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In this follow-up report of a trial of CMV hyperimmune globulin in pregnant women with primary CMV infection, hyperimmune globulin did not improve hearing or developmental outcomes in children at the age of 2 years.

AbstractObjectiveTo determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).DesignLiving systematic review and meta-analysis.Data sourcesMedline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 6 October 2020, along with preprint servers, social media, and reference lists.Study selectionCohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.Data extractionAt least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.Results192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19.ConclusionPregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit.Systematic review registrationPROSPERO CRD42020178076.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.

BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance.

The objective of this review was to describe the clinical characteristics, risk factors, and outcomes of infective endocarditis (IE) in pregnancy and the postpartum period. We conducted a systematic review of Ovid MEDLINE, Ovid Embase, Web of Science, and Scopus from January 1, 1988, through October 31, 2012. Included studies reported on women who met the modified Duke criteria for the diagnosis of IE and were pregnant or postpartum. We included 72 studies that described 90 cases of peripartum IE, mostly affecting native valves (92%). Risk factors associated with IE included intravenous drug use (14%), congenital heart disease (12%), and rheumatic heart disease (12%). The most common pathogens were streptococcal (43%) and staphylococcal (26%) species. Septic pulmonary, central, and other systemic emboli were common complications. Of the 51 pregnancies, there were 41 (80%) deliveries with survival to discharge, 7 (14%) fetal deaths, 1 (2%) medical termination of pregnancy, and 2 (4%) with unknown status. Maternal mortality was 11%. Infective endocarditis is a rare, life-threatening infection in pregnancy. Risk factors are changing with a marked decrease in rheumatic heart disease and an increase in intravenous drug use. The cases reported in the literature were commonly due to streptococcal organisms, involved the right-sided valves, and were associated with intravenous drug use.

Trichomonas vaginalis is the most common curable sexually transmissible infection worldwide, with high rates in women of reproductive age. There have been inconsistent findings about the impact of infection and its treatment in pregnancy. We conducted a meta-analysis to determine the association between T. vaginalis and perinatal outcomes. Electronic databases were searched to May 2013. Included studies reported perinatal outcomes in women infected and uninfected with T. vaginalis. Meta-analysis calculated a pooled relative risk (RR) and 95% confidence interval (CI) using either a fixed-or random-effects model. Study bias was assessed using funnel plots. Of 178 articles identified, 11 studies met the inclusion criteria. The study populations, outcomes, and quality varied. T. vaginalis in pregnancy was associated with an increased risk of preterm birth (RR, 1.42; 95% CI, 1.15—1.75; 9 studies; n = 81,101; I² = 62.7%), preterm premature rupture of membranes (RR, 1.41; 95% CI, 1.10—1.82; 2 studies; n = 14,843; I² = 0.0%) and small for gestational age infants (RR, 1.51; 95% CI, 1.32—1.73; 2 studies; n = 14,843; I² = 0.0%). Sensitivity analyses of studies that accounted for coinfection with other sexually transmissible infection found a slightly reduced RR of 1.34 for preterm birth (95% CI, 1.19—1.51; 6 studies; n = 72,077; I² = 11.2%), and in studies where no treatment was confirmed, the RR was 1.83 (95% CI, 0.98—3.41; 3 studies; n = 1795; I 2 = 22.3%). Our review provides strong evidence that T. vaginalis in pregnancy is associated with an increased risk of preterm birth. Based on fewer studies, there were also substantial increases in the risk of preterm premature rupture of membranes and small for gestational age infants. Further studies that address the current gaps in evidence on treatment effects in pregnancy are needed.

Background Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis. Methods This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days. Discussion GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study will provide data on the frequency of maternal sepsis and uptake of effective diagnostic and therapeutic interventions in obstetrics in different hospitals and countries. We will also be able to explore links between interventions and maternal and perinatal outcomes and identify priority areas for action.

The main goal of this manuscript was to investigate the neurodevelopment of children exposed by Zika virus in the intrauterine period who are asymptomatic at birth. Newborns with documented Zika virus exposure during the intrauterine period who were asymptomatic at birth were followed in the first two years of life for neurodevelopment using Bayley III test. Children were classified as having normal or delayed neurodevelopment for age based on most recent Bayley III evaluation results. Eighty-four infants were included in the study. The first Bayley III evaluation was performed at a mean chronological age of 9.7±3.1 month; 13 children (15%) had a delay in one of the three domains, distributed as follow: 10 (12%) in the language domain and 3 (3.5%) in the motor domain. The most recent Bayley III evaluation was performed at a mean age 15.3±3.1 months; 42 children (50%) had a delay in one of the three domains: 4 (5%) in cognition, 31 (37%) in language, and 20 (24%) in motor performance. There were no statistical differences in Gender, Gestational Age, Birth Weight and Head Circurference at birth between children with normal and delayed neurodevelopment for age. A very high proportion of children exposed ZIKV during pregnancy who were asymptomatic at birth demonstrated a delay in neurodevelopment, mainly in the language domain, the first two years of life.

Tuberculosis (TB) disease adversely affects mother and child, and strategies to control TB in this group are important. The aim of this study was to analyze the epidemiology of TB in pregnancy, and to establish whether pregnancy is an independent risk factor for TB. The United Kingdom-wide cohort study was based on the General Practitioner Research Database (GPRD), enrolling all women with pregnancies between 1996 and 2008. Incidence rates and incidence rate ratios (IRRs) of TB events during pregnancy, 6 months postpartum, and outside pregnancy were calculated and compared by Poisson regression. A nested self-controlled case series compared the risk of TB in these periods, adjusting for individual and time-bound confounders. The crude TB rate for the combined pregnancy and postpartum period was 15.4 per 100,000 person-years, significantly higher than outside of pregnancy (9.1 per 100,000 person-years; P = 0.02). Adjusting for age, region, and socioeconomic status the postpartum TB risk was significantly higher than outside pregnancy (IRR, 1.95; 95% confidence interval [CI], 1.24-3.07), whereas there was no significant increase during pregnancy (IRR, 1.29; 95% CI, 0.82-2.03). These observations were confirmed in the self-controlled case series (IRR, 1.62; 95% CI, 1.01-2.58 and IRR, 1.03; 95% CI, 0.64-1.65, respectively). The incidence of TB diagnosis is significantly increased postpartum. Although we did not find an increase during pregnancy, the postpartum incidence may reflect an increase during pregnancy given diagnostic, immunological and administrative delays. Clinicians' awareness should be improved and the effectiveness of public health policy measures such as targeted screening of pregnant and postpartum women in high-risk groups should be evaluated.

Pelvic inflammatory disease (PID), the infection and inflammation of the female genital tract, results in serious reproductive morbidity including infertility and ectopic pregnancy. Bacterial vaginosis (BV) is a complex alteration of the vaginal flora that has been implicated in PID. The role of BV in the etiology and pathogenesis of PID has not been studied extensively. Our objective was to extensively review data related to the relationship between BV and PID (n = 19 studies). Several studies found a link between BV and cervicitis, endometritis, and salpingitis. Furthermore, it seems that some BV-associated organisms are associated with PID, whereas others are not. However, studies demonstrating an independent association between BV-associated organisms and PID are sparse. In addition, a causal association between BV and PID has not been established. Prospective studies are needed to further delineate the role of BV in PID, with particular focus on individual BV-associated organisms.