Maternal and perinatal health research during emerging and ongoing epidemic threats: a landscape analysis and expert consultation.

INTRODUCTION: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner. METHODS: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of Science, Google Scholar and PubMed augmented by key informant interviews. Findings were reviewed and Quid analysis was performed to identify clusters and connectors across research networks followed by two expert consultations. These formed the basis for the development of an operational framework for maternal and perinatal research during epidemics. RESULTS: Ninety-four relevant research efforts were identified. Although well suited to generating epidemiological data, the entire infrastructure to support a robust research response remains insufficient, particularly for use of medical products in pregnancy. Limitations in global governance, coordination, funding and data-gathering systems have slowed down research responses. CONCLUSION: Leveraging current research efforts while engaging multinational and regional networks may be the most effective way to scale up maternal and perinatal research preparedness and response. The findings of this landscape analysis and proposed operational framework will pave the way for developing a roadmap to guide coordination efforts, facilitate collaboration and ultimately promote rapid access to countermeasures and clinical care for pregnant women and their offspring in future epidemics.

Neurodevelopmental assessment of normocephalic children born to Zika virus exposed and unexposed pregnant people.

BACKGROUND: Studies examining the association between in utero Zika virus (ZIKV) exposure and child neurodevelopmental outcomes have produced varied results. METHODS: We aimed to assess neurodevelopmental outcomes among normocephalic children born from pregnant people enrolled in the Zika in Pregnancy in Honduras (ZIPH) cohort study, July-December 2016. Enrollment occurred during the first prenatal visit. Exposure was defined as prenatal ZIKV IgM and/or ZIKV RNA result at enrollment. Normocephalic children, >6 months old, were selected for longitudinal follow-up using the Bayley Scales of Infant and Toddler Development (BSID-III) and the Ages & Stages Questionnaires: Social-Emotional (ASQ:SE-2). RESULTS: One hundred fifty-two children were assessed; after exclusion, 60 were exposed and 72 were unexposed to ZIKV during pregnancy. Twenty children in the exposed group and 21 children in the unexposed group had a composite score <85 in any of the BSID-III domains. Although exposed children had lower cognitive and language scores, differences were not statistically significant. For ASQ:SE-2 assessment, there were not statistically significant differences between groups. CONCLUSIONS: This study found no statistically significant differences in the neurodevelopment of normocephalic children between in utero ZIKV exposed and unexposed. Nevertheless, long-term monitoring of children with in utero ZIKV exposure is warranted. IMPACT: This study found no statistically significant differences in the neurodevelopment in normocephalic children with in utero Zika virus exposure compared to unexposed children, although the exposed group showed lower cognitive and language scores that persisted after adjustment by maternal age and education and after excluding children born preterm and low birth weight from the analysis. Children with prenatal Zika virus exposure, including those normocephalic and have no evidence of abnormalities at birth, should be monitored for neurodevelopmental delays. Follow-up is important to be able to detect developmental abnormalities that might not be detected earlier in life.

Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed. METHODS: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185). RESULTS: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons. CONCLUSION: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed.

COVID-19 mitigation measures increase preterm birth and low birth weight in the public healthcare system in Uruguay.

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on preterm birth (PB) and low birth weight (LBW), comparing public and private healthcare systems of the National Integrated Health System in Uruguay, where the mitigation measures for the COVID-19 pandemic generated an immediate socioeconomic and psychological crisis, which caused a sharp widening of existing socioeconomic inequalities. METHODS: A national observational study was conducted comparing perinatal outcomes in the first 6 months of 2020 (period of the pandemic without pregnancy infections), which was the beginning of the pandemic, with the same period of the previous year 2019 (pre-pandemic period with no mitigation measures) among pregnant women from the public and private health systems. Data were retrieved from the national database (Informatic Perinatal System) and analyzed by healthcare system category. RESULTS: A total of 36 559 deliveries were assessed: 18 563 in the 2019 study period and 17 996 in the 2020 study period. In the public system, there was a significant increase in the risk of LBW (adjusted relative risk [aRR] 1.12, 95% confidence interval [CI] 1.05-1.36) and of the composite outcome (PB or LBW) (aRR 1.15, 95% CI 1.04-1.26). In the private system, by contrast, there was a non-statistically significant decrease of LBW and there were no changes in the incidence of PB and the composite outcome in 2020. CONCLUSION: The different evolution of birth outcomes in the public and private systems suggests an unequal impact of mitigation measures on populations of different socioeconomic levels. Given that no COVID-19 infections were identified in pregnant women during the study period, this research offers an opportunity to differentiate the biologic effects of the virus from the psychological and social impacts derived from containment measures. GOV IDENTIFIER: NCT05087160.

Data collection systems for active safety surveillance of vaccines during pregnancy in low- and middle-income countries: developing and piloting an assessment tool (VPASS).

BACKGROUND: There is an urgent need for active safety surveillance to monitor vaccine exposure during pregnancy in low- and middle-income countries (LMICs). Existing maternal, newborn, and child health (MNCH) data collection systems could serve as platforms for post-marketing active surveillance of maternal immunization safety. To identify sites using existing systems, a thorough assessment should be conducted. Therefore, this study had the objectives to first develop an assessment tool and then to pilot this tool in sites using MNCH data collection systems through virtual informant interviews. METHODS: We conducted a rapid review of the literature to identify frameworks on population health or post-marketing drug surveillance. Four frameworks that met the eligibility criteria were identified and served to develop an assessment tool capable of evaluating sites that could support active monitoring of vaccine safety during pregnancy. We conducted semi-structured interviews in six geographical sites using MNCH data collection systems (DHIS2, INDEPTH, and GNMNHR) to pilot domains included in the assessment tool. RESULTS: We developed and piloted the "VPASS (Vaccines during Pregnancy - sites supporting Active Safety Surveillance) assessment tool" through interviews with nine stakeholders, including central-level systems key informants and site-level managers from DHIS2 and GNMNHR; DHIS2 in Kampala (Uganda) and Kigali (Rwanda); GNMNHR from Belagavi (India) and Lusaka (Zambia); and INDEPTH from Nanoro (Burkina Faso) and Manhica (Mozambique). The tool includes different domains such as the system's purpose, the scale of implementation, data capture and confidentiality, type of data collected, the capability of integration with other platforms, data management policies and data quality monitoring. Similarities among sites were found regarding some domains, such as data confidentiality, data management policies, and data quality monitoring. Four of the six sites met some domains to be eligible as potential sites for active surveillance of vaccinations during pregnancy, such as a routine collection of MNCH individual data and the capability of electronically integrating individual MNCH outcomes with information related to vaccine exposure during pregnancy. Those sites were: Rwanda (DHIS2), Manhica (IN-DEPTH), Lusaka (GNMNHR), and Belagavi (GNMNHR). CONCLUSION: This study's findings should inform the successful implementation of active safety surveillance of vaccines during pregnancy by identifying and using active individual MNCH data collection systems in LMICs.

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.

Estimation of the morbidity and mortality of congenital Chagas disease: A systematic review and meta-analysis.

Chagas disease is caused by the parasite Trypanosoma cruzi which can be transmitted from mother to baby during pregnancy. There is no consensus on the proportion of infected infants with clinical signs of congenital Chagas disease (cCD). The objective of this systematic review is to determine the burden of cCD. Articles from journal inception to 2020 reporting morbidity and mortality associated with cCD were retrieved from academic search databases. Observational studies, randomized-control trials, and studies of babies diagnosed with cCD were included. Studies were excluded if they were case reports or series, without original data, case-control without cCD incidence estimates, and/or did not report number of participants. Two reviewers screened articles for inclusion. To determine pooled proportion of infants with cCD with clinical signs, individual clinical signs, and case-fatality, random effects meta-analysis was performed. We identified 4,531 records and reviewed 4,301, including 47 articles in the narrative summary and analysis. Twenty-eight percent of cCD infants showed clinical signs (95% confidence interval (CI) = 19.0%, 38.5%) and 2.2% of infants died (95% CI = 1.3%, 3.5%). The proportion of infected infants with hepatosplenomegaly was 12.5%, preterm birth 6.0%, low birth weight 5.8%, anemia 4.9%, and jaundice 4.7%. Although most studies did not include a comparison group of non-infected infants, the proportion of infants with cCD with clinical signs at birth are comparable to those with congenital toxoplasmosis (10.0%-30.0%) and congenital cytomegalovirus (10.0%-15.0%). We conclude that cCD burden appears significant, but more studies comparing infected mother-infant dyads to non-infected ones are needed to determine an association of this burden to cCD.

Epigenetic signature of exposure to maternal Trypanosoma cruzi infection in cord blood cells from uninfected newborns.

Aims: To assess the epigenetic effects of in utero exposure to maternal Trypanosoma cruzi infection. Methods: We performed an epigenome-wide association study to compare the DNA methylation patterns of umbilical cord blood cells from uninfected babies from chagasic and uninfected mothers. DNA methylation was measured using Infinium EPIC arrays. Results: We identified a differential DNA methylation signature of fetal exposure to maternal T. cruzi infection, in the absence of parasite transmission, with 12 differentially methylated sites in B cells and CD4+ T cells, including eight protein-coding genes. Conclusion: These genes participate in hematopoietic cell differentiation and the immune response and may be involved in immune disorders. They also have been associated with several developmental disorders and syndromes.

Maternal infection with Trypanosoma cruzi, the parasite that causes Chagas disease, may influence fetal development, even in the absence of parasite transmission. Thus we investigated how exposure to maternal infection might lead to changes in gene expression in the infant, by examining changes in DNA methylation in the umbilical cord blood. We found that exposure to maternal infection alters DNA methylation of at least 12 sites, including eight genes. Expression of these genes may be altered, which may affect blood cell function, the immune response and newborn development later in life. Further studies should monitor newborns from infected mothers to better assess their health and possible longer term effects.

Understanding perinatal patient's health preferences and patient-provider relationships to prevent congenital syphilis in California and Louisiana.

BACKGROUND: Congenital syphilis (CS) has reemerged as a global maternal and child health crisis. Kern County, California and East Baton Rouge Parish, Louisiana are among the highest CS morbidity regions in the United States. We previously reported on social-ecological and structural barriers to prenatal care and maternal syphilis testing and treatment in these two regions. The aim of this study was to examine perinatal patient's health preferences and perceptions of patient-provider relationships in the prenatal care clinic setting. METHODS: Between May 2018 and January 2019 we conducted 20 in-depth qualitative interviews with prenatal providers and 8 focus group discussions with pregnant and postpartum individuals in Kern County and East Baton Rouge Parish. We applied an adapted health services framework to analyze participants' understanding of health disparities and vulnerable populations; perinatal patient's health and prenatal care preferences; and participants' perspectives of clinical encounters in the context of prenatal care and maternal syphilis testing and treatment. RESULTS: Site-specific determinants of syphilis infection emerged but participants from both locations felt CS prevention efforts should be prioritized among youth, racial/ethnic minority populations, people experiencing socioeconomic limitations and people with other commonly occurring health conditions. Although perinatal patients expressed clear health preferences, they reported inconsistent receipt of respectful, patient-centered care. Inconsistencies were connected with limited ethnic and cultural competence among providers, and implicit, negative attitudes toward patients using substances, experiencing homelessness, or engaging in sex work. Providers clearly aimed to offer high quality prenatal care. However, some clinic and health systems level factors were thought to reduce positive and communicative patient-provider relationships, contributing to gaps in use of prenatal care and syphilis testing and treatment. CONCLUSIONS: Our findings suggest that interventions tailored to address setting-specific determinants (including clinic and health system factors) of disparities in CS risk could improve pregnant people's access to prenatal care and ensure they and their sex partners receive timely syphilis screening and treatment. We recommend all prenatal care providers receive training on how to identify and mitigate implicit biases and provide competent and compassionate patient-centered care.

Gaps in the congenital syphilis prevention cascade: qualitative findings from Kern County, California.

BACKGROUND: Congenital syphilis is preventable through timely access to prenatal care, syphilis screening and treatment of pregnant women diagnosed as infected. In 2018, California had the second highest number of congenital syphilis cases in the United States (U.S.), a nearly twofold increase in cases since 2014. This study assessed gaps in preventing congenital syphilis in the high morbidity region of Kern County, California. METHODS: Between May 2018 and January 2019, we conducted five focus group discussions with pregnant/postpartum women and ten semi-structured interviews with prenatal care providers in Kern County. Focus group and interview data were recorded, transcribed, and analyzed to identify emergent themes pertaining to facilitators and barriers at each step (prenatal care, syphilis screening and treatment) in the congenital syphilis prevention cascade. RESULTS: Gaps in congenital syphilis prevention discussed in focus group discussions with pregnant/postpartum women were related to limited prenatal care access, social-, economic-, and cultural-barriers, and substance use and co-occurring intimate partner/domestic violence. The gaps identified from interviews with prenatal care providers included social economic vulnerabilities of pregnant women and stigma and shame around the vulnerabilities, distrust in medical system, prenatal substance use, limited prenatal substance use disorder treatment facilities, and inadequate provider training on context-specific congenital syphilis management strategies. Gaps in partner notification, screening and treatment for syphilis were brought up by pregnant/postpartum women and prenatal care providers. CONCLUSIONS: Congenital syphilis continues to increase in Kern County and throughout the U.S. In high syphilis morbidity areas, comprehensive and tailored public health approaches addressing setting-specific gaps in prenatal screening and treatment are needed.

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.

Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection.

Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most diagnosis is based on serological tests, but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples from a cohort of well-characterized T. cruzi-infected women to evaluate the reactivity of two rapid diagnostic tests and one enzyme-linked immunosorbent assay (ELISA). Our cohort was derived from a previous study on congenital transmission of T. cruzi and consisted of 481 blood/plasma samples from Argentina (n = 149), Honduras (n = 228), and Mexico (n = 104), with at least one positive T. cruzi PCR. Reactivity of the three tests ranged from 70.5% for the Wiener ELISA to 81.0% for the T-Detect and 90.4% for the Stat-Pak rapid tests. Test reactivity varied significantly among countries and was highest in Argentina and lowest in Mexico. When considering at least two reactive serological tests to confirm seropositivity, over 12% of T. cruzi infection cases from Argentina were missed by serological tests, over 21% in Honduras, and an alarming 72% in Mexico. Differences in test performance among countries were not due to differences in parasitemia, but differences in antibody levels against ELISA antigens were observed. Geographic differences in T. cruzi parasite strains as well as genetic differences among human populations both may contribute to the discrepancies in serological testing. Improvements in serological diagnostics for T. cruzi infections are critically needed to ensure an optimum identification of cases.

Self-reported oil spill exposure and birth outcomes among southern Louisiana women at the time of the Gulf oil spill: The GROWH study.

BACKGROUND: The chemical, physical, economic, and social effects of a major oil spill might adversely affect pregnancy health. OBJECTIVES: To examine the relationship between oil spill exposure and birth outcomes in a cohort of women living near the Gulf of Mexico at the time of the 2010 oil spill. METHODS: Between 2012 and 2016, 1375 women reported their exposure to the oil spill, and at least one livebirth. Five hundred and three had births both before and after the oil spill. Indicators of oil spill exposure included self-reported financial consequences, direct contact with oil, traumatic experiences, loss of use of the coast, and involvement in litigation. Birth outcomes were low birthweight (LBW; birthweight <2500 g) and preterm birth (PTB; >3 weeks early). Women who were not pregnant at the time of the interview (n = 1001) self-reported outcomes, while women who were pregnant (n = 374) primarily had them abstracted from medical records (n = 374). All pregnancies prior to the oil spill were considered unexposed; those after the oil spill were considered exposed or unexposed depending on interview responses. Generalized estimating equations were used to control for clustering within women, with control for confounders. RESULTS: The most common type of exposure was economic (49%), but 302 women (22.0%) reported some degree of direct contact with the oil. Associations between most indicators of oil spill exposure and pregnancy outcomes were null, although when all pregnancies were examined, associations were seen with high levels of contact with oil for LBW (adjusted Odds Ratio [aOR] 2.19, 95% CI, 1.29-3.71) and PTB (aOR 2.27, 1.34-3.87). DISCUSSION: In this community-based cohort, we did not find associations between report of exposure to the oil spill, with the possible exception of high oil contact in some analyses, and birth outcomes. Research incorporating specific biomarkers of oil spill exposure and stress biomarkers would be valuable, to allow for assessing both perceived and actual exposure, especially when direct toxicant exposure is minimal.

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.

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.