BACKGROUND: The JYNNEOS vaccine (two doses given 28 days apart) was recommended in the United States for people at high risk of exposure to monkeypox virus during the 2022 mpox outbreak. Our objective was to assess the safety of JYNNEOS using two complementary epidemiologic methods. METHODS: This observational cohort included patients of eight large integrated healthcare organizations who received JYNNEOS. Adverse events were identified using ICD-10 coded diagnoses assigned to medical visits. The first analysis used standardized incidence ratios (SIR) to compare the observed incidence of ten prespecified adverse events of special interest (AESI) during the 28 days after receipt of each dose of JYNNEOS to the expected incidence adjusted for several risk factors. The second analysis used tree-based data mining to identify temporal clustering of cases for more than 60,000 diagnoses and diagnosis groups within 70-days after JYNNEOS dose 1 administration. RESULTS: The SIR analysis included 53,583 adults who received JYNNEOS dose 1 and 38,206 who received dose 2. Males received 92% of the doses. There were no statistically significant elevated SIRs for any of the ten AESI. The tree-based data mining analysis included 36,912 vaccinees. Analysis of diagnoses in inpatient, emergency department, and outpatient settings identified statistically significant clusters of visits for rash and unspecified adverse effects. CONCLUSIONS: No new or unexpected safety concerns were identified. AESI did not occur more frequently than expected by chance alone. Non-serious medically attended adverse events, such as rash, have been previously reported and occurred infrequently.

IMPORTANCE: Although influenza vaccination has been found to be safe in pregnancy, few studies have assessed repeated influenza vaccination over successive pregnancies, including 2 vaccinations in a year, in terms of adverse perinatal outcomes. OBJECTIVE: To examine the association of seasonal influenza vaccination across successive pregnancies with adverse perinatal outcomes and whether the association varies by interpregnancy interval (IPI) and vaccine type (quadrivalent or trivalent). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included individuals with at least 2 successive singleton live-birth pregnancies between January 1, 2004, and December 31, 2018. Data were collected from the Vaccine Safety Datalink, a collaboration between the Centers for Disease Control and Prevention and integrated health care organizations. Data analysis was performed between January 8, 2021, and July 17, 2024. EXPOSURES: Influenza vaccination was identified using vaccine administration codes. The vaccinated cohort consisted of people who received influenza vaccines during the influenza season (August 1 through April 30) in 2 successive pregnancies. The comparator cohort consisted of people identified as unvaccinated during both pregnancies. MAIN OUTCOMES AND MEASURES: Main outcomes were risk of preeclampsia or eclampsia, placental abruption, fever, preterm birth, preterm premature rupture of membranes, chorioamnionitis, and small for gestational age among individuals with and without vaccination in both pregnancies. Adjusted relative risks (RRs) from Poisson regression were used to assess the magnitude of associations. The associations with adverse outcomes by IPI and vaccine type were evaluated. RESULTS: Of 82 055 people with 2 singleton pregnancies between 2004 and 2018, 44 879 (54.7%) had influenza vaccination in successive pregnancies. Mean (SD) age at the start of the second pregnancy was 32.2 (4.6) years for vaccinated individuals and 31.2 (5.0) years for unvaccinated individuals. Compared with individuals not vaccinated in both pregnancies, vaccination in successive pregnancies was not associated with increased risk of preeclampsia or eclampsia (adjusted RR, 1.10; 95% CI, 0.99-1.21), placental abruption (adjusted RR, 1.01; 95% CI, 0.84-1.21), fever (adjusted RR, 0.87; 95% CI, 0.47-1.59), preterm birth (adjusted RR, 0.83; 95% CI, 0.78-0.89), preterm premature rupture of membranes (RR, 1.00; 95% CI, 0.94-1.06), chorioamnionitis (adjusted RR, 1.03; 95% CI, 0.90-1.18), or small for gestational age birth (adjusted RR, 0.99; 95% CI, 0.93-1.05). IPI and vaccine type did not modify the observed associations. CONCLUSIONS AND RELEVANCE: In this large cohort study of successive pregnancies, influenza vaccination was not associated with increased risk of adverse perinatal outcomes, irrespective of IPI and vaccine type. Findings support recommendations to vaccinate pregnant people or those who might be pregnant during the influenza season.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccination is recommended in pregnancy to reduce the risk of severe morbidity from COVID-19. However, vaccine hesitancy persists among pregnant people, with risk of stillbirth being a primary concern. Our objective was to examine the association between COVID-19 vaccination and stillbirth. METHODS: We performed a matched case-control study in the Vaccine Safety Datalink (VSD). Stillbirths and live births were selected from singleton pregnancies among persons aged 16-49 years with at least one prenatal, delivery, or postpartum visit at eight participating VSD sites. Stillbirths identified through diagnostic codes were adjudicated to confirm the outcome, date, and gestational age at fetal death. Confirmed antepartum stillbirths that occurred between February 14, 2021, and February 27, 2022, then were matched 1:3 to live births by pregnancy start date, VSD site, and maternal age at delivery. Associations among antepartum stillbirth and COVID-19 vaccination in pregnancy, vaccine manufacturer, number of vaccine doses received, and vaccination within 6 weeks before stillbirth (or index date in live births) were evaluated using conditional logistic regression. RESULTS: In the matched analysis of 276 confirmed antepartum stillbirths and 822 live births, we found no association between COVID-19 vaccination during pregnancy and stillbirth (38.4% stillbirths vs 39.3% live births in vaccinated individuals, adjusted odds ratio [aOR] 1.02, 95% CI, 0.76-1.37). Furthermore, no association between COVID-19 vaccination and stillbirth was detected by vaccine manufacturer (Moderna: aOR 1.00, 95% CI, 0.62-1.62; Pfizer-BioNTech: aOR 1.00, 95% CI, 0.69-1.43), number of vaccine doses received during pregnancy (1 vs 0: aOR 1.17, 95% CI, 0.75-1.83; 2 vs 0: aOR 0.98, 95% CI, 0.81-1.17), or COVID-19 vaccination within the 6 weeks before stillbirth or index date compared with no vaccination (aOR 1.16, 95% CI, 0.74-1.83). CONCLUSION: No association was found between COVID-19 vaccination and stillbirth. These findings further support recommendations for COVID-19 vaccination in pregnancy.

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.

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.

BACKGROUND: Understanding the long-term impact of the COVID-19 pandemic on health care utilization is important to health care organizations and policy makers for strategic planning, as well as to researchers when designing studies that use observational electronic health record data during the pandemic period. OBJECTIVE: To evaluate changes in health care utilization across all care settings among a large diverse insured population in the United States during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort study within 8 health care organizations participating in the Vaccine Safety Datalink Project using electronic health record data from members of all ages during January 1, 2017 - December 31, 2021. The visit rates per person-year were calculated monthly during the study period for four health care settings combined as well as by inpatient, emergency department (ED), outpatient, and telehealth settings, both among all members and members without COVID-19. Difference-in-difference analysis and interrupted time series analysis were performed to assess the changes in visit rates from the pre-pandemic period (January 2017 to February 2020) to the early pandemic period (April 2020 to December 2020) and the later pandemic period (July 2021 to December 2021), respectively. An exploratory analysis was also conducted to assess trends through June 2023 at one of the largest sites, Kaiser Permanente Southern California (KPSC). RESULTS: The study included more than 11 million members from 2017 to 2021. Compared with the pre-pandemic period, we found reductions in visit rates during the early pandemic period for all in-person care settings. During the later pandemic period, overall utilization reached 8.36 visits per person-year, exceeding the pre-pandemic level of 7.49 visits per person-year in 2019 (adjusted percent change = 5.1%; 95% CI 0.6% to 9.9%); inpatient and ED visits returned to pre-pandemic levels, 0.103 and 0.275 visits per person-year respectively among all members, although they remained 7.5% and 8.0% lower than pre-pandemic levels among members without a documented history of COVID-19. Telehealth visits, which were approximately 42% of the volume of outpatient visits during the later pandemic period, were increased by 97.5% (95% CI 86.0% to 109.7%) from 0.865 visits per person-year in 2019 to 2.35 visits per person-year in the later pandemic period. The trends in KPSC were like those of the entire study population. Visit rates from January 2022 to June 2023 were stable and appeared to be a continuation of the utilization levels observed at the end of 2021. CONCLUSIONS: Telehealth services became a mainstay of the health care system during the late COVID-19 pandemic period. Inpatient and ED visits returned to pre-pandemic levels, although they remained low among members without evidence of COVID-19. Our findings provide valuable information for longer-term strategic resource allocation for patient care in the post-pandemic period and for designing observational studies involving the pandemic period.

Vaccination equity is a national priority, but the extent to which participants in vaccine safety studies reflect the US population is unclear. The Vaccine Safety Datalink (VSD) is a collaboration between the CDC and thirteen healthcare organizations and databases, known as “sites”, with over 15 million members as of 2023. Sites contribute electronic health record data toward large studies of vaccine safety and coverage. 1 The aim of this study was to describe the reporting of race and ethnicity in Vaccine Safety Datalink (VSD) publications from 2011-2022.

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.

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.

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.

In the Vaccine Safety Datalink (VSD), we previously reported no association between COVID-19 vaccination in early pregnancy and spontaneous abortion (SAB). The current study aims to understand how time since vaccine roll-out or other methodologic factors could affect results. Using a case-control design and generalized estimating equations, we estimated the odds ratios (OR) of COVID-19 vaccination in the 28 days before a SAB or last date of the surveillance period (index date) in ongoing pregnancies and occurrence of SAB, across cumulative 4-week periods from December 2020 through June 2021. Using data from a single site, we evaluated alternate methodologic approaches: increasing the exposure window to 42 days, modifying the index date from the last day to the midpoint of the surveillance period, and constructing a cohort design with a time-dependent exposure model. A protective effect (OR 0.78; 95% Confidence Interval (CI): 0.69-0.89), observed with 3-cumulative periods ending March 8, 2021, was attenuated when surveillance extended to June 28, 2021 (OR: 1.02; 95% CI: 0.96-1.08). We observed a lower OR for a 42-day as compared to a 28-day window. The time-dependent model showed no association. Timing of the surveillance appears to be an important factor affecting the observed vaccine-SAB association.

JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended in the United States for persons exposed to or at high risk for exposure to Monkeypox virus during the 2022 monkeypox (mpox) outbreak (1). JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged ≥18 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2). On August 9, 2022, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for administration of 0.1 mL doses by intradermal injection for adults aged ≥18 years as a strategy to increase vaccine supply, and administration of 0.5 mL doses subcutaneously for persons aged <18 years (3). During May 22-October 21, 2022, a total of 987,294 JYNNEOS vaccine doses were administered in the United States. CDC has monitored JYNNEOS vaccine safety using the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for vaccine recipients of all ages, and through single-patient emergency Investigational New Drug (EIND) procedures for persons aged <18 years vaccinated before August 9, 2022. The most common adverse health events reported to VAERS for adults were nonserious and included injection site reactions, which was consistent with the prelicensure studies. Adverse health events were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare in adults, and no serious adverse events have been identified among persons aged <18 years. Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety.

BACKGROUND: Temporal associations between Kawasaki disease (KD) and childhood vaccines have been reported. Limited data on KD following 13-valent pneumococcal conjugate (PCV13) and rotavirus vaccines are available. METHODS: We conducted a self-controlled risk interval study using Vaccine Safety Datalink electronic health record data to investigate the risk of KD following PCV13 and rotavirus vaccines in children <2 years of age who were born from 2006 to 2017. All hospitalized KD cases identified by International Classification of Diseases diagnosis codes that fell within predefined risk (days 1-28 postvaccination) and control (days 29-56 for doses 1 and 2, and days 43-70 for doses 3 and 4) intervals were confirmed by manual chart review. RESULTS: During the study period, 655 cases of KD were identified by International Classification of Diseases codes. Of these, 97 chart-confirmed cases were within risk or control intervals. In analyses, the age-adjusted relative risk for KD following any dose of PCV13 was 0.75 (95% confidence interval, 0.47-1.21). Similarly, the age-adjusted relative risk for KD following any dose of rotavirus vaccine was 0.66 (95% CI, 0.40-1.09). Overall, there was no evidence of an elevated risk of KD following PCV13 or rotavirus vaccines by dose. In addition, no statistically significant temporal clustering of KD cases was identified during days 1 to 70 postvaccination. CONCLUSIONS: PCV13 and rotavirus vaccination were not associated with an increased risk of KD in children <2 years of age. Our findings provide additional evidence for the overall safety of PCV13 and rotavirus vaccines.

OBJECTIVE: To assess the association between cumulative aluminum exposure from vaccines before age 24 months and persistent asthma at age 24 to 59 months. METHODS: A retrospective cohort study was conducted in the Vaccine Safety Datalink (VSD). Vaccination histories were used to calculate cumulative vaccine-associated aluminum in milligrams (mg). The persistent asthma definition required one inpatient or 2 outpatient asthma encounters, and 2 long-term asthma control medication dispenses. Cox proportional hazard models were used to evaluate the association between aluminum exposure and asthma incidence, stratified by eczema presence/absence. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) per 1 mg increase in aluminum exposure were calculated, adjusted for birth month/year, sex, race/ethnicity, VSD site, prematurity, medical complexity, food allergy, severe bronchiolitis, and health care utilization. RESULTS: The cohort comprised 326,991 children, among whom 14,337 (4.4%) had eczema. For children with and without eczema, the mean (standard deviation [SD]) vaccine-associated aluminumexposure was4.07mg (SD0.60) and 3.98mg (SD0.72), respectively. Among children with and without eczema, 6.0% and 2.1%, respectively, developed persistent asthma. Among children with eczema, vaccine-associated aluminum was positively associated with persistent asthma (aHR 1.26 per 1 mg increase in aluminum, 95% CI 1.07, 1.49); a positive association was also detected among children without eczema (aHR 1.19, 95% CI 1.14, 1.25). CONCLUSION: In a large observational study, a positive association was found between vaccine-related aluminum exposure and persistent asthma. While recognizing the small effect sizes identified and the potential for residual confounding, additional investigation of this hypothesis appears warranted.

IMPORTANCE: After SARS-CoV-2 infection, many patients present with persistent symptoms for at least 6 months, collectively termed post-COVID conditions (PCC). However, the impact of PCC on health care utilization has not been well described. OBJECTIVES: To estimate COVID-19-associated excess health care utilization following acute SARS-CoV-2 infection and describe utilization for select PCCs among patients who had positive SARS-CoV-2 test results (including reverse transcription-polymerase chain reaction and antigen tests) compared with control patients whose results were negative. DESIGN, SETTING, AND PARTICIPANTS: This matched retrospective cohort study included patients of all ages from 8 large integrated health care systems across the United States who completed a SARS-CoV-2 diagnostic test during March 1 to November 1, 2020. Patients were matched on age, sex, race and ethnicity, site, and date of SARS-CoV-2 test and were followed-up for 6 months. Data were analyzed from March 18, 2021, to June 8, 2022. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Ratios of rate ratios (RRRs) for COVID-19-associated health care utilization were calculated with a difference-in-difference analysis using Poisson regression models. RRRs were estimated overall, by health care setting, by select population characteristics, and by 44 PCCs. COVID-19-associated excess health care utilization was estimated by health care setting. RESULTS: The final matched cohort included 127 859 patients with test results positive for SARS-CoV-2 and 127 859 patients with test results negative for SARS-CoV-2. The mean (SD) age of the study population was 41.2 (18.6) years, 68 696 patients in each group (53.7%) were female, and each group included 66 211 Hispanic patients (51.8%), 9122 non-Hispanic Asian patients (7.1%), 7983 non-Hispanic Black patients (6.2%), and 34 326 non-Hispanic White patients (26.9%). Overall, SARS-CoV-2 infection was associated with a 4% increase in health care utilization over 6 months (RRR, 1.04 [95% CI, 1.03-1.05]), predominantly for virtual encounters (RRR, 1.14 [95% CI, 1.12-1.16]), followed by emergency department visits (RRR, 1.08 [95% CI, 1.04-1.12]). COVID-19-associated utilization for 18 PCCs remained elevated 6 months from the acute stage of infection, with the largest increase in COVID-19-associated utilization observed for infectious disease sequelae (RRR, 86.00 [95% CI, 5.07-1458.33]), COVID-19 (RRR, 19.47 [95% CI, 10.47-36.22]), alopecia (RRR, 2.52 [95% CI, 2.17-2.92]), bronchitis (RRR, 1.85 [95% CI, 1.62-2.12]), pulmonary embolism or deep vein thrombosis (RRR, 1.74 [95% CI, 1.36-2.23]), and dyspnea (RRR, 1.73 [95% CI, 1.61-1.86]). In total, COVID-19-associated excess health care utilization amounted to an estimated 27 217 additional medical encounters over 6 months (212.9 [95% CI, 146.5-278.4] visits per 1000 patients). CONCLUSIONS AND RELEVANCE: This cohort study documented an excess health care burden of PCC in the 6 months after the acute stage of infection. As health care systems evolve during a highly dynamic and ongoing global pandemic, these data provide valuable evidence to inform long-term strategic resource allocation for patients previously infected with SARS-CoV-2.

Pregnant women with symptomatic coronavirus disease 2019 (Covid-19) have a higher risk of adverse outcomes than do women who are not pregnant.1,2 In part because of these findings, Covid-19 vaccination has been recommended for pregnant women. However, uptake has been lower in pregnant women than among women who are not pregnant.3,4 The concern of many women regarding safety remains a barrier to maternal vaccination.

OBJECTIVES: Having accurate influenza vaccination coverage estimates can guide public health activities. The objectives of this study were to (1) validate the accuracy of electronic health record (EHR)-based influenza vaccination data among pregnant women compared with survey self-report and (2) assess whether survey respondents differed from survey nonrespondents by demographic characteristics and EHR-based vaccination status. METHODS: This study was conducted in the Vaccine Safety Datalink, a network of 8 large medical care organizations in the United States. Using EHR data, we identified all women pregnant during the 2018-2019 or 2019-2020 influenza seasons. Surveys were conducted among samples of women who did and did not appear vaccinated for influenza according to EHR data. Separate surveys were conducted after each influenza season, and respondents reported their influenza vaccination status. Analyses accounted for the stratified design, sampling probability, and response probability. RESULTS: The survey response rate was 50.5% (630 of 1247) for 2018-2019 and 41.2% (721 of 1748) for 2019-2020. In multivariable analyses combining both survey years, non-Hispanic Black pregnant women had 3.80 (95% CI, 2.13-6.74) times the adjusted odds of survey nonresponse; odds of nonresponse were also higher for Hispanic pregnant women and women who had not received (per EHR data) influenza vaccine during current or prior influenza seasons. The sensitivity, specificity, and positive predictive value of EHR documentation of influenza vaccination compared with self-report were ≥92% for both survey years combined. The negative predictive value of EHR-based influenza vaccine status was 80.5% (95% CI, 76.7%-84.0%). CONCLUSIONS: EHR-based influenza vaccination data among pregnant women were generally concordant with self-report. New data sources and novel approaches to mitigating nonresponse bias may be needed to enhance influenza vaccination surveillance efforts.

BACKGROUND: The COVID-19 pandemic caused an abrupt drop in in-person health care (inpatient, Emergency Department, outpatient) and an increase in telehealth care, which poses challenges in vaccine safety studies that identify outcomes from in-person encounters. We examined the changes in incidence rates of selected encounter-based outcomes during the COVID-19 pandemic. METHODS: We assembled a cohort of members from 8 Vaccine Safety Datalink sites from January 1, 2017 through December 31, 2020. Using ICD-10 diagnosis codes or laboratory criteria, we identified 21 incident outcomes in traditional in-person settings and all settings. We defined 4 periods in 2020: January-February (pre-pandemic), April-June (early pandemic), July-September (middle pandemic), and October-December (late pandemic). We defined four corresponding periods in each year during 2017-2019. We calculated incidence rates, conducted difference in difference (DiD) analyses, and reported ratios of incidence rate ratios (RRR) to examine changes in rates from pre-pandemic to early, middle, and late pandemic in 2020, after adjusting for changes across similar periods in 2017-2019. RESULTS: Among>10 million members, regardless of setting and after adjusting for changes during 2017-2019, we found that incidence rates of acute disseminated encephalomyelitis, encephalitis/myelitis/encephalomyelitis/meningoencephalitis, and thrombotic thrombocytopenic purpura did not significantly change from the pre-pandemic to early, middle or late pandemic periods (p-values0.05). Incidence rates decreased from the pre-pandemic to early pandemic period during 2020 for acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, convulsions/seizures, Guillain-Barr syndrome, immune thrombocytopenia (ITP), narcolepsy/cataplexy, hemorrhagic stroke, ischemic stroke, and venous thromboembolism (p-values<0.05). Incidence rates of Bell's palsy, ITP, and narcolepsy/cataplexy were higher in all settings than in traditional in-person settings during the three pandemic periods (p-values<0.05). CONCLUSION: Rates of some clinical outcomes during the pandemic changed and should not be used as historical background rates in vaccine safety studies. Inclusion of telehealth visits should be considered for vaccine studies involving Bell's palsy, ITP, and narcolepsy/cataplexy.

OBJECTIVES: Safety studies assessing the association between the entire recommended childhood immunization schedule and autoimmune diseases, such as type 1 diabetes mellitus (T1DM), are lacking. To examine the association between the recommended immunization schedule and T1DM, we conducted a retrospective cohort study of children born between 2004 and 2014 in 8 US health care organizations that participate in the Vaccine Safety Datalink. METHODS: Three measures of the immunization schedule were assessed: average days undervaccinated (ADU), cumulative antigen exposure, and cumulative aluminum exposure. T1DM incidence was identified by International Classification of Disease codes. Cox proportional hazards models were used to analyze associations between the 3 exposure measures and T1DM incidence. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated. Models were adjusted for sex, race and ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and study site. RESULTS: In a cohort of 584 171 children, the mean ADU was 38 days, the mean cumulative antigen exposure was 263 antigens (SD = 54), and the mean cumulative aluminum exposure was 4.11 mg (SD = 0.73). There were 1132 incident cases of T1DM. ADU (aHR = 1.01; 95% CI, 0.99-1.02) and cumulative antigen exposure (aHR = 0.98; 95% CI, 0.97-1.00) were not associated with T1DM. Cumulative aluminum exposure >3.00 mg was inversely associated with T1DM (aHR = 0.77; 95% CI, 0.60-0.99). CONCLUSIONS: The recommended schedule is not positively associated with the incidence of T1DM in children. These results support the safety of the recommended childhood immunization schedule.

IMPORTANCE: The COVID-19 pandemic has affected routine vaccine delivery in the US and globally. The magnitude of these disruptions and their association with childhood vaccination coverage are unclear. OBJECTIVES: To compare trends in pediatric vaccination before and during the pandemic and to evaluate the proportion of children up to date (UTD) with vaccinations by age, race, and ethnicity. DESIGN, SETTING, AND PARTICIPANTS: This surveillance study used a prepandemic-postpandemic control design with data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Children from age groups younger than 24 months and 4 to 6, 11 to 13, and 16 to 18 years were included if they had at least 1 week of health system enrollment from January 5, 2020, through October 3, 2020, over periods before the US COVID-19 pandemic (January 5, 2020, through March 14, 2020), during age-limited preventive care (March 15, 2020, through May 16, 2020), and during expanded primary care (May 17, 2020, through October 3, 2020). These individuals were compared with those enrolled during analogous weeks in 2019. EXPOSURES: This study evaluated UTD status among children reaching specific ages in February, May, and September 2020, compared with those reaching these ages in 2019. MAIN OUTCOMES AND MEASURES: Weekly vaccination rates for routine age-specific vaccines and the proportion of children UTD for all age-specific recommended vaccines. RESULTS: Of 1 399 708 children in 2019 and 1 402 227 in 2020, 1 371 718 were female (49.0%) and 1 429 979 were male (51.0%); 334 216 Asian individuals (11.9%), 900 226 were Hispanic individuals (32.1%), and 201 619 non-Hispanic Black individuals (7.2%). Compared with the prepandemic period and 2019, the age-limited preventive care period was associated with lower weekly vaccination rates, with ratios of rate ratios of 0.82 (95% CI, 0.80-0.85) among those younger than 24 months, 0.18 (95% CI, 0.16-0.20) among those aged 4 to 6 years, 0.16 (95% CI, 0.14-0.17) among those aged 11 to 13 years, and 0.10 (95% CI, 0.08-0.13) among those aged 16 to 18 years. Vaccination rates during expanded primary care remained lower for most ages (ratios of rate ratios: <24 months, 0.96 [95% CI, 0.93-0.98]; 11-13 years, 0.81 [95% CI, 0.76-0.86]; 16-18 years, 0.57 [95% CI, 0.51-0.63]). In September 2020, 74% (95% CI, 73%-76%) of infants aged 7 months and 57% (95% CI, 56%-58%) of infants aged 18 months were UTD vs 81% (95% CI, 80%-82%) and 61% (95% CI, 60%-62%), respectively, in September 2019. The proportion UTD was lowest in non-Hispanic Black children across most age groups, both during and prior to the COVID-19 pandemic (eg, in May 2019, 70% [95% CI, 64%-75%] of non-Hispanic Black infants aged 7 months were UTD vs 82% [95% CI, 81%-83%] in all infants aged 7 months combined). CONCLUSIONS AND RELEVANCE: As of September 2020, childhood vaccination rates and the proportion who were UTD remained lower than 2019 levels. Interventions are needed to promote catch-up vaccination, particularly in populations at risk for underimmunization.

IMPORTANCE: Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy. OBJECTIVES: To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population. DESIGN, SETTING, AND PARTICIPANTS: This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021. EXPOSURES: Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2. MAIN OUTCOMES AND MEASURES: Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted. RESULTS: A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273. CONCLUSIONS AND RELEVANCE: In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.

Background: Identifying pregnancy episodes and accurately estimating their beginning and end dates are imperative for observational maternal vaccine safety studies using electronic health record (EHR) data. Methods: We modified the Vaccine Safety Datalink (VSD) Pregnancy Episode Algorithm (PEA) to include both the International Classification of Disease, ninth revision (ICD-9 system) and ICD-10 diagnosis codes, incorporated additional gestational age data, and validated this enhanced algorithm with manual medical record review. We also developed the new Dynamic Pregnancy Algorithm (DPA) to identify pregnancy episodes in real time. Results: Around 75% of the pregnancy episodes identified by the enhanced VSD PEA were live births, 12% were spontaneous abortions (SABs), 10% were induced abortions (IABs), and 0.4% were stillbirths (SBs). Gestational age was identified for 99% of live births, 89% of SBs, 69% of SABs, and 42% of IABs. Agreement between the PEA-assigned and abstractor-identified pregnancy outcome and outcome date was 100% for live births, but was lower for pregnancy losses. When gestational age was available in the medical record, the agreement was higher for live births (97%), but lower for pregnancy losses (75%). The DPA demonstrated strong concordance with the PEA and identified pregnancy episodes ⩾6 months prior to the outcome date for 89% of live births. Conclusion: The enhanced VSD PEA is a useful tool for identifying pregnancy episodes in EHR databases. The DPA improves the timeliness of pregnancy identification and can be used for near real-time maternal vaccine safety studies. Plain Language Summary: Improving identification of pregnancies in the Vaccine Safety Datalink electronic medical record databases to allow for better and faster monitoring of vaccination safety during pregnancy Introduction: It is important to monitor of the safety of vaccines after they have been approved and licensed by the Food and Drug Administration, especially among women vaccinated during pregnancy. The Vaccine Safety Datalink (VSD) monitors vaccine safety through observational studies within large databases of electronic medical records. Since 2012, VSD researchers have used an algorithm called the Pregnancy Episode Algorithm (PEA) to identify the medical records of women who have been pregnant. Researchers then use these medical records to study whether receiving a particular vaccine is linked to any negative outcomes for the woman or her child. Methods: The goal of this study was to update and enhance the PEA to include the full set of medical record diagnostic codes [both from the older International Classification of Disease, ninth revision (ICD-9 system) and the newer ICD-10 system] and to incorporate additional sources of data about gestational age. To ensure the validity of the PEA following these enhancements, we manually reviewed medical records and compared the results with the algorithm. We also developed a new algorithm, the Dynamic Pregnancy Algorithm (DPA), to identify women earlier in pregnancy, allowing us to conduct more timely vaccine safety assessments. Results: The new version of the PEA identified 2,485,410 pregnancies in the VSD database. The enhanced algorithm more precisely estimated the beginning of pregnancies, especially those that did not result in live births, due to the new sources of gestational age data. Conclusion: Our new algorithm, the DPA, was successful at identifying pregnancies earlier in gestation than the PEA. The enhanced PEA and the new DPA will allow us to better evaluate the safety of current and future vaccinations administered during or around the time of pregnancy. © The Author(s), 2021.

COVID-19 vaccines are critical for ending the COVID-19 pandemic; however, current data about vaccination coverage and safety in pregnant women are limited. Pregnant women are at increased risk for severe illness and death from COVID-19 compared with nonpregnant women of reproductive age, and are at risk for adverse pregnancy outcomes, such as preterm birth (1-4). Pregnant women are eligible for and can receive any of the three COVID-19 vaccines available in the United States via Emergency Use Authorization.* Data from Vaccine Safety Datalink (VSD), a collaboration between CDC and multiple integrated health systems, were analyzed to assess receipt of ≥1 dose (first or second dose of the Pfizer-BioNTech or Moderna vaccines or a single dose of the Janssen [Johnson & Johnson] vaccine) of any COVID-19 vaccine during pregnancy, receipt of first dose of a 2-dose COVID-19 vaccine (initiation), or completion of a 1- or 2-dose COVID-19 vaccination series. During December 14, 2020-May 8, 2021, a total of 135,968 pregnant women were identified, 22,197 (16.3%) of whom had received ≥1 dose of a vaccine during pregnancy. Among these 135,968 women, 7,154 (5.3%) had initiated and 15,043 (11.1%) had completed vaccination during pregnancy. Receipt of ≥1 dose of COVID-19 vaccine during pregnancy was highest among women aged 35-49 years (22.7%) and lowest among those aged 18-24 years (5.5%), and higher among non-Hispanic Asian (Asian) (24.7%) and non-Hispanic White (White) women (19.7%) than among Hispanic (11.9%) and non-Hispanic Black (Black) women (6.0%). Vaccination coverage increased among all racial and ethnic groups over the analytic period, likely because of increased eligibility for vaccination(†) and increased availability of vaccine over time. These findings indicate the need for improved outreach to and engagement with pregnant women, especially those from racial and ethnic minority groups who might be at higher risk for severe health outcomes because of COVID-19 (4). In addition, providing accurate and timely information about COVID-19 vaccination to health care providers, pregnant women, and women of reproductive age can improve vaccine confidence and coverage by ensuring optimal shared clinical decision-making.

OBJECTIVE: The Mind, Exercise, Nutrition, Do It! 7-13 (MEND 7-13) program was adapted in 2016 by five Denver Health federally qualified health centers (DH FQHC) into MEND+, integrating clinician medical visits into the curriculum and tracking health measures within an electronic health record (EHR). We examined trajectories of body mass index (BMI, kg/m(2)) percentile, and systolic and diastolic blood pressures (SBP & DBP) among MEND+ attendees in an expanded age range of 4-17 years, and comparable non-attendees. METHODS: Data from April 2015 to May 2018 were extracted from DH FQHC EHR for children eligible for MEND+ referral (BMI ≥85(th) percentile). The sample included 347 MEND+ attendees and 21,061 non-attendees. Mixed-effects models examined average rate of change for BMI percent of the 95(th) percentile (%BMIp95), SBP, and DBP, after completion of the study period. RESULTS: Most children were ages 7-13 years, half were male, and most were Hispanic. An average of 4.2 MEND+ clinical sessions were attended. Before MEND+, %BMIp95 increased by 0.247 units/month among MEND+ attendees. After attending, %BMIp95 decreased by 0.087 units/month (p<0.001). Eligible non-attendees had an increase of 0.084/month in %BMIp95. Before MEND+ attendance, SBP and DBP increased by 0.041 and 0.022/month, respectively. After MEND+ attendance, SBP and DBP decreased by 0.254 /month (p<0.001) and 0.114/month (p<0.01), respectively. SBP and DBP increased by 0.032 and 0.033/month in eligible non-attendees, respectively. CONCLUSIONS: %BMIp95, SBP, and DBP significantly decreased among MEND+ attendees when implemented in community-based clinical practice settings at DH FQHC.

PURPOSE: Given the 2015 transition to International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic coding, updates to our previously published algorithms for major structural birth defects (BDs) were necessary. Aims of this study were to update, validate, and refine algorithms for identifying selected BDs, and then to use these algorithms to describe BD prevalence in the Vaccine Safety Datalink (VSD) population. METHODS: We converted our ICD-9-CM list of selected BDs to ICD-10-CM using available crosswalks with manual review of codes. We identified, chart reviewed, and adjudicated a sample of infants in the VSD with ≥2 ICD-10-CM diagnoses for one of seven common BDs. Positive predictive values (PPVs) were calculated; for BDs with sub-optimal PPV, algorithms were refined. Final automated algorithms were applied to a cohort of live births delivered 10/1/2015-9/30/2017 at eight VSD sites to estimate BD prevalence. RESULTS: Of 573 infants with ≥2 diagnoses for a targeted BD, on adjudication, we classified 399 (69.6%) as probable cases, 31 (5.4%) as possible cases and 143 (25.0%) as not having the targeted BD. PPVs for the final BD algorithms ranged from 0.76 (hypospadias) to 1.0 (gastroschisis). Among 212,857 births over two years following transition to ICD-10-CM coding, prevalence for the full list of selected defects in the VSD was 1.8%. CONCLUSIONS: Algorithms can identify infants with selected BDs using automated healthcare data with reasonable accuracy. Our updated algorithms can be used in observational studies of maternal vaccine safety and may be adapted for use in other surveillance systems.

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19), possibly related to changes in their immune system and respiratory physiology* (1). Further, adverse birth outcomes, such as preterm delivery and stillbirth, might be more common among pregnant women infected with SARS-CoV-2, the virus that causes COVID-19 (2,3). Information about SARS-CoV-2 infection during pregnancy is rapidly growing; however, data on reasons for hospital admission, pregnancy-specific characteristics, and birth outcomes among pregnant women hospitalized with SARS-CoV-2 infections are limited. During March 1-May 30, 2020, as part of Vaccine Safety Datalink (VSD)(†) surveillance of COVID-19 hospitalizations, 105 hospitalized pregnant women with SARS-CoV-2 infection were identified, including 62 (59%) hospitalized for obstetric reasons (i.e., labor and delivery or another pregnancy-related indication) and 43 (41%) hospitalized for COVID-19 illness without an obstetric reason. Overall, 50 (81%) of 62 pregnant women with SARS-CoV-2 infection who were admitted for obstetric reasons were asymptomatic. Among 43 pregnant women hospitalized for COVID-19, 13 (30%) required intensive care unit (ICU) admission, six (14%) required mechanical ventilation, and one died from COVID-19. Prepregnancy obesity was more common (44%) among pregnant women hospitalized for COVID-19 than that among asymptomatic pregnant women hospitalized for obstetric reasons (31%). Likewise, the rate of gestational diabetes (26%) among pregnant women hospitalized for COVID-19 was higher than it was among women hospitalized for obstetric reasons (8%). Preterm delivery occurred in 15% of pregnancies among 93 women who delivered, and stillbirths (fetal death at ≥20 weeks' gestation) occurred in 3%. Antenatal counseling emphasizing preventive measures (e.g., use of masks, frequent hand washing, and social distancing) might help prevent COVID-19 among pregnant women,(§) especially those with prepregnancy obesity and gestational diabetes, which might reduce adverse pregnancy outcomes.

INTRODUCTION: Children may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration. METHODS: In six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003-2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR. RESULTS: Among 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups. CONCLUSIONS: HZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.

BACKGROUND AND OBJECTIVES: After the 1996 introduction of routine varicella vaccination in the United States, most studies evaluating pediatric herpes zoster (HZ) incidence reported lower incidence over time, with varying degrees of decline. Using the combined databases of 6 integrated health care organizations, we examined HZ incidence in children over a 12-year period in the varicella vaccine era. METHODS: This study included children aged 0 through 17 years from 2003 through 2014. Using electronic medical records, we identified HZ cases through International Classification of Diseases, Ninth Revision diagnosis code 053. We calculated HZ incidence rates per 100 000 person years of health plan membership for all children and among children who were vaccinated versus unvaccinated. We calculated rates for the 12-year period and examined temporal trends. Among children who were vaccinated, we compared HZ rates by month and year of age at vaccination. RESULTS: The study included 6 372 067 children with >/=1 month of health plan membership. For the 12-year period, the crude HZ incidence rate for all subjects was 74 per 100 000 person years, and the rate among children who were vaccinated was 38 per 100 000 person years, which was 78% lower than that among children who were unvaccinated (170 per 100 000 person years; P < .0001). Overall HZ incidence declined by 72% (P < .0001) from 2003 through 2014. Annual rates in children who were vaccinated were consistently lower than in children who were unvaccinated. CONCLUSIONS: With this population-based study, we confirm the decline in pediatric HZ incidence and the significantly lower incidence among children who are vaccinated, reinforcing the benefit of routine varicella vaccination to prevent pediatric HZ.

PURPOSE: To evaluate the safety of live attenuated influenza vaccine (LAIV) in children 2 through 17 years of age. METHODS: The study was conducted in 6 large integrated health care organizations participating in the Vaccine Safety Datalink (VSD). Trivalent LAIV safety was assessed in children who received LAIV between September 1, 2003 and March 31, 2013. Eighteen pre-specified adverse event groups were studied, including allergic, autoimmune, neurologic, respiratory, and infectious conditions. Incident rate ratios (IRRs) were calculated for each adverse event, using self-controlled case series analyses. For adverse events with a statistically significant increase in risk, or an IRR > 2.0 regardless of statistical significance, manual medical record review was performed to confirm case status. RESULTS: During the study period, 396 173 children received 590 018 doses of LAIV. For 13 adverse event groups, there was no significant increased risk of adverse events following LAIV. Five adverse event groups (anaphylaxis, syncope, Stevens-Johnson syndrome, adverse effect of drug, and respiratory failure) met criteria for manual medical record review. After review to confirm cases, 2 adverse event groups remained significantly associated with LAIV: anaphylaxis and syncope. One confirmed case of anaphylaxis was observed following LAIV, a rate of 1.7 per million LAIV doses. Five confirmed cases of syncope were observed, a rate of 8.5 per million doses. CONCLUSIONS: In a study of trivalent LAIV safety in a large cohort of children, few serious adverse events were detected. Anaphylaxis and syncope occurred following LAIV, although rarely. These data provide reassurance regarding continued LAIV use.

BACKGROUND: The risk of febrile seizure is temporarily increased for a few days after the administration of certain vaccines in children aged six to 23 months. Our objective was to determine the febrile seizure risk following vaccination in children aged one to five months, when six different vaccines are typically administered. METHODS: We identified emergency department visits and inpatient admissions with International Classification of Diseases, Ninth Revision, febrile seizure codes among children enrolled in nine Vaccine Safety Datalink participating health care organizations from 2006 through 2011. Febrile seizures were confirmed by medical record abstraction. We used the self-controlled risk-interval method to compare the incidence of febrile seizure during postvaccination days 0 to 1 (risk interval) versus days 14 to 20 (control interval). RESULTS: We identified 15 febrile seizure cases that occurred after 585,342 vaccination visits. The case patients were aged three to five months. The patients had received a median of four (range two to six) vaccines simultaneously. The incidence rate ratio of febrile seizure after vaccination was 23 (95% confidence interval 5.13 to 100.8), and the attributable risk was 3.92 (95% confidence interval 1.68 to 6.17) febrile seizure cases per 100,000 persons vaccinated. CONCLUSIONS: Vaccination in children aged three to five months was associated with a large relative risk of febrile seizure on the day of and the day after vaccination, but the risk was small in absolute terms. Postvaccination febrile seizure should not be a concern for the vast majority of children receiving vaccines, but clinicians might take this risk into consideration when evaluating and treating children susceptible to seizures precipitated by fever.