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Adverse pregnancy and neonatal outcomes associated with Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum: a systematic review and meta-analysis protocol.

ABSTRACT: INTRODUCTION:Several bacterial sexually transmitted and genital mycoplasma infections during pregnancy have been associated with poor pregnancy and perinatal outcomes. Comprehensive and systematic information about associations between sexually transmitted infections (STI) and genital infections in pregnancy and adverse perinatal outcomes is needed to improve understanding about the evidence for causal associations between these infections and adverse pregnancy and neonatal outcomes. Our primary objective is to systematically review the literature about associations between: (1) Neisseria gonorrhoeae in pregnancy and preterm birth; (2) Mycoplasma genitalium in pregnancy and preterm birth; (3) M. hominis, Ureaplasma urealyticum and/or U. parvum in pregnancy and preterm birth. METHODS AND ANALYSIS:We will undertake a systematic search of Medline, Excerpta Medica database and the Cochrane Library and Cumulative Index to Nursing and Allied Health Literature. Following an initial screening of titles by one reviewer, abstracts will be independently assessed by two reviewers before screening of full-text articles. To exclude a manuscript, both reviewers need to agree on the decision. Any discrepancies will be resolved by discussion, or the adjudication of a third reviewer. Studies will be included if they report testing for one or more of N. gonorrhoeae, M. genitalium, M. hominis, U. urealyticum and/or U. parvum during pregnancy and report pregnancy and/or birth outcomes. In this review, the primary outcome is preterm birth. Secondary outcomes are premature rupture of membranes, low birth weight, spontaneous abortion, stillbirth, neonatal mortality and ophthalmia neonatorum. We will use standard definitions, or definitions reported by study authors. We will examine associations between exposure and outcome in forest plots, using the I2 statistic to examine between study heterogeneity. Where appropriate, we will use meta-analysis to combine results of individual studies. ETHICS AND DISSEMINATION:This systematic review of published literature does not require ethical committee approval. Results of this review will be published in a peer reviewed, open access journal. PROSPERO REGISTRATION NUMBER:CRD42016050962.

SUBMITTER: Vallely LM

PROVIDER: S-EPMC6278811 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Adverse pregnancy and neonatal outcomes associated with <i>Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum:</i> a systematic review and meta-analysis protocol.

Vallely Lisa M LM Egli-Gany Dianne D Pomat William W Homer Caroline Se CS Guy Rebecca R Wand Handan H Silver Bronwyn B Rumbold Alice R AR Kaldor John M JM Low Nicola N Vallely Andrew J AJ

BMJ open 20181128 11

<h4>Introduction</h4>Several bacterial sexually transmitted and genital mycoplasma infections during pregnancy have been associated with poor pregnancy and perinatal outcomes. Comprehensive and systematic information about associations between sexually transmitted infections (STI) and genital infections in pregnancy and adverse perinatal outcomes is needed to improve understanding about the evidence for causal associations between these infections and adverse pregnancy and neonatal outcomes. Our ...[more]

PMID: 30498048

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Project description:BACKGROUND: Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA) are sexually transmitted bacteria among humans implicated in a variety of disease states including but not limited to: nongonococcal urethritis, infertility, adverse pregnancy outcomes, chorioamnionitis, and bronchopulmonary dysplasia in neonates. There are 10 distinct serotypes of UUR and 4 of UPA. Efforts to determine whether difference in pathogenic potential exists at the ureaplasma serovar level have been hampered by limitations of antibody-based typing methods, multiple cross-reactions and poor discriminating capacity in clinical samples containing two or more serovars. RESULTS: We determined the genome sequences of the American Type Culture Collection (ATCC) type strains of all UUR and UPA serovars as well as four clinical isolates of UUR for which we were not able to determine serovar designation. UPA serovars had 0.75-0.78 Mbp genomes and UUR serovars were 0.84-0.95 Mbp. The original classification of ureaplasma isolates into distinct serovars was largely based on differences in the major ureaplasma surface antigen called the multiple banded antigen (MBA) and reactions of human and animal sera to the organisms. Whole genome analysis of the 14 serovars and the 4 clinical isolates showed the mba gene was part of a large superfamily, which is a phase variable gene system, and that some serovars have identical sets of mba genes. Most of the differences among serovars are hypothetical genes, and in general the two species and 14 serovars are extremely similar at the genome level. CONCLUSIONS: Comparative genome analysis suggests UUR is more capable of acquiring genes horizontally, which may contribute to its greater virulence for some conditions. The overwhelming evidence of extensive horizontal gene transfer among these organisms from our previous studies combined with our comparative analysis indicates that ureaplasmas exist as quasi-species rather than as stable serovars in their native environment. Therefore, differential pathogenicity and clinical outcome of a ureaplasmal infection is most likely not on the serovar level, but rather may be due to the presence or absence of potential pathogenicity factors in an individual ureaplasma clinical isolate and/or patient to patient differences in terms of autoimmunity and microbiome.

Project description:Background and purposeLactobacilli play a vital role in protecting the vagina against pathogens. Cytokines are vital components of defense against infections in women. The genital mycoplasmas, Mycoplasma genitalium and Ureaplasma urealyticum, are associated with various infectious diseases in adults and infants. The objective of our study is to identify differences in cytokine profile and Lactobacillus species dominance between a study group of non-pregnant pre-menopausal women with genital M. genitalium or U. urealyticum colonization and a control group of non-pregnant pre-menopausal women without genital M. genitalium or U. urealyticum colonization.MethodsA real-time polymerase chain reaction was performed to measure Lactobacillus species in vaginal swab samples. Cytokine analysis was performed using multiplex immunoassay techniques. Analysis of variance confirmed a significant difference in cytokine profiles between patient groups, with t-tests identifying the most significantly different cytokines. Categorical data analysis identified significant patterns of relative Lactobacillus species dominance in the study group.ResultsLactobacillus iners was the predominant Lactobacillus species in the control group (p = 0.005). There were no dominant Lactobacillus species observed in the study group. Vascular endothelial growth factor A (p = 0.002), interleukin-8 (p = 0.001), and interleukin-1β (p = 0.049) were expressed significantly higher in the study group, whereas interleukin-1 receptor antagonist (p < 0.001), interleukin-10 (p = 0.001), interleukin-12 (p = 0.002), and interferon-γ (p = 0.022) were expressed higher in the control group. Association matrices for cytokines were significantly different between two groups (p < 0.001), with mostly negative associations in the control group and mostly positive associations in the study group.ConclusionCytokine levels, their associations, and the patterns of Lactobacillus species dominance are observed to significantly diverge on the basis of M. genitalium and U. urealyticum colonization among non-pregnant pre-menopausal women.

Dataset Information

Adverse pregnancy and neonatal outcomes associated with Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum: a systematic review and meta-analysis protocol.

Publications

Adverse pregnancy and neonatal outcomes associated with <i>Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum:</i> a systematic review and meta-analysis protocol.

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