COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes

Background We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783). Methods We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR’s results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables. Results We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28–100%), mild respiratory symptoms (20–79%), raised C-reactive protein (28–96%), lymphopenia (34–80%), and pneumonia signs in diagnostic imaging (7–99%). The most frequent maternal outcomes were C-section (23–96%) and preterm delivery (14–64%). Most of their babies were asymptomatic (16–93%) or presented fever (0–50%), low birth weight (5–43%) or preterm delivery (2–69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36–2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05–4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks. Conclusion This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.Fil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Bardach, Ariel Esteban. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Comandé, Daniel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Berrueta, Mabel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Argento, Fernando J.. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Rodriguez Cairoli, Federico. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Zamora, Natalia. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Santa María, Victoria. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Xiong, Xu. University of Tulane; Estados UnidosFil: Zaraa, Sabra. University of Washington; Estados UnidosFil: Mazzoni, Agustina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Buekens, Pierre. University of Tulane; Estados Unido

Maternal and neonatal data collection systems in low- and middle-income countries: Scoping review protocol

Background: Pregnant women and neonates represent one of the most vulnerable groups, especially in low- and middle-income countries (LMICs). A recent analysis reported that most vaccine pharmacovigilance systems in LMICs consist of spontaneous (passive) adverse event reporting. Thus, LMICs need effective active surveillance approaches, such as pregnancy registries. We intend to identify currently active maternal and neonatal data collection systems in LMICs, with the potential to inform active safety electronic surveillance for novel vaccines using standardized definitions. Methods: A scoping review will be conducted based on established methodology. Multiple databases of indexed and grey literature will be searched with a specific focus on existing electronic and paper-electronic systems in LMICs that collect continuous, prospective, and individual-level data from antenatal care, delivery, neonatal care (up to 28 days), and postpartum (up to 42 days) at the facility and community level, at the national and district level, and at large hospitals. Also, experts will be contacted to identify unpublished information on relevant data collection systems. General and specific descriptions of Health Information Systems (HIS) extracted from the different sources will be combined and duplicated HIS will be removed, producing a list of unique statements. We will present a final list of Maternal, Newborn, and Child Health systems considered flexible enough to be updated with necessary improvements to detect, assess and respond to safety concerns during the introduction of vaccines and other maternal health interventions. Selected experts will participate in an in-person consultation meeting to select up to three systems to be further explored in situ. Results and knowledge gaps will be synthesized after expert consultation.Fil: Berrueta, Mabel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Xiong, Xu. University of Tulane; Estados UnidosFil: Stergachis, Andy. University of Washington; Estados UnidosFil: Zaraa, Sabra. University of Washington; Estados UnidosFil: Buekens, Pierre. University of Tulane; Estados UnidosFil: Absalon, Judith. No especifíca;Fil: Anderson, Steve. No especifíca;Fil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Madhi, Shabir A.. No especifíca;Fil: McClure, Elizabeth. No especifíca;Fil: Munoz, Flor M.. No especifíca;Fil: Mwamwitwa, Kissa W.. No especifíca;Fil: Nakimuli, Annettee. No especifíca;Fil: Clark Nelson, Jennifer. No especifíca;Fil: Noguchi, Lisa. No especifíca;Fil: Panagiotakopoulos, Lakshmi. No especifíca;Fil: Sevene, Esperanca. No especifíca;Fil: Zuber, Patrick. No especifíca;Fil: Belizan, Maria. No especifíca;Fil: Bergel, Eduardo. No especifíca;Fil: Rodriguez Cairoli, Federico. No especifíca;Fil: Castellanos, Fabricio. No especifíca;Fil: Ciganda, Alvaro. No especifíca;Fil: Comande, Daniel. No especifíca;Fil: Pingray, Veronica. No especifíca

Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review.

BACKGROUND: Pregnant women with COVID-19 are at an increased risk of severe COVID-19 illness as well as adverse pregnancy and birth outcomes. Many countries are vaccinating or considering vaccinating pregnant women with limited available data about the safety of this strategy. Early identification of safety concerns of COVID-19 vaccines, including their components, or their technological platforms is therefore urgently needed. METHODS: We conducted a rapid systematic review, as the first phase of an ongoing full systematic review, to evaluate the safety of COVID-19 vaccines in pregnant women, including their components, and their technological platforms (whole virus, protein, viral vector or nucleic acid) used in other vaccines, following the Cochrane methods and the PRISMA statement for reporting (PROSPERO-CRD42021234185).We searched literature databases, COVID-19 and pregnancy registries from inception February 2021 without time or language restriction and explored the reference lists of relevant systematic reviews retrieved. We selected studies of any methodological design that included at least 50 pregnant women or pregnant animals exposed to the vaccines that were selected for review by the COVAX MIWG in August 2020 or their components or platforms included in the COVID-19 vaccines, and evaluated adverse events during pregnancy and the neonatal period.Pairs of reviewers independently selected studies through the COVIDENCE web software and performed the data extraction through a previously piloted online extraction form. Discrepancies were resolved by consensus. RESULTS: We identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals) and 12 pregnancy registries were included.Most studies (89%) were conducted in high-income countries. The most frequent study design was cohort studies (n=21), followed by surveillance studies, randomized controlled trials, and registry analyses. Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures during the three trimesters of pregnancy.The most frequent exposure was to AS03 adjuvant in the context of A/H1N1 pandemic influenza vaccines (n=24), followed by aluminum-based adjuvants (n=11). Aluminum phosphate was used in Respiratory Syncytial Virus Fusion candidate vaccines (n=3) and Tdap vaccines (n=3). Different aluminum-based adjuvants were used in hepatitis vaccines. The replication-deficient simian adenovirus ChAdOx1 was used for a Rift Valley fever vaccine. Only one study reported exposure to messenger RNA (mRNA) COVID-19 vaccines that also used lipid nanoparticles. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03) - corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines that were selected for review by the COVAX MIWG or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted given their novelty. Our findings support current WHO guidelines recommending that pregnant women may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease

Performance assessment of point-of-dispensing practices of donated oncology medicines: The Max Foundation

Thesis (Master's)--University of Washington, 2018Background Cancer is one of the leading causes of morbidity and mortality worldwide, yet financial barriers limit access to life-saving oncology drugs in low- and middle-income countries (LMICs). For the past 15 years, the Glivec® International Patient Assistance Program (GIPAP), established by Novartis and implemented in partnership with The Max Foundation, has been improving patient access to quality assured oncology drugs in LMICs. However, there have been no performance assessments to-date of medicine-related services at point-of-dispensing sites. The primary goal of this study was to evaluate the quality of performance at 48 point-of-dispensing sites located in 41 LMICs. By doing so, the evaluation establishes a baseline of the procedures’ weaknesses and the strengths for continuous quality improvement. Methods A cross-sectional embedded mixed-method study was conducted. We performed a secondary data analysis of pre-recorded data collected from January 2017 until December 2017, using a checklist and a site report template. The analysis consisted of analysis and interpretation of descriptive statistics and a directed approach to content analysis to assess the quality of ten quality categories, including storage conditions, diagnostics, and adverse event reporting. The quality of data collected was also assessed in terms of completeness and content validity. The results were used to develop a set of recommendations for future performance assessments of point-of-dispensing sites. Results Fourteen point-of-dispensing sites were classified as top performers, while 24 were classified as average performers and seven sites were called to implement most improvements. Data were 100% complete for four out of 10 selected quality categories; the other categories had 2-38% missing values. Content validity was “good” in eight quality categories, “average” in two categories and “poor” in one category. Conclusion The quality of the performance in point-of-dispensing sites as well as the quality of the performance of the assessment tool can be improved. Completeness and content validity of data collected was not achieved at a number of sites. Seven recommendations are proposed to address weaknesses of measurement procedures and data collection to ensure better performance and performance assessment at point-of-dispensing sites in the future

Health and Economic Burden of Substandard and Falsified Medicines

Thesis (Ph.D.)--University of Washington, 2023One in 10 medical products in low- and middle-income countries (LMICs) are reportedly substandard or falsified (SF). Poor quality medicines burden health systems and individuals by diverting resources to harmful or ineffective products, prolonging illnesses and increasing risks of complications and mortality. While several models have been developed to estimate the health and economic impact of SF medicines, they have been applied solely to specific medicines (i.e., antimalarials and antibiotics) in a small number of settings. In order to address this gap and advance the field, this dissertation aimed to develop tools to help countries assess their health and economic burden from SF medicines more broadly. First, we developed a conceptual framework as a guide for the estimation of the health and economic burden of SF medicines by identifying high priority medicines and evaluating data availability, gaps and modeling approaches. Second, we developed an adaptable model as a tool that can be used to estimate the health and economic burden of any medicine in any country. Third, we applied it oxytocin in Kenya as a case study. Finally, we developed a comprehensive disease-specific model for oxytocin that captures all relevant aspects of disease progression and specifications to generate more accurate estimates and to compare its findings to those generated by an adaptable model. The adaptable model estimated that among 1.2 million pregnant patients delivering in healthcare facilities in Kenya yearly, the burden of SF oxytocin (assuming a prevalence of 7%) is estimated be responsible for 2,493 additional cases of postpartum bleeding, 25 hysterectomies, 26 deaths and over 420 years of life lost. The economic burden was estimated to be approximately $1,240,000 from a societal perspective, reflecting approximately$300,000 due to early death and lost productivity and approximately $940,000 in direct medical costs annually. For the same population, the oxytocin-specific model estimated that 7$1,970,000 from a societal perspective, reflecting approximately $740,000 due to early death and lost productivity and approximately$1,220,000 in direct medical costs. The magnitude of the burden generated by the oxytocin-specific model was comparable to the adaptable model. but the results yielded were more accurate. These findings demonstrate that SF oxytocin is an urgent issue to be addressed and Kenya and that the adaptable model can be leveraged by relevant stakeholders as a tool to generate high-level estimates on the health and economic burden of any medicine in their country. The significance of this study lies in its ability to provide policymakers in Kenya with crucial information that will assist them in making informed decisions about the issue of SF oxytocin and in its potential to provide other key stakeholders tools to generate locally specific and policy-relevant evidence on the burden of other SF medicines

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

INTRODUCTION: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions. METHODS AND ANALYSIS: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence

Safety of components and platforms of COVID-19 vaccines considered for use in pregnancy: A rapid review.

BACKGROUND: Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed. METHODS: We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185). RESULTS: We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n = 24) and aluminum-based adjuvants (n = 11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease