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

June 2007
Best Practice & Research Clinical Obstetrics & Gynaecology 21(3):375-90

DOI:10.1016/j.bpobgyn.2006.12.005

Source
PubMed

Authors:

Medical University of Vienna

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.

Prevalence of bacterial vaginosis among pregnant women attending antenatal care in low‐ and middle‐income countries between 2000 and 2020: A systematic review and meta‐analysis

Article

Full-text available

Jun 2024

Background Bacterial vaginosis increases risk of preterm birth and low birthweight, adverse pregnancy outcomes that disproportionately affect low‐ and middle‐income countries (LMICs). Objectives We aimed to estimate the prevalence of bacterial vaginosis among pregnant women attending antenatal care in LMICs between 2000 and 2020. Search Strategy We conducted a systematic review of PubMed, Embase and five regional databases. Selection Criteria We included studies conducted in LMICs and published between 2000 and 2020 in which bacterial vaginosis prevalence was reported among pregnant women attending antenatal care. Data Collection and Analysis We corrected point estimates and applied random‐effects models to generate pool prevalence estimates. We carried out subgroup analyses by study year, country‐income level, HIV prevalence, sample size, diagnostic method, trimester of pregnancy, presence of symptoms at diagnosis and risk of bias. Main Results Of 1132 publications, 74 studies met inclusion criteria, contributing 80 data points from 46 661 pregnant women. Overall pooled mean prevalence across LMICs was 15.7%. Regional prevalence ranged from 25.1% in sub‐Saharan Africa to 7.4% in Central and Southern Asia. Prevalence was 33.4% in studies where HIV prevalence was ≥10%, and 6.6% in which HIV prevalence was <10%. The prevalence of bacterial vaginosis among pregnant women who were symptomatic was 24.2% versus 11.8% among those without associated symptoms. Conclusions Bacterial vaginosis prevalence is high. World Health Organization guidelines recommend screening and treatment for symptomatic pregnant women. This recommendation should be extended to include all pregnant women who have HIV infection. Research is needed to characterise biological mechanisms of bacterial vaginosis that lead to preterm birth and low birthweight, and to investigate antenatal interventions that may better interrupt these pathways.

Role of vulvovaginal candidiasis infection in infertility: systematic review and meta-analysis

Article

Dec 2023

To evaluate the relationship between fungal infection in the female genital tract and infertility. A systematic review was carried out, and the search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane Library databases until August 2022. The search strategy used standardized keywords such as “candidiasis” and “infertility,” combined with their respective synonyms. The search was limited to human studies, with no language restrictions. Primary articles that evaluated women of reproductive age with and without infertility and related to the presence or absence of candidiasis were included. For the analyses, the odds ratio association measure was used with a confidence interval of 95% using RevMan software (version 5.4). Eight studies, published between 1995 and 2021 in different countries around the world, were included in this systematic review. Two studies were excluded after sensitivity analysis. A total of 909 participants were included in the group of infertile women and 2363 women in the control group. The age of the evaluated women varied between 18 and 50 years. The random effect model was used and showed no significant difference when comparing candidiasis between fertile and infertile women (odds ratio: 1.44; 95% confidence interval 0.86, 2.41 p= 0.17). There was no association between candidiasis and female sterility.

Bacterial Vaginosis and Post-Operative Pelvic Infections

Article

Full-text available

Apr 2023

Bacterial vaginosis (BV) represents a condition in which the normal protective Lactobacilli, especially those that produce H2O2, are replaced by high quantities of facultative anaerobes, leading to gynecologic and obstetric post-operative complications. BV is an important cause of obstetric and gynecological adverse sequelae and it could lead to an increased risk of contracting sexually transmitted infections such as gonorrhea, genital herpes, Chlamydia, Trichomonas, and human immunodeficiency virus. Herein, we reviewed bacterial vaginosis and its association with post-operative pelvic infections. In Obstetrics, BV has been associated with increased risk of preterm delivery, first-trimester miscarriage in women undergoing in vitro fertilization, preterm premature rupture of membranes, chorioamnionitis, amniotic fluid infections, postpartum and postabortal endomyometritis as well as postabortal pelvic inflammatory disease (PID). In gynecology, BV increases the risk of post-hysterectomy infections such as vaginal cuff cellulitis, pelvic cellulitis, pelvic abscess, and PID. BV is often asymptomatic, can resolve spontaneously, and often relapses with or without treatment. The American College of Obstetricians and Gynecologists recommends testing for BV in women having an increased risk for preterm delivery. Women with symptoms should be evaluated and treated. Women with BV undergoing gynecological surgeries must be treated to reduce the frequency of post-operative pelvic infections. Metronidazole and clindamycin are the mainstays of therapy. Currently, there is no consensus on pre-surgery screening for BV; decisions are made on a case-by-case basis.

Risk factors for preterm birth: an umbrella review of meta-analyses of observational studies

Article

Full-text available

Dec 2023
BMC MED

Background Preterm birth defined as delivery before 37 gestational weeks is a leading cause of neonatal and infant morbidity and mortality. The aim of this study is to summarize the evidence from meta-analyses of observational studies on risk factors associated with PTB, evaluate whether there are indications of biases in this literature, and identify which of the previously reported associations are supported by robust evidence. Methods We searched PubMed and Scopus until February 2021, in order to identify meta-analyses examining associations between risk factors and PTB. For each meta-analysis, we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. Evidence was graded as robust, highly suggestive, suggestive, and weak. Results Eighty-five eligible meta-analyses were identified, which included 1480 primary studies providing data on 166 associations, covering a wide range of comorbid diseases, obstetric and medical history, drugs, exposure to environmental agents, infections, and vaccines. Ninety-nine (59.3%) associations were significant at P < 0.05, while 41 (24.7%) were significant at P < 10⁻⁶. Ninety-one (54.8%) associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in 37 (22.3%) and 12 (7.2%) associations, respectively. We evaluated all associations according to prespecified criteria. Seven risk factors provided robust evidence: amphetamine exposure, isolated single umbilical artery, maternal personality disorder, sleep-disordered breathing (SDB), prior induced termination of pregnancy with vacuum aspiration (I-TOP with VA), low gestational weight gain (GWG), and interpregnancy interval (IPI) following miscarriage < 6 months. Conclusions The results from the synthesis of observational studies suggest that seven risk factors for PTB are supported by robust evidence. Routine screening for sleep quality and mental health is currently lacking from prenatal visits and should be introduced. This assessment can promote the development and training of prediction models using robust risk factors that could improve risk stratification and guide cost-effective preventive strategies. Trial registration PROSPERO 2021 CRD42021227296.

Effect of bacterial vaginosis on induced labour in the third trimester of pregnancy: A retrospective cohort study

Preprint

Full-text available

Dec 2023

Purpose The aim of this study was to investigate the hypothesis that pregnant women diagnosed with bacterial vaginosis (BV) may encounter more adverse outcomes during induced labour. Methods The study population consisted of 474 pregnant women who were categorized into two groups based on the findings of a vaginal discharge test: BV group and the nonvaginitis group. The BV group consisted of both the BV group and the BV + vulvovaginal candidiasis(VVC) group. Based on the Bishop score, labour induction was performed utilizing diverse techniques, such as the insertion of a dinoprostone plug, and amniotomy in conjunction with oxytocin. The statistical analysis of the experimental data was conducted using SPSS software. Results Compared to the nonvaginitis group, the BV group exhibited a higher incidence of caesarean section and a lower incidence of vaginal delivery (24.24% vs. 11.99%; 75.76% vs. 88.01%; P = 0.001). Additionally, the BV group experienced a greater occurrence of adverse maternal and infant outcomes, including increased postpartum bleeding, postpartum haemorrhage, blood transfusion, chorioamnionitis, postpartum urinary retention, puerperal infection, meconium-stained amniotic fluid, neonatal infection, and admission to the neonatal intensive care unit (p༜0.05). In comparison to the BV + VVC group, the BV group exhibited elevated levels of postpartum bleeding, postpartum haemorrhage (PPH), blood transfusion, chorioamnionitis, meconium-stained amniotic fluid, neonatal infection (n,%) and admission to the neonatal intensive care unit (n,%) (p༜0.05). After controlling for age, BMI, Bishop score, history of vaginitis during pregnancy, and mode of induction, statistically significant differences in adverse maternal and child outcomes between BV and nonvaginitis groups persisted. Conclusion BV during the third trimester of pregnancy has been correlated with a significant increase in the incidence of caesarean section following labour induction in primiparous women, as well as adverse outcomes for both mothers and infants. It is imperative for clinicians to allocate greater attention towards the assessment of BV during the third trimester of pregnancy.

Vaginal Microbial Network Analysis Reveals Novel Taxa Relationships among Adolescent and Young Women with Incident Sexually Transmitted Infection Compared with Those Remaining Persistently Negative over a 30-Month Period

Article

Full-text available

Aug 2023

A non-optimal vaginal microbiome (VMB) is typically diverse with a paucity of Lactobacillus crispatus and is often associated with bacterial vaginosis (BV) and sexually transmitted infections (STIs). Although compositional characterization of the VMB is well-characterized, especially for BV, knowledge remains limited on how different groups of bacteria relate to incident STIs, especially among adolescents. In this study, we compared the VMB (measured via 16S ribosomal RNA gene amplicon sequencing) of Kenyan secondary school girls with incident STIs (composite of chlamydia, gonorrhea, and trichomoniasis) to those who remained persistently negative for STIs and BV over 30 months of follow-up. We applied microbial network analysis to identify key taxa (i.e., those with the greatest connectedness in terms of linkages to other taxa), as measured by betweenness and eigenvector centralities, and sub-groups of clustered taxa. VMB networks of those who remained persistently negative reflected greater connectedness compared to the VMB from participants with STI. Taxa with the highest centralities were not correlated with relative abundance and differed between those with and without STI. Subject-level analyses indicated that sociodemographic (e.g., age and socioeconomic status) and behavioral (e.g., sexual activity) factors contribute to microbial network structure and may be of relevance when designing interventions to improve VMB health.

A Narrative Review Discussing the Obstetric Repercussions Due to Alterations of Personalized Bacterial Sites Developed within the Vagina, Cervix, and Endometrium

Article

Full-text available

Aug 2023

Background: The reproductive tract microbiota that evolved as an integrative component has been studied intensively in the last decade. As a result, novel research, clinical opportunities, and perspectives have been derived following the close investigation of this microecological environment. This has paved the way for an update to and improvement of the management strategies and therapeutic approaches. However, obscurities, contradictions, and controversies arise regarding the ascension route from the vagina to the endometrium via the cervix, with finality in adverse obstetric outcomes. Methods: Starting from these considerations, we aimed to gather all existing data and information from four major academic databases (PubMed, ISI Web of Knowledge, Scopus, and ScienceDirect) published in the last 13 years (2010-2023) using a controlled vocabulary and dedicated terminology to enhance the coverage, identification, and sorting of potentially eligible studies. Results: Despite the high number of returned entries (n = 804), only a slight percentage (2.73%) of all manuscripts were deemed eligible following two rounds of evaluation. Cumulatively, a low level of Lactobacillus spp. and of other core microbiota members is mandatory, with a possible eubiosis-to-dysbiosis transition leading to an impairment of metabolic and endocrine network homeostasis. This transposes into a change in the pro-inflammatory landscape and activation of signaling pathways due to activity exerted by the bacterial lipopolysaccharides (LPSs)/endotoxins that further reflect a high risk of miscarriage in various stages. While the presence of some pathogenic entities may be suggestive of an adverse obstetric predisposition, there are still pros and cons of the role of specific strains, as only the vagina and cervix have been targeted as opposed to the endometrium, which recently started to be viewed as the key player in the vagina-cervix-endometrium route. Consequently, based on an individual's profile, diet, and regime, antibiotics and probiotics might be practical or not. Conclusions: Resident bacteria have a dual facet and are beneficial for women's health, but, at the same time, relaying on the abundance, richness, and evenness that are definitory indexes standing as intermediaries of a miscarriage.

The Role of Lactic Acid in the Management of Bacterial Vaginosis: A Systematic Literature Review

Article

Full-text available

Jun 2022

Bacterial vaginosis (BV) is a common infection characterized by an imbalance in the vaginal microbiome. Alongside the extensive research for effective therapies, treatment recommendations for symptomatic BV with antibiotics have been developed and are currently available. However, the recurrence of BV remains a considerable challenge given that about 60% of women experience BV relapse within six months after initial treatment. In addition, clear guidelines on the treatment of asymptomatic BV during pregnancy or for BV mixed infections are still missing. Lactic acid has been put forward as a potential treatment or for prophylaxis of BV due to its ability to restore the imbalance of the vaginal microbiota and to promote the disruption of vaginal pathogenic bacterial biofilms, which might trigger BV recurrence. This review evaluates the clinical evidence regarding the efficacy and prophylactic potential of lactic acid in BV through a systematic literature search. In addition, a treatment regimen consisting of lactic acid as a standalone treatment or in combination with current recommended therapies for practice is suggested based on these findings and stratified according to BV severity, pregnancy status, and coincidence with vulvovaginal candidosis (VVC) or trichomoniasis.

Investigating Bacterial Vaginal Discharge Etiology in Pregnant Women by Microscopic Examination and PCR

Article

Full-text available

Sep 2022

The association between vaginal hygiene practices and spontaneous preterm birth: A case-control study

Article

Full-text available

Jun 2022
PLOS ONE

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.

Tratamiento de la Vaginosis Bacteriana recurrente, actualización 2023

Article

Full-text available

Nov 2024

Franklin Espitia de la Hoz

Introducción: a pesar de los múltiples tratamientos para la vaginosis bacteriana, más de la mitad de las mujeres experimentan recurrencia de los síntomas. Objetivo: evaluar la efectividad y seguridad de las intervenciones terapéuticas en el manejo de la vaginosis bacteriana recurrente, en mujeres no gestantes. Métodos: se realizó una búsqueda sistemática de la literatura en diferentes bases de datos electrónicas (MEDLINE, Scopus, Embase, Biblioteca Cochrane, entre otras); entre 1990 y 2023. Se utilizaron términos de búsqueda libres y estandarizados. Los desenlaces evaluados fueron el tiempo de retardo en la aparición de VB mayor a 12 meses y las reacciones adversas. Resultados: se tuvieron en cuenta 84 publicaciones. El metronidazol y la clindamicina siguen siendo el régimen terapéutico recomendado en el tratamiento de la vaginosis bacteriana aguda, y en la recurrente; el secnidazol y nifuratel han mostrado su positivo efecto, escalonando una posición entre estos regímenes (los cuales no solo podrían aumentar las tasas de curación clínica y microbiológica, sino disminución en la recurrencia). La proporción de reacciones adversas fueron más notables con los nitroimidazoles y la clindamicina, sin hallarse reportes del nifuratel. Conclusión: la revisión mostró que en el tratamiento de la vaginosis bacteriana recurrente no se observan diferencias significativas entre los regímenes tradicionales, lo mismo sucede con la seguridad, ya que las reacciones adversas son escasas y no suelen ser graves. Se necesitan ensayos clínicos que ayuden a aumentar las opciones de tratamiento para la VB recurrente, dándole paso al nifuratel y a otras opciones terapéuticas.

Therapy Effect Comparison of Oral Probiotic to Oral Antibiotic on Reducing The Risk of Premature Birth in Pregnant Women with Bacterial Vaginosis : A Systematic Review

Article

Jul 2024

Prevalence and associated factors of bacterial vaginosis among pregnant women in Hue, Vietnam

Article

Full-text available

Jun 2024

Introduction: Bacterial vaginosis (BV) is the most frequent vaginal infection affecting women of childbearing age worldwide. It is associated with significant adverse healthcare outcomes, especially during pregnancy. Although screening for BV could reduce potential pregnancy-related obstetric complications, there is no routine screening of pregnant women for BV in Vietnam. We aimed to identify the prevalence of BV among pregnant women and the associated factors in two tertiary hospitals in Hue, Vietnam. Methodology: This cross-sectional descriptive study included 885 pregnant women in third trimester, who received routine antenatal care in the Hue Central Hospital and Hue University Hospital of Medicine and Pharmacy, Hue city, Thua Thien Hue province, Vietnam. Gram-stained vaginal smears were used for calculating the Nugent score and recording the fungal elements. Results: In total, 435 (49.1%) women had a normal BV score, 352 (39.8%) had intermediate vaginal microbiota, and 98 (11.1%) had BV. Among the 98 women with BV, 71 (72.4%) also had fungal infection. There was a significant association of BV with discharge (p = 0.004) and abnormal cervix (p = 0.014). BV was significantly more frequent among the women who reported previous abortion or miscarriage (p = 0.007). Conclusions: About a tenth of women in Thua Thien Hue province have BV in the third trimester of pregnancy being associated with previous adverse outcome. Discharge with fishy odour is still a characteristic feature among subtle clinical presentations of BV. Better awareness about this disease and routine test-and-treat management during pregnancy may improve pregnancy outcome.

Bacterial vaginosis in pregnant women: A comparison of the Nugent Score with a multiplex PCR

Article

Jun 2024

New insight about the role of microbiome and probiotics in female reproduction: A review 6

Article

May 2024

Rania Alkhalili

Characteristics of cervicovaginal microflora at different cervical maturity during late pregnancy: A nested case-control study

Article

Full-text available

Mar 2024
PLOS ONE

Objective The mechanism of cervical ripening in late pregnancy is still unclear. The vaginal microbiome has been reported to correlate with the preterm birth and short cervix in pregnant women. However, the associations between the cervical maturity and the vaginal microbiome are still poorly understood. We aim to analyze the cervicovaginal microflora in women with ripe cervix and in those who are unripe when delivering at term. Methods Cervicovaginal swabs were collected between 40 and 41 weeks of gestation from the following 2 different groups of patients: ripe group (n = 25) and unripe group (n = 25). Samples were tested using 16S ribosomal RNA gene high-throughput sequencing and analyzed by bioinformatics platform. Results This study highlights the relationship between cervical maturity during late pregnancy and the composition of the cervicovaginal microflora. Both α- and β-diversity analyses demonstrated significant differences between women with a ripe cervix and those with an unripe cervix. Notably, the Lactobacillus profile was found to be closely linked to cervical maturity. There was a significant difference in the vaginal community state type, with CST IV being more prevalent in women with an unripe cervix. Furthermore, the association between CST IV and the unripe cervix group, as indicated by the odds ratio of 8.6, underscores its relevance in evaluating cervical maturity, when compared to other Lactobacillus-dominant community state types. Additionally, several bacterial taxa, particularly Lactobacillus, exhibited differential relative abundances between the two groups. Conclusion This study provided significant evidence regarding the relationship between the vaginal microbiome and cervical maturity, highlighting the differential diversity, community state types, and specific bacterial taxa, such as Lactobacillus, that are associated with cervical maturation status. These findings contributed to our understanding of the dynamics of the cervicovaginal microflora during late pregnancy and its implications for cervical health.

Evaluation of Various Diagnostic Strategies for Bacterial Vaginosis, Including a New Approach Based on MALDI-TOF Mass Spectrometry

Article

Full-text available

Jan 2024

Bacterial vaginosis (BV) is a common dysbiosis of unclear etiology but with potential consequences representing a public health problem. The diagnostic strategies vary widely. The Amsel criteria and Nugent score have obvious limitations, while molecular biology techniques are expensive and not yet widespread. We set out to evaluate different diagnostic strategies from vaginal samples using (1) a combination of abnormal vaginal discharge and vaginal pH > 4.5; (2) the Amsel-like criteria (replacing the “whiff test” with “malodorous discharge”); (3) the Nugent score; (4) the molecular quantification of Fannyhessea vaginae and Gardnerella vaginalis (qPCR); (5) and MALDI-TOF mass spectrometry (we also refer to it as “VAGI-TOF”). Overall, 54/129 patients (42%) were diagnosed with BV using the combination of vaginal discharge and pH, 46/118 (39%) using the Amsel-like criteria, 31/130 (24%) using qPCR, 32/130 (25%) using “VAGI-TOF”, and 23/84 (27%) using the Nugent score (not including the 26 (31%) with intermediate flora). Of the 84 women for whom the five diagnostic strategies were performed, the diagnosis of BV was considered for 38% using the combination of vaginal discharge and pH, 34.5% using the Amsel-like criteria, 27% using the Nugent score, 25% using qPCR, and 25% using “VAGI-TOF”. When qPCR was considered as the reference, the sensitivity rate for BV was 76.2% for the combination of vaginal discharge and pH, 90.5% for the Amsel-like criteria, 95.2% for the Nugent score, and 90.5% for “VAGI-TOF”, while the specificity rates were 74.6%, 84.1%, 95.3%, and 95.3%, respectively. When the Nugent score was considered as the reference, the sensitivity for BV was 69.6% for the combination of vaginal discharge and pH, 82.6% for the Amsel-like criteria, 87% for qPCR, and 78.7% for “VAGI-TOF”, while the specificity rates were 80%, 94.3%, 100%, and 97.1%, respectively. Overall, the use of qPCR and “VAGI-TOF” provided a consistent diagnosis of BV, followed by the Nugent score. If qPCR seems tedious and for some costly, “VAGI-TOF” could be an inexpensive, practical, and less time-consuming alternative.

Psychosocial impact of recurrent urogenital infections: a review

Article

Full-text available

Dec 2023

Recurrent urogenital infections such as bacterial vaginosis, vulvovaginal candidiasis, and urinary tract infections have a high prevalence and pronounced psychosocial impact. However, no review has compared the psychosocial impacts across infection types. This narrative review discusses the impact of common recurrent urogenital infections on psychosocial aspects, including quality of life, stress, mental health, sexual health, work productivity, race and ethnicity, and satisfaction of medical care. Validated questionnaires show that women with recurrent vulvovaginal candidiasis and urinary tract infections have decreased scores on all aspects of quality of life. Those with recurrent vulvovaginal candidiasis and urinary tract infections show lower mental health scores compared to the general population, with increased risk of anxiety and depression. Recurrent urogenital infections affect sexual relationships and intimacy, including avoidance due to symptoms or as a method of prevention. Recurrent infections also increase medical cost and negatively affect work productivity, leading to a combined estimated cost of over US$13 billion per year. There are clear effects of racial inequality involving minority populations that affect diagnosis, treatment, prevalence, and reporting of recurrent urogenital infections. Satisfactory medical treatment improves quality of life and mental health in those suffering from these conditions. Research evaluating psychosocial aspects of recurrent urogenital infections is variable and is not comparable across vulvovaginal conditions. Even so, psychosocial factors are important in understanding contribution and consequence of urogenital infections. Education, awareness, normalization, community support, and access to care can help to alleviate the negative implications of recurrent urogenital infections.

Profiling of vaginal Lactobacillus jensenii isolated from preterm and full-term pregnancies reveals strain-specific factors relating to host interaction

Article

Full-text available

Nov 2023

Each year, 15 million infants are born preterm (<37 weeks gestation), representing the leading cause of mortality for children under the age of five. Whilst there is no single cause, factors such as maternal genetics, environmental interactions, and the vaginal microbiome have been associated with an increased risk of preterm birth. Previous studies show that a vaginal microbiota dominated by Lactobacillus is, in contrast to communities containing a mixture of genera, associated with full-term birth. However, this binary principle does not fully consider more nuanced interactions between bacterial strains and the host. Here, through a combination of analyses involving genome-sequenced isolates and strain-resolved metagenomics, we identify that L. jensenii strains from preterm pregnancies are phylogenetically distinct from strains from full-term pregnancies. Detailed analysis reveals several genetic signatures that distinguish preterm birth strains, including genes predicted to be involved in cell wall synthesis, and lactate and acetate metabolism. Notably, we identify a distinct gene cluster involved in cell surface protein synthesis in our preterm strains, and profiling the prevalence of this gene cluster in publicly available genomes revealed it to be predominantly present in the preterm-associated clade. This study contributes to the ongoing search for molecular biomarkers linked to preterm birth and opens up new avenues for exploring strain-level variations and mechanisms that may contribute to preterm birth.

The Maternal Microbiome and Gestational Diabetes Mellitus: Cause and Effect

Article

Full-text available

Aug 2023

Gestational diabetes mellitus (GDM) is a growing public health concern that affects many pregnancies globally. The condition is associated with adverse maternal and neonatal outcomes including gestational hypertension, preeclampsia, placental abruption, preterm birth, stillbirth, and fetal growth restriction. In the long-term, mothers and children have an increased risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease. Accumulating evidence suggest that alterations in the maternal microbiome may play a role in the pathogenesis of GDM and adverse pregnancy outcomes. This review describes changes in the maternal microbiome during the physiological adaptations of pregnancy, GDM and adverse maternal and neonatal outcomes. Findings from this review highlight the importance of understanding the link between the maternal microbiome and GDM. Furthermore, new therapeutic approaches to prevent or better manage GDM are discussed. Further research and clinical trials are necessary to fully realize the therapeutic potential of the maternal microbiome and translate these findings into clinical practice.

Exploring the relationship between bacterial vaginosis and socioeconomic factors in Bundelkhand region: A cross-sectional study

Article

Full-text available

Jun 2023

Bacterial vaginosis (BV) is a common condition affecting women of reproductive age, which can cause a range of adverse health outcomes. The cross-sectional study aims to investigate the association between BV and socioeconomic factors, including age groups, education level, income, and hygiene measures, in the Bundelkhand region of India, with the goal of informing public health interventions to reduce the burden of Bacterial Vaginosis. The study included 250 symptomatic pregnant women (with written consent) from different socioeconomic backgrounds and locations within the Bundelkhand region. Vaginal swabs were taken and Nugent's score was calculated to determine the presence of BV. The diagnosis of bacterial vaginosis was based on Amsel's criteria, which includes the pH of vaginal secretion, the presence of clue cells, and the whiff's test. The study found that the overall prevalence of bacterial vaginosis among 250 symptomatic pregnant women attending the Obstetrics and Gynaecology Department of Maharani Laxmi Bai Medical College of Jhansi was 28%. Women in the 40-49 years of age group had the highest prevalence of BV (75%), and illiterate women had the highest prevalence (39.58%). Women with poor personal hygiene had a higher prevalence of BV (42.5%) and those in the low-income group (LIG) had the highest prevalence (38%). The study suggests that age, education level, menstrual and personal hygiene, and income may be associated with the prevalence of bacterial vaginosis. This study found a high prevalence of bacterial vaginosis among women in the Bundelkhand region, with education level, menstrual hygiene, and personal hygiene being associated risk factors. Continued research and investment in public health initiatives are necessary to improve women's health outcomes and quality of life in this underserved area.

Analysis of vaginal infections in pregnant women: A clinical study

Article

Jan 2018

Dr. Anshu Mishra

Recurrent MiscarriageGreen‐top Guideline No. 17

Article

Full-text available

Jun 2023
BJOG-INT J OBSTET GY

Key recommendations In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m², smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT‐A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C]

Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications

Article

Full-text available

May 2023

As the leading cause of neonatal morbidity and mortality, preterm birth is recognized as a major public health concern around the world. The purpose of this review is to analyze the connection between infections and premature birth. Spontaneous preterm birth is commonly associated with intrauterine infection/inflammation. The overproduction of prostaglandins caused by the inflammation associated with an infection could lead to uterine contractions, contributing to preterm delivery. Many pathogens, particularly Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Actinomyces, Candida spp., and Streptococcus spp. have been related with premature delivery, chorioamnionitis, and sepsis of the neonate. Further research regarding the prevention of preterm delivery is required in order to develop effective preventive methods with the aim of reducing neonatal morbidity.

Bacterial Vaginosis—Vaginal Polymicrobial Biofilms and Dysbiosis

Article

Full-text available

May 2023

Background: Bacterial vaginosis (BV) is the most common genital disease worldwide in women of sexually active age, with a prevalence of 23-29%. Its traditional definition as dysbiosis, i.e., a disruption of the normal balance of the vaginal microbiota, with a massive increase of facultative and obligate anaerobic bacteria (mainly Gardnerella spp.) and a loss of lactobacilli, accurately describes the change in the vaginal microbiota, but does not explain the underlying pathophysiology. Methods: This review is based on information in pertinent articles retrieved by a selective literature search and on the authors' own research findings. Results: Fluorescent in situ hybridization (FISH) has revealed Gardnerella spp.-dominated polymicrobial vaginal biofilm as a cause of ascending gynecologic and pregnancy-related infections, preterm birth, and infertility in patients with BV. The biofilm-induced disturbance of epithelial homeostasis favors co-infection with pathogens of sexually transmitted infection (STI). Standard antibiotic therapy is ineffective against biofilms, and there is thus a recurrence rate above 50%. The characteristic biofilm can be followed as a diagnostic marker and is considered evidence of sexual transmission when heterosexual couples and ejaculate samples are examined. FISH studies have shown that, in addition to biofilm-related vaginosis, there are other dysbiotic changes in the vaginal microbiota that have not yet been characterized in detail. It is therefore justified to speak of a "bacterial vaginosis syndrome." Conclusion: The simplistic view of BV as dysbiosis, characterizable by microscopic reference methods, has so far led to inadequate therapeutic success. An evaluation of molecular genetic testing methods that would be suitable for routine use and the development of therapeutic agents that are effective against biofilms are urgently needed if the "bacterial vaginosis syndrome" is to be effectively treated.

Effect of vaginal probiotics containing Lactobacillus casei rhamnosus (Lcr regenerans) on vaginal dysbiotic microbiota and pregnancy outcome, prospective, randomized study

Article

Full-text available

May 2023

The intermediate bacterial microbiota is a heterogeneous group that varies in the severity of the dysbiosis, from minor deficiency to total absence of vaginal Lactobacillus spp. We treated women with this vaginal dysbiosis in the first trimester of pregnancy using a vaginally applied lactobacilli preparation to restore the normal microbiota in order to delay the preterm delivery rate. Pregnant women with intermediate microbiota of the vagina and a Nugent score of 4 were enrolled in two groups: intermediate vaginal microbiota and a Nugent score of 4 with lactobacilli (IMLN4) and intermediate vaginal microbiota and a Nugent score of 4 without lactobacilli (IM0N4), with and without vaginal lactobacilli at baseline, respectively. Half of the women in each group received the treatment. Among women without lactobacilli (the IM0N4 group), the Nugent sore decreased by 4 points only in the women who received treatment, and gestational age at delivery and neonatal birthweight were both significantly higher in the treated subgroup than in the untreated subgroup (p = 0.047 and p = 0.016, respectively). This small study found a trend toward a benefit of treatment with vaginal lactobacilli during pregnancy.

Reproductive tract microbiome and therapeutics of infertility

Article

Full-text available

Apr 2023

Background The microbiome is still a new area of research in human health and disease, especially in reproductive health. The present article aims to aid the perception on reproductive tract microbiome that may enable better management of its dysbiosis causing reproductive dysfunctions. Main body In recent years, identification of microbiota in every part of human body has been eased by next-generation sequencing-based tools. It has been demonstrated that resident microbiota is vital for normal reproductive functions. The development of disease may result owing to changes in the microbiota brought about by internal or external factors. Female reproductive microbiota may be crucial in the success of assisted reproductive technologies such as embryo implantation and prenatal care. Though much has been learned about the vaginal microbiota, the uterine microbiome has gotten very little research attention. The impacts of well-known microorganisms including Chlamydia trachomatis , Mycoplasma tuberculosis , and Neisseria gonorrhoeae have been well documented, resulting in subclinical alterations that are considered risk factors for infertility and poor reproductive outcomes. Research on microbiota of male reproductive system is still in its early stages, and there are numerous questions concerning how inflammation and urogenital infections might impact male fertility. Certain microorganisms reportedly can directly affect spermatozoon function without even inducing oxidative stress or inflammatory cytokines, but via adhering to the spermatozoon or producing soluble factors capable of altering sperm motility and/or inducing apoptosis. Conclusion The presence of specific microbiota in the reproductive tract, regardless of their pathogenicity, or the alteration of the reproductive tract resident microbiota may pose issues with fertilization, implantation, pregnancy as well as embryo development. This may result in the failure of fertility treatments and a reduction in the number of live births.

Association between the vaginal and uterine microbiota and the risk of early embryonic arrest

Article

Full-text available

Mar 2023

The aim of this study was to explore the microecological distribution and differences in the uterus and vaginal microbiome in women with early embryonic arrest and those with normal pregnancy by high-throughput sequencing. We systematically sampled the vaginal and uterine microbiomes of 56 pregnant women, namely, 38 patients with early embryonic arrest and 18 pregnant women with normal pregnancy-induced abortion. We obtained colonization data by 16S rRNA gene amplicon sequencing. In the vagina, Lactobacillus, Bacteroidetes and Helicobacter exhibited significant differences between the groups. We further found that Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri and Lactobacillus jensenii were the most dominant Lactobacillus species and that L. iners was significantly different between the groups. Receiver operating characteristic (ROC) curve analysis confirmed that Ensifer had the highest predictive value for early embryonic arrest. In the uterine cavity, we determined that Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria were the dominant bacteria at the phylum level and that Bacteroides, Pseudarthrobacter, Lactobacillus and Ralstonia were the dominant genera. Further classification of Lactobacillus revealed that L. iners, L. crispatus, L. gasseri, and L. jensenii were the main species. There was a significant difference in L. jensenii between the normal pregnancy group and early embryonic arrest group. Random forest analysis revealed 18 different genera in the uterus, and ROC curve analysis indicated that Candidatus Symbiobacter, Odoribacter, Blautia, Nocardioides and Ileibacterium had a certain predictive value.

Lactoferrin supplementation during pregnancy - a review of the literature and current recommendations

Article

Mar 2023

Pregnancy is a period which requires special care and attention. Maintaining health during pregnancy helps to avoid birth related complications and is the best way of promoting a healthy birth. Besides a daily intake of folic acid, iron, iodine, vitamin D3 and A, calcium and polyunsaturated fatty-acids, as recommended by health agencies, supplementation of lactoferrin - a protein of multidirectional biological activity and proven safety of use - seems to be beneficial. A wide range of lactoferrin biological roles (including regulation of iron balance, modulation of immune responses, antimicrobial, antiviral, antioxidant, and anti-inflammatory activity) may contribute to better pregnancy and birth related outcomes.

Updates on Group B Streptococcus Infection in the Field of Obstetrics and Gynecology

Article

Full-text available

Dec 2022

Group B Streptococcus (GBS, Streptococcus agalactiae) is a Gram-positive bacterium that is commonly found in the gastrointestinal and urogenital tracts. However, its colonization during pregnancy is an important cause of maternal and neonatal morbidity and mortality worldwide. Herein, we specifically looked at GBS in relation to the field of Obstetrics (OB) along with the field of Gynecology (GY). In this review, based on the clinical significance of GBS in the field of OBGY, topics of how GBS is being detected, treated, and should be prevented are addressed.

Impact of bacterial vaginosis on the reproductive outcomes of IVF: meta-analysis

Article

Jul 2022

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.

Microbiome-producing SCFAs are associated with preterm birth via trophoblast function modulation

Article

Nov 2024

Although preterm birth (PTB) is one of the major causes of perinatal mortality and neonatal morbidity, little is known about its complex etiology. An abnormal cervicovaginal microbiome during pregnancy is associated with an increased risk of PTB. The cervicovaginal microbiota and its active metabolites, such as short-chain fatty acids (SCFAs), might be effectively used to predict and diagnose PTB. However, the roles of these proteins and the underlying mechanisms involved remain elusive. We conducted 16S rRNA gene sequencing and used a targeted metabolomics approach to study cervicovaginal swabs obtained from 51 singleton pregnancies and 52 twin pregnancies in the second trimester. Next, functional in vitro experiments were performed to investigate the roles and mechanisms of SCFAs in placental trophoblast cells (HTR8/SVneo cells). Significant cervicovaginal microbiome dysbiosis, characterized by a substantial reduction in the abundance of lactobacilli and overgrowth of anaerobes, was revealed in the second trimester and was strongly associated with subsequent PTB ( P = 0.036). Among the paired samples ( n = 103), acetic acid was significantly greater in the preterm group than in the term group ( P = 0.047). Data obtained from integrated gas chromatography‒mass spectrometry and 16S RNA studies revealed metabolites that were distinctly associated with particular microbial communities. Gardnerella vaginalis was the species most positively associated with acetic acid content. In addition, we identified a marker set consisting of the pregnancy type, acetic acid concentration, and community state type to accurately diagnose PTB. Acetate was associated with increased interleukin (IL)-8 and IL-6 levels and extravillous trophoblast cell migration and invasion through the activation of the extracellular signal-regulated kinase 1/2 signaling pathway in HTR8/SVneo cells. Cervicovaginal microbiota dysbiosis is an important etiological factor of PTB. The cervicovaginal microbiota and its active metabolites can be efficiently used to predict and diagnose PTB. Our findings enrich the microbiota–placenta axis theory and contribute to the development of microecological products for pregnancy. IMPORTANCE Preterm birth (PTB) is a leading cause of infant mortality and long-term health issues, affecting millions of families worldwide. Despite its prevalence, the exact causes of PTB remain unclear. Our study reveals that certain bacteria and their metabolic byproducts in the cervicovaginal environment, specifically short-chain fatty acids (SCFAs), are linked to the risk of preterm birth. By analyzing samples from pregnant women, we found that an imbalance in the vaginal microbiota and increased levels of SCFAs are associated with changes in cells that can lead to early labor. This research provides new insights into how the microbiome influences pregnancy outcomes and highlights potential biomarkers for predicting preterm birth. Understanding these microbial influences could lead to innovative strategies for early diagnosis and prevention, ultimately improving maternal and infant health.

Bacterial vaginosis as a factor associated with adverse pregnancy outcomes

Article

Dec 2023

Bacterial vaginosis is the most common disease of the genitals and affects 20–70% of women. This non-inflammatory syndrome is characterized by dysbiosis of the vaginal microbiota and is accompanied by a decrease in the number of lactobacilli. Bacterial vaginosis in 60% of pregnant women is asymptomatic, but can lead to obstetric complications such as late miscarriage, premature birth, fetal growth restriction, premature rupture of membranes, choriominionitis, postpartum endometritis, and sepsis. The clinical picture of bacterial vaginosis in pregnant women is the same as in non-pregnant women, namely homogeneous whitish-gray discharge from the genital tract, often with an unpleasant “fishy” smell, rarely itching and/or burning in the genital area and urethra, as well as soreness during urination (dysuria), with no signs of an inflammation detected in the genitals. Diagnosis of bacterial vaginosis in pregnant women, as well as in non-pregnant women, is based on the use of clinical and laboratory methods. Multiplex tests based on the nucleic acid amplification method, such as real-time polymerase chain reaction, are very popular for the diagnosis of bacterial vaginosis in this country. The Femoflor-16 Reagent Kit (DNA Technology CJSC, Moscow, Russia) is designed to detect the DNA of opportunistic microorganisms, lactobacilli DNA and human genomic DNA (as a control for taking biological material). Examination of pregnant women, especially in case of complaints of vaginal discharge, should be carried out when registering for pregnancy in order to start treatment early and prevent adverse pregnancy outcomes for the mother and fetus. Biofilms formed by microorganisms in bacterial vaginosis, especially G. vaginalis, limit the penetration of antibacterial agents to bacteria, their concentration being lower than therapeutic one, which leads to ineffective treatment. There remain many unexplored issues related to changes in the epidemiology of bacterial vaginosis, an increase in the frequency of relapses against the background of increasing resistance of microorganisms associated with bacterial vaginosis to antibiotics, and the development of agents that affect bacterial films.

Prematurity and Stillbirth: Causes and Prevention

Chapter

Jan 2024

Systematic review and meta-analysis of maternal and fetal outcomes among pregnant women with bacterial vaginosis

Article

Aug 2023
EUR J OBSTET GYN R B

Background: Women of childbearing age are commonly affected by bacterial vaginosis (BV). Maternal-fetal outcomes associated with BV during pregnancy can be fatal for both the mother and the newborn. Aim: To identify maternal and fetal outcomes in pregnant women with BV encountered globally, highlight their prevalence, and identify maternal-fetal outcomes associated with BV. Methods: The databases Embase, PubMed, Web of Science and Global Index Medicus were searched from inception until December 2022. No restrictions on time or geographical location were imposed when searching for published articles that examined maternal-fetal outcomes in pregnant women with BV. A random effects model was used to perform the meta-analysis. Sources of heterogeneity were investigated using subgroup analysis, and publication bias was assessed using funnel plots and Egger tests. Findings: In total, 26 of the 8983 articles retrieved from the databases met the inclusion criteria and were included in this study. Twenty-two maternal outcomes and 22 fetal outcomes were recorded among pregnant women with BV worldwide. This study determined the prevalence of maternal-fetal outcomes reported in three or more studies. Among fetal outcomes, preterm birth (PTB) had the highest prevalence [17.9%, 95% confidence interval (CI) 13-23.3%], followed by mechanical ventilation (15.2%, 95% CI 0-45.9%), low birth weight (LBW) (14.2%, 95% CI 9.1-20.1%) and neonatal intensive care unit admission (11.2%, 95% CI 0-53.5%). BV was associated with PTB [odds ratio (OR) 1.76, 95% CI 1.32-2.35], LBW (OR 1.73, 95% CI 1.41-2.12) and birth asphyxia (OR 2.90, 95% CI 1.13-7.46). Among maternal outcomes, premature rupture of membranes (PROM) had the highest prevalence (13.2%, 95% CI 6.1-22.3%). BV was associated with the following maternal outcomes: intrauterine infection (OR 2.26, 95% CI 1.44-3.56), miscarriage (OR 2.34, 95% CI 1.18-4.64) and PROM (OR 2.59, 95% CI 1.39-4.82). Maternal and fetal outcomes were most prevalent in women whose BV was diagnosed using the Amsel criteria (37.2%, 95% CI 23-52.6%) and in the third trimester (29.6%, 95% CI 21.2-38.8%). Although reported in fewer than three studies, some maternal-fetal outcomes are highly prevalent, such as respiratory distress (76.67%, 95% CI 57.72-90.07%), dyspareunia (68.33%, 95% CI 55.04-79.74%) and malodorous discharge (85.00%, 95% CI 73.43-92.90%). Conclusion: BV has been associated with several adverse maternal-fetal outcomes around the world. While BV is a common vaginal infection, the types of maternal-fetal outcomes from pregnant women with BV vary by country.

Reassessing Preterm Birth Prevention After the Withdrawal of 17-α Hydroxyprogesterone Caproate

Article

Jul 2023

Kent Heyborne

The U.S. Food and Drug Administration has recently withdrawn approval for 17-α hydroxyprogesterone caproate for prevention of recurrent preterm birth, and recent studies have called into question benefits of the pessary in the setting of a short cervix. Obstetric health care professionals are once again left with limited remaining options for preterm birth prevention. This narrative review summarizes the best current evidence on the use of vaginal progesterone, low-dose aspirin, and cerclage for the prevention of preterm birth; attempts to distill possible lessons learned from studies of progesterone and pessary, as well as their implementation into practice; and highlights areas where inroads into preterm birth prevention may be possible outside of the progesterone-aspirin-cerclage paradigm.

Intrauterine colonization with Gardnerella vaginalis and Mobiluncus mulieris induces maternal inflammation but not preterm birth in a mouse model

Article

Jul 2023

Problem: Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with Lactobacillus-deficient vaginal microbial communities. One proposed mechanism is that vaginal microbes ascend through the cervix, colonize the uterus, and activate inflammatory pathways leading to sPTB. This study assessed whether intrauterine colonization with either Gardnerella vaginalis and Mobiluncus mulieris alone is sufficient to induce maternal-fetal inflammation and induce sPTB. Method of study: C56/B6J mice, on embryonic day 15, received intrauterine inoculation of saline or 108 colony-forming units of G. vaginalis (n = 30), M. mulieris (n = 17), or Lactobacillus crispatus (n = 16). Dams were either monitored for maternal morbidity and sPTB or sacrificed 6 h post-infusion for analysis of bacterial growth and cytokine/chemokine expression in maternal and fetal tissues. Results: Six hours following intrauterine inoculation with G. vaginalis, M. mulieris, or L. crispatus, live bacteria were observed in both blood and amniotic fluid, and a potent immune response was identified in the uterus and maternal serum. In contrast, only a limited immune response was identified in the amniotic fluid and the fetus after intrauterine inoculation. High bacterial load (108 CFU/animal) of G. vaginalis was associated with maternal morbidity and mortality but not sPTB. Intrauterine infusion with L. crispatus or M. mulieris at 108 CFU/animal did not induce sPTB, alter pup viability, litter size, or maternal mortality. Conclusions: Despite inducing an immune response, intrauterine infusion of live G. vaginalis or M. mulieris is not sufficient to induce sPTB in our mouse model. These results suggest that ascension of common vaginal microbes into the uterine cavity alone is not causative for sPTB.

Formulation and Characterization of Pressure-Assisted Microsyringe 3D-Printed Scaffolds for Controlled Intravaginal Antibiotic Release

Article

May 2023

Bacterial vaginosis (BV) is a highly recurrent vaginal condition linked with many health complications. Topical antibiotic treatments for BV are challenged with drug solubility in vaginal fluid, lack of convenience and user adherence to daily treatment protocols, among other factors. 3D-printed scaffolds can provide sustained antibiotic delivery to the female reproductive tract (FRT). Silicone vehicles have been shown to provide structural stability, flexibility, and biocompatibility, with favorable drug release kinetics. This study formulates and characterizes novel metronidazole-containing 3D-printed silicone scaffolds for eventual application to the FRT. Scaffolds were evaluated for degradation, swelling, compression, and metronidazole release in simulated vaginal fluid (SVF). Scaffolds retained high structural integrity and sustained release. Minimal mass loss (<6%) and swelling (<2%) were observed after 14 days in SVF, relative to initial post-cure measurements. Scaffolds cured for 24 hr (50°C) demonstrated elastic behavior under 20% compression and 4.0 N load. Scaffolds cured for 4 hr (50°C), followed by 72 hr (4°C), demonstrated the highest, sustained, metronidazole release (4.0 and 27.0 µg/mg) after 24 hr and 14 days, respectively. Based upon daily release profiles, it was observed that the 24 hr timepoint had the greatest metronidazole release of 4.08 μg/mg for scaffolds cured at 4 hr at 50°C followed by 72 hr at 4°C. For all curing conditions, release of metronidazole after 1 and 7 days showed >4.0-log reduction in Gardnerella concentration. Negligible cytotoxicity was observed in treated keratinocytes comparable to untreated cells, This study shows that pressure-assisted microsyringe 3D-printed silicone scaffolds may provide a versatile vehicle for sustained metronidazole delivery to the FRT.

Biological and pathological mechanisms leading to the birth of a small vulnerable newborn

Article

Full-text available

May 2023
LANCET

The pathway to a thriving newborn begins before conception and continues in utero with a healthy placenta and the right balance of nutrients and growth factors that are timed and sequenced alongside hormonal suppression of labour until a mature infant is ready for birth. Optimal nutrition that includes adequate quantities of quality protein, energy, essential fats, and an extensive range of vitamins and minerals not only supports fetal growth but could also prevent preterm birth by supporting the immune system and alleviating oxidative stress. Infection, illness, undernourishment, and harmful environmental exposures can alter this trajectory leading to an infant who is too small due to either poor growth during pregnancy or preterm birth. Systemic inflammation suppresses fetal growth by interfering with growth hormone and its regulation of insulin-like growth factors. Evidence supports the prevention and treatment of several maternal infections during pregnancy to improve newborn health. However, microbes, such as Ureaplasma species, which are able to ascend the cervix and cause membrane rupture and chorioamnionitis, require new strategies for detection and treatment. The surge in fetal cortisol late in pregnancy is essential to parturition at the right time, but acute or chronically high maternal cortisol levels caused by psychological or physical stress could also trigger labour onset prematurely. In every pathway to the small vulnerable newborn, there is a possibility to modify the course of pregnancy by supporting improved nutrition, protection against infection, holistic maternal wellness, and healthy environments.

Fabrication and characterization of bioprints with Lactobacillus crispatus for vaginal application

Article

Apr 2023

Bacterial vaginosis (BV) is characterized by low levels of lactobacilli and overgrowth of potential pathogens in the female genital tract. Current antibiotic treatments often fail to treat BV in a sustained manner, and > 50% of women experience recurrence within 6 months post-treatment. Recently, lactobacilli have shown promise for acting as probiotics by offering health benefits in BV. However, as with other active agents, probiotics often require intensive administration schedules incurring difficult user adherence. Three-dimensional (3D)-bioprinting enables fabrication of well-defined architectures with tunable release of active agents, including live mammalian cells, offering the potential for long-acting probiotic delivery. One promising bioink, gelatin alginate has been previously shown to provide structural stability, host compatibility, viable probiotic incorporation, and cellular nutrient diffusion. This study formulates and characterizes 3D-bioprinted Lactobacillus crispatus-containing gelatin alginate scaffolds for gynecologic applications. Different weight to volume (w/v) ratios of gelatin alginate were bioprinted to determine formulations with highest printing resolution, and different crosslinking reagents were evaluated for effect on scaffold integrity via mass loss and swelling measurements. Post-print viability, sustained-release, and vaginal keratinocyte cytotoxicity assays were conducted. A 10:2 (w/v) gelatin alginate formulation was selected based on line continuity and resolution, while degradation and swelling experiments demonstrated greatest structural stability with dual genipin and calcium crosslinking, showing minimal mass loss and swelling over 28 days. 3D-bioprinted L. crispatus-containing scaffolds demonstrated sustained release and proliferation of live bacteria over 28 days, without impacting viability of vaginal epithelial cells. This study provides in vitro evidence for 3D-bioprinted scaffolds as a novel strategy to sustain probiotic delivery with the ultimate goal of restoring vaginal lactobacilli following microbiological disturbances.

Risk factors for preterm labor: An Umbrella Review of meta-analyses of observational studies

Preprint

Full-text available

Feb 2023

Preterm birth defined as delivery before 37 gestational weeks, is a leading cause of neonatal and infant morbidity and mortality. Understanding its multifactorial nature may improve prediction, prevention and the clinical management. We performed an umbrella review to summarize the evidence from meta-analyses of observational studies on risks factors associated with PTB, evaluate whether there are indications of biases in this literature and identify which of the previously reported associations are supported by robust evidence. We included 1511 primary studies providing data on 170 associations, covering a wide range of comorbid diseases, obstetric and medical history, drugs, exposure to environmental agents, infections and vaccines. Only seven risk factors provided robust evidence. The results from synthesis of observational studies suggests that sleep quality and mental health, risk factors with robust evidence should be routinely screened in clinical practice, should be tested in large randomized trial. Identification of risk factors with robust evidence will promote the development and training of prediction models that could improve public health, in a way that offers new perspectives in health professionals.

Lactobacilli and Their Probiotic Effects in the Vagina of Reproductive Age Women

Article

Full-text available

Mar 2023

In the present narrative review, the probiotic effects of vaginal Lactobacillus spp. are described in detail, covering the importance of the differential production of lactic acid, the lactic acid D/L isoforms, the questionable in vivo effect of hydrogen peroxide, as well as bacteriocins and other core proteins produced by vaginal Lactobacillus spp. Moreover, the microbe–host interaction is explained with emphasis on the vaginal mucosa. To understand the crucial role of Lactobacillus spp. dominance in the vaginal microbiota, different dysbiotic states of the vagina are explained including bacterial vaginosis and aerobic vaginitis. Finally, this review takes on the therapeutic aspect of live lactobacilli in the context of bacterial vaginosis. Until recently, there was very low-quality evidence to suggest that any probiotic might aid in reducing vaginal infections or dysbiosis. Therefore, clinical usage or over the counter usage of probiotics was not recommended. However, recent progress has been made, moving from probiotics that are typically regulated as food supplements to so-called live biotherapeutic products that are regulated as medical drugs. Thus, recently, a phase 2b trial using a Lactobacillus crispatus strain as a therapeutic add-on to standard metronidazole showed significant reduction in the recurrence of bacterial vaginosis by 12 weeks compared to placebo. This may constitute evidence for a brighter future where the therapeutic use of lactobacilli can be harnessed to improve women’s health.

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta‐analysis

Article

Jan 2023

Background: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. Objectives: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. Data sources: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). Study selection and data extraction: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. Results: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2 = 62%, and 0.59 (95% CI 0.42, 0.82), I2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I2 = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. Conclusions: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

Diseases during pregnancy in a large unselected South American sample

Article

Full-text available

Dec 2022

Objective: Our aim was to describe the prevalence of diseases during pregnancy and the association between fetal exposure to the most frequent maternal diseases and the risk of preterm (PTB) and/or small for gestational age (SGA) newborns in an unselected sample of women who gave birth in South American countries. Methods: We conducted a descriptive, cross-sectional study including 56,232 mothers of non-malformed infants born between 2002 and 2016, using data from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Diseases with higher- than-expected PTB/SGA frequencies were identified. Odds ratios of confounding variables for diseases and birth outcomes were calculated with a multivariable logistic regression. Results: Of the 14 most reported diseases, hypertension, genitourinary infection, epilepsy, hypothyroidism, diabetes, and HIV/AIDS showed higher PTB and/or SGA frequencies. Advanced and low maternal age, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with PTB, while advanced maternal age, primigravidity, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with SGA. After adjusting for the associated variables, the identified illnesses maintained their association with PTB and all, except epilepsy, with SGA. Conclusion: The description of an unselected population of mothers allowed identifying the most frequent diseases occurring during gestation and their impact on pregnancy outcomes. Six diseases were associated with PTB and two with SGA newborns. To the best of our knowledge, there are no similar reports about women not intentionally selected by specific diseases during pregnancy in South American populations.

Monofilament versus multifilament suture for cervical cerclage: A multi-center randomized controlled trial

Article

Dec 2022

The role of platelet-lymphocyte ratio and neutrophil-lymphocyte ratio in early gestational week in predicting missed abortion

Article

Full-text available

Oct 2022

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).

Diversity of the gut, vaginal and oral microbiome among pregnant women in South Africa with and without pre-eclampsia

Article

Full-text available

Sep 2022

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.

Bacterial vaginosis, vulvovaginal candidiasis, and trichomonal vaginitis in reproductive-age women in Yunnan, China: a descriptive study

Article

Aug 2022

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.

Female reproductive tract microbiota and recurrent pregnancy loss: a nested case-control study

Article

Full-text available

Jun 2022

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.

Dominant Lactobacillus spp. in different conditions of vaginal microbiocenosis

Article

Jul 2022

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.

Prospective randomised controlled trial of an infection screening program to reduce the rate of preterm delivery

Article

Full-text available

Aug 2004

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.

Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation

Article

Full-text available

Mar 1991

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.

Bacterial vaginosis and vaginal microorganisms in idiopathic premature labor and association with pregnancy outcome

Article

Full-text available

Jan 1994

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.

The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network

Article

Full-text available

Mar 1998

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.

Spontaneous recovery of bacterial vaginosis during pregnancy is not associated with an improved perinatal outcome

Article

Full-text available

Feb 1998

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.

Prematurity in multiple gestations: Identification of patients who are at low risk

Article

Full-text available

Jun 2002
AM J OBSTET GYNECOL

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.

Socioeconomic and environmental risk factors of bacterial vaginosis in early pregnancy

Article

Full-text available

Feb 2002

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.

Quantitative Microbiologic Models for Preterm Delivery

Article

Full-text available

Mar 2003
J CLIN MICROBIOL

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.

A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour

Article

Full-text available

Apr 2003

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.

Periodontal Disease and Preterm Birth: Results of a Pilot Intervention Study

Article

Full-text available

Aug 2003

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.

Identification and H2O2 Production of Vaginal Lactobacilli from Pregnant Women at High Risk of Preterm Birth and Relation with Outcome

Article

Full-text available

Feb 2004
J CLIN MICROBIOL

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.

Abnormal vaginal flora in the first trimester, but not full-blown bacterial vaginosis, is associated with preterm birth

Article

Dec 1998

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.

Association between bacterial vaginosis or chlamydial infection and miscarriage before 16 weeks' gestation: prospective community based cohort study

Article

Dec 2002

Pippa Oakeshott

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.

The preterm prediction study: Risk factors in twin gestations

Article

Oct 1996
AM J OBSTET GYNECOL

OBJECTIVE: Our purpose was to determine the association between the presence of bacterial vaginosis, fetal fibronectin, and a short cervix and the risk of spontaneous preterm birth of twins. STUDY DESIGN: We prospectively screened 147 women with twins at 24 and 28 weeks' gestation for more than 50 potential risk factors for spontaneous preterm birth. We also measured cervical length with ultrasound scans and tested for the presence of bacterial vaginosis. Fetal fibronectin level was evaluated every 2 weeks from 24 to 30 weeks' gestation. Outcomes included spontaneous preterm birth at <32 weeks, <35 weeks, and <37 weeks. RESULTS: Among twin as compared with singleton pregnancies, a cervical length ≤25 mm was more common at both 24 and 28 weeks, a statistically significant difference. There were no significant differences in most other risk factors. Of the factors evaluated by means of univariate analysis at 24 weeks, only a short cervix (≤25 mm) was consistently associated with spontaneous preterm birth. The odds ratios and 95% confidence interval for spontaneous preterm birth at <32 weeks, <35 weeks, and <37 weeks were 6.9 (2.0 to 24.2), 3.2 (1.3 to 7.9), and 2.8 (1.1 to 7.7). At 28 weeks, a cervical length ≤25 mm was not a strong predictor of spontaneous preterm birth. At both 28 weeks (odds ratio, 9.4; confidence interval, 1.0 to 67.7) and 30 weeks (odds ratio, 46.1; confidence interval, 4.2 to 1381), a positive fetal fibronectin result was significantly associated with spontaneous preterm birth at <32 weeks. Bacterial vaginosis at 24 or 28 weeks was not associated with spontaneous preterm birth of twins. Multivariate analysis confirmed the association between cervical length ≤25 mm at the 24-week visit and spontaneous preterm birth and also confirmed that at 24 weeks the other risk factors were less consistently and often not statistically significantly associated with spontaneous preterm birth. Of the risk factors evaluated at 28 weeks, only a positive fetal fibronectin was associated with a significantly increased risk for spontaneous preterm birth. CONCLUSIONS: Most known risk factors for spontaneous preterm birth were not significantly associated with spontaneous preterm birth of twins. At 24 weeks, cervical length ≤25 mm was the best predictor of spontaneous preterm birth at <32 weeks, <35 weeks, and <37 weeks. Of the risk factors evaluated at 28 weeks, fetal fibronectin was the only statistically significant predictor of spontaneous preterm birth at <32 weeks. (Am J Obstet Gynecol 1996;175:1047-53.)

A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study - Reply

Article

Aug 2006
BJOG-INT J OBSTET GY

The Preterm Prediction Study: Fetal Fibronectin, Bacterial Vaginosis, and Peripartum Infection

Article

May 1996
OBSTET GYNECOL

Objective: To determine the relation between vaginal and upper genital tract infection and cervical-vaginal fetal fibronectin levels. Methods: We screened 2899 women at ten centers every 2 weeks from 23-24 to 30 weeks' gestation for cervical and vaginal fetal fibronectin. A positive test was defined as a level of at least 50 ng/mL. The relation between a positive test and bacterial vaginosis at 23-24 weeks at clinical or histologic chorioamnionitis at delivery plus neonatal sepsis was determined. Results: Fetal fibronectin was present in 4.0% of cervical and/or vaginal samples at 23-24 weeks and was nearly twice as common in women with bacterial vaginosis. Adjusting for the presence of bacterial vaginosis, race, and parity, women positive for fetal fibronectin were much more likely to have clinical chorioamnionitis (mean +/- standard deviation gestational age 30.6 +/- 4.1 weeks), with an odds ratio of 16.4 and 95% confidence interval of 7.1-37.8, and neonatal sepsis (6.3 and 2.0-20.0, respectively), than those who were fetal fibronectin-negative. A positive cervical fetal fibronectin test was a better predictor of clinical chorioamnionitis and neonatal sepsis than was a vaginal test or a combination of vaginal and cervical tests. Among 40 women who delivered before 32 weeks and had placental histology available for evaluation, ten had a positive cervical and/or vaginal fetal fibronectin test before delivery; all ten had histologic evidence of chorioamnionitis, compared with only 13 of 30 women (43%) who were fetal fibronectin-negative (P = .02). Conclusion: Women with bacterial vaginosis were more likely to have a positive fetal fibronectin test than uninfected women. Women with a positive fetal fibronectin test who delivered before 32 weeks' gestation all had evidence of histologic chorioamnionitis. Women positive for fetal fibronectin also had a 16-fold increase in clinical chorioamnionitis and a sixfold increase in neonatal sepsis. There is strong evidence that upper genital tract infection and cervical and/or vaginal fetal fibronectin are closely linked. (C) 1996 The American College of Obstetricians and Gynecologists

A general parametric approach to the meta-Analysis of randomized clinical trials

Article

Nov 1991
STAT MED

Meta-analysis provides a systematic and quantitative approach to the summary of results from randomized studies. Whilst many authors have published actual meta-analyses concerning specific therapeutic questions, less has been published about comprehensive methodology. This article presents a general parametric approach, which utilizes efficient score statistics and Fisher's information, and relates this to different methods suggested by previous authors. Normally distributed, binary, ordinal and survival data are considered. Both the fixed effects and random effects model for treatments are described.

Methods for combining randomized clinical trials: Strengths and limitations

Article

Apr 1987
STAT MED

David Demets

Methods for combining data from several studies exist and appear to be quite useful. None satisfactorily addresses the question of what studies should be combined. This issue is the most serious methodological limitation. Even studies with statistically significant interaction might still be combined if the effect were in the same direction. Thus, substantial scientific input is required as to what criteria must be met by each potential study. Much can be learned from combining or pooling data but it must be done cautiously. Pooling exercises do not replace well designed prospective clinical trials. Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful.

The Utility of fFN for the Prediction of Preterm Birth in Twin Gestations

Article

Jul 2004
J Obstet Gynecol Neonatal Nurs

Objective: To determine the sensitivity, specificity, and positive predictive value (PPV) of fetal fibronectin (fFN) and to determine its usefulness, in conjunction with selected other clinical assessment measures, in the prediction of preterm birth for women with twin gestations. Design: A prospective, descriptive, longitudinal design. Setting: An obstetrical high-risk clinic that received patient referrals from several surrounding communities in central Texas. Patients/participants: Forty-eight women identified with twin gestations prior to the 22nd week of pregnancy; primarily of Hispanic ethnicity. Main outcome measures: A substantial number of outcome variables were assessed in this study. In the present report, data derived from weekly assessments for the identification of the presence of fFN, the diagnosis of bacterial vaginosis, and the measurement of cervical length were reviewed for their relationship to prematurity, birth weight, birth weight discordancy and placental chorionicity. Results: The relative risk of birth prior to 35 weeks gestation, fetal death, or discordance of twin birth weights of greater than 20% was 2.22 (CI: 1.09, 4.55, P < 0.015) when fFN was found to be positive at any weekly testing after 22 to 24 weeks gestation (sensitivity 76.82%, specificity 58.33%, PPV 66.7%). The presence of fFN was most highly predictive of preterm birth when performed during the 24th to 28th gestational week. Shorter cervical lengths were highly correlated with preterm birth (r = -0.6). An association between bacterial vaginosis and preterm birth was not demonstrated in this sample. Conclusion: Sampling for the presence of fetal fibronectin can be easily accomplished by RNs in labor triage units and by advanced practice nurses in outpatient settings. The identification of fFN, particularly during the 24 to 28 weeks gestational time frame, is highly predictive of preterm birth, and particularly so for women with twin gestations.

Bacterial vaginosis in early pregnancy and pregnancy outcome

Article

Sep 1992
OBSTET GYNECOL

We assessed the association between bacterial vaginosis in early pregnancy and adverse pregnancy outcome. Vaginal swabs for bacterial culture, Gram stain, and Papanicolaou stain were taken at the first prenatal visit between 8-17 weeks' gestation in 790 healthy nulliparous women. Culture-proven bacterial vaginosis was detected in 169 of 790 women (21.4%), 167 (98.8%) of whom could also be identified by Gram stain. Papanicolaou smears were available from 299 women, among whom 101 had bacterial vaginosis on culture; of these 101, 78 (77.2%) could be detected by Papanicolaou stain. Of the 751 women whose clinical follow-up was completed, 42 had been treated for preterm uterine contractions (preterm labor), but only 17 delivered between 20-36 weeks' gestation (preterm birth). Premature rupture of membranes (PROM) occurred more than 6 hours before delivery in 80 cases (nine preterm and 71 term). Bacterial vaginosis in early pregnancy predicted preterm labor, preterm birth, or preterm PROM with a sensitivity of 41-67%, specificity of 79%, and negative predictive value of 96-99%, but the positive predictive value was low at 4-11%. However, bacterial vaginosis was associated with a 2.6-fold risk (95% confidence interval [CI] 1.3-4.9) for preterm labor, a 6.9-fold risk (95% CI 2.5-18.8) for preterm birth, and a 7.3-fold risk (95% CI 1.8-29.4) for preterm PROM. Bacterial vaginosis in early pregnancy can be detected reliably by Gram stain and, in most cases, by Papanicolaou smear. Although bacterial vaginosis is associated with preterm labor, preterm birth, and preterm PROM, the clinical usefulness of its assessment is limited because of the high rate of false-positive findings.

Adjunctive clindamycin therapy for preterm labor: Results of a double-blind, placebo-controlled trial

Article

Nov 1991
AM J OBSTET GYNECOL

A double-blind, placebo-controlled, randomized trial was conducted to evaluate the efficacy, safety, and tolerance of a course of clindamycin (administered for 3 days intravenously and 4 days orally) among hospitalized women with preterm labor at less than or equal to 34 weeks' gestation who were treated with tocolytics. One hundred three woman-perinate pairs were analyzed. Univariate analysis demonstrated that pregnancies were continued longer in women treated with clindamycin than in women who received placebo (clindamycin-treated group, 35 days; placebo-treated group, 25 days; p = 0.02). Survival analysis showed that pregnancy continued at least 35.5 days in 50% of clindamycin-treated women versus 20 days for control women (p = 0.03). Obstetric and microbiologic parameters associated with treatment outcomes were also sought. Women with bacterial vaginosis more often delivered preterm (p = 0.03; relative risk, 1.4; 95% confidence interval, 1.04 to 2.0). Among women with bacterial vaginosis, trends for increased duration of pregnancy (clindamycin-treated group, 36 days; placebo-treated group, 19 days), increased birth weight (clindamycin-treated group, 2634 gm; placebo-treated group, 2256 gm), and increased mean gestational age at delivery (clindamycin-treated group, 35 weeks; placebo-treated group, 34 weeks) were associated with clindamycin treatment. Women with either group B streptococcus, Chlamydia trachomatis, Trichomonas vaginalis, or Staphylococcus aureus were more likely to have preterm premature rupture of membranes (p = 0.01). Clindamycin treatment of these women reduced the incidence of preterm premature rupture of membranes to that of uninfected subjects. Stratification by gestational age at enrollment showed clindamycin treatment to be associated with an increased interval to delivery only among mothers enrolled before 33 weeks' gestation (clindamycin-treated group, 40 days; placebo-treated group, 28 days; p less than 0.05). Treatment with clindamycin appeared safe and well tolerated, with benefits limited to women who were less than or equal to 32 weeks' gestation.

Antenatal microbiologic and maternal risk factors associated with pematurity

Article

Dec 1990
AM J OBSTET GYNECOL

In a prospective study of 202 women (gestational age 24 ± 4 weeks), we evaluated possible influences of lower genital tract infection or bacterial conditions on obstetric outcomes, including preterm labor, preterm premature rupture of membranes, and preterm birth. The presence of bacterial vaginosis (18.7%) was associated with an increased risk of preterm labor (relative risk, 2.6; 95% confidence interval, 1.08 to 6.46). For women with bacterial vaginosis who also had Mobiluncus species morphotypes identified on Gram stain, the relative risk of preterm labor was 3.8 (95% confidence interval, 1.32 to 11.5). Presence of vaginal Mycoplasma hominis (10.8% of patients) was associated with both preterm labor (relative risk, 1.8; 95% confidence interval, 0.77 to 4.4) and preterm birth (relative risk, 5.1; 95% confidence interval, 1.45 to 17.9). Recovery of Staphylococcus aureus (3.0%) was associated with preterm labor (relative risk, 3.1; 95% confidence interval 1.12 to 8.7). Identification of two or more bacterial-linked abnormalities was also associated with preterm labor (relative risk, 3.3; 95% confidence interval, 1.44 to 7.58). An increased level of vaginal wash protease (≥10 trypsin units) (16%) was associated with preterm labor and was noted in 50% of women with preterm premature rupture of membranes. A history of prior preterm birth was the single best historical predictor of both preterm labor (relative risk, 3.6; 95% confidence interval, 1.92 to 6.83) and preterm birth (relative risk, 6.7; 95% confidence interval, 2.2 to 20.4). History of three or more abortions, antenatal urinary tract infection, and occurrence of medical complications during pregnancy also correlated with increased risk of preterm labor. These findings affirm and refine associations of various maternal reproductive tract infections with preterm labor, premature rupture of membranes, and birth, allowing for controlled treatment trials aimed at prevention of preterm birth.

Diagnosis of bacterial vaginosis by dried Gram stain of vaginal fluid

Article

Aug 1983

To determine whether bacterial vaginosis (BV), also known as nonspecific vaginitis, could be diagnosed by evaluating a Gram stain of vaginal fluid, we examined samples from 60 women of whom 25 had clinical evidence of BV and 35 had candidal vaginitis or normal examinations. An inverse relationship between the quantity of the Lactobacillus morphotype (large gram-positive rods) and of the Gardnerella morphotype (small gram-variable rods) was noted on Gram stain (P less than 0.001). When Gram stain showed a predominance (3 to 4+) of the Lactobacillus morphotype with or without the Gardnerella morphotype, it was interpreted as normal. When Gram stain showed mixed flora consisting of gram-positive, gram-negative, or gram-variable bacteria and the Lactobacillus morphotype was decreased or absent (0 to 2+), the Gram stain was interpreted as consistent with BV. Gram stain was consistent with BV in 25 of 25 women given a clinical diagnosis of BV and in none of 35 women with candidal vaginitis or normal examinations. Duplicate slides prepared from 20 additional specimens of vaginal fluid were stained by two methods and examined by three evaluators. Interevaluator interpretations and intraevaluator interpretations of duplicate slides were in agreement with one another and with the clinical diagnosis greater than or equal to 90% of the time. We concluded that a microscopically detectable change in vaginal microflora from the Lactobacillus morphotype, with or without the Gardnerella morphotype (normal), to a mixed flora with few or no Lactobacillus morphotypes (BV) can be used in the diagnosis of BV.

Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations

Article

Feb 1983
AM J MED

Numerous previous studies of nonspecific vaginitis have yielded contradictory results regarding its cause and clinical manifestations, due to a lack of uniform case definition and laboratory methods. We studied 397 consecutive unselected female university students and applied sets of well defined criteria to distinguish nonspecific vaginitis from other forms of vaginitis and from normal findings. Using such criteria, we diagnosed nonspecific vaginitis in up to 25 percent of our study population; asymptomatic disease was recognized in more than 50 percent of those with nonspecific vaginitis. A clinical diagnosis of nonspecific vaginitis, based on simple office procedures, was correlated with both the presence and the concentration of Gardnerella vaginalis (Hemophilus vaginalis) in vaginal discharge, and with characteristic biochemical findings in vaginal discharge. Nonspecific vaginitis was also correlated with a history of sexual activity, a history of previous trichomoniasis, current use of nonbarrier contraceptive methods, and, particularly, use of an intrauterine device. G. vaginalis was isolated from 51.3 percent of the total population using a highly selective medium that detected the organism in lower concentration in vaginal discharge than did previously used media. Practical diagnostic criteria for standard clinical use are proposed. Application of such criteria should assist in clinical management of nonspecific vaginitis and in further study of the microbiologic and biochemical correlates and the pathogenesis of this mild but quite prevalent disease.

The Preterm Prediction Study: significance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

Article

Oct 1995
AM J OBSTET GYNECOL

Our purpose was to evaluate the association of bacterial vaginosis, trichomonas vaginitis, and monilial vaginitis with spontaneous preterm birth at < 35 weeks 0 days. A total of 2929 women at 10 centers were studied at 24 and 28 weeks' gestation by Gram stain of vaginal smear, wet mount, and 10% potassium hydroxide preparations to detect vaginal infections. The rates of detected infection at 24 and 28 weeks, respectively, were bacterial vaginosis 23.4% and 19.4%, trichomonas 3.3% and 2.7%, and monilia 21.1% and 19.5%. The occurrence of bacterial vaginosis at 28 weeks was associated with an increased risk of spontaneous preterm birth, odds ratio 1.84 (95% confidence interval 1.15 to 2.95, p < 0.01). Detection of Trichomonas vaginalis (by wet mount) or monilia (by potassium hydroxide preparation) had no significant associations with preterm birth. The presence of bacterial vaginosis at 28 weeks' gestation is associated with an increased risk of spontaneous preterm birth.

Association between Bacterial Vaginosis and Preterm Delivery of a Low-Birth-Weight Infant. The Vaginal Infections and Prematurity Study Group

Article

Jan 1996

Bacterial vaginosis is believed to be a risk factor for preterm delivery. We undertook a study of the association between bacterial vaginosis and the preterm delivery of infants with low birth weight after accounting for other known risk factors. In this cohort study, we enrolled 10,397 pregnant women from seven medical centers who had no known medical risk factors for preterm delivery. At 23 to 26 weeks' gestation, bacterial vaginosis was determined to be present or absent on the basis of the vaginal pH and the results of Gram's staining. The principal outcome variable was the delivery at less than 37 weeks' gestation of an infant with a birth weight below 2500 g. Bacterial vaginosis was detected in 16 percent of the 10,397 women. The women with bacterial vaginosis were more likely to be unmarried, to be black, to have low incomes, and to have previously delivered low-birth-weight infants. In a multivariate analysis, the presence of bacterial vaginosis was related to preterm delivery of a low-birth-weight infant (odds ratio, 1.4; 95 percent confidence interval, 1.1 to 1.8). Other risk factors that were significantly associated with such a delivery in this population were the previous delivery of a low-birth-weight infant (odds ratio, 6.2; 95 percent confidence interval, 4.6 to 8.4), the loss of an earlier pregnancy (odds ratio, 1.7; 1.3 to 2.2), primigravidity (odds ratio, 1.6; 1.1 to 1.9), smoking (odds ratio, 1.4; 1.1 to 1.7); and black race (odds ratio, 1.4; 1.1 to 1.7). Among women with bacterial vaginosis, the highest risk of preterm delivery of a low-birth-weight infant was found among those with both vaginal bacteroides and Mycoplasma hominis (odds ratio, 2.1; 95 percent confidence interval, 1.5 to 3.0). Bacterial vaginosis was associated with the preterm delivery of low-birth-weight infants independently of other recognized risk factors.

Reduced Incidence of Preterm Delivery With Metronidazole and Erythromycin in Women With Bacterial Vaginosis

Article

Jun 1996

Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery. We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks' gestation. In 624 pregnant women at risk for delivering prematurely, vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks' gestation. We then performed a 2:1 double-blind randomization to treatment with metronidazole and erythromycin (433 women) or placebo (191 women). After treatment, the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time (a mean of 27.6 weeks' gestation). A total of 178 women (29 percent) delivered infants at less than 37 weeks' gestation. Eight women were lost to follow-up. In the remaining population, 110 of the 426 women assigned to metronidazole and erythromycin (26 percent) delivered prematurely, as compared with 68 of the 190 assigned to placebo (36 percent, P = 0.01). However, the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis (rate of preterm delivery, 31 percent with treatment vs. 49 percent with placebo; P = 0.006). Of the 358 women who did not have bacterial vaginosis when initially examined, 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely (P = 0.55). The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery (preterm delivery in the treatment group, 39 percent; and in the placebo group, 57 percent; P = 0.02) and in women who weighed less than 50 kg before pregnancy (preterm delivery in the treatment group, 14 percent; and in the placebo group, 33 percent; P = 0.04). Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery.

Abnormal bacterial colonisation of the genital tract and subsequent pretenn delivery and late miscamage

Article

Jan 1994

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.

Bacterial vaginosis and prematurity in Indonesia: Association in early and late pregnancy

Article

Jul 1993
AM J OBSTET GYNECOL

Our objective was to examine the association between preterm delivery and bacterial vaginosis in early and late pregnancy. We evaluated 490 pregnant women at three hospitals in Jakarta, Indonesia, for bacterial vaginosis at 16 to 20 weeks' and 28 to 32 weeks' gestation and observed them through delivery. We found significant associations between preterm delivery (gestational age < 37 weeks) and bacterial vaginosis diagnosed at 16 to 20 weeks' gestation (odds ratio 2.0, 95% confidence interval 1.0 to 3.9) but not with bacterial vaginosis diagnosed at 28 to 32 weeks' gestation (odds ratio 1.5, 95% confidence interval 0.7 to 3.0). The rates of preterm delivery were almost doubled for women who had bacterial vaginosis in early pregnancy (20.5%) as compared with women who had bacterial vaginosis only in late pregnancy (10.7%). Only bacterial vaginosis diagnosed early in the second trimester of pregnancy

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

Abstract

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