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IntroductionDespite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.MethodsWe screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.ResultsWe screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.ConclusionsThis analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Background: Studies evaluating the association between the vaginal microbiota and miscarriage have produced variable results. Objective: This study evaluated the association between periconceptual and first‐trimester vaginal microbiota and women's risk for miscarriage. Methods: At monthly preconception visits and at 9–12 weeks gestation, women collected vaginal swabs for molecular characterisation of the vaginal microbiota. Participants who became pregnant were followed to identify miscarriage versus pregnancy continuing to at least 20 weeks gestation. Results: Forty‐five women experienced miscarriage and 144 had pregnancies continuing to ≥20 weeks. A principal component analysis of periconceptual and first‐trimester vaginal bacteria identified by 16S rRNA gene PCR with next‐generation sequencing did not identify distinct bacterial communities with miscarriage versus continuing pregnancy. Using taxon‐directed quantitative PCR assays, increasing concentrations of Megasphaera hutchinsoni, Mageeibacillus indolicus, Mobiluncus mulieris and Sneathia sanguinegens/vaginalis were not associated with miscarriage. In exploratory analyses, these data were examined as a binary exposure to allow for multivariable modelling. Detection of Mobiluncus mulieris in first‐trimester samples was associated with miscarriage (adjusted relative risk [aRR] 2.14, 95% confidence interval [CI] 1.08, 4.22). Additional analyses compared women with early first‐trimester miscarriage (range 4.7–7.3 weeks) to women with continuing pregnancies. Mobiluncus mulieris was detected in all eight (100%) first‐trimester samples from women with early first‐trimester miscarriage compared to 101/192 (52.6%) samples from women with continuing pregnancy (model did not converge). Detection of Mageeibacillus indolicus in first‐trimester samples was also associated with early first‐trimester miscarriage (aRR 4.10, 95% CI 1.17, 14.31). Conclusions: The primary analyses in this study demonstrated no association between periconceptual or first‐trimester vaginal microbiota and miscarriage. Exploratory analyses showing strong associations between first‐trimester detection of Mobiluncus mulieris and Mageeibacillus indolicus and early first‐trimester miscarriage suggest the need for future studies to determine if these findings are reproducible. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is Mycoplasma genitalium -infection associated with reduced fecundability? SUMMARY ANSWER Preconception M. genitalium -infection was associated with 27% lower fecundability though confidence intervals were wide, and the association between M. genitalium and fecundability may be dependent on concurrent bacterial vaginosis (BV). WHAT IS KNOWN ALREADY M. genitalium has been associated with cervicitis, pelvic inflammatory disease, infertility, and preterm birth, but the extent to which M. genitalium is causally related to adverse reproductive sequelae in women is debated. STUDY DESIGN, SIZE, DURATION Kenyan women enrolled in a prospective preconception cohort provided vaginal fluid specimens and underwent monthly pregnancy testing. Stored samples from 407 women who had been trying to conceive for ≤6 months were tested for M. genitalium using a nucleic acid amplification test. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on first day of last menstrual period, sexual behavior, pregnancy status, and vaginal specimens were collected at monthly preconception visits. The association between M. genitalium detected at the visit prior to each pregnancy test and fecundability was estimated using discrete time proportional probabilities models. Secondary analyses explored the influence of concurrent BV on the association between M. genitalium and fecundability. MAIN RESULTS AND THE ROLE OF CHANCE The 407 participants experienced 1220 menstrual cycles and 213 pregnancies. The prevalence of M. genitalium at enrollment was 7.7%. After adjustment for age, frequency of condomless sex in the last 4 weeks, and study site, M. genitalium was associated with a 27% lower fecundability, but confidence intervals were wide (adjusted fecundability ratio (aFR) 0.73, 95% CI 0.44, 1.23). In secondary analyses, when compared to cycles without M. genitalium or BV at the visit prior, women with both M. genitalium and BV at the visit prior had a 51% lower fecundability (aFR = 0.49, 95% CI 0.22, 1.09) whereas there was no association of M. genitalium alone (aFR = 0.98 (95% CI 0.54, 1.76)), and a smaller reduction in fecundability for women with BV only (aFR = 0.80 (95% CI 0.60, 1.07)). LIMITATIONS, REASONS FOR CAUTION Results should be interpreted cautiously given the relatively low prevalence of M. genitalium and wide confidence intervals. WIDER IMPLICATIONS OF THE FINDINGS In this cohort of Kenyan women trying to conceive, the association between M. genitalium and fecundability was influenced by concurrent BV status, suggesting there may be a synergistic effect of M. genitalium and BV on fecundability. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-RSM). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were completed using REDCap electronic data capture tools hosted at the University of Washington's Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation and consulting fees from Lupin Pharmaceuticals. L.E.M. receives research funding and material for research studies, paid to the University of Washington, from Hologic Corporation and Nabriva Therapeutics, travel support from Hologic, and consulting fees from Health Advances. E.M.L.'s contributions to this study primarily occurred while affiliated with the University of Washington; at the time of submission, E.M.L. was an employee of and holds stock or stock grants for AbbVie, Inc. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background Women's increased risk of HIV acquisition during pregnancy and postpartum may be mediated by changes in vaginal microbiota and/or cytokines. Methods A cohort of 80 Kenyan women who were HIV-1 seronegative contributed 409 vaginal samples at 6 pregnancy time points: periconception, positive pregnancy test result, first trimester, second trimester, third trimester, and postpartum. Concentrations of vaginal bacteria linked with HIV risk and Lactobacillus spp were measured using quantitative polymerase chain reaction. Cytokines were measured by immunoassay. Results Based on Tobit regression, later pregnancy time points were associated with lower concentrations of Sneathia spp (P =.01), Eggerthella sp type 1 (P =.002), and Parvimonas sp type 2 (P =.02) and higher concentrations of Lactobacillus iners (P <.001), Lactobacillus crispatus (P <.001), Lactobacillus vaginalis (P <.001), interleukin 6 (P <.001), TNF (P =.004), C-X-C motif chemokine ligand 10 (CXCL10; P <.001), C-C motif ligand 3 (P =.009), C-C motif ligand 4 (P <.001), C-C motif ligand 5 (P =.002), interleukin 1β (P =.02), and interleukin 8 (P =.002). Most cervicovaginal cytokines and vaginal bacteria clustered separately in principal component analysis, except for CXCL10, which did not group with either cytokines or bacteria. The shift toward a Lactobacillus -dominated microbiota during pregnancy mediated the relationship between pregnancy time point and CXCL10. Conclusions Increases in proinflammatory cytokines, but not vaginal bacterial taxa linked with higher HIV risk, could provide an explanation for increased HIV susceptibility during pregnancy and postpartum. [ABSTRACT FROM AUTHOR]