Comparison of MMP-3, MMP-9, TIMPs levels and MMP:TIMPs ratios in maternal serum among groups.

<p>Results are expressed as median (interquartile range) (ng/ml), group differences were evaluated with the Mann-Whitney <i>U</i>-test.</p><p>PTB, preterm birth; PT, preterm; AT, at term; NS, not significant.</p>$<p>Unadjusted P values and Bonferroni-adjusted P values (adjusted for 11 tests) between brackets.</p

Serum sTREM-1 concentrations among groups.

<p>Median sTREM-1 concentrations are significantly elevated in women in labor (either term or preterm) vs. non-laboring controls. sTREM-1 levels are significantly higher in preterm vs. term labor. Horizontal bars denote the median value for each study group.</p

Overview of studies included in meta-analysis BV – CIN.

**<p>Incidence study.</p><p>Abbreviations: CIN =  Cervical Intraepithelial Neoplasia, Hist =  Histology, Cyt =  Cytology, LSIL =  Low-grade Squamous Intraepithelial Lesion, HSIL =  High-grade Intraepithelial Lesion, BV =  Bacterial Vaginosis, Mod Amsel =  Modified Amsel criteria.</p><p>Participants: referred (women referred to colposcopy clinic because of abnormal Pap-smear), attendees (women attending family planning or obstetrics and gynaecology clinics), screened (population sample, screening), mix (referred, attendees and/or screened); two studies include HIV-infected women.</p

Box plots according to BV diagnostic criteria and study population.

<p>Each box plot represents a summary of 5 data: 25th and 75th percentile or inter-quartile range of the data (left and right edge of box, respectively), the median (vertical band near the middle of the box), the minimum and maximum data value (ends of horizontal lines or whiskers). Full horizontal lines represent OR and its 95% CI according to BV diagnosis (left) and stratified by study population (right), estimated by random effects regression model. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045201#pone-0045201-g004" target="_blank"><i><u>Figure 4a</u></i>:</a> Difference in odds ratio (logarithmic scale) depending on BV diagnostic criteria: Clue cells only (one study using Modified Amsel, i.e. presence of clue cells and positive amine whiff test) versus more stringent criteria (strict), including Nugent and Amsel. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045201#pone-0045201-g004" target="_blank"><i><u>Figure 4b</u></i>:</a> Difference in odds ratios (logarithmic scale) depending on study population, stratified as screened women and women with an indication smear (e.g. referred for colposcopy or obstetric/gynaecologic clinic attendees). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045201#pone-0045201-g004" target="_blank"><i><u>Figure 4c:</u></i></a> Difference in odds ratio (logarithmic scale) depending on CIN diagnostic criteria: Cytology versus Histology. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045201#pone-0045201-g004" target="_blank"><i><u>Figure 4d:</u></i></a> Difference in odds ration (logarithmic scale) depending on developing state of the country, stratified as developing and industrialized.</p

Overview of Dutch studies using the KOPAC system.

**<p>Incidence study.</p><p>Abbreviations: CL =  Cervical Lesions, Cyt =  Cytology, P =  Plaveiselcelepitheel (KOPAC system), LSIL =  Low-grade Squamous Intraepithelial Lesion, HSIL =  High-grade Intraepithelial Lesion, BV =  Bacterial Vaginosis.</p

Baseline characteristics and obstetric outcome of the study population (n = 166).

<p>Me, Median; IQR, interquartile range; BMI, body mass index; GA, gestational age; PTB, preterm birth; AT, at term.</p><p>Group differences were evaluated with Fisher’s Exact test for categorical variables and Mann-Whitney <i>U</i>-test for continuous variables.</p

Box plots showing the difference in BV prevalence depending on BV diagnostic criteria (Amsel, Clue cells only and Nugent).

<p>Comparison between data distribution (box plots) and estimated average (full vertical line).</p

Vaginal microbiota communities identified by clustering techniques in 17 articles.

<p>qPCR = quantitative polymerase chain reaction.</p>1<p>Includes direct sequencing (next generation sequencing) of DNA extracted from vaginal samples (10), sequencing of culture colonies (2), fingerprinting (3), and qPCR (2); the 5 studies using DNA hybridisation techniques did not employ data clustering and this technique is therefore not represented in this table.</p>2<p>One qPCR study only assessed <i>L. iners</i> and the other qPCR study did not find clusters dominated by just one <i>Lactobacillus</i> species.</p>3<p>Other than <i>Lactobacillus</i> spp., the 25 most abundant taxa in the 10 direct sequencing studies consistently (in at least 50% of studies) include: <u>Phylum Actinobacteria</u>: <i>G. vaginalis</i>, <i>A. vaginae</i>, <i>Eggerthella</i> spp., <i>Mobiluncus</i> spp.; <u>Phylum Fermicutes</u>: <i>Lachnospiraceae</i> (including BVAB1-3), <i>Dialister</i> spp., <i>Megasphaera</i> spp., <i>Parvimonas</i> (formerly <i>Peptostreptococcus</i>) spp., <i>Veillonella</i> spp., <i>Streptococcus</i> spp., <i>Staphylococcus,</i> spp., <i>Gemella</i> spp.; <u>Phylum Sfingobacteria</u>: <i>Prevotella</i> spp., <i>Porphyromonas</i> spp., <i>Bacteroides</i> spp.; <u>Phylum Fusobacteria</u>: <i>Sneathia</i> spp., <i>Leptotrichia</i> spp.; <u>Phylum Tenericutes</u>: <i>Mycoplasma</i> spp., <i>Ureaplasma</i> spp.; <u>Phylum Proteobacteria</u>: <i>Escherichia/Shigella</i> spp.</p>4<p>Includes <i>Streptococcus</i> spp., <i>Staphylococcus</i> spp., <i>Escherichia/Shigella</i> spp., <i>Proteus</i> spp.</p

Forest plot of studies included in meta-analysis BV – CIN.

<p>Each study is represented by a black square and a horizontal line, which corresponds to the odds ratio (OR) and its symmetric 95% confidence interval (CI). The area of the square reflects the weight each study contributes to the meta-analysis. The diamond at the bottom of the graph represents the combined OR and its 95% CI, calculated using a random effects model. The solid vertical line corresponds to no association (OR 1.0), the dotted vertical line to the combined OR (1.51). The OR (or estimates ES), 95% CI and weights are also given in tabular form.</p

Characteristics of molecular vaginal microbiota articles published between 1 January 2008 and 15 November 2013.

<p>BV = bacterial vaginosis; DGGE = Denaturing Gradient Gel Electrophoresis; HIV = human immunodeficiency virus; HPV = human papillomavirus; IVF = in-vitro fertilisation; LH-PCR = Length Heterogeneity PCR; NGS = next generation sequencing; qPCR = quantitative polymerase chain reaction; Randomly Amplified Polymorphic DNA (RAPD); STD clinic = sexually transmitted disease clinic; STI = sexually transmitted infection; TRLFP = Terminal Restriction Fragment Length Polymorphism; USA = United States of America; VMB = vaginal microbiota; WSW = women having sex with women.</p>1<p>Until 15 November 20131;</p>2<p>One article could include more than one category;</p>3<p>Europe other: Sweden (4), Greenland (1), Estonia (1), Austria (1);</p>4<p>Asia other: Japan (2), South Korea (1);</p>5<p>East Africa: Kenya (3), Tanzania (1);</p>6<p>West Africa: Burkina Faso (1), Ghana, Togo, Guinea and Mali (1);</p>7<p>Central America: Mexico (2), Costa Rica (1);</p>8<p>5 publications representing only 3 studies;</p>9<p>Genes sequenced: 16S rRNA gene V1–V2 (8), V2–V3 (2), V3 (2), V3–V5 (3), V4–V6 (2), V6 (2), V6–V9 (1), chaperonin gene (1), and not reported (1);</p>10<p>Fingerprinting techniques used: TRFLP (5), DGGE (5), RAPD (2), and LH-PCR (1);</p>11<p>Hybridisation techniques used: DNA microarray (4) and Luminex (oligonucleotides coupled to beads; 1);</p>12<p>Descriptive other includes effects of race/ethnicity, pregnancy, menstrual cycle, menopause, tampon/pad use, vaginal douching, sexual debut and other sexual and contraceptive behaviours;</p>13<p>Cervical or endometrial microbiota (3) and oral and/or rectal reservoirs (3);</p>14<p>Other confirmed infections: Candidiasis (2), cervicitis (1), endometritis (1), and gingivitis (1).</p