Vulvovaginal yeast infections during pregnancy and perinatal outcomes: systematic review and meta-analysis

(2023) 23:116 Gigi et al. BMC Women’s Health https://doi.org/10.1186/s12905-023-02258-7 BMC Women’s Health Open Access RESEARCH Vulvovaginal yeast infections during pregnancy and perinatal outcomes: systematic review and meta‑analysis Ranjana M. S. Gigi1,2,3, Diana Buitrago‑Garcia1,4, Katayoun Taghavi1, Cara‑Mia Dunaiski5, Janneke H. H. M. van de Wijgert6, Remco P. H. Peters2,7,8 and Nicola Low1* Abstract Background Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse pregnancy outcomes. Symptomatic yeast infections are likely to cause more inflam‑ mation than asymptomatic. The objective of this study was to investigate associations between symptomatic and asymptomatic vulvovaginal yeast infections in pregnancy and perinatal outcomes. Methods We did a systematic review and searched eight databases until 01 July 2022. We included studies reporting on pregnant women with and without laboratory confirmed vulvovaginal yeast infection and preterm birth or eight other perinatal outcomes. We used random effects meta-analysis to calculate summary odds ratios (OR), 95% confi‑ dence intervals (CI) and prediction intervals for the association between yeast infection and outcomes. We described findings from studies with multivariable analyses. We assessed the risk of bias using published tools. Results We screened 3909 references and included 57 studies. Only 22/57 studies reported information about participant vulvovaginal symptoms. Preterm birth was an outcome in 35/57 studies (49,161 women). In 32/35 stud‑ ies with available data, the summary OR from univariable analyses was 1.01 (95% CI 0.84–1.21, I2 60%, prediction interval 0.45–2.23). In analyses stratified by symptom status, we found ORs of 1.44 (95% CI 0.92–2.26) in two studies with ≥ 50% symptomatic participants, 0.84 (95% CI 0.45–1.58) in seven studies with < 50% symptomatic participants, and 1.12 (95% CI 0.94–1.35) in four studies with asymptomatic participants. In three studies with multivariable analysis, adjusted ORs were greater than one but CIs were compatible with there being no association. We did not find asso‑ ciations between vulvovaginal yeast infection and any secondary outcome. Most studies were at high risk of bias in at least one domain and only three studies controlled for confounding. Conclusions We did not find strong statistical evidence of an increased risk for preterm birth or eight other adverse perinatal outcomes, in pregnant women with either symptomatic or asymptomatic vulvovaginal yeast infection. The available evidence is insufficient to make recommendations about testing and treatment of vulvovaginal yeast infec‑ tion in pregnancy. Future studies should assess vulvovaginal symptoms, yeast organism loads, concomitant vaginal or cervical infections, and microbiota using state-of-the-art diagnostics. Systematic review registration PROSPERO CRD42020197564 Keywords Vaginal candida, Vaginal yeast, Pregnancy, Preterm birth, Adverse perinatal outcomes, Systematic review *Correspondence: Nicola Low Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Gigi et al. BMC Women’s Health (2023) 23:116 Background Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse perinatal outcomes [1]. Preterm birth is the most common cause of neonatal death worldwide [2]. The causes of preterm birth include socio-economic factors, underlying maternal conditions, foetal conditions, and infectious causes [3]. Infectious causes include upper, and possibly lower, genital tract infections [4], with some evidence that early preterm birth is more commonly infection-related than late preterm birth [5]. Vulvovaginal yeast infections caused by Candida species, are more common in pregnant women than non-pregnant women [1, 6, 7], potentially because of hormonal and immunological changes that occur during pregnancy [8]. It is not known whether yeast organism loads are higher in pregnant than non-pregnant women or whether they are associated with levels of inflammation or adverse perinatal outcomes [9]. Microorganisms in the female genital tract may have direct pathogenic effects in pregnancy through infection of the amniotic cavity and/or through stimulating inflammatory cascades [4]. Besides prostaglandins, chemokines and pro-inflammatory cytokines can ripen the cervix and induce contractions [10]. These pathways may be activated by infections during pregnancy and lead to preterm birth [10]. Yeast infections in the female genital tract cause inflammation and therefore increase proinflammatory mediators in the vaginal fluid, such as interleukin-8, which have been associated with preterm birth [11, 12]. A systematic review reporting on studies of asymptomatic Candida colonization published up to May 2020 did not find an association with adverse pregnancy outcomes [13]. Symptomatic yeast infections are likely to cause more inflammation than asymptomatic infection, however. The objective of this study was to investigate associations between both symptomatic and asymptomatic vulvovaginal yeast infections in pregnancy and preterm birth and other perinatal outcomes. Methods We did a systematic review and registered the protocol in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42020197564). We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines for reporting the review [14]. Search strategy We searched Medline (Ovid), PubMed, Embase (Ovid), the Cochrane Library, CINAHL, African Index Medicus, LILACS and ClinicalTrials.gov (Supplementary search strategy, Additional File 1) from inception until 01 July Page 2 of 12 2022 without language restrictions. Additional studies were retrieved by checking reference lists of relevant a (...truncated)