Genital Mycoplasmas and Biomarkers of Inflammation and Their Association With Spontaneous Preterm Birth and Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis

Nathalia M Noda-Nicolau; Ourlad Alzeus G Tantengco; Jossimara Polettini; Mariana C Silva; Giovana F C Bento; Geovanna C Cursino; Camila Marconi; Ronald F Lamont; Brandie D Taylor; Márcia G Silva; Daniel Jupiter; Ramkumar Menon

doi:10.3389/fmicb.2022.859732

Genital Mycoplasmas and Biomarkers of Inflammation and Their Association With Spontaneous Preterm Birth and Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis

Front Microbiol. 2022 Mar 30:13:859732. doi: 10.3389/fmicb.2022.859732. eCollection 2022.

Affiliations

¹ Department of Pathology, Botucatu Medical School, Universidade Estadual Paulista, Botucatu, Brazil.
² Division of Basic and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States.
³ Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines.
⁴ Graduate Program in Biomedical Sciences, Universidade Federal da Fronteira Sul, Passo Fundo, Brazil.
⁵ Department of Basic Pathology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil.
⁶ Research Unit of Gynaecology and Obstetrics, Department of Gynecology and Obstetrics, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁷ Division of Surgery, Northwick Park Institute for Medical Research, University College London, London, United Kingdom.
⁸ Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, United States.

Abstract

Genital mycoplasmas (GM), such as Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum, and Ureaplasma urealyticum are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of membranes (PPROM). This study determined the association between GM and such adverse pregnancy outcomes. We searched for studies published 1980-2019 in MEDLINE, EMBASE, and Web of Science. Studies were eligible when GM was detected during pregnancy. We included 93 and 51 studies in determining the prevalence and the inflammatory biomarkers associated with GM, respectively, using the "metafor" package within R. The protocol was registered with PROSPERO (registration no. CRD42016047297). Women with the studied adverse pregnancy outcomes had significantly higher odds of presence with GM compared to women who delivered at term. For PTB, the odds ratios were: M. hominis (OR: 2.25; CI: 1.35-3.75; I ²: 44%), M. genitalium (OR: 2.04; CIL 1.18-3.53; I ²: 20%), U. parvum (OR: 1.75; CI: 1.47-2.07; I ²: 0%), U. urealyticum (OR: 1.50; CI: 1.08-2.07; I ²: 58%). SPTL had significantly higher odds with M. hominis (OR: 1.96; CI: 1.19-3.23; I ²: 1%) or U. urealyticum (OR: 2.37; CI: 1.20-4.70; I ²: 76%) compared to women without SPTL. Women with PPROM had significantly higher odds with M. hominis (OR: 2.09; CI: 1.42-3.08; I ²: 0%) than women without PPROM. However, our subgroup analysis based on the diagnostic test and the sample used for detecting GM showed a higher prevalence of GM in maternal samples than in fetal samples. GM presence of the cervix and vagina was associated with lower odds of PTB and preterm labor (PTL). In contrast, GM presence in the AF, fetal membrane, and placenta was associated with increased odds of PTB and PTL. However, genital mycoplasmas may not elicit the massive inflammation required to trigger PTB. In conclusion, GM presence in the fetal tissues was associated with significantly increased odds of PTB and PTL.

Keywords: Mycoplasma species; Ureaplasma species; inflammatory cytokines; pregnancy; pregnancy adverse outcomes; preterm birth.

Publication types

Review