of BV in their sexual partners. Registration of anamnestic, clinical and laboratory data in dynamics was carried out by means of patient questionnaires. Results. In men with NSU sexual partners suffered from BV more than 2 times more than the sexual partners of healthy men. Urethritis in patients with negative BV status of sexual partners is significantly associated with young age, higher number of sexual partners and the presence of foreskin. The course of urethritis in patients in this subgroup, compared to the subgroup where the partners did not have BV, was accompanied by significantly less pronounced clinical manifestations and laboratory signs. Summary. The data obtained confirm the possibility of developing BV-associated urethritis in men. The characteristic signs of such urethritis are a low degree of inflammation in the urethra and the paucity of clinical manifestations of the disease, and risk factors for its development are young age, absence of circumcision and risky sexual behavior.
Article
Full-text available
Research question: Is the composition of the endometrial or vaginal microbiota associated with recurrent pregnancy loss (RPL)? Design: Endometrial and vaginal samples were collected from 47 women with two or more consecutive pregnancy losses and 39 healthy control women without a history of pregnancy loss, between March 2018 and December 2020 at Helsinki University Hospital, Helsinki, Finland. The compositions of the endometrial and vaginal microbiota, analysed using 16S rRNA gene amplicon sequencing, were compared between the RPL and control women, and between individual vaginal and endometrial samples. The mycobiota composition was analysed using internal transcribed spacer 1 amplicon sequencing for a descriptive summary. The models were adjusted for body mass index, age and parity. False discovery rate-corrected P-values (q-values) were used to define nominal statistical significance at q < 0.05. Results: Lactobacillus crispatus was less abundant in the endometrial samples of women with RPL compared with controls (mean relative abundance 17.2% versus 45.6%, q = 0.04). Gardnerella vaginalis was more abundant in the RPL group than in controls in both endometrial (12.4% versus 5.8%, q < 0.001) and vaginal (8.7% versus 5.7%, q = 0.002) samples. The individual vaginal and endometrial microbial compositions correlated strongly (R = 0.85, P < 0.001). Fungi were detected in 22% of the endometrial and 36% of the vaginal samples. Conclusions: Dysbiosis of the reproductive tract microbiota is associated with RPL and may represent a novel risk factor for pregnancy losses.
Article
The vaginal microbiota is a primary non-specific barrier that protects against various bacterial, viral and fungal pathogens. A normal microflora of the female genital tract is represented by aerobes, facultative and strict anaerobes. Bacteria of the genus Lactobacillus spp. dominate the majority of women of reproductive age. They have high protective properties against other microorganisms. Lactobacillus spp. prevent an excessive reproduction of opportunistic and pathogenic microorganisms in the vaginal biotope due to the synthesis of short-chain acids that maintain the pH value in the normal range. As a rule, one or two species of Lactobacillus spp. dominate in the vaginal biotope, which are responsible for ensuring homeostasis of the vaginal microflora. At the same time, various Lactobacillus spp. differ in their protective properties. L. crispatus is a marker of the stability of the vaginal microflora. With the dominance of this type of lactobacillus, the authors of the studies observed a low risk of bacterial vaginosis, aerobic vaginitis, and unwanted obstetric complications during pregnancy and in assisted reproductive technology protocols, as well as a reduced risk of infection with sexually transmitted infections and human papillomavirus. L. gasseri and L. iners were more often detected in women with intermediate microflora or with dysbiosis. L. iners, unlike L. crispatus, has reduced protective properties and is widespread in dysbiotic conditions of the vaginal microflora. The detection of L. iners can serve as a prognostic sign of the development of pathological conditions of the vaginal microflora.
Article
Problem: Unknown or idiopathic infertility has been associated to urogenital tract dysbiosis, reducing pregnancy and delivery ratios during assisted reproductive treatments (ART). The PS11610 strain has shown extraordinary antimicrobial activity in vitro against urogenital pathogens as well as other probiotic characteristics. Therefore, an intervention study was performed to evaluate the effect of L. salivarius PS11610 on the microbial composition of urogenital tract in infertile couples with bacterial dysbiosis. Method of study: 17 couples undergoing ART diagnosed of unknown infertility were selected. After confirming urogenital dysbiosis, they started a 6-month treatment with L. salivarius PS11610 (1 dose / 12 h for female and 1 dose / 24 h for male). Vaginal, seminal, glans, uterine and plasma samples were collected for determination of the microbiome and immune profile at the beginning and the end of the treatment. Results: Supplementation with L. salivarius PS11610 significantly modified the urogenital microbiome composition in male and female samples, solving dysbiosis of 67% of the couples. Pathogens disappeared from the vaginal samples whereas Lactobacilli percentage increased after 3 and 6 months of treatment. Moreover, L. salivarius PS11610 changed the uterine microbiome that could be associated with a change of the uterine immune profile. Additionally, the probiotic intake could be associated with the observed change in the systemic immunological profile of couples. Finally, the pregnant and delivery ratio were improved. Conclusions: Probiotic supplementation with L. salivarius PS11610 improved the male and female urogenital tract microbiome, modulating the immune system and increasing pregnancy success in couples undergoing ART. This article is protected by copyright. All rights reserved.
Article
E.V. Shaposhnikova Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation Infections contribute greatly to the unfavorable course of pregnancy and gestational complications. Published data suggest a significant role of mixed infections and coinfections in vulvovaginitis as well as their association with intraamniotic infections caused by multiple microbes. This paper analyzes the studies on the current diagnostic and treatment approaches to mixed-etiology vulvovaginitis during pregnancy depending on gestational age and whether a medication is incorporated into the current clinical guidelines. The use of combination drugs with confirmed efficacy and broad-spectrum antimicrobial, fungicide, and antiprotozoal activity considering risk-benefit ratio for the mother and the child is highlighted. The efficacy of topical combination of metronidazole and miconazole for mixed-etiology vulvovaginitis during pre-pregnancy preparation and pregnancy based on various dosing regimens and the duration of use is addressed. Keywords: pregnancy, vulvovagini tis, bacterial vaginosis, topical treatment, metronidazole, miconazole. For citation: Shaposhnikova E.V. Current treatment approaches to mixed-etiology vulvovaginitis during pregnancy. Russian Journal of Woman and Child Health. 2021;4(1):5–11. DOI: 10.32364/2618-8430-2021-4-1-5-11.
Article
Bacterial vaginosis increases the risk of sexually transmitted infections, including HIV, and treatment is crucial to avoid complications. This article reviews the evidence-based options for treating bacterial vaginosis to improve patient outcomes.
Article
Background: Complications associated with preterm birth (PTB) are the largest contributor to under-five mortality globally. Success in reaching the Sustainable Development Goal target requires identifying potentially modifiable risk factors for PTB, estimating the relative importance of these risk factors, and identifying/implementing effective prevention strategies to address them. Methods: We conducted a literature review to define risk relationships and estimate prevalence for established risk factors for spontaneous PTB (sPTB). We then estimated population attributable fractions (PAF) for the sPTB risk factors identified in the review as statistically significant for the 81 low- and middle-income (LMIC) countries included in the Countdown 2030 initiative. We summed country-level findings to produce PAFs for each risk factor and regional estimates for sub-Saharan Africa and South Asia. Results: Forty-four potential sPTB risk factors were identified. and the final analysis included twenty-four risk factors with evidence of significant associations with sPTB. A second model with three additional risk factors with borderline insignificant associations was also run. Taken together, the twenty-four risk factors had a total PAF of 73% for all 81 countries and 77% and 72% of sPTB in sub-Saharan Africa and South Asia, respectively. For all countries, maternal undernutrition had the highest PAF (17.5%), followed by maternal infections (16.6%), environmental exposures (16%) and pregnancy history (8.7%). Conclusions: While multiple risk factors contribute to sPTB, no single risk factor addresses a predominant fraction, and 27% of spontaneous preterm births are not associated with risk factors that we identified. Despite the significant role of preterm birth in child survival, there are major data gaps in LMIC settings. Furthermore, there is a paucity of evidence for effective interventions to prevent preterm birth. Preventing sPTB requires understanding underlying mechanisms leading to sPTB in different populations, and the identification/implementation of effective interventions.
Article
Objectives We aimed to investigate changes in vaginal microbiota during pregnancy, and the association between vaginal dysbiosis and reproductive outcomes. Methods A total of 730 (week 24) and 666 (week 36) vaginal samples from 738 unselected pregnant women were studied by microscopy (Nugent score) and characterized by 16S rRNA gene sequencing. A novel continuous vaginal dysbiosis score was developed based on these methods using a supervised partial least squares model. Results Among women with bacterial vaginosis in week 24 (N=53), 47% (N=25) also had bacterial vaginosis in week 36. In contrast, among women without bacterial vaginosis in week 24, only 3% (N=18) developed bacterial vaginosis in week 36. Vaginal samples dominated by Lactobacillus (L.) crispatus (OR 0.35 [0.20-0.60]) and L. iners (OR 0.40 [0.23-0.68]) in week 24 were significantly more stable by week 36 when compared to other vaginal community state types. Vaginal dysbiosis score at week 24 was associated with a significant increased risk of emergency, but not elective, cesarean section (OR 1.37 [1.15-1.64], P<0.001), suggesting a 37% increased risk per standard deviation increase in vaginal dysbiosis score. Conclusions Changes in vaginal microbiota from week 24 to week 36 correlated with bacterial vaginosis status and vaginal community state type. A novel vaginal dysbiosis score was associated with a significantly increased risk of emergency, but not elective, cesarean section. This was not found for bacterial vaginosis or any vaginal community state type and could point to the importance of investigating vaginal dysbiosis as a nuanced continuum instead of crude clusters.
Article
Full-text available
Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age, and is associated with a substantial burden on women’s physical, emotional, sexual and social lives, as well as being linked to a number of gynaecological and obstetrical complications and adverse pregnancy outcomes. Antibiotics, such as metronidazole or clindamycin, are recommended as first-line treatment for BV, but may be associated with antibiotic resistance, high rates of recurrence and poor patient treatment satisfaction. Astodrimer sodium gel is a novel, non-antibiotic treatment for BV that is not systemically absorbed. It prevents pathogenic bacteria from adhering to the vaginal wall, and disrupts and inhibits the formation of pathogenic bacterial biofilms. Clinical cure rates of 50–57% were observed in patients with BV treated with astodrimer sodium compared with 17–21% treated with placebo (p < 0.001) in Phase 3 trials. In a separate Phase 3 trial, recurrence of BV occurred in 44% of patients treated with astodrimer sodium compared with 54% of patients who received placebo (p = 0.015). Astodrimer sodium is well tolerated, with vulvovaginal candidosis being the only treatment-related adverse event reported to occur more often than with placebo. The availability of astodrimer sodium, a well-tolerated, convenient, non-antibiotic treatment for BV, represents significant progress in the treatment of this burdensome condition.
Article
Full-text available
Background: Rheumatic diseases and vaginal infections both increase the risk of preterm birth. It is unclear if pregnant women with rheumatic disease are more likely to experience vaginal infections, which might potentially accumulate modifiable risk factors. Objective: In this study, we sought to evaluate the vaginal microbiota of pregnant women with inflammatory rheumatic and inflammatory bowel disease. Methods: A total of 539 asymptomatic women with singleton pregnancy were routinely screened for an abnormal vaginal microbiota between 10+0 and 16+0 gestational weeks. Vaginal smears were Gram-stained and microscopically analyzed. Those with inflammatory diseases (with or without immunomodulatory therapy) were assigned to the case group and matched in a 1:3 ratio to healthy pregnant controls. Results: Overall, an abnormal vaginal microbiota occurred more frequently among women of the case group, compared to those of the control group (33.8% vs. 15.6%; 95% CI 1.78-4.27, p<0.001). In particular, Candida colonization (22.3% vs. 9.2%; 95% CI 1.69-4.75, p<0.001), but also bacterial vaginosis (14.9% vs. 7.2%; 95% CI 1.25-4.1, p=0.006) occurred more often in the case than in the control group. No significant difference was found with regard to the occurrence of an abnormal vaginal microbiota between subgroups with and without immunomodulatory treatment (37.0% vs. 27.1%; 95% CI 0.29-1.35, p=0.232). Conclusion: Pregnant women with inflammatory rheumatic and inflammatory bowel disease are at risk for bacterial vaginosis and Candida colonization, which might pose a risk for preterm birth. Prospective studies are needed to further evaluate the influence of autoimmune conditions and immunosuppressive therapy on the vaginal microbiota.
Article
The aim of this study was to characterise the structure of vaginal microbiota in unexplained recurrent miscarriage (RM). The vaginal bacterial communities of 16 patients with RM and 20 healthy volunteers were sampled. Then, the microbiomes of bacterial profiles of RM patients and healthy volunteers were compared by sequencing the V3–V4 regions of the bacterial 16S ribosomal RNA gene using the Illumina MiSeq platform (Illumina, San Diego, CA). Taxonomic analysis demonstrated that abundance of Lactobacillus and Gardnerella were significantly different between the RM and control groups. Furthermore, at the genus level, Lactobacillus was the most dominant genus in the two groups. Statistically significant differences were observed in three genera between RM and control groups. In the control group, two bacterial taxa were significantly more abundant (Lactobacillus and Gardnerella), while only one taxon was overrepresented in the RM group (Atopobium). These present findings provide experimental evidence supporting vaginal microbiota dysbiosis in women with RM. • Impact statement • What is already known on this subject? Currently, bacterial vaginosis is thought to be mainly due to the vaginal dysbacteriosis, which can induce unexplained recurrent miscarriage, premature rupture of membranes, low birth weight premature birth, premature birth, chorioamnionitis and series of diseases. • What do the results of this study add? The current study demonstrated that Lactobacillus and Gardnerella were significantly decreased in RM patients compared to healthy control, while Atopobium was overrepresented in the RM group. • What are the implications of these findings for clinical practice and/or further research? Clinically, women with RM might benefit from vaginal microbiota treatment, adjuvant therapy with Lactobacillus-based live biotherapeutics.
Preprint
Full-text available
Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome, characterised by low levels of lactobacilli and overgrowth of a diverse group of bacteria, and associated with higher risk of a variety of infections, surgical complications, cancer and spontaneous preterm birth (PTB). Despite the lack of a consistently applicable aetiology, Prevotella spp. are often associated with both BV and PTB and P. bivia has known symbiotic relationships with both Peptostreptococcus anaerobius and Gardnerella vaginalis. Higher risk of PTB can also be predicted by a composite of metabolites linked to bacterial metabolism but their specific bacterial source remains poorly understood. Here we characterise diversity of metabolic strategies among BV associated bacteria and lactobacilli and the symbiotic metabolic relationships between P. bivia and its partners and show how these influence the availability of metabolites associated with BV/PTB and/or pro- or anti-inflammatory immune responses. We confirm a commensal relationship between Pe. anaerobius and P. bivia, refining its mechanism; P. bivia supplies tyrosine, phenylalanine, methionine, uracil and proline, the last of which leads to a substantial increase in overall acetate production. In contrast, our data indicate the relationship between P. bivia and G. vaginalis strains, with sequence variant G2, is mutualistic with outcome dependent on the metabolic strategy of the G. vaginalis strain. Seven G. vaginalis strains could be separated according to whether they performed mixed acid fermentation (MAF) or bifid shunt (BS). In co-culture, P. bivia supplies all G. vaginalis strains with uracil and received substantial amounts of asparagine in return. Acetate production, which is lower in BS strains, then matched that of MAF strains while production of aspartate increased for the latter. Taken together, our data show how knowledge of inter- and intra-species metabolic diversity and the effects of symbiosis may refine our under-standing of the mechanism and approach to risk prediction in BV and/or PTB.
Article
Background: Bacterial vaginosis- a condition defined by a shift from Lactobacillus dominance to a polymicrobial, anaerobic bacterial community - increases the risk of acquiring sexually transmitted infections and other complications of the female reproductive tract . Antibiotic treatment frequently fails to return the microbiome to an optimal Lactobacillus-dominated state. No criteria currently exist to identify patients likely to experience treatment failure. Objective(s): We sought to identify pre-treatment community signatures associated with treatment failure through 16S rRNA gene analysis. Study design: Twenty-eight women enrolled in an oral metronidazole treatment trial of BV were studied. Cervicovaginal lavage samples were collected prior to metronidazole treatment, and again at 7 and 30-days post-treatment. Cervicovaginal lavage DNA was amplified and sequenced using a paired-end, V4 region, 2x150 MiSeq run. Results: Of the 28 women, 25% failed to clear bacterial vaginosis, 35.7% demonstrated a transient clearance - shifting to community-type 2 (Lactobacillus iners dominant, CT2) at visit 2 only; 7.1% demonstrated delayed clearance - reaching CT2 at the final visit only; and 32.1% of patients experienced sustained bacterial vaginosis clearance. Examination of community composition and structure demonstrated that both richness and evenness were significantly lower for women who sustained clearance, while women who failed to clear bacterial vaginosis possessed the highest median levels of richness, evenness, and diversity pre-treatment. Soluble immune factors in the lower reproductive improved significantly following a shift from CT4 to a Lactobacillus-dominant microbiome, with samples categorized as CT2 possessing significantly higher levels of SLPI, GROa, and MIP3a and significantly lower levels of ICAM-1. While shifts to Lactobacillus-dominance improved markers of mucosal tissue health, these gains were only temporary amongst women who experienced recurrence. Conclusions: Assemblies of highly diverse microbiota are associated with the enhanced resilience of bacterial vaginosis to standard metronidazole treatment. These communities may be foundational to treatment resistance or simply an indication of a well-established community made possible by canonical biofilm forming taxa. Future studies must target the transcriptional activity of these communities under the pressure of antibiotic treatment to resolve the mechanisms of their resistance.
Article
Full-text available
Background: The definition of abortion was made by the World Health Organization based on the weight of the pregnancy material or the duration of pregnancy. According to this expression, the expulsion of all or some of the pregnancy material weighing less than 500 grams or before the 20th week of pregnancy from the uterine cavity is called abortion. Platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), which are among the inflammation parameters likely to be increased in abortion, were compared in groups that resulted in abortion and did not result in abortion.Methods: The study included 120 patients who had a diagnosis of <14 weeks of abortion and 120 healthy pregnant women who applied to the gynecology and obstetrics clinic of a tertiary care hospital between January 2018 and December 2021. Those who had a previous fetal heartbeat or intracavitary pregnancy and aborted before the 14th gestational week were included in the selection of the abortus group.Results: NLR and PLR were analyzed with ROC curve analysis. The area under the curve (AUC) for NLR was 0.498, with 95% confidence intervals (0.424-0.572), and was not statistically significant (p=0.38). The area under the curve (AUC) for PLR was 0.480 at 95% confidence intervals (0.406-0.557), and was not statistically significant (p=0.38).Conclusions: NLR and PLR ratios were similar in both groups. As a result of the present study, it was found that there were no significant differences between the abortion NLR and PLR values between the groups (p>0.05).
Article
Full-text available
Because of hormonal and immunologic changes, there are significant changes in the oral microbiome that emerge during pregnancy. Recent evidence further suggests that there is an association between the presence of periodontal disease and a pregnancy-associated oral dysbiosis. Although this oral dysbiosis and pathogenic periodontal bacteria are considered to be associated with adverse pregnancy outcomes, it is still not clear how an oral dysbiosis during pregnancy can modulate oral diseases and birth outcomes. To develop preventive or therapeutic interventions, it is critical to understand the oral microbiome changes that emerge during pregnancy and their association with adverse pregnancy outcomes. In the present review, we summarize the current literature on normal changes in the oral microbiome that occur during pregnancy; the pathogenic changes in the oral microbiome believed to occur in association with adverse pregnancy outcomes; and the association between the placental microbiome and the oral microbiome.
Article
Full-text available
To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women. Multicentre, prospective, randomised controlled trial. Non-hospital based antenatal clinics. 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection. In the intervention group, the women's obstetricians received the test results and women received standard treatment and follow up for any detected infection. In the control group, the results of the vaginal smears were not revealed to the caregivers. The primary outcome variable was preterm delivery at less than 37 weeks. Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage. Outcome data were available for 2058 women in the intervention group and 2097 women in the control group. In the intervention group, the number of preterm births was significantly lower than in the control group (3.0% v 5.3%, 95% confidence interval 1.2 to 3.6; P = 0.0001). Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and <or= 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group. Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women.
Article
Full-text available
The purpose of the study was to examine intercenter variability in the interpretation of Gram-stained vaginal smears from pregnant women. The intercenter reliability of individual morphotypes identified on the vaginal smear was evaluated by comparing them with those obtained at a standard center. A new scoring system that uses the most reliable morphotypes from the vaginal smear was proposed for diagnosing bacterial vaginosis. This scoring system was compared with the Spiegel criteria for diagnosing bacterial vaginosis. The scoring system (0 to 10) was described as a weighted combination of the following morphotypes: lactobacilli, Gardnerella vaginalis or bacteroides (small gram-variable rods or gram-negative rods), and curved gram-variable rods. By using the Spearman rank correlation to determine intercenter variability, gram-positive cocci had poor agreement (0.23); lactobacilli (0.65), G. vaginalis (0.69), and bacteroides (0.57) had moderate agreement; and small (0.74) and curved (0.85) gram-variable rods had good agreement. The reliability of the 0 to 10 scoring system was maximized by not using gram-positive cocci, combining G. vaginalis and bacteroides morphotypes, and weighting more heavily curved gram-variable rods. For comparison with the Spiegel criteria, a score of 7 or higher was considered indicative of bacterial vaginosis. The standardized score had improved intercenter reliability (r = 0.82) compared with the Spiegel criteria (r = 0.61). The standardized score also facilitates future research concerning bacterial vaginosis because it provides gradations of the disturbance of vaginal flora which may be associated with different levels of risk for pregnancy complications.
Article
Full-text available
To find out whether women with bacterial vaginosis detected early in pregnancy are at increased risk of preterm delivery. Prospective description cohort study. Antenatal clinic in a district general hospital. 783 women examined during their first antenatal clinic visit and screened for recognised risk factors for preterm delivery and the presence of bacterial vaginosis or intermediate abnormal flora detected by examination of a vaginal smear stained by Gram's method. Gestational age at delivery classified as late miscarriage (16-24 weeks' gestation), preterm delivery (24-37 weeks' gestation), term delivery (> or = 37 weeks' gestation). Multiple logistic analysis showed that there was an increased incidence of preterm delivery in women with a previous preterm delivery (9/24; odds ratio 25; 95% confidence interval 9 to 70; P < 0.001) and bacterial vaginosis (9/115; 2.8; 1.1 to 7.4; P = 0.04). A further logistic analysis of data from women recruited before 16 weeks' gestation showed that preterm deliveries or late miscarriages occurred more often in women with bacterial vaginosis (12/77; 5.5; 2.3 to 13.3; P < 0.001). Late miscarriage and preterm delivery are associated with the presence of bacterial vaginosis in early pregnancy. This is independent of recognised risk factors such as previous preterm delivery.
Article
Full-text available
The vaginal microflora of 49 women in idiopathic preterm labor was compared with that of 38 term controls to determine whether the presence of bacterial vaginosis (BV) and/or specific microorganisms would influence the rate of preterm delivery. Demographic factors, pregnancy outcome, and reproductive history were also studied. BV, as defined by the presence of clue cells in a vaginal wet mount and characteristic microbial findings in a stained vaginal smear and vaginal culture, was more common in women with preterm labor and delivery than in controls (P < 0.01). The condition, diagnosed in 41% of women who had both preterm labor and delivery (n = 22) and in 11% each of women who had preterm labor but term delivery (n = 27) and controls, was associated with a 2.1-fold risk (95% confidence intervals, 1.2 to 3.7) for preterm birth prior to 37 weeks of gestation. BV was associated with low birth weight. Of 49 women with preterm labor, 67% (8 of 12) of women with BV were delivered of low-birth-weight neonates (< 2,500 g) compared with 22% (8 of 37) of women without the condition (P < 0.0005). The presence of hydrogen peroxide-producing facultative Lactobacillus spp. was strongly negatively associated with both preterm delivery and BV. BV-associated microorganisms, i.e., Mobiluncus, Prevotella, and Peptostreptococcus species, Porphyromonas asaccharolytica, Fusobacterium nucleatum, Mycoplasma hominis, and high numbers of Gardnerella vaginalis were significantly associated with preterm delivery; all species also strongly associated with BV (P = 0.0001 for each comparison). Mobiluncus curtisii and Fusobacterium nucleatum were recovered exclusively from women with preterm delivery. Our study clearly indicates that BV and its associated organisms are correlated with idiopathic premature delivery.
Article
Full-text available
This study was undertaken to determine the relationship between fetal fibronectin, short cervix, bacterial vaginosis, other traditional risk factors, and spontaneous preterm birth. From 1992 through 1994, 2929 women were screened at the gestational age 22 to 24 weeks. The odds ratios for spontaneous preterm birth were highest for fetal fibronectin, followed by a short cervix and history of preterm birth. These factors, as well as bacterial vaginosis, were more strongly associated with early than with late spontaneous preterm birth. Bacterial vaginosis was more common--and a stronger predictor of spontaneous preterm birth--in Black women, while body mass index less than 19.8 was a stronger predictor in non-Black women. This analysis suggests a pathway leading from Black race through bacterial vaginosis and fetal fibronectin to spontaneous preterm birth. Prior preterm birth is associated with spontaneous preterm birth through a short cervix. Fetal fibronectin and a short cervix are stronger predictors of spontaneous preterm birth than traditional risk factors. Bacterial vaginosis was found more often in Black than in non-Black women and accounted for 40% of the attributable risk for spontaneous preterm birth at less than 32 weeks.
Article
Full-text available
Bacterial vaginosis in pregnant women is an established risk factor for premature labor, rupture of membranes, and preterm delivery, but information on its natural history during pregnancy is limited. In this study, 635 pregnant women at less than 35 weeks' gestation were screened for bacterial vaginosis. The prevalence of bacterial vaginosis, as assessed by Gram stain examination of vaginal smears, was 19.7% (125/635). Ninety-two women were retested 4 to 8 weeks later, and bacterial vaginosis persisted in 51.1% (47/92). The incidence of preterm delivery was significantly increased in women with bacterial vaginosis at enrollment (RR 3.1, 95% CI: 1.8-5.4). However, the risk of prematurity was similar in women with or without a persistence of bacterial vaginosis. These results suggest that the diagnosis of bacterial vaginosis at any point during pregnancy is associated with an increased risk of perinatal complications in spite of spontaneous recovery in subsequent examinations.
Article
Full-text available
The purpose of this study was to evaluate a strategy for the identification of patients with multiple gestations who are at low risk for preterm delivery. A prospective observational study among patients with twin and triplet gestations. At 20 and 24 weeks of gestation, screening for bacterial vaginosis and fetal fibronectin was performed, followed by digital and sonographic assessment of the cervix. The treating physicians were blinded to test results. At the 24-week examination, specificities for delivery at >32 weeks of gestation for digital examination (92.9%), fetal fibronectin level (93.9%), cervical length on sonographic scan (85.1%), and combined fetal fibronectin level and cervical length (81.3%) did not differ statistically. Negative predictive values for these tests were >or=95%. All tests performed better at 24 weeks of gestation than at 20 weeks of gestation. At 24 weeks of gestation, a normal digital examination, a negative fetal fibronectin level, a normal cervical length on sonographic scan, or the combination of a negative fetal fibronectin level and a normal cervical length each confer a similarly high likelihood of delivery at >32 weeks of gestation in women with multiple gestations.
Article
Full-text available
The main aim of this prospective study was to determine the socioeconomic, demographic and environmental factors that may be associated with the occurrence of bacterial vaginosis at early pregnancy in an indigent population from Central Poland. A group of 196 pregnant women was selected randomly from the patients of 10 district maternity units in the Lodz region, Central Poland. Only singleton pregnancies between 8 and 16 week of gestation were qualified for inclusion in the survey. A standard questionnaire covering medical, socioeconomic, demographic, constitutional and environmental items was administered to every subject and was verified with medical records. Cervico-vaginal swabs were collected from the women under study and tested for bacterial vaginosis (BV) according to Spiegel's criteria. Based on the results of Gram stain, BV was diagnosed in 51 women (28.5%), grade I microflora among 66 (36.9%) and grade II among 62 women (34.6%). In the univariate analysis, only single marital status proved to be an important risk factor associated with BV during pregnancy, this was confirmed in the multivariate analysis. Pregnant women who present risk factors for abnormal cervico-vaginal microflora should be covered by comprehensive prenatal surveillance, which enables early detection and treatment of this pathology. Research that identifies the causal pathways and mechanisms through which social disadvantage leads to a higher risk of preterm birth may help to reduce current socioeconomic and demographic disparities and improve pregnancy outcome.
Article
Full-text available
Preterm delivery (PTD) is the leading cause of infant morbidity and mortality in the United States. An epidemiological association between PTD and various bacteria that are part of the vaginal microflora has been reported. No single bacterial species has been identified as being causally associated with PTD, suggesting a multifactorial etiology. Quantitative microbiologic cultures have been used previously to define normal vaginal microflora in a predictive model. These techniques have been applied to vaginal swab cultures from pregnant women in an effort to develop predictive microbiologic models for PTD. Logistic regression analysis with microbiologic information was performed for various risk groups, and the probability of a PTD was calculated for each subject. Four predictive models were generated by using the quantitative microbiologic data. The area under the curve (AUC) for the receiver operating curves ranged from 0.74 to 0.94, with confidence intervals (CI) ranging from 0.62 to 1. The model for the previous PTD risk group with the highest percentage of PTDs had an AUC of 0.91 (CI, 0.79 to 1). It may be possible to predict PTD by using microbiologic risk factors measured once the gestation period has reached the 20-week time point.
Article
Full-text available
In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour.
Article
Full-text available
Previous case-control and prospective studies have shown an association between the presence of periodontitis and the risk of preterm birth (PTB). The goal of this pilot trial was to determine the feasibility of conducting a trial to determine whether treatment of periodontitis reduces the risk of spontaneous preterm birth (SPTB). Three hundred sixty-six (366) women with periodontitis between 21 and 25 weeks' gestation were recruited and randomized to one of three treatment groups with stratification on the following two factors: 1) previous SPTB at <35 weeks and 2) body mass index <19.8 or bacterial vaginosis as assessed by Gram stain. The treatment groups consisted of: 1) dental prophylaxis plus placebo capsule; 2) scaling and root planing (SRP) plus placebo capsule; and 3) SRP plus metronidazole capsule (250 mg t.i.d. for one week). An additional group of 723 pregnant women meeting the same criteria for periodontitis and enrolled in a prospective study served as an untreated reference group. The rate of PTB at <35 weeks was 4.9% in the prophylaxis group, compared to 3.3% in the SRP plus metronidazole group and 0.8% in the SRP plus placebo group (P = 0.75 and 0.12, respectively). The rate of PTB at <35 weeks was 6.3% in the reference group. This trial indicates that performing SRP in pregnant women with periodontitis may reduce PTB in this population. Adjunctive metronidazole therapy did not improve pregnancy outcome. Larger trials will be needed to achieve statistical significance, especially at less than 35 weeks gestational age.
Article
Full-text available
Lactobacilli, principally the strains that are hydrogen peroxide (H2O2) producing, may have a protective effect against vaginal colonization by pathogenic species such as those that cause bacterial vaginosis. Previous reports have also suggested that H2O2-producing lactobacilli in the vagina may protect pregnant women against ascending infection of the chorioamniotic membranes and uterine cavity. We report the identification and H2O2 production of lactobacilli isolated from vaginal swabs collected at 20 weeks' gestation from a population of pregnant women at high risk of preterm birth. We also report the correlation between identification and H2O2 production in relation to the outcomes of chorioamnionitis and preterm birth. Lactobacilli were identified by partial 16S rRNA gene sequencing. H2O2 production by isolates was determined by a semiquantitative method. The most commonly isolated species were L. crispatus, L. gasseri, L. vaginalis and L. jensenii. Amounts of H2O2 produced by lactobacilli varied widely. The presence of lactobacilli producing high levels of H2O2 in the vagina of this population of pregnant women was associated with a reduced risk of bacterial vaginosis at 20 weeks' gestation and subsequent chorioamnionitis. L. jensenii and L. vaginalis produced the highest levels of H2O2. We postulate that H2O2-producing lactobacilli are able to reduce the incidence of ascending infections of the uterus and the subsequent production of proinflammatory molecules which are important in the pathogenesis of chorioamnionitis and preterm birth.
Article
Objective: To investigate whether there is a correlation between vaginal flora at early gestation and premature delivery and low birth weight. Methods: The study group comprised 197 consecutive women who attended routine prenatal care in Flanders, Belgium, during the first trimester (≤14 weeks) and whose pregnancy continued beyond 20 weeks of pregnancy. Vaginal microbiological flora were studied by microscopy of wet mount or Pap smear. Bacterial vaginosis was assessed either clinically (Amsell), microscopically (clue cells) or by culture of bacterial vaginosis-associated bacteria. Results: The presence of an intermediate form of vaginal flora disturbance at the first prenatal visit, rather than full-blown bacterial vaginosis, was associated with low birth weight and preterm birth (relative risk 4.3; 95% confidence interval 1.6-11.4; p = 0.006). The clinical signs and symptoms, as well as the results of vaginal bacterial culture in women with this intermediate flora differed entirely from those found in women with bacterial vaginosis. Conclusion: Disturbed vaginal flora and signs of vaginitis at early gestation are associated with preterm birth, but full-blown anaerobic bacterial vaginosis is not. Clinical assessment of the vaginal flora, combined with microscopy, was superior to culture results. It could be of importance in future studies to rethink the classification of the different types of abnormal vaginal flora.
Article
Objectives: To assess whether bacterial vaginosis or chlamydial infection before 10 weeks9 gestation is associated with miscarriage before 16 weeks. Design: Prospective cohort study. Setting: 32 general practices and five family planning clinics in south London. Participants: 1216 pregnant women, mean age 31, presenting before 10 weeks9 gestation. Main outcome measure: Prevalence of miscarriage before 16 weeks9 gestation. Results: 121 of 1214 women (10.0%, 95% confidence interval 8.3% to 11.7%) miscarried before 16 weeks. 174 of 1201 women (14.5%, 12.5% to 16.5%) had bacterial vaginosis. Compared with women who were negative for bacterial vaginosis those who were positive had a relative risk of miscarriage before 16 weeks9 gestation of 1.2 (0.7 to 1.9). Bacterial vaginosis was, however, associated with miscarriage in the second trimester at 13-15 weeks (3.5, 1.2 to 10.3). Only 29 women (2.4%, 1.5% to 3.3%) had chlamydial infection, of whom one miscarried (0.32, 0.04 to 2.30). Conclusion: Bacterial vaginosis is not strongly predictive of early miscarriage but may be a predictor after 13 weeks9 gestation. The prevalence of Chlamydia was too low to assess the risk, but it is unlikely to be a major risk factor in pregnant women.