Interactive effects of bacterial vaginal colonization and HIV on pregnancy outcomes: A Systematic Review and Meta-analysis

Interactive effects of bacterial vaginal colonization and HIV on pregnancy outcomes: A Systematic Review and Meta-analysis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 25 February 2025 V1 Latest version Share on Interactive effects of bacterial vaginal colonization and HIV on pregnancy outcomes: A Systematic Review and Meta-analysis Authors : Dismas Matovelo 0000-0003-1048-6166 [email protected] , Quinn Goddard , Paul Sabuni , Benson Kidenya , Jennifer Downs , Moke Magoma , Jeremiah Seni , and Katie Chaput Authors Info & Affiliations https://doi.org/10.22541/au.174047959.93494344/v1 175 views 116 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: HIV and lower genital tract bacterial colonization independently have documented associations with pregnancy outcomes, which is compounded by rapidly escalating antimicrobial resistance. Objectives: To determine interactive effects of HIV and bacterial colonization on low birthweight and preterm birth. Search Strategy: To identify relevant studies, we systematically searched databases (Medline, Embase, CINAHL, Scopus, Web of Science, Cochrane Library, and African Journals Online) from inception until December 2023. Selection criteria: we included observational studies that reported on pregnancy outcomes stratified by vaginal colonization and HIV status. Data collection and analysis: Meta-analysis was conducted using random-effects modelling, reported as pooled log-odds ratios. Main results: We included 13 studies in which 5,807 were identified. The pooled prevalence of bacterial colonization was 26%(95%CI:17.3-37.4). There was no significant effect of HIV status and vaginal colonization on birth weight(OR:1.2; 95%CI: −2.57, 2.20) but borderline increased odds of preterm birth(OR:2.64; 95%CI:−0.01,1.94, p =0.05). There were no significant associations between HIV and bacterial colonization(OR:1.08; 95%CI:−0.91,1.07) nor in antimicrobial resistance between pregnant women with HIV and those without. Conclusions: Bacterial colonization is prevalent among pregnant women, but there is no clear evidence to suggest that HIV and lower genital tract bacterial colonization interact to affect birth weight or preterm birth. Research with large sample sizes, strict selection criteria, reliable/valid measurement, and adequate control for confounding variables, with birthweight and gestational age as continuous outcomes, are still needed to provide robust evidence. Funding: NIH-Fogarty International; D43 Research Training Grant to CUHAS and Global Affairs-Canada; Study in Canada Scholarship provided financial support. Keywords: vaginal bacterial colonization, HIV, adverse pregnancy outcomes, preterm birth, low birth weight. Interactive effects of bacterial vaginal colonization and HIV on pregnancy outcomes: A Systematic Review and Meta-analysis Dismas Matovelo 1* , Quinn Goddard 2 , Paul Sabuni 1 , Benson Kidenya 1 , Jennifer Downs 1,3 , Moke Magoma 4 , Jeremiah Seni 1 , Kathleen Helen Chaput 2 1 Catholic University of Health and Allied Sciences, Weill Bugando School of Medicine, Mwanza, Tanzania. 2 University of Calgary, Cumming School of Medicine, Calgary, Canada 3 Center for Global Health, Weill Cornell Medicine, New York, USA 4 Engender Health, Dar es Salaam, Tanzania Corresponding author: Dismas Matovelo; E-mail: [email protected] Abstract Background: HIV and lower genital tract bacterial colonization independently have documented associations with pregnancy outcomes, which is compounded by rapidly escalating antimicrobial resistance. Objectives: To determine interactive effects of HIV and bacterial colonization on low birthweight and preterm birth. Search Strategy: To identify relevant studies, we systematically searched databases (Medline, Embase, CINAHL, Scopus, Web of Science, Cochrane Library, and African Journals Online) from inception until December 2023. Selection criteria: we included observational studies that reported on pregnancy outcomes stratified by vaginal colonization and HIV status. Data collection and analysis: Meta-analysis was conducted using random-effects modelling, reported as pooled log-odds ratios. Main results: We included 13 studies in which 5,807 were identified. The pooled prevalence of bacterial colonization was 26%(95%CI:17.3-37.4). There was no significant effect of HIV status and vaginal colonization on birth weight(OR:1.2; 95%CI: −2.57, 2.20) but borderline increased odds of preterm birth(OR:2.64; 95%CI:−0.01,1.94, p =0.05). There were no significant associations between HIV and bacterial colonization(OR:1.08; 95%CI:−0.91,1.07) nor in antimicrobial resistance between pregnant women with HIV and those without. Conclusions: Bacterial colonization is prevalent among pregnant women, but there is no clear evidence to suggest that HIV and lower genital tract bacterial colonization interact to affect birth weight or preterm birth. Research with large sample sizes, strict selection criteria, reliable/valid measurement, and adequate control for confounding variables, with birthweight and gestational age as continuous outcomes, are still needed to provide robust evidence. Funding: NIH-Fogarty International; D43 Research Training Grant to CUHAS and Global Affairs-Canada; Study in Canada Scholarship provided financial support. Keywords: vaginal bacterial colonization, HIV, adverse pregnancy outcomes, preterm birth, low birth weight. INTRODUCTION Lower genital tract bacterial colonization (LGTBC) is usually polymicrobial, affecting up to 50% of women during pregnancy, intrapartum, and postpartum, and varying across trimesters due to hormonal changes, host genetics, behaviour, nutrition, and environment 1-3[] . Vaginal bacterial composition during gestation typically remains relatively stable among pregnant women not living with HIV 4[] . In contrast, the increase in pro-inflammatory responses and the release of cytokines associated with HIV, disrupt the integrity of the vaginal mucosal epithelium. This loss in integrity results in the vaginal mucosa of HIV-infected pregnant women being characterized by a diverse microbiota predominantly comprised of anaerobic species 3[] . Accordingly, studies have reported a higher prevalence of LGTBC among pregnant women with HIV 5[] . However, others report no differences 6-8[] . Estimates of the burden of LGTBC during pregnancy, regardless of HIV status, vary widely, with prevalences from 1.5-73.5% 910[, ] . Over the past decade, it has become clear that although a healthy placenta has no microbiome, it is still susceptible to pathogenic colonization, commonly GBS 11[] . Placental bacterial colonization can affect placental development and function, impacting fetal growth and development. Disrupted placental function can lead to SGA, IUGR, preterm labour and birth, rupture of membranes (ROM), chorioamnionitis, neonatal sepsis, and low birthweight (LBW) 1112[, ] . These factors contribute to a series of short and long-term adverse effects such as neonatal sepsis and delayed child developmental milestones 1112[, ] . The impact of bacterial colonization in pregnancy is disproportionately felt in Low-Middle Income Countries (LMICs)—while optimizing surveillance and treatment in high-income countries (HICs) has recently significantly reduced occurrence of LGTBC in pregnancy 13[] , such routine surveillance is lacking in most LMICs. The rapidly escalating antimicrobial resistance (AMR) burden has complicated empirical treatment in LMICs1415[, ]. The burden of HIV is also disproportionately felt in LMICs, with approximately 70% of people living with HIV in sub-Saharan Africa 1617[, ] . LBW and PTB globally affected an estimated 19.8 and 13.4 million births in 2020, respectively, with increased mortality risks, particularly in the neonatal period, and long-term adverse health outcomes throughout life 121819[, ] . However, there is a paucity of evidence on the association between HIV infection, LGTBC and birth outcomes. To bridge this knowledge gap, we performed a systematic review and meta-analysis to quantitatively assess the prevalence of LGTBC and their association with pregnancy outcomes in HIV-infected and HIV-uninfected individuals. We hypothesize that concurrent HIV infection and LGTBC will increase the odds of unfavourable pregnancy outcomes (e.g., PTB, LBW). METHODS Objective The current review examined the interactive effects of LGTBC and HIV infection during pregnancy on birthweight and preterm birth, intrauterine growth restriction (IUGR), and small for gestation age (SGA). As a secondary outcome, we assessed the prevalence of antimicrobial resistance (AMR) among HIV-infected vs -uninfected pregnant women. This review followed PRISMA guidelines (Appendix 1)20[] and was registered with PROSPERO 21[] (CRD42023485123). Search Strategy A comprehensive search strategy was developed in consultation with a health sciences research librarian and reviewed by two perinatal researchers (Appendix 2). Our controlled vocabulary search included the following exploded keywords: Vaginitis, ”Genital Diseases, Female”, ”Reproductive Tract Infections”, vagina, bacteria, Escherichia coli, ”Klebsiella pneumoniae”, ”streptococcal infections”, HIV, HIV Seropositivity, HIV Infections, HIV Seronegativity, Pregnancy, Pregnant Women, Pregnancy Trimester, Third, and pregnancy outcome . We applied the search strategy in MEDLINE (Ovid), EMBASE (Ovid), CINAHL, Scopus, Web of Science and the Cochrane Library, African Journals Online, and PubMed to identify studies up until December 31, 2023, with no restrictions on language. Web of Science, Google and Google Scholar were used to search for grey literature. We modified indexing terms such as Medical Subject Headings (MESH) or field tags according to each database and linked terms using “AND” and “OR” Boolean operator terms. We hand-searched by scanning references, “cited-by”, and “similar articles” lists for eligible studies. No filters were applied. Eligibility criteria We included any original, quantitative, observational studies in peer-reviewed journals that reported on LGTBC and HIV status in the context of our target pregnancy outcomes (LBW, PTB, IUGR, SGA) and/or AMR of bacterial isolates obtained during pregnancy. Specifically, eligible studies involved pregnant women of any age tested for LGTBC at any point during their gestation. Studies must have had an exposure arm with pregnant women with HIV infection and a control arm with those without HIV. Studies must have measured birth weight and/or preterm birth as a pregnancy outcome to document the differences in associations between LGTBC and birth weight among pregnant women with and without HIV. The outcomes involved aggregate counts for preterm birth (<37 weeks completed gestation) and low birth weight (<2500g). We included grey literature and published abstracts in the review’s narrative summary. Study selection We used Covidence to collate our initial search results and remove duplicates before screening. Two independent authors (DM and QG) screened titles and abstracts and assigned a ‘yes’, ‘no’, or ‘maybe’ to their eligibility for inclusion. Studies marked as ”yes” or ”maybe” underwent a full-text review, during which reasons for exclusion were documented. A third author (KHC) resolved any conflicts in decision-making. Data Extraction and Critical Appraisal DM and QG independently extracted data using Covidence (exported into Microsoft Excel 2023). We extracted: a) first author’s name, b) publication year, c) region/country, d) study design, e) sample size, f) type of LGTBC sample collected, and g) microorganisms involved. To assess the target outcomes, we extracted the number of individuals who had the unfavourable birth outcome of interest (e.g., preterm birth) and the favourable converse (e.g., term birth), stratified by HIV and LGTBC status (regardless of microorganism due to small number of studies). Discrepancies were resolved by a third individual (KHC). If desired data were unavailable for extraction, we contacted authors thrice between January and June 2024 to obtain missing data points. Studies were excluded from the meta-analysis if the authors were unreachable or unable to share the required data. Non-English studies were evaluated using Google Translate and then extracted in consultation with a native speaker—however, no non-English studies qualified for extraction. Quality assessment We used the Newcastle-Ottawa Scale (NOS) since all eligible studies were observational 22[] . The NOS scale consists of eight sections that evaluate an article based on selection criteria, comparability, exposure assessment, and outcomes. We added topic-specific criteria to make it more relevant to an epidemiological context—specifically, we added criteria for controlling additional confounders (such as co-morbidities), defining key variables (such as LGTBC), and reporting sample, exposure, and control group details). The first (DM) and second (QG) authors performed quality assessment and verified it by the senior author (KHC). Each included study received a score corresponding to the number of quality criteria satisfied and was categorized as low (0-5), medium (6-7), and high (8-10) quality. Studies of any quality were included in the review, but only those scoring ≥6 were included in the meta-analysis. Data analysis A narrative analysis summarizes the characteristics of the included studies. We quantified the pooled interactive effect of LGTBC and HIV on pregnancy outcomes and the association between HIV and LGTBC, using random-effects maximum likelihood forest plots to calculate log-odds ratios (OR) and their corresponding 95% confidence intervals. We employed a continuity correction of 0.5 for insufficient cell sizes 23[] . We assessed heterogeneity using Cochrane’s Q value and Higgins I-squared (I 2 ), considering I 2 values of 0–40% as low, 50–70% as moderate, and >70% as high heterogeneity 22[] . We conducted all analyses using Stata version 18.0. Results We identified 5,805 identified studies (initially 7,005, 1,198 duplicates removed; Medline=981, Embase=1,137, Web of Science= 276, CINAHL=4,075, Scopus=459, Cochrane=61, and grey literature (ProQuest)=14). DM and QG screened titles and abstracts with high inter-rater agreement (proportionate agreement=0.97), deeming 5,719 irrelevant. Two additional studies were identified through hand-searching reference lists, leaving 86 studies for full-text assessment. From that, 13 studies were identified for inclusion in the systematic review (Figure S1, Table 1). All identified studies were rated as 7 or higher by the first and second authors on the NOS. No studies were excluded based on quality (Table 2). Figure 1: PRISMA flowchart diagram of the study selection Since most included studies did not report all data required for meta-analysis, we contacted the authors from all studies to request additional data. All included studies were conducted between 2006 and 2023. Four were cross-sectional, seven were cohort, and two were case-control studies. All except three were conducted in Africa. We found no other published systematic reviews on this topic. The overall sample size of all included studies was 6,073 participants, with individual study sample sizes ranging from 75 to 1,857. The prevalence of LGTBC ranged from 3.3% to 69.3% (Table 1). Testing and diagnostic criteria for LGTBC varied (Table 2). 3.1 Narrative review All identified studies measured our variables of interest; however, very few stratified the data according to our purposes. This narrative review summarizes only the results reported in the studies, and the data included in our meta-analysis was largely obtained directly from the authors upon request. Studies varied according to the association between LGTBC, HIV, and low birthweight, while Makinde et al 24[] and Gudza-Mugabe et al 25[] found no association, Nyemba et al 26[] found that LGTBC (here, C. trachomatis and N. gonorrhoea ) at the first antenatal care (ANC) visit in individuals with HIV led to an increased risk of adverse birth outcomes. Results for PTB were more consistent: Nyemba et al 26[] , Smullin et al 27[] , and Short et al 28[] all found an elevated risk of PTB in the interaction between LGTBC and HIV status. However, Gudza-Mugabe et al 25[] and Price et al 29[] found that individuals with HIV infection were more likely to give birth prematurely, regardless of vaginal microbiota, suggesting LGTBC did not modify the relationship between HIV status and PTB. Ravindran et al 30[] found that incident HIV infection, as well as LGTBC (here, C. trachomatis and N. gonorrhoeae) , all independently increased the risk of PTB. El Beitune et al 31[] found no significant difference in birth outcomes by maternal HIV status. Benedetto et al 32[] found that cervicovaginal infections (BV, C. trachomatis ) increased the chance of PTB. Foessleitner et al 33[] found that PTB birth was equally likely regardless of HIV status. Govender et al 34[] analyzed the prevalence of genital mycoplasmas, ureaplasmas, and Chlamydia trachomatis to HIV status, finding no association between HIV status and LGTBC, as well as preterm delivery and LGTBC. Several additional studies examined our variables of interest, but we could not include them due to lack of access to the original data. Zenebe et al 35[] found that mean birthweight was higher in babies born to HIV-uninfected women. Joachim et al 36[] found no significant association between infant birthweight and GBS carriage. Seale et al 37[] found that women with GBS had an equal likelihood of very PTB and very LBW. Madrid et al 38[] found that mothers with HIV were at no higher risk of GBS colonization. Morgan et al 39[] found that HIV-positive individuals had a higher chance of PTB but that the likelihood of GBS colonization did not differ by HIV status. Only two studies analyzed SGA: while Temmerman et al 40[] found mothers with HIV were more likely to give birth to SGA infants, Gudza-Mugabe et a l 25[] found no difference in SGA by maternal HIV status. None of the included studies analyzed IUGR. It is important to note that bacterial species varied across studies (i.e., GBS , C. trachomatis, N. gonorrhoeae ), potentially underpinning the differing results. 3.2 Meta-Analysis Primary Outcomes: Five studies examined low birthweight as an outcome, with an overall sample of 3,520 pregnant individuals, 784 (22.2%) of whom had LGTBC and 1,284 (36.4%) had HIV. Six studies examined preterm birth, with a total sample of 5,164 pregnant individuals, 1,356 (26.3%) of which had LGTBC and 1,372 (26.6%) had HIV. We had insufficient data to generate meaningful pooled estimates for IUGR or SGA. Low Birthweight : We observed no significant interaction between HIV status and LGTBC on low birth weight (log OR=0.19, 95%CI= -2.57,2.20, equivalent OR=1.21, p =0.88). The high heterogeneity between studies ( I 2 =88.73%; Q =19.84, p =0.00) indicates low reliability for the pooled estimate (Figure 2). Figure 2: Interactive effect of HIV and bacterial colonization on birthweight Preterm Birth: Overall, we found borderline-significant increased odds of preterm birth among individuals with HIV and LGTBC, compared to those without (log OR=0.97, 95% CI=-0.01, 1.94, p =0.05; equivalent OR: 2.64). Moderate heterogeneity was observed between the included studies ( I 2 =53.76%; Q =16.78, p =0.02), indicating moderate estimate reliability(Figure 3). The methods of calculating gestational age varied (last menstrual period, 252641[, ] ultrasound dating, 29[] fundal height, 30[] or unspecified 2728[, ] ) potentially contributing to heterogeneity. Figure 3: Interactive effect of HIV and bacterial colonization on preterm birth Heterogeneity and Publication Bias We lacked enough studies to evaluate sources of heterogeneity or publication bias effectively. Due to the relatively small number of studies and the fact that almost all data used in the review was obtained from contacting authors, publication bias was not assessed because it was underpowered. Secondary Outcome: In assessing antimicrobial resistance (AMR), we found that six different types of bacterial isolates were examined in the included studies, with the highest pooled prevalence being bacterial vaginosis (33.9%) (Table 3). All studies testing AMR evaluated GBS , facilitating meaningful pooled estimates of the association between HIV and GBS in terms of AMR. Figure 4: Association between HIV status and Bacterial Colonization There was no significant association between HIV status and LGTBC (log-OR=0.08 [-0.91, 1.07]; equivalent OR=1.08) (Figure 4). Likewise, we found no significant difference in log odds of AMR between HIV-positive and HIV-negative individuals for each antibiotic examined (Ampicillin: log-OR=0.47[-0.94, 1.87]; equivalent OR=1.60, Ceftriaxone: log-OR=0.28[-1.77, 2.33]; equivalent OR=1.32, Clindamycin: log-OR=0.48[-1.28, 2.24], equivalent OR=1.61, Erythromycin: logOR=1.14[-0.83, 3.11], equivalent OR=3.12, Penicillin: log-OR=0.42 [-0.94, 1.77], equivalent OR=1.42). Heterogeneity was low to moderate for most antibiotics, except for erythromycin (I 2 =75.79) (Figure S2:A-E). We could not pool proportions of antimicrobial resistance across antibiotic types due to aggregate reporting of AMR and lack of individual participant data. Discussion 4.1 Main findings From the 13 studies included, we found the odds of preterm birth among those with HIV and LGTBC was 2.64 times greater than those without HIV or colonization, albeit with borderline non-significance (OR:2.64, p =0.05). No significant interactive effect between HIV and vaginal bacterial colonization on low birthweight was observed (OR:1.21, p =0.88). We found a pooled prevalence of bacterial colonization of 26% (95%CI:17.3%, 37.4%) among pregnant women but no significant difference in colonization by HIV status in pregnant women (OR:1.08; 95%CI:−0.91,1.07). Similarly, no significant differences in AMR were found between those living with HIV and those without for ampicillin, ceftriaxone, clindamycin, erythromycin, or penicillin. 4.2 Strengths We found no previous systematic review or meta-analysis that assessed the potential interactive relationship between HIV status, LGTBC and LBW. One of the strengths of this study is the inclusion of studies examining direct vaginal colonization. Previous studies evaluated rectal colonization only, meaning previous evidence may include pathogens not present in the lower genital tract. Thus, it may not influence pregnancy to the same extent 4243[, ] . Although our review’s large pooled sample size ( n =6,073) and the high quality of included studies are strengths, the limited number of studies coupled with the moderate to high heterogeneity of estimates limit the reliability. 4.3 Limitations Although this systematic review and meta-analysis presents up-to-date global evidence on the prevalence of vaginal bacterial colonization and pregnancy outcomes, it is not without limitations. The majority of the included studies are from Africa, where the prevalence of HIV infection is high. Comparatively, there is a lack of studies from Asia, Europe, and North and South America. Therefore, generalizability is limited to African populations, as the overall sample does not represent a global population. Further, most included studies recruited participants and/or laboratory samples through hospitals or from mothers who presented for routine ANC or delivery at tertiary hospitals. This could skew the estimated prevalence towards urban settings and underestimate the associations in rural areas or smaller local health centres serving individuals of more vulnerable socioeconomic status. The risk of antimicrobial-resistant organisms likely differs in these tertiary hospitals compared to rural settings (e.g., people seeking care at tertiary hospitals may have greater or more frequent exposure to antibiotics). There may be some publication bias toward studies reporting elevated odds of adverse outcomes. However, our null results suggest this bias is likely minimal. 4.4 Interpretation While we found a borderline-significant increase in the odds of preterm birth, preterm birth remains a rare outcome. Therefore, even with pooling study results, we may have lacked the statistical power to assess the effect adequately. However, our findings regarding preterm birth are similar to those from previous reviews evaluating HIV status independently—for instance, Xiao et al. found an increased odds of preterm birth among individuals with HIV compared to those without 44[] . While one of the studies included in our review found a decreased risk of preterm birth in HIV-positive individuals with colonization, this finding may be attributable to the small sample size of HIV-positive participants in this study ( n =10), as well as the fact that they did not recruit based on HIV status and only happened to retain cases of HIV acquired during the study period in their originally HIV-negative cohort 30[] . Turning to low birthweight, our null finding differs from previous reviews, which have demonstrated that HIV-exposed neonates are at higher risk for GBS neonatal disease 45[] and that low birthweight is more prevalent in neonates from women living with HIV 44[] . Therefore, we were likely underpowered to detect the interactive effect. Unfortunately, we could not model the pooled effect on gestational age or birthweight outcomes as continuous variables due to data limitations. Future studies should report incidences of both continuous and categorical outcome measures to allow for a more nuanced assessment of this relationship. We observed moderate heterogeneity among our included studies. This may be due to varying patterns of pathogenic bacteria colonizing the lower genital tract, and bacterial vaginosis is a clinical syndrome caused by a group of bacterial species rather than a single pathogen. Additionally, some methodological differences in the studies could contribute to our results, including differential methods and criteria for testing for bacterial colonization among groups with and without HIV, differing methods of defining preterm birth, and selection and inclusion criteria. Further heterogeneity may stem from differences in population characteristics, study designs and geographical locations. However, we were underpowered to perform any sensitivity analyses to evaluate sources of heterogeneity. We also found that the overall odds of bacterial colonization did not differ significantly between those living with HIV and those without. This finding is congruent with a review by Cools et al., which showed no difference between HIV status and rectovaginal colonization 45[] . However, few of these studies were designed to assess the association between HIV status and bacterial colonization as a primary outcome. Future prospective cohort studies with strong selection and recruitment strategies, along with adequate confounding control in the analysis, are necessary to confirm whether HIV status impacts the odds of bacterial colonization in pregnancy. While we found no significant difference in AMR by HIV status, sample sizes were small, and a lack of individual-level data meant we could not pool across antibiotic types, limiting statistical power. Future studies should consider including measures of resistance to one or more antibiotics to allow for pooled estimates without the potential for double-counting. A meta-analysis found those with HIV were more likely to be colonized with resistant bacterial strains 46[] , it remains unclear if similar patterns persist during pregnancy. The result of this meta-analysis indicates we are in desperate need of further studies to quantify the magnitude of impact that HIV infection and LGTBC interactively have on pregnancy outcomes. Further research conducted with large sample sizes, substantial selection criteria, reliable and valid measurement, adequate control for confounding variables, and the assessment of birthweight and gestational age at delivery as continuous outcomes are desirable to strengthen the evidence in this area of research. Since LGTBC in HICs tends to be predominantly Gram-positive while in LMICs tends to be predominantly Gram-negative—more associated with neonatal sepsis and mortality—emphasizes the need for further research considering a geographical context. Further, there is still no global consensus on routine screening of pregnant women for lower genital tract pathogenic bacteria. Future research in this area would be vital in informing the development of a standardized vaginal bacterial screening during pregnancy that takes HIV status into account, which could act to improve the identification of bacterial infections and potentially reduce any associated adverse outcomes. Conclusion Bacterial colonization is prevalent among pregnant women, but there is no clear evidence to suggest that HIV and lower genital tract bacterial colonization interact to affect birth weight or preterm birth. Research with large sample sizes, strict selection criteria, reliable, valid measurement, and adequate control for confounding variables, with birthweight and gestational age as continuous outcomes, are still needed to provide robust evidence. Declaration 6.1 Author contributions DM and KHC developed the protocol and were involved in the design, selection of study, data extraction, quality assessment, statistical analysis, results interpretation and development of the initial and final drafts of the manuscript; JS, JD, and MM conceived the project, designed the study and did several reviews of the manuscripts; DM, QG and KHC were involved in screening, quality assessment, data extraction, statistical analysis and revising subsequent manuscript drafts; PS and BK were involved in data analysis, synthesis and review of the manuscript. All authors read and approved the final draft of the manuscript. 6.2 Ethical statement Ethical approval was not required since this study relied solely on published data. However, permission for publication was sought from the CUHAS/BMC Research & Ethical Committee (CREC/640/2023). 6.3 Funding NIH-Fogarty International; D43 Research Training Grant to CUHAS and Global Affairs-Canada Study in Canada Scholarship provided financial support for this project. 6.4 Competing interests Authors declare that they have no competing interests. 6.5 Data availability The data analyzed during the current systematic review and meta-analysis are available and publicised (Appendix 3). 6.6 Acknowledgements We want to thank the University of Calgary staff, particularly Sophie Petit from the Indigenous, Local & Global Health (ILGH) office and Dianne Lorenzetti from the University Library, for their assistance with developing the search strategy. We also extend our gratitude to all the authors of the studies included in this systematic review and meta-analysis. 6.7 Abbreviations AMR, Antimicrobial Resistance; AMSTAR, Assessing the Methodological Quality of Systematic Reviews; ANC, Antenatal Care; CINAHL, Cumulative Index to Nursing and Allied Health Literature; CMA, Comprehensive Meta-Analysis; CI, Confidence Interval; HICs, High-Income Countries; HIV, Human Immunodeficiency Virus; IUGR, Intrauterine Growth restrictions; LBW, Low Birth Weight; LMICs, Low-Middle Income Countries; MESH, Medical Subject Headings; OR, Odds ratio; NIH, National Institutes of Health; NOS, New Castle-Ottawa Scale; PCR, Polymerase Chain Reaction; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SGA, Small for Gestation; SD-Standard Deviation; SSA, Sub-Saharan Africa. References 1. 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Table 1: Characteristics of the included studies HIV+ n (%) HIV- n (%) 1 Madrid., et al 38[] 2018 Mozambique Cohort 320 117(36.6) 203(64.4) 120(37.5) 32.3%-42.9% GBS & E. coli 2 Nyemba., et al 26[] 2022 South Africa Cohort 619 486(78.5) 133(21.5) 198(32.0) 27.6%-34.9% Chlamydia trachomatis, Neisseria gonorrhoea 3 Gudza-Mugabe., et al 25[] 2020 Zimbabwe Cohort 356 42(11.8) 314(88.2) 88(24.7) 20.4%-29.3% Bacterial vaginosis 4 Njoku., et al 47[] 2018 Nigeria Cross-sectional 168 84(50.0) 84(50.0) 18(10.7) 6.4%-15.9% Group B Streptococcus 5 Price., et al 29[] 2021 Zambia Cohort 363 85(23.4) 278(76.6) 221(60.9) 55.8%-65.8% Bacterial vaginosis 6 Biobaku., et al 48[] 2017 Nigeria Cross-sectional 198 67(33.8) 131(66.2) 36(18.2) 13.1%-23.9% Group B Streptococcus 7 Smullin., et al 27[] 2020 South Africa Cohort 197 92(46.7) 105(53.3) 35(17.8) 12.7%-23.4% Mycoplasma genitalium 8 Short., et al 28[] 2020 UK Cohort 75 53(54.6) 22(45.4) 52(69.3) 58.4%-79.3% Bacterial vaginosis 9 Makinde., et al 24[] 2022 Nigeria Cross-sectional 244 122(50.0) 122(50.0) 8(3.3) 1.4%-5.9% Group B Streptococcus 10 Morgan., et al 39[] 2023 United States of America Case-control 225 75(33.3) 150(66.7) 77(34.2) 28.2%-40.6% Group B Streptococcus 11 Ravindran, et al 30[] 2021 Kenya Cohort 1244 10(0.01) 1234 (99.99) 302(24.3) 21.9%-26.7% Chlamydia trachomatis, Neisseria gonorrhoea 12 Gray, et al 41[] 2011 Malawi Case-control 1857 402 (21.7) 1454 (78.3) 390 (21.0) 19.2%-22.9% Group B Streptococcus 13 El Beitune et al 31[] 2006 Brazil Cross-sectional 207 101 (48.8) 106 (51.1) 35 (16.9) 12.1%-22.3% Group B Streptococcus Overall 6073 1736 (28.6) 4336 (71.4) 1580 (26.0) 17.3%-37.4% Table 2: Distribution of vaginal bacterial colonization among pregnant women n (%) n (%) NOS Madrid (2018) 120 Culture E.coli 44(36.7) 28.2%-45.5% 76(63.3) 54.5%-71.8% 8 Nyemba (2022) 198 Culture Chlamydia trachomatis, Neisseria gonorrhoea 163(82.3) 76.7%-87.3% 35(17.7) 12.7%-23.3% 8 Gudza-Mugabe (2020) 88 PCR & DNA Sequencing Bacterial vaginosis 18(20.5) 12.6%-29.6% 70(79.5) 70.4%-87.4% 7 Njoku (2018) 18 Culture Group B Streptococcus 13(72.2) 48.9%-90.9% 5(27.8) 9.1%-51.1% 8 Price (2021) 221 Metagenomic Sequencing Bacterial vaginosis 85(38.7) 32.1%-45.0% 136(61.5) 55.0%-67.9% 8 Biobaku (2017) 36 Culture Group B Streptococcus 13(36.1) 21.1%-52.6% 23(63.9) 47.4%-78.9% 10 Smullin (2020) 35 Culture mycoplasma genitalium 22(62.9) 46.1%-78.2% 13(37.1) 21.8%-53.9% 8 Short (2020) 52 DNA Sequencing Bacterial vaginosis 42(80.8) 68.8%-90.5% 10(19.2) 9.5%-31.2% 7 Makinde (2022) 8 Culture Group B Streptococcus 4(50.0) 15.3%-84.7% 4(50.0) 15.3%-84.7% 8 Morgan (2023) 77 Culture Group B Streptococcus 31(40.3) 29.5%-51.5% 46(59.7) 48.5%-70.5% 7 Ravindran (2021) 302 Culture Chlamydia trachomatis, Neisseria gonorrhoea 4(0.01) 0.0%-3.0% 296(99.99) 97.0%-99.7% 8 Gray (2011) 390 Culture Group B Streptococcus 77(19.4) 15.9%-23.8% 313(21.7) 76.2%-84.1% 7 El Beitune (2006) 35 culture Group B streptococcus 20(19.8%) 40.3%-73.2% 15(14.1%) 26.8%-59.7% 7 Table 3: Vaginal colonization bacterial isolate types Group B Streptococcus 243139414748[, ] 6 3129 632 20.2%. 18.8%-21.6% Mycoplasma genitalium 27[] 1 197 35 17.8%, 12.7%-23.4% Bacterial vaginosis 252829[, ] 3 794 269 33.9%, 30.6%-37.2% Neisseria Gonorrhoea 26[] 1 619 35 5.7%, 4.0%-7.6% Chlamydia trachomatis 26[] 1 619 158 25.5%, 22.2%-29.0% Escherichia coli 38[] 1 320 52 16.2%, 12.4%-20.5% Any STI in pregnancy 2627[, ] 2 816 311 38.1%, 34.8%-41.5% Chlamydia trachomatis & Neisseria gonorrhoea 30[] 1 1244 302 24.3%, 21.9%-26.7% Figure 2: Effect of HIV and colonization on birthweight. Figure 3: Effect of HIV and colonization on preterm birth. Figure 4: Association between HIV and Colonization Information & Authors Information Version history V1 Version 1 25 February 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords antenatal care epidemiology epidemiology: perinatal infectious disease: microbiology meta-analysis preterm labour: clinical research systematic reviews Authors Affiliations Dismas Matovelo 0000-0003-1048-6166 [email protected] Catholic University of Health And Allied Sciences Weill Bugando School of Medicine View all articles by this author Quinn Goddard University of Calgary Cumming School of Medicine View all articles by this author Paul Sabuni Catholic University of Health And Allied Sciences Weill Bugando School of Medicine View all articles by this author Benson Kidenya Catholic University of Health And Allied Sciences Weill Bugando School of Medicine View all articles by this author Jennifer Downs Catholic University of Health And Allied Sciences Weill Bugando School of Medicine View all articles by this author Moke Magoma Engender Health View all articles by this author Jeremiah Seni Catholic University of Health And Allied Sciences Weill Bugando School of Medicine View all articles by this author Katie Chaput University of Calgary Cumming School of Medicine View all articles by this author Metrics & Citations Metrics Article Usage 175 views 116 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Dismas Matovelo, Quinn Goddard, Paul Sabuni, et al. 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