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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.
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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.
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Mycoplasma genitalium , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Kenia/epidemiología , Estudios Prospectivos , Estudios de Cohortes , FertilidadRESUMEN
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 1ß (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.
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Infecciones por VIH , Mediadores de Inflamación , Embarazo , Femenino , Humanos , Kenia/epidemiología , Ligandos , Vagina/microbiología , Bacterias , Periodo Posparto , Citocinas , Infecciones por VIH/complicaciones , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: Availability of laboratory confirmation of sexually transmitted infections is increasing in low- and middle-income countries, but costs continue to limit their access. Chlamydia trachomatis (CT) is a sexually transmitted infection of significant clinical importance, particularly among women. This study aimed to develop a risk score to identify women with a higher likelihood of CT infection, who could then be prioritized for laboratory testing, in a population of Kenyan women planning pregnancies. METHODS: Women with fertility intentions were included in this cross-sectional analysis. Logistic regression was used to estimate odds ratios for the association between demographic, medical, reproductive, and behavioral characteristics and the prevalence of CT infection. A risk score was developed and validated internally based on the regression coefficients in the final multivariable model. RESULTS: The prevalence of CT was 7.4% (51 of 691). A risk score for predicting CT infection, with scores 0 to 6, was derived from participants' age, alcohol use, and presence of bacterial vaginosis. The prediction model yielded an area under the receiver operating curve of 0.78 (95% confidene interval [Cl], 0.72-0.84). A cutoff of ≤2 versus >2 identified 31.8% of women as higher risk with moderate sensitivity (70.6%; 95% Cl, 56.2-71.3) and specificity (71.3%; 95% Cl, 67.7-74.5). The bootstrap-corrected area under the receiver operating curve was 0.77 (95% Cl, 0.72-0.83). CONCLUSIONS: In similar populations of women planning pregnancies, this type of risk score could be useful for prioritizing women for laboratory testing and would capture most women with CT infections while performing more costly testing in less than half of the population.
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Infecciones por Chlamydia , Chlamydia trachomatis , Enfermedades de Transmisión Sexual , Femenino , Humanos , Embarazo , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Estudios Transversales , Kenia/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
INTRODUCTION: Despite 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: This 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.
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COVID-19 , Mujeres Embarazadas , Recién Nacido , Embarazo , Femenino , Humanos , Estudios Prospectivos , SARS-CoV-2RESUMEN
OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.
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COVID-19 , Enfermedades Cardiovasculares , Infecciones por VIH , Hipertensión , Complicaciones del Embarazo , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , COVID-19/epidemiología , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , Delgadez , SARS-CoV-2 , Resultado del Embarazo/epidemiología , Factores de Riesgo , Complicaciones del Embarazo/epidemiología , Periodo PospartoRESUMEN
BACKGROUND: Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. METHODS: We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. RESULTS: We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1ß, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. CONCLUSIONS: Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
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Elafina , beta-Defensinas , Femenino , Factor Estimulante de Colonias de Granulocitos , Humanos , Inmunoglobulinas , Factores Inmunológicos , Interferones , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-16 , Interleucina-1alfa , Interleucina-6 , Interleucinas , Lactoferrina , Ciclo Menstrual , Muramidasa , ProgesteronaRESUMEN
OBJECTIVE: To compare patient satisfaction with anesthesia after first-trimester surgical abortion among patients receiving intravenous (IV) ketamine compared with IV fentanyl for procedural sedation. METHODS: This was a randomized noninferiority trial comparing IV ketamine to IV fentanyl for first-trimester surgical abortion up to 13 6/7 weeks of gestation. Patients were randomized to receive either ketamine 200-500 micrograms/kg IV over 2 minutes, repeated every 5 minutes until appropriate analgesia was achieved, or fentanyl 0.5-1 micrograms/kg IV over 2 minutes, repeated every 5 minutes until appropriate analgesia was achieved. All patients received midazolam 2 mg IV. The primary outcome, patient satisfaction, was measured using the Iowa Satisfaction with Anesthesia Scale immediately postprocedure. Secondary outcomes included postoperative pain, additional pain medication necessary during the procedure and on discharge, physician satisfaction, and time to discharge. We calculated a sample size of 84 with a noninferiority margin of 0.6 on the Iowa Satisfaction with Anesthesia Scale with 80% power, one-sided type 1 error of 0.025, and further increased this number to 110 to account for potential dropout. RESULTS: From April to October 2021, 184 patients were screened and 110 were randomized (57 to ketamine and 53 to fentanyl). Demographics were similar between groups. The primary outcome, patient satisfaction with anesthesia, was noninferior in the ketamine group (mean score 2.4, SD 0.8) as compared with the fentanyl group (mean score 2.2, SD 0.9) with a risk difference of 0.20 (95% CI 0.11-0.52). More hallucinations were reported in the ketamine group. Otherwise, secondary outcomes were similar between the groups. CONCLUSION: Compared with IV fentanyl, IV ketamine is noninferior for patient satisfaction with anesthesia when used for procedural sedation for first-trimester outpatient surgical abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04871425.
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Fentanilo , Ketamina , Embarazo , Femenino , Humanos , Ketamina/uso terapéutico , Método Doble Ciego , Midazolam , Dolor/tratamiento farmacológicoRESUMEN
BACKGROUND: Periodontitis has been associated with adverse pregnancy outcomes. Little is known about the burden and risk factors for periodontitis among reproductive age women in sub-Saharan Africa. This analysis aimed to determine the prevalence and correlates of periodontitis among Kenyan women planning to conceive. METHODS: HIV-seronegative, reproductive-age women who were planning to conceive were enrolled and underwent a periodontal examination. Following the US Centers for Disease Control and Prevention clinical case definitions, the presence and severity of periodontitis was determined by establishing the level of clinical periodontal attachment loss and graded in three categories: no/mild, moderate, and severe. Secondary outcomes included the scores on the Gingival Index and Decayed, Missing, and Filled Teeth (DMFT) Index. Correlates of periodontitis were examined using univariable and multivariable logistic regression. RESULTS: Of the 647 women in the study, 84% (n = 541) had no/mild periodontitis, 15% (n = 97) had moderate periodontitis, and 1% (n = 9) had severe periodontitis. Mild gingivitis was present in 61% (n = 396) of women, while 27% (n = 176) had moderate gingivitis, and 1% (n = 9) had severe gingivitis. The majority (75%, n = 487) of women had a DMFT index in the very low range (score < 5). Periodontitis was observed in 12% (12/101) of nulliparous women compared to 13% (36/286) of women with one prior delivery (prevalence ratio [PR] 1.03, 95% confidence interval [95% CI] 0.57-1.96), 21% (36/170) of women with two prior deliveries (PR 1.78, 95% CI 0.97-3.26), and 24% (22/90) of women with 3 or more prior deliveries (PR 2.06, 95% CI 1.08-3.92). CONCLUSION: This study demonstrated a substantial prevalence of moderate-severe periodontitis among women planning to conceive in Kenya. These results highlight the need to address the oral care needs of reproductive age women, particularly those with multiple prior pregnancies.
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Gingivitis , Periodontitis , Femenino , Gingivitis/epidemiología , Humanos , Kenia/epidemiología , Índice Periodontal , Periodontitis/complicaciones , Embarazo , PrevalenciaRESUMEN
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.
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COVID-19 , Adolescente , COVID-19/epidemiología , Niño , Femenino , Humanos , Recién Nacido , Metaanálisis como Asunto , Periodo Posparto , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Intravaginal washing, practised by a significant proportion of women globally, is associated with acquisition of human immunodeficiency virus (HIV), sexually transmitted infections and bacterial vaginosis (BV). A single prior study among women in the United States found that vaginal washing was associated with lower fecundability. OBJECTIVE: To examine the association between vaginal washing and fecundability among Kenyan women. METHODS: HIV-negative Kenyan women who were trying to conceive and reported no history of infertility care-seeking were followed prospectively for incident pregnancy for up to six months. At monthly visits, participants reported the first day of last menstrual period, sexual behaviour, vaginal washing behaviour, underwent pregnancy testing and provided vaginal swabs for detection of BV by Gram stain (Nugent score ≥7). Discrete time proportional probability models were used to estimate fecundability ratio (FR) and 95% confidence interval (CI) comparing menstrual cycles when women reported vaginal washing to menstrual cycles when no vaginal washing was reported. RESULTS: Four hundred and fifty-eight women contributed 1,376 menstrual cycles and 255 pregnancies. At enrolment, a third (35.2%, 161 of 458) of participants reported vaginal washing with the majority using water only (73.9%, 119 of 161). After adjustment for age, frequency of unprotected intercourse and study site, vaginal washing in the prior four weeks was associated with a 29% lower fecundability (adjusted FR [aFR] 0.71, 95% CI 0.53, 0.94), which did not change after further adjustment for BV at the visit prior to each pregnancy test (aFR 0.71, 95% CI 0.54, 0.95). CONCLUSIONS: Periconceptual vaginal washing may reduce fecundability. Potential mechanisms include vaginal washing-associated changes in the vaginal microbiota, inflammation, disruption of cervical mucus and effects on sperm function. Vaginal washing has no known health benefits, and cessation may improve women's likelihood of conceiving.
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Fertilidad , Tiempo para Quedar Embarazada , Estudios de Cohortes , Femenino , Fertilización , Humanos , Lactante , Recién Nacido , Kenia/epidemiología , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: To examine the association between cultivable vaginal Lactobacillus and fecundability in Kenyan women attempting nonmedically assisted conception. DESIGN: Prospective preconception cohort. SETTING: Nairobi and Mombasa, Kenya. PATIENT(S): Women trying to conceive who reported ≤3 months of pre-enrollment conception attempt time. INTERVENTION(S): Cultivable Lactobacillus (primary), Lactobacillus morphotypes on Gram stain (secondary). MAIN OUTCOME MEASURE(S): Participants reported the first day of their last menstrual period and recent sexual behavior, underwent pregnancy testing, and provided vaginal specimen samples for Lactobacillus culture and Gram stain at ≤6 monthly preconception visits. The outcome was fecundability-the per-menstrual cycle probability of pregnancy. Associations between cultivable Lactobacillus and Lactobacillus morphotypes on Gram stain at the visit before each pregnancy test and fecundability were estimated using proportional probabilities models to generate fecundability ratios (FRs). RESULT(S): A total of 458 women contributed 1,376 menstrual cycles. At enrollment, 65.3% (n = 299) of participants had cultivable Lactobacillus, 47.4% (n = 217) had cultivable hydrogen peroxide producing Lactobacillus, and 64.6% (n = 296) had Lactobacillus detected on Gram stain. In unadjusted analysis, there was no association between cultivable Lactobacillus at the prior visit and fecundability (FR, 0.92; 95% CI, 0.73-1.16); results were similar after adjustment for age, frequency of condomless sex, and study site (adjusted FR, 0.92; 95% CI, 0.72-1.18). Lactobacillus on Gram stain at the visit prior was associated with modestly higher fecundability (adjusted FR, 1.18; 95% CI, 0.92-1.51). CONCLUSION(S): Cultivable Lactobacillus was not associated with fecundability, although Lactobacillus morphotypes detected on Gram stain were somewhat associated with increased fecundability. The relationship between vaginal Lactobacillus and fecundity may be species-specific.
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Fertilidad/fisiología , Fertilización/fisiología , Lactobacillus/aislamiento & purificación , Atención Preconceptiva/métodos , Tiempo para Quedar Embarazada/fisiología , Vagina/microbiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Kenia/epidemiología , Persona de Mediana Edad , Atención Preconceptiva/tendencias , Embarazo , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate whether same-day administration of mifepristone and misoprostol, compared with misoprostol alone, reduces the duration of second-trimester induction of labor for termination of pregnancy or increases the rate of fetal expulsion within 24 hours. STUDY DESIGN: We conducted a retrospective analysis of patients undergoing induction of labor for pregnancy termination in the second trimester between 2009 and 2018. We compared patients who received mifepristone on the same day as the first dose of misoprostol to those who received misoprostol alone. The primary outcome was expulsion within 24 hours after the first dose of misoprostol. RESULTS: Two hundred ninety-eight patients met criteria for inclusion, of whom 94 (31.5%) received same-day mifepristone. Expulsion within 24 hours occurred in 93.6% of the mifepristone-plus-misoprostol group and 79.9% of the misoprostol-only group (RR 1.17, 95%CI 1.07-1.28). Expulsion within 12 hours occurred in 56.4% of the mifepristone-plus-misoprostol group and 34.0% of the misoprostol-only group (RR 1.66, 95%CI 1.28-2.16). After adjusting for demographic and clinical characteristics, the rate of expulsion within 24 hours was similar between groups (RR 1.07, 95%CI 0.92-1.26), while the rate of expulsion within 12 hours remained different (RR 1.69, 95%CI 1.01-2.83). Median time to expulsion was shorter in the mifepristone-plus-misoprostol group than the misoprostol-only group (689 minutes vs 901 minutes, p < 0.001). CONCLUSION(S): Patients who received mifepristone on the same day as misoprostol had a shorter duration of induction termination and higher rate of success within 12 hours.
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Abortivos no Esteroideos , Abortivos Esteroideos , Aborto Inducido , Misoprostol , Femenino , Humanos , Mifepristona/farmacología , Embarazo , Segundo Trimestre del Embarazo , Estudios RetrospectivosRESUMEN
ABSTRACT: There are minimal data on the BVBlue test for diagnosis of bacterial vaginosis (BV) in Africa. Among 701 Kenyan women, compared with Nugent score ≥7, the BVBlue test had moderate sensitivity (81.9%; 95% confidence interval, 76.5%-86.5%) and high specificity (92.4%; 95% confidence interval, 89.5%-94.6%). This test may provide a complimentary approach to syndromic management.
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Vaginosis Bacteriana , Estudios de Cohortes , Femenino , Humanos , Kenia/epidemiología , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Vaginosis Bacteriana/diagnóstico , Vaginosis Bacteriana/epidemiologíaRESUMEN
Pregnancy risk assessment for patients with adult congenital heart disease (ACHD) must include physiologic and anatomic impacts. We aimed to determine whether maternal cardiac and pregnancy outcomes vary by disease severity defined according to the following 3 different classifications: ACHD anatomic severity, ACHD physiologic class, and modified World Health Organization (mWHO) class. Cardiac outcomes included a composite of arrhythmia, heart failure, stroke, and thromboembolism. Pregnancy outcomes included a composite of intrauterine growth restriction, preterm birth, preeclampsia, or postpartum hemorrhage. We employed generalized estimating equations to account for multiple pregnancies. Of the 245 pregnancies, 17.1% were preterm and 45.7% were cesarean deliveries. Cardiac hospitalizations occurred in 22.0% and arrhythmias in 12.7%. Cardiac outcomes tended to be more prevalent in people with more severe heart disease. Pregnancy outcomes were U-shaped or less prevalent in people with more severe disease. There was a 2.9-fold increased risk for the composite cardiac outcome for complex anatomy (adjusted incidence rate ratio 2.90, 95% confidence interval 1.08 to 7.81, p = 0.04), a 9.4-fold increased risk for physiologic class C or D (9.37, 1.28 to 68.79, p = 0.03), and a fourfold increased risk for mWHO class III or IV (3.99, 1.53 to 10.40, p = 0.005). There was a lower risk for the composite pregnancy outcome for mWHO class II or II to III (0.54, 0.36 to 0.79, p = 0.002) but no association with anatomy or physiology. In conclusion, physiologic class may be most accurately associated with adverse outcomes and therefore efforts to optimize hemodynamics before pregnancy may help to mitigate the risk.
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Cardiopatías Congénitas/clasificación , Complicaciones Cardiovasculares del Embarazo/clasificación , Resultado del Embarazo/epidemiología , Medición de Riesgo/métodos , Adulto , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/epidemiología , Humanos , Morbilidad/tendencias , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Washingtón/epidemiologíaRESUMEN
IMPORTANCE: Current guidelines for postmenopausal recurrent urinary tract infection (rUTI) prevention recommend the use of vaginal topical estrogen products but not systemic estrogens. Studies show that vaginal estrogen decreases the risk of rUTI, but evidence against use of systemic estrogen is less convincing. OBJECTIVE: We performed a comprehensive literature review to evaluate the effect of systemic estrogen on UTI occurrence among postmenopausal women. EVIDENCE REVIEW: MEDLINE (PubMed), EMBASE, and CINAHL were searched for manuscripts published in English between January 1990 and July 2020. The search terms were "urinary tract infection" and "estrogen." Inclusion criteria were studies of postmenopausal women who received systemic estrogen therapy (any regimen) that reported UTI frequency during any follow-up period. Case studies, commentaries, and reviews were excluded. A priori specifications of seven study criteria were set representing the ideal study for assessing efficacy of systemic estrogen for rUTI prevention and were used to evaluate each included study. FINDINGS: Searches identified 281 results, and after deduplication and review, 8 studies met inclusion criteria: 4 randomized controlled trials, 1 secondary analysis of a randomized controlled trial, 1 prospective cohort study, 1 case-control study, and 1 cross-sectional study. Of the eight included studies, only two enrolled postmenopausal women with a rUTI diagnosis, four had sufficient sample size to detect a clinically meaningful difference between systemic estrogen versus placebo, two used dosage regimens anticipated to achieve a therapeutic effect, and three assessed UTI rates for an adequate duration of 6âmonths or more (the standard minimum duration of time needed to make a diagnosis of rUTI). Overall, none of the studies met all predefined criteria for the ideal study to assess the efficacy of systemic estrogen for rUTI prevention. CONCLUSIONS AND RELEVANCE: UTIs will continue to be a significant cause of morbidity and hospitalizations in postmenopausal women unless more research is done to better understand the role of estrogen on UTI rates. The evidence arguing use (or abandonment) of systemic estrogen for the prevention of rUTI is based on few studies with substantial methodologic limitations; there is significant room for improvement.
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Posmenopausia , Infecciones Urinarias , Estudios de Casos y Controles , Estudios Transversales , Estrógenos , Femenino , Humanos , Estudios Prospectivos , Infecciones Urinarias/prevención & controlRESUMEN
STUDY QUESTION: Is bacterial vaginosis (BV) associated with fecundability? SUMMARY ANSWER: Women with BV may be at increased risk for sub-fecundity. WHAT IS KNOWN ALREADY: While BV has been associated with poor IVF outcomes, the association between vaginal microbiota disruption and non-medically assisted conception has not been thoroughly explored. STUDY DESIGN, SIZE, DURATION: Kenyan women with fertility intent were enrolled in prospective cohort that included monthly preconception visits with vaginal fluid specimen collection and pregnancy testing. Four hundred fifty-eight women attempting pregnancy for ≤3 menstrual cycles at enrollment were eligible for this fecundability analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: At monthly preconception visits, participants reported the first day of last menstrual period and sexual behavior, underwent pregnancy testing and provided vaginal specimens. Discrete time proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% CI in menstrual cycles with and without BV (Nugent score ≥ 7) at the visit prior to each pregnancy test. We also assessed the association between persistent BV (BV at two consecutive visits) and fecundability. MAIN RESULTS AND THE ROLE OF CHANCE: Participants contributed 1376 menstrual cycles; 18.5% (n = 255) resulted in pregnancy. After adjusting for age, frequency of condomless sex and study site, BV at the visit prior to pregnancy testing was associated with a 17% lower fecundability (adjusted FR (aFR) 0.83, 95% CI 0.6-1.1). Persistent BV was associated with a 43% reduction in fecundability compared to cycles characterized by optimal vaginal health (aFR 0.57, 95% CI 0.4-0.8). LIMITATIONS, REASONS FOR CAUTION: Detection of vaginal microbiota disruption using Gram stain and a point-of-care test for elevated sialidase identified a non-optimal vaginal environment, but these non-specific methods may miss important relationships that could be identified by characterizing individual vaginal bacteria and bacterial communities using molecular methods. In addition, results may be subject to residual confounding by condomless sex as this was reported for the prior month rather than for the fertile window during each cycle. WIDER IMPLICATIONS OF THE FINDINGS: Given the high global prevalence of BV and infertility, an association between BV and reduced fecundability could have important implications for a large number of women who wish to conceive. Multi-omics approaches to studying the vaginal microbiota may provide key insights into this association and identify potential targets for intervention. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-R.S.M.). 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 made possible 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 has received honoraria for consulting from Lupin Pharmaceuticals. L.E.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for service on scientific advisory boards from Hologic and Nabriva Therapeutics. TRIAL REGISTRATION NUMBER: N/A.
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Vaginosis Bacteriana , Estudios de Cohortes , Femenino , Fertilidad , Humanos , Kenia/epidemiología , Embarazo , Estudios Prospectivos , Vaginosis Bacteriana/complicaciones , Vaginosis Bacteriana/epidemiologíaRESUMEN
BACKGROUND: During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood. OBJECTIVE: This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State. RESULTS: A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%). CONCLUSION: The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.
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COVID-19/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Grupos Raciales/estadística & datos numéricos , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Washingtón/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001). CONCLUSION: Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.
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COVID-19/mortalidad , Muerte Materna , Resultado del Embarazo , Índice de Severidad de la Enfermedad , Adulto , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Retrospectivos , Washingtón/epidemiología , Adulto JovenRESUMEN
We found low prevalence of SARS-CoV-2 (2.7% [5/188]) among pregnant and postpartum patients with universal testing. Prevalence among symptomatic patients was similar under initial targeted screening (22.2% [4/18]) and universal approaches (19.1% [8/42]). Among 170 asymptomatic patients, 2 were positive or inconclusive, respectively; repeat testing at 24 hours was negative.