-
BMJ Open Aug 2023Maternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in...
Prevention of maternal and neonatal death/infections with a single oral dose of azithromycin in women in labour in low-income and middle-income countries (A-PLUS): a study protocol for a multinational, randomised placebo-controlled clinical trial.
INTRODUCTION
Maternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in preventing many of these deaths. A randomised clinical trial conducted in a single site in The Gambia showed that treatment with an oral dose of 2 g azithromycin versus placebo for all women in labour reduced certain maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. In a large, multinational randomised trial, we will evaluate the impact of azithromycin given in labour to improve maternal and newborn outcomes.
METHODS AND ANALYSIS
This randomised, placebo-controlled, multicentre clinical trial includes two primary hypotheses, one maternal and one neonatal. The maternal hypothesis is to test whether a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labour will reduce maternal death or sepsis. The neonatal hypothesis will test whether this intervention will reduce intrapartum/neonatal death or sepsis. The intervention is a single, prophylactic intrapartum oral dose of 2 g azithromycin, compared with a single intrapartum oral dose of an identical appearing placebo. A total of 34 000 labouring women from 8 research sites in sub-Saharan Africa, South Asia and Latin America will be randomised with a one-to-one ratio to intervention/placebo. In addition, we will assess antimicrobial resistance in a sample of women and their newborns.
ETHICS AND DISSEMINATION
The study protocol has been reviewed and ethics approval obtained from all the relevant ethical review boards at each research site. The results will be disseminated via peer-reviewed journals and national and international scientific forums.
TRIAL REGISTRATION NUMBER
NCT03871491 (https://clinicaltrials.gov/ct2/show/NCT03871491?term=NCT03871491&draw=2&rank=1).
Topics: Infant, Newborn; Female; Humans; Azithromycin; Perinatal Death; Developing Countries; Communicable Diseases; Sepsis; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37648383
DOI: 10.1136/bmjopen-2022-068487 -
BMJ Open Dec 2023Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be...
INTRODUCTION
Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth.
METHODS AND ANALYSIS
This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and at <27 weeks of gestation, confirmed by ultrasound. At enrolment and 30-34 weeks of pregnancy, participants receive on-site tests for and , with treatment if test results are positive. At these visits, additional vaginal specimens are taken for: PCR detection and quantification of , spp., , and ; microscopy and Nugent scoring; and for 16S ribosomal RNA gene sequencing and quantification. Pregnancy outcomes are collected from a postnatal visit and birth registers. The primary outcome is gestational age at birth. Statistical analyses will explore associations between specific microorganisms and gestational age at birth. To explore the association with the quantity of microorganisms, we will construct an index of microorganism load and use mixed-effects regression models and classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth.
ETHICS AND DISSEMINATION
This protocol has approvals from the University of Cape Town Research Ethics Committee and the Canton of Bern Ethics Committee. Results from this study will be uploaded to preprint servers, submitted to open access peer-reviewed journals and presented at regional and international conferences.
TRIAL REGISTRATION NUMBER
NCT06131749; Pre-results.
Topics: Child; Female; Pregnancy; Infant, Newborn; Humans; Child, Preschool; Premature Birth; Pregnant Women; Cohort Studies; HIV Infections; Gestational Age; Pregnancy Complications, Infectious; Reproductive Tract Infections; South Africa; Pregnancy Outcome; Chlamydia trachomatis; Mycoplasma Infections
PubMed: 38154893
DOI: 10.1136/bmjopen-2023-081562 -
Turkiye Parazitolojii Dergisi Dec 2023is the causative agent of toxoplasmosis and is a parasite of high medical importance with a wide host variety. Bacterial, viral, and parasitic infections during...
OBJECTIVE
is the causative agent of toxoplasmosis and is a parasite of high medical importance with a wide host variety. Bacterial, viral, and parasitic infections during pregnancy may predispose women to pregnancy complications. Preeclampsia of unknown etiology causes special conditions such as systemic vascular endothelial damage due to insufficient trophoblastic invasion and abnormal placentation. There are data of an association between various maternal infections and preeclampsia/eclampsias. The aim of the study was to compare and analyze the relationship between the presence of IgM and IgG antibodies in pregnant women with pre-eclampsia and in normotensive healthy pregnant women who were in the control group.
METHODS
In this study, 176 pregnant women who applied to our hospital between January 2019 and December 2020 were included. 88 (50%) of the pregnant women had pre-eclampsia and 88 (50%) were normotensive. The presence of IgM and IgG antibodies in blood taken from pregnant women with pre-eclampsia and control group was investigated using ELISA.
RESULTS
Because of the study, both groups were found to be seronegative in terms of IgM by ELISA. IgG was found to be seropositive in 24 (27.3%) pregnant women with pre-eclampsia and 18 (20.5%) normotensive pregnant women. There was no statistically significant difference between the two groups in terms of IgM and IgG seropositivity (X=0.289, p>0.05) (p<0.05).
CONCLUSION
Because of the study, no statistically significant difference was found between pregnant women with pre-eclampsia and those with toxoplasmosis. It was thought that further studies should be conducted to discuss the hormonal, vascular, etc. factors occurring in the pathogenesis of preeclampsia of effect of preparing the ground for the changes and to reveal the existence of a possible relationship between pre-eclampsia and seropositivity.
Topics: Female; Pregnancy; Humans; Toxoplasma; Pre-Eclampsia; Seroepidemiologic Studies; Antibodies, Protozoan; Immunoglobulin M; Toxoplasmosis; Pregnancy Complications, Parasitic; Risk Factors; Immunoglobulin G
PubMed: 38149440
DOI: 10.4274/tpd.galenos.2023.80664 -
BMC Pregnancy and Childbirth Dec 2023Pertussis and influenza cause significant morbidity and mortality in pregnancy and the neonatal period. Maternal vaccination in pregnancy would reduce harm, but low... (Review)
Review
BACKGROUND
Pertussis and influenza cause significant morbidity and mortality in pregnancy and the neonatal period. Maternal vaccination in pregnancy would reduce harm, but low vaccine uptake is a concern. This scoping review aimed to understand the reasons for, and approaches, to non-uptake of pertussis and influenza vaccinations in pregnant women in the UK and Ireland.
METHODS
The inclusion criteria of this scoping review consist of pregnant women who avail of pertussis and influenza vaccines in the UK and Ireland. MEDLINE, EMBASE, Web of Science and CINAHL databases were searched in June 2021 and updated in October 2022. Searches were limited to English language reports published after 2011. We followed the Joanna Briggs Institute guidance on scoping reviews. Data were extracted and charted.
RESULTS
Five themes emerged from the literature. Acceptability, as well as organisational and awareness issues, were overarching themes regarding reasons for and approaches to non-uptake of the vaccines respectively. Other themes included healthcare professional factors, information interpretation and pregnancy-related factors.
CONCLUSIONS
Women need clear, comprehensible information, ideally provided by their healthcare professionals, in a way that is meaningful and addresses their circumstances and risk perceptions. This research will serve as a base for future work that aims behaviour science interventions at the wider pregnant population as well as the target groups that have been identified in this review.
Topics: Infant, Newborn; Female; Humans; Pregnancy; Pregnant Women; Whooping Cough; Influenza, Human; Ireland; Pertussis Vaccine; Pregnancy Complications, Infectious; Vaccination; Influenza Vaccines; United Kingdom
PubMed: 38087222
DOI: 10.1186/s12884-023-06171-7 -
The Journal of Maternal-fetal &... Dec 2023This retrospective, single-center case series was designed to characterize the effects of perinatal COVID-19 diagnosis on obstetric and neonatal outcomes in a...
This retrospective, single-center case series was designed to characterize the effects of perinatal COVID-19 diagnosis on obstetric and neonatal outcomes in a predominantly high-risk, urban Black population.: Data were collected retrospective chart review on all COVID-19-positive obstetric patients and their neonates who presented to the University of Chicago Medical Center between March 2020 and November 2020, before the availability of the COVID-19 vaccine. Patient demographics, delivery outcomes, COVID-19 symptoms, treatment, and outcomes were analyzed. A total of 56 COVID-19-positive obstetric patients were included in the study, of which four were lost to follow-up before delivery. The median age of patients was 27 years (IQR 23, 32), with 73.2% publicly insured and 66.1% Black. Patients had a median body mass index (BMI) of 31.6 kg/m (IQR 25.9, 35.5). 3.6% of patients had chronic hypertension, 12.5% had diabetes, and 16.1% had asthma. Perinatal complications were common. Twenty-six patients (50.0%) had a diagnosis of a hypertensive disorder of pregnancy (HDP). 28.8% had gestational hypertension, and 21.2% had preeclampsia (with and without severe features). The rate of maternal ICU admission was 3.6%. Furthermore, 23.5% of patients delivered preterm (<37 weeks gestation), and 50.9% of infants were admitted to the Neonatal Intensive Care Unit (NICU). In our study of a predominantly Black, publicly-insured, unvaccinated group of COVID-19-positive pregnant patients, we found high rates of hypertensive disorders of pregnancy, preterm delivery, and NICU admission compared to rates reported in existing literature before widespread vaccine availability. Our findings suggest that SARS-CoV-2 infection during pregnancy, irrespective of maternal disease severity, may exacerbate existing obstetric health disparities by disproportionately impacting Black, publicly insured patients. Larger comparative studies are needed to better characterize possible racial and socioeconomic disparities in obstetric outcomes in the setting of SARS-CoV-2 infection during pregnancy. These studies should examine the pathophysiology of SARS-CoV-2 infection during pregnancy, as well as potential associations between adverse perinatal outcomes and disparities in access to care, COVID-19 vaccination, and other social determinants of health amongst more vulnerable populations infected with SARS-CoV-2 during pregnancy.
Topics: Pregnancy; Infant, Newborn; Female; Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Retrospective Studies; COVID-19 Testing; Pregnancy Complications, Infectious; Premature Birth; Pregnancy Outcome
PubMed: 37005011
DOI: 10.1080/14767058.2023.2196364 -
AJOG Global Reports Nov 2023Maternal sepsis is a leading cause of maternal death in the United States. Approximately two-thirds of maternal deaths because of sepsis are related to delayed...
BACKGROUND
Maternal sepsis is a leading cause of maternal death in the United States. Approximately two-thirds of maternal deaths because of sepsis are related to delayed recognition or treatment. New early warning systems using a 2-step approach have been developed for the early recognition of sepsis in obstetrics; however, their performance has not been validated.
OBJECTIVE
This study aimed to assess the performance of 3 primary screening tools introduced by the Society of Obstetric Medicine Australia and New Zealand and the California Maternal Quality Care Collaborative for use in the first step of their 2-step early warning systems. The obstetrically modified quick Sequential (sepsis-related) Organ Failure Assessment score tool, the obstetrically modified Systemic Inflammatory Response Syndrome tool, and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool were evaluated for the early detection of sepsis in patients with clinically diagnosed chorioamnionitis.
STUDY DESIGN
This was a retrospective cohort study using prospectively collected clinical data at a tertiary care center and an affiliated healthcare system. The electronic health records were searched to identify and verify cases with clinically diagnosed chorioamnionitis between November 2017 and September 2022. The flow sheet for every patient was reviewed to determine when criteria were met for any of the 3 tools. The performance of these tools was analyzed using their sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curve for the identification of sepsis.
RESULTS
There were 545 cases that had the requisite data for inclusion in the analysis. Of note, 11 patients met the criteria for sepsis. Both the obstetrically modified Systemic Inflammatory Response Syndrome and obstetrically modified Systemic Inflammatory Response Syndrome 1 tools had overall similar test characteristics, which were notably different from the obstetrically modified quick Sequential Organ Failure Assessment tool. The screen-positive rate of the obstetrically modified quick Sequential Organ Failure Assessment tool (1.5%; 95% confidence interval, 0.6%-2.9%) was lower than that of the obstetrically modified Systemic Inflammatory Response Syndrome tool (60.0%; 95% confidence interval, 55.7%-64.1%) and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool (50.0%; 95% confidence interval, 45.8%-54.3%). The sensitivities of the obstetrically modified Systemic Inflammatory Response Syndrome tool (100.0%; 95% confidence interval, 71.5%-100.0%) and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool (100.0%; 95% confidence interval, 71.5%-100.0%) were higher than that of the obstetrically modified quick Sequential Organ Failure Assessment tool (18.0%; 95% confidence interval, 2.3%-51.8%). All 3 tools had high negative predictive values; however, their positive predictive values were poor.
CONCLUSION
This study demonstrated that all 3 tools had limitations in screening for sepsis among patients with a clinical diagnosis of chorioamnionitis. The obstetrically modified quick Sequential Organ Failure Assessment tool missed more than half of the sepsis cases and, thus, had poor performance as a primary screening tool for sepsis. Both the obstetrically modified Systemic Inflammatory Response Syndrome and obstetrically modified Systemic Inflammatory Response Syndrome 1 tools captured all sepsis cases; however, they tended to overdetect sepsis.
PubMed: 37885969
DOI: 10.1016/j.xagr.2023.100271 -
Frontiers in Public Health 2023Syphilis remains a global public health problem, with growing incidence in most regions of the world, particularly among women of childbearing age. This alarming trend... (Review)
Review
Syphilis remains a global public health problem, with growing incidence in most regions of the world, particularly among women of childbearing age. This alarming trend has led to an increase in cases of congenital syphilis, resulting in devastating consequences. While the implementation of measures by the World Health Organization (WHO) and various governments has contributed to a decline in the global incidence of congenital syphilis, many countries are facing an escalating crisis, as incidence continues to rise. This mini-review aims to provide an overview of the current state of this disease in different parts of the world, focusing on the most affected populations and highlighting congenital syphilis as a marker of vulnerability. It also focuses on Switzerland, a country with a robust economy, to identify shortcomings in the healthcare system that contribute to the persistence of congenital syphilis, even though the infection is easily detectable and treatable. In conclusion, this mini-review highlights the persistent risk of congenital syphilis worldwide, regardless of country prevalence or economic status, and underscores the need for sustained efforts to reach underserved women, emphasizing the vital role of comprehensive training for healthcare professionals.
Topics: Pregnancy; Female; Humans; Syphilis, Congenital; Pregnancy Complications, Infectious; Switzerland; Infectious Disease Transmission, Vertical; Syphilis
PubMed: 37780442
DOI: 10.3389/fpubh.2023.1265725 -
PLoS Pathogens Aug 2023Zika virus (ZIKV) can be transmitted vertically from mother to fetus during pregnancy, resulting in a range of outcomes including severe birth defects and fetal/infant...
Zika virus (ZIKV) can be transmitted vertically from mother to fetus during pregnancy, resulting in a range of outcomes including severe birth defects and fetal/infant death. Potential pathways of vertical transmission in utero have been proposed but remain undefined. Identifying the timing and routes of vertical transmission of ZIKV may help us identify when interventions would be most effective. Furthermore, understanding what barriers ZIKV overcomes to effect vertical transmission may help improve models for evaluating infection by other pathogens during pregnancy. To determine the pathways of vertical transmission, we inoculated 12 pregnant rhesus macaques with an African-lineage ZIKV at gestational day 30 (term is 165 days). Eight pregnancies were surgically terminated at either seven or 14 days post-maternal infection. Maternal-fetal interface and fetal tissues and fluids were collected and evaluated for ZIKV using RT-qPCR, in situ hybridization, immunohistochemistry, and plaque assays. Four additional pregnant macaques were inoculated and terminally perfused with 4% paraformaldehyde at three, six, nine, or ten days post-maternal inoculation. For these four cases, the entire fixed pregnant uterus was evaluated with in situ hybridization for ZIKV RNA. We determined that ZIKV can reach the MFI by six days after infection and infect the fetus by ten days. Infection of the chorionic membrane and the extraembryonic coelomic fluid preceded infection of the fetus and the mesenchymal tissue of the placental villi. We did not find evidence to support a transplacental route of ZIKV vertical transmission via infection of syncytiotrophoblasts or villous cytotrophoblasts. The pattern of infection observed in the maternal-fetal interface provides evidence of paraplacental vertical ZIKV transmission through the chorionic membrane, the outer layer of the fetal membranes.
Topics: Humans; Animals; Pregnancy; Female; Zika Virus; Macaca mulatta; Zika Virus Infection; Placenta; Pregnancy Complications, Infectious; Fetal Death; Infectious Disease Transmission, Vertical; Extraembryonic Membranes
PubMed: 37549143
DOI: 10.1371/journal.ppat.1011274 -
The Lancet. Global Health Nov 2023This study estimated ethnoracial inequalities in maternal and congenital syphilis in Brazil, understanding race as a relational category product of a sociopolitical...
BACKGROUND
This study estimated ethnoracial inequalities in maternal and congenital syphilis in Brazil, understanding race as a relational category product of a sociopolitical construct that functions as an essential tool of racism and its manifestations.
METHODS
We linked routinely collected data from Jan 1, 2012 to Dec 31, 2017 to conduct a population-based study in Brazil. We estimated the attributable fraction of race (skin colour) for the entire population and specific subgroups compared with White women using adjusted logistic regression. We also obtained the attributable fraction of the intersection between two social markers (race and education) and compared it with White women with more than 12 years of education as the baseline.
FINDINGS
Of 15 810 488 birth records, 144 564 women had maternal syphilis and 79 580 had congenital syphilis. If all women had the same baseline risk as White women, 35% (95% CI 34·89-36·10) of all maternal syphilis and 41% (40·49-42·09) of all congenital syphilis would have been prevented. Compared with other ethnoracial categories, these percentages were higher among Parda/Brown women (46% [45·74-47·20] of maternal syphilis and 52% [51·09-52·93] of congenital syphilis would have been prevented) and Black women (61% [60·25-61·75] of maternal syphilis and 67% [65·87-67·60] of congenital syphilis would have been prevented). If all ethnoracial groups had the same risk as White women with more than 12 years of education, 87% of all maternal syphilis and 89% of all congenital syphilis would have been prevented.
INTERPRETATION
Only through effective control of maternal syphilis among populations at higher risk (eg, Black and Parda/Brown women with lower educational levels) can WHO's global health initiative to eliminate mother-to-child transmission of syphilis be made feasible. Recognising that racism and other intersecting forms of oppression affect the lives of minoritised groups and advocating for actions through the lens of intersectionality is imperative for attaining and guaranteeing health equity. Achieving health equality needs to be addressed to achieve syphilis control. Given the scale and complexity of the problem (which is unlikely to be unique to Brazil), structural issues and social markers of oppression, such as race and education, must be considered to prevent maternal and congenital syphilis and improve maternal and child outcomes globally.
FUNDING
Wellcome Trust, CNPq-Brazil.
TRANSLATION
For the Portuguese translation of the abstract see Supplementary Materials section.
Topics: Pregnancy; Female; Humans; Syphilis, Congenital; Syphilis; Pregnancy Complications, Infectious; Brazil; Longitudinal Studies; Infectious Disease Transmission, Vertical
PubMed: 37858584
DOI: 10.1016/S2214-109X(23)00405-9 -
MBio Oct 2023Bacteria such as GBS can cause infections during pregnancy leading to preterm births, stillbirths, and neonatal infections. The interaction between host and bacterial...
Bacteria such as GBS can cause infections during pregnancy leading to preterm births, stillbirths, and neonatal infections. The interaction between host and bacterial factors during infections in the placenta is not fully understood. GBS secretes a hyaluronidase enzyme that is thought to digest host hyaluronan into immunosuppressive disaccharides that dampen TLR2/4 signaling, leading to increased bacterial dissemination and adverse outcomes. In this study, we show that GBS HylB mediates immune suppression and promotes bacterial infection during pregnancy that requires TLR2, TLR4, and IL-10. Understanding the interaction between host and bacterial factors can inform future therapeutic strategies to mitigate GBS infections.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Hyaluronoglucosaminidase; Toll-Like Receptor 2; Interleukin-10; Streptococcus agalactiae; Pregnancy Complications, Infectious; Streptococcal Infections
PubMed: 37747229
DOI: 10.1128/mbio.02049-23