Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals.

Importance: Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. Objective: To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. Design, Setting, and Participants: This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Exposures: Self-reported or electronic health record (EHR)-derived race, ethnicity, and preferred language. Main Outcomes and Measures: Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. Results: There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; χ21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ21 = 22.8; P = .002). Conclusions and Relevance: Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.

Influenza vaccination accuracy among adults: Self-report compared with electronic health record data.

OBJECTIVE: To assess the validity of electronic health record (EHR)-based influenza vaccination data among adults in a multistate network. METHODS: Following the 2018-2019 and 2019-2020 influenza seasons, surveys were conducted among a random sample of adults who did or did not appear influenza-vaccinated (per EHR data) during the influenza season. Participants were asked to report their influenza vaccination status; self-report was treated as the criterion standard. Results were combined across survey years. RESULTS: Survey response rate was 44.7% (777 of 1740) for the 2018-2019 influenza season and 40.5% (505 of 1246) for the 2019-2020 influenza season. The sensitivity of EHR-based influenza vaccination data was 75.0% (95% confidence interval [CI] 68.1, 81.1), specificity 98.4% (95% CI 92.9, 99.9), and negative predictive value 73.9% (95% CI 68.0, 79.3). CONCLUSIONS: In a multistate research network across two recent influenza seasons, there was moderate concordance between EHR-based vaccination data and self-report.

Completion of multidose vaccine series in early childhood: current challenges and opportunities.

PURPOSE OF REVIEW: Completion of all doses in multidose vaccine series provides optimal protection against preventable infectious diseases. In this review, we describe clinical and public health implications of multidose vaccine series noncompletion, including current challenges to ensuring children receive all recommended vaccinations. We then highlight actionable steps toward achieving early childhood immunization goals. RECENT FINDINGS: Although coverage levels are high for most early childhood vaccinations, rates of completion are lower for vaccinations that require multiple doses. Recent research has shown that lower family socioeconomic status, a lack of health insurance coverage, having multiple children in the household, and moving across state lines are associated with children failing to complete multidose vaccine series. These findings provide contextual evidence to support that practical challenges to accessing immunization services are impediments to completion of multidose series. Strategies, including reminder/recall, use of centralized immunization information systems, and clinician prompts, have been shown to increase immunization rates. Re-investing in these effective interventions and modernizing the public health infrastructure can facilitate multidose vaccine series completion. SUMMARY: Completion of multidose vaccine series is a challenge for immunization service delivery. Increased efforts are needed to address remaining barriers and improve vaccination coverage in the United States.

COVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic.

During the COVID-19 pandemic, candidate COVID-19 vaccines were being developed for potential use in the United States on an unprecedented, accelerated schedule. It was anticipated that once available, under U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) or FDA approval, COVID-19 vaccines would be broadly used and potentially administered to millions of individuals in a short period of time. Intensive monitoring in the post-EUA/licensure period would be necessary for timely detection and assessment of potential safety concerns. To address this, the Centers for Disease Control and Prevention (CDC) convened an Advisory Committee on Immunization Practices (ACIP) work group focused solely on COVID-19 vaccine safety, consisting of independent vaccine safety experts and representatives from federal agencies - the ACIP COVID-19 Vaccine Safety Technical Work Group (VaST). This report provides an overview of the organization and activities of VaST, summarizes data reviewed as part of the comprehensive effort to monitor vaccine safety during the COVID-19 pandemic, and highlights selected actions taken by CDC, ACIP, and FDA in response to accumulating post-authorization safety data. VaST convened regular meetings over the course of 29 months, from November 2020 through April 2023; through March 2023 FDA issued EUAs for six COVID-19 vaccines from four different manufacturers and subsequently licensed two of these COVID-19 vaccines. The independent vaccine safety experts collaborated with federal agencies to ensure timely assessment of vaccine safety data during this time. VaST worked closely with the ACIP COVID-19 Vaccines Work Group; that work group used safety data and VaST's assessments for benefit-risk assessments and guidance for COVID-19 vaccination policy. Safety topics reviewed by VaST included those identified in safety monitoring systems and other topics of scientific or public interest. VaST provided guidance to CDC's COVID-19 vaccine safety monitoring efforts, provided a forum for review of data from several U.S. government vaccine safety systems, and assured that a diverse group of scientists and clinicians, external to the federal government, promptly reviewed vaccine safety data. In the event of a future pandemic or other biological public health emergency, the VaST model could be used to strengthen vaccine safety monitoring, enhance public confidence, and increase transparency through incorporation of independent, non-government safety experts into the monitoring process, and through strong collaboration among federal and other partners.

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older - United States, 2024.

At its October 2023 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the Recommended Adult Immunization Schedule for Ages 19 Years or Older, United States, 2024. The adult immunization schedule, which can be found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules), is published annually to consolidate and summarize updates to ACIP recommendations on the vaccination of adults and to assist health care providers in implementing current ACIP recommendations. The 2024 immunization schedule includes several changes to the cover page, tables, notes, and appendix from the 2023 immunization schedule.† In addition, the 2024 adult immunization schedule includes a new addendum section that summarizes new or updated ACIP recommendations that will occur before the next annual update to the adult immunization schedule. Health care providers are advised to use the cover page, tables, notes, appendix, and addendum together to determine recommended vaccinations for patient populations.

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2024.

At its October 2023 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger, United States, 2024. The child and adolescent immunization schedule, which can be found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules), is published annually to consolidate and summarize updates to ACIP recommendations on the vaccination of children and adolescents and to assist health care providers in implementing current ACIP recommendations. The 2024 immunization schedule includes several changes to the cover page, tables, notes, and appendix from the 2023 immunization schedule.† In addition, the 2024 child and adolescent immunization schedule includes a new addendum section to summarize new or updated ACIP recommendations that will occur before the next annual update to the child and adolescent immunization schedule. Health care providers are advised to use the cover page, tables, notes, appendix, and addendum together to identify the recommended immunizations for patient populations.

Development of COVID-19 vaccine policy - United States, 2020-2023.

COVID-19 vaccines represent a great scientific and public health achievement in the face of overwhelming pressures from a global pandemic, preventing millions of hospitalizations and deaths due to COVID-19 vaccines in the United States. Over 675 million doses of COVID-19 vaccines have been administered in the United States, and over 80% of the U.S. population has had at least 1 dose of a COVID-19 vaccine. Over the course of the COVID-19 pandemic in the United States, over one million people died from COVID-19, and over six million were hospitalized. It has been estimated that COVID-19 vaccines prevented more than 18 million additional hospitalizations and more than 3 million additional deaths due to COVID-19 in the United States. From the beginning of the COVID-19 pandemic in 2020 through June 2023, ACIP had 35 COVID-19 focused meetings and 24 votes for COVID-19 vaccine recommendations. ACIP had the critical task of rapidly and thoroughly reviewing emerging and evolving data on COVID-19 epidemiology and vaccines, as well as making comprehensive population-based recommendations for vaccine policy and considerations for implementation through a transparent and evidence-based framework. Safe and effective COVID-19 vaccines, recommended through transparent policy discussions with ACIP, remain the best tool we have to prevent serious illness, hospitalization and death from COVID-19.

Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States: The contribution of vaccine-related attitudes.

OBJECTIVE: Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States have been documented. This study assessed the contribution of vaccine-related attitudes to coverage disparities. METHODS: Surveys were conducted following the 2019-2020 and 2020-2021 influenza seasons in a US research network. Using electronic health record data to identify pregnant women, random samples were selected for surveying; non-Hispanic Black women and influenza-unvaccinated women were oversampled. Regression-based decomposition analyses were used to assess the contribution of vaccine-related attitudes to racial and ethnic differences in influenza vaccination. Data were combined across survey years, and analyses were weighted and accounted for survey design. RESULTS: Survey response rate was 41.2% (721 of 1748) for 2019-2020 and 39.3% (706 of 1798) for 2020-2021. Self-reported influenza vaccination was higher among non-Hispanic White respondents (79.4% coverage, 95% CI 73.1%-85.7%) than Hispanic (66.2% coverage, 95% CI 52.5%-79.9%) and non-Hispanic Black (55.8% coverage, 95% CI 50.2%-61.4%) respondents. For all racial and ethnic groups, a high proportion (generally >80%) reported being seen for care, recommended for influenza vaccination, and offered vaccination. In decomposition analyses, vaccine-related attitudes (e.g., worry about vaccination causing influenza; concern about vaccine safety and effectiveness) explained a statistically significant portion of the observed racial and ethnic disparities in vaccination. Maternal age, education, and health status were not significant contributors after controlling for vaccine-related attitudes. CONCLUSIONS: In a setting with relatively high influenza vaccination coverage among pregnant women, racial and ethnic disparities in coverage were identified. Vaccine-related attitudes were associated with the disparities observed.

Influenza vaccination coverage among persons ages six months and older in the Vaccine Safety Datalink in the 2017-18 through 2022-23 influenza seasons.

BACKGROUND: In the United States, annual vaccination against seasonal influenza is recommended for all people ages ≥ 6 months. Vaccination coverage assessments can identify populations less protected from influenza morbidity and mortality and help to tailor vaccination efforts. Within the Vaccine Safety Datalink population ages ≥ 6 months, we report influenza vaccination coverage for the 2017-18 through 2022-23 seasons. METHODS: Across eight health systems, we identified influenza vaccines administered from August 1 through March 31 for each season using electronic health records linked to immunization registries. Crude vaccination coverage was described for each season, overall and by self-reported sex; age group; self-reported race and ethnicity; and number of separate categories of diagnoses associated with increased risk of severe illness and complications from influenza (hereafter referred to as high-risk conditions). High-risk conditions were assessed using ICD-10-CM diagnosis codes assigned in the year preceding each influenza season. RESULTS: Among individual cohorts of more than 12 million individuals each season, overall influenza vaccination coverage increased from 41.9 % in the 2017-18 season to a peak of 46.2 % in 2019-20, prior to declaration of the COVID-19 pandemic. Coverage declined over the next three seasons, coincident with widespread SARS-CoV-2 circulation, to a low of 40.3 % in the 2022-23 season. In each of the six seasons, coverage was lowest among males, 18-49-year-olds, non-Hispanic Black people, and those with no high-risk conditions. While decreases in coverage were present in all age groups, the declines were most substantial among children: 2022-23 season coverage for children ages six months through 8 years and 9-17 years was 24.5 % and 22.4 % (14 and 10 absolute percentage points), respectively, less than peak coverage achieved in the 2019-20 season. CONCLUSIONS: Crude influenza vaccination coverage increased from 2017 to 18 through 2019-20, then decreased to the lowest level in the 2022-23 season. In this insured population, we identified persistent disparities in influenza vaccination coverage by sex, age, and race and ethnicity. The overall low coverage, disparities in coverage, and recent decreases in coverage are significant public health concerns.

Use of Updated COVID-19 Vaccines 2023-2024 Formula for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices - United States, September 2023.

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.

Simultaneous administration of mRNA COVID-19 bivalent booster and influenza vaccines.

The U.S. Food and Drug Administration authorized use of mRNA COVID-19 bivalent booster vaccines on August 31, 2022. Currently, CDC's clinical guidance states that COVID-19 and other vaccines may be administered simultaneously. At time of authorization and recommendations, limited data existed describing simultaneous administration of COVID-19 bivalent booster and other vaccines. We describe simultaneous influenza and mRNA COVID-19 bivalent booster vaccine administration between August 31-December 31, 2022, among persons aged ≥6 months in the Vaccine Safety Datalink (VSD) by COVID-19 bivalent booster vaccine type, influenza vaccine type, age group, sex, and race and ethnicity. Of 2,301,876 persons who received a COVID-19 bivalent booster vaccine, 737,992 (32.1%) received simultaneous influenza vaccine, majority were female (53.1%), aged ≥18 years (91.4%), and non-Hispanic White (55.7%). These findings can inform future VSD studies on simultaneous influenza and COVID-19 bivalent booster vaccine safety and coverage, which may have implications for immunization service delivery.

Influenza Vaccination Among Pregnant People Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic.

There are limited data on influenza vaccination coverage among pregnant people in the United States during the coronavirus disease 2019 (COVID-19) pandemic. Within the Vaccine Safety Datalink, we conducted a retrospective cohort study to examine influenza vaccination coverage during the 2016-2017 through the 2021-2022 influenza seasons among pregnant people aged 18-49 years. Using influenza vaccines administered through March each season, we assessed crude coverage by demographic and clinical characteristics. Annual influenza vaccination coverage increased from the 2016-2017 season (63.0%) to a high of 71.0% in the 2019-2020 season. After the start of the COVID-19 pandemic, it decreased to a low of 56.4% (2021-2022). In each of the six seasons, coverage was lowest among pregnant people aged 18-24 years and among non-Hispanic Black pregnant people. The 2021-2022 season had the lowest coverage across all age and race and ethnicity groups. The recent decreases highlight the need for continued efforts to improve coverage among pregnant people.

Identification of Spatial Clusters of Undervaccination Patterns Among Children Aged <24 Months Using Immunization Information System Data, Montana, 2015-2019.

OBJECTIVE: Spatial clustering of undervaccination leads to increased risk of vaccine-preventable diseases. We identified spatial clustering of undervaccination patterns among children aged <24 months in Montana. METHODS: We used Montana's immunization information system data to analyze deidentified vaccination records of children aged <24 months born from January 2015 through November 2017. We measured 3 outcomes that were not mutually exclusive: not completing the combined 7-vaccine series by age 24 months, having an undervaccination pattern indicative of parental hesitancy, and having an undervaccination pattern indicative of structural barriers to timely vaccination. Using geomasked residential addresses, we conducted separate Bernoulli spatial scans with a randomization P < .01 to identify spatial clusters consisting of ≥100 children for each outcome and calculated the relative risk of having the undervaccination pattern inside versus outside the cluster. RESULTS: Of 31 201 children aged <24 months included in our study, 11 712 (37.5%) had not completed the combined 7-vaccine series by age 24 months, and we identified 5 spatial clusters of this outcome across Montana. We identified 4 clusters of undervaccination patterns indicative of parental vaccine hesitancy, all in western Montana. The cluster with the largest relative risk (2.3) had a radius of 23.7 kilometers (n = 762 children, P < .001). We also identified 4 clusters of undervaccination patterns indicative of structural barriers, with 3 of the largest clusters in eastern Montana. CONCLUSION: In Montana, different strategies to increase routine and timely childhood vaccination are needed in distinct areas of this large and predominantly rural state. Immunization information system data can pinpoint areas where interventions to increase vaccination uptake are needed.

Failure to Complete Multidose Vaccine Series in Early Childhood.

BACKGROUND: Most early childhood immunizations require 3 to 4 doses to achieve optimal protection. Our objective was to identify factors associated with starting but not completing multidose vaccine series. METHODS: Using 2019 National Immunization Survey-Child data, US children ages 19 to 35 months were classified in 1 of 3 vaccination patterns: (1) completed the combined 7-vaccine series, (2) did not initiate ≥1 of the 7 vaccine series, or (3) initiated all series, but did not complete ≥1 multidose series. Associations between sociodemographic factors and vaccination pattern were evaluated using multivariable log-linked binomial regression. Analyses accounted for the survey's stratified design and complex weighting. RESULTS: Among 16 365 children, 72.9% completed the combined 7-vaccine series, 9.9% did not initiate ≥1 series, and 17.2% initiated, but did not complete ≥1 multidose series. Approximately 8.4% of children needed only 1 additional vaccine dose from 1 of the 5 multidose series to complete the combined 7-vaccine series. The strongest associations with starting but not completing multidose vaccine series were moving across state lines (adjusted prevalence ratio [aPR] = 1.45, 95% confidence interval [CI]: 1.18-1.79), number of children in the household (2 to 3: aPR = 1.29, 95% CI: 1.05-1.58; 4 or more: aPR = 1.68, 95% CI: 1.30-2.18), and lack of insurance coverage (aPR = 2.03, 95% CI: 1.42-2.91). CONCLUSIONS: More than 1 in 6 US children initiated but did not complete all doses in multidose vaccine series, suggesting children experienced structural barriers to vaccination. Increased focus on strategies to encourage multidose series completion is needed to optimize protection from preventable diseases and achieve vaccination coverage goals.

Safety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink.

BACKGROUND: Traditional active vaccine safety monitoring involves pre-specifying health outcomes and biologically plausible outcome-specific time windows of concern, limiting the adverse events that can be evaluated. In this study, we used tree-based scan statistics to look broadly for >60,000 possible adverse events after bivalent COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees aged ≥5 years receiving Moderna or Pfizer-BioNTech bivalent COVID-19 vaccine through November 2022 were followed for 56 days post-vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within the hierarchical ICD-10-CM diagnosis code "tree" and temporally within post-vaccination follow-up. The conditional self-controlled tree-temporal scan statistic was used, conditioning on total number of cases of each diagnosis and total number of cases of any diagnosis occurring during the scanning risk window across the entire tree. P = 0.01 was the pre-specified cut-off for statistical significance. RESULTS: Analysis included 352,509 doses of Moderna and 979,189 doses of Pfizer-BioNTech bivalent vaccines. After Moderna vaccination, no statistically significant clusters were found. After Pfizer-BioNTech, there were clusters of unspecified adverse events (Days 1-3, p = 0.0001-0.0007), influenza (Days 35-56, p = 0.0001), cough (Days 44-55, p = 0.0002), and COVID-19 (Days 52-56, p = 0.0004). CONCLUSIONS: For Pfizer-BioNTech only, we detected clusters of: (1) unspecified adverse effects, as have been observed in other vaccine studies using this method, and (2) respiratory disease toward the end of follow-up. The respiratory clusters were likely due to overlap of follow-up with the spread of respiratory syncytial virus, influenza, and COVID-19, i.e., confounding by seasonality. The untargeted nature of the method and its inherent adjustment for the many diagnoses and risk intervals evaluated are unique advantages. Limitations include susceptibility to time-varying confounding, lower statistical power for assessing risks of specific outcomes than in traditional studies targeting fewer outcomes, and the possibility of missing adverse events not strongly clustered in time or within the "tree."

Interim Recommendations for Use of Bivalent mRNA COVID-19 Vaccines for Persons Aged ≥6 Months - United States, April 2023.

Throughout the national public health emergency declared in response to the COVID-19 pandemic, CDC, guided by the Advisory Committee on Immunization Practices (ACIP), has offered evidence-based recommendations for the use of COVID-19 vaccines in U.S. populations after each regulatory action by the Food and Drug Administration (FDA). During August 2022-April 2023, FDA amended its Emergency Use Authorizations (EUAs) to authorize the use of a single, age-appropriate, bivalent COVID-19 vaccine dose (i.e., containing components from the ancestral and Omicron BA.4/BA.5 strains in equal amounts) for all persons aged ≥6 years, use of bivalent COVID-19 vaccine doses for children aged 6 months-5 years, and additional bivalent doses for immunocompromised persons and adults aged ≥65 years (1). ACIP voted in September 2022 on the use of the bivalent vaccine, and CDC made recommendations after the September vote and subsequently, through April 2023, with input from ACIP. This transition to a single bivalent COVID-19 vaccine dose for most persons, with additional doses for persons at increased risk for severe disease, facilitates implementation of simpler, more flexible recommendations. Three COVID-19 vaccines are currently available for use in the United States and recommended by ACIP: 1) the bivalent mRNA Pfizer-BioNTech COVID-19 vaccine, 2) the bivalent mRNA Moderna COVID-19 vaccine, and 3) the monovalent adjuvanted, protein subunit-based Novavax COVID-19 vaccine.* As of August 31, 2022, monovalent mRNA vaccines based on the ancestral SARS-CoV-2 strain are no longer authorized for use in the United States (1).

Medically Attended Acute Adverse Events in Pregnant People After Coronavirus Disease 2019 (COVID-19) Booster Vaccination.

In this multisite, observational, matched cohort study of more than 80,000 pregnant people, receipt of an mRNA monovalent coronavirus disease 2019 (COVID-19) booster vaccination in pregnancy was not associated with increased risk for thrombocytopenia, myocarditis, venous thromboembolism, ischemic stroke, or other serious adverse events within 21 or 42 days after booster vaccination. The mRNA monovalent COVID-19 booster in pregnancy was associated with an increased risk for medically attended malaise or fatigue within 7 days of vaccination (adjusted rate ratio [aRR] 3.64, 95% CI 2.42-5.48) and lymphadenopathy or lymphadenitis within 21 days (aRR 3.25, 95% CI 1.67-6.30) or 42 days (aRR 2.18, 95% CI 1.33-3.58) of vaccination. Our findings are consistent with prior evaluations of the primary COVID-19 vaccine series and are reassuring with respect to COVID-19 booster vaccination in pregnancy.

COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion.

Importance: Adherence to COVID-19 booster vaccine recommendations has lagged in pregnant and nonpregnant adult populations. One barrier to booster vaccination is uncertainty regarding the safety of booster doses among pregnant people. Objective: To evaluate whether there is an association between COVID-19 booster vaccination during pregnancy and spontaneous abortion. Design, Setting, and Participants: This observational, case-control, surveillance study evaluated people aged 16 to 49 years with pregnancies at 6 to 19 weeks' gestation at 8 health systems in the Vaccine Safety Datalink from November 1, 2021, to June 12, 2022. Spontaneous abortion cases and ongoing pregnancy controls were evaluated during consecutive surveillance periods, defined by calendar time. Exposure: Primary exposure was receipt of a third messenger RNA (mRNA) COVID-19 vaccine dose within 28 days before spontaneous abortion or index date (midpoint of surveillance period in ongoing pregnancy controls). Secondary exposures were third mRNA vaccine doses in a 42-day window or any COVID-19 booster in 28- and 42-day windows. Main Outcomes and Measures: Spontaneous abortion cases and ongoing pregnancy controls were identified from electronic health data using a validated algorithm. Cases were assigned to a single surveillance period based on pregnancy outcome date. Eligible ongoing pregnancy time was assigned to 1 or more surveillance periods as an ongoing pregnancy-period control. Generalized estimating equations were used to estimate adjusted odds ratios (AOR) with gestational age, maternal age, antenatal visits, race and ethnicity, site, and surveillance period as covariates and robust variance estimates to account for inclusion of multiple pregnancy periods per unique pregnancy. Results: Among 112 718 unique pregnancies included in the study, the mean (SD) maternal age was 30.6 (5.5) years. Pregnant individuals were Asian, non-Hispanic (15.1%); Black, non-Hispanic (7.5%); Hispanic (35.6%); White, non-Hispanic (31.2%); and of other or unknown (10.6%); and 100% were female. Across eight 28-day surveillance periods, among 270 853 ongoing pregnancy-period controls, 11 095 (4.1%) had received a third mRNA COVID-19 vaccine in a 28-day window; among 14 226 cases, 553 (3.9%) had received a third mRNA COVID-19 vaccine within 28 days of the spontaneous abortion. Receipt of a third mRNA COVID-19 vaccine was not associated with spontaneous abortion in a 28-day window (AOR, 0.94; 95% CI, 0.86-1.03). Results were consistent when using a 42-day window (AOR, 0.97; 95% CI, 0.90-1.05) and for any COVID-19 booster in a 28-day (AOR, 0.94; 95% CI, 0.86-1.02) or 42-day (AOR, 0.96; 95% CI, 0.89-1.04) exposure window. Conclusions and Relevance: In this case-control surveillance study, COVID-19 booster vaccination in pregnancy was not associated with spontaneous abortion. These findings support the safety of recommendations for COVID-19 booster vaccination, including in pregnant populations.

Tdap vaccination during pregnancy and risk of chorioamnionitis and related infant outcomes.

INTRODUCTION: An increased risk of chorioamnionitis in people receiving tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy has been reported. The importance of this association is unclear as additional study has not demonstrated increased adverse infant outcomes associated with Tdap vaccination in pregnancy. METHODS: We conducted a retrospective observational cohort study of pregnant people ages 15-49 years with singleton pregnancies ending in live birth who were members of 8 Vaccine Safety Datalink (VSD) sites during October 2016-September 2018. We used a time-dependent covariate Cox model with stabilized inverse probability weights applied to evaluate associations between Tdap vaccination during pregnancy and chorioamnionitis and preterm birth outcomes. We used Poisson regression with robust variance with stabilized inverse probability weights applied to evaluate the association of Tdap vaccination with adverse infant outcomes. We performed medical record reviews on a random sample of patients with ICD-10-CM-diagnosed chorioamnionitis to determine positive predictive values (PPV) of coded chorioamnionitisfor "probable clinical chorioamnionitis," "possible clinical chorioamnionitis," or "histologic chorioamnionitis." RESULTS: We included 118,211 pregnant people; 103,258 (87%) received Tdap vaccine during pregnancy; 8098 (7%) were diagnosed with chorioamnionitis. The adjusted hazard ratio for chorioamnionitis in the Tdap vaccine-exposed group compared to unexposed was 0.96 (95% CI 0.90-1.03). There was no association between Tdap vaccine and preterm birth or adverse infant outcomes associated with chorioamnionitis. Chart reviews were performed for 528 pregnant people with chorioamnionitis. The PPV for clinical (probable or possible clinical chorioamnionitis) was 48% and 59% for histologic chorioamnionitis. The PPV for the combined outcome of clinical or histologic chorioamnionitis was 81%. CONCLUSIONS AND RELEVANCE: Tdap vaccine exposure during pregnancy was not associated with chorioamnionitis, preterm birth, or adverse infant outcomes. ICD-10 codes for chorioamnionitis lack specificity for clinical chorioamnionitis and should be a recognized limitation when interpreting results.