The safety of live attenuated influenza vaccine in children and adolescents 2 through 17 years of age: A Vaccine Safety Datalink study.

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.

Safety of repeated doses of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in adults and adolescents.

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Association Between Estimated Cumulative Vaccine Antigen Exposure Through the First 23 Months of Life and Non-Vaccine-Targeted Infections From 24 Through 47 Months of Age.

Importance: Some parents are concerned that multiple vaccines in early childhood could weaken their child's immune system. Biological data suggest that increased vaccine antigen exposure could increase the risk for infections not targeted by vaccines. Objective: To examine estimated cumulative vaccine antigen exposure through the first 23 months of life in children with and without non-vaccine-targeted infections from 24 through 47 months of age. Design, Setting, and Participants: A nested case-control study was conducted in 6 US health care organizations participating in the Vaccine Safety Datalink. Cases were identified by International Classification of Diseases codes for infectious diseases in the emergency department and inpatient medical settings and then validated by medical record review. Cases of non-vaccine-targeted infection were matched to controls by age, sex, health care organization site, and chronic disease status. Participants were children ages 24 through 47 months, born between January 1, 2003, and September 31, 2013, followed up until December 31, 2015. Exposures: Cumulative vaccine antigen exposure, estimated by summing the number of antigens in each vaccine dose received from birth through age 23 months. Main Outcomes and Measures: Non-vaccine-targeted infections, including upper and lower respiratory infections and gastrointestinal infections, from 24 through 47 months of age, and the association between these infections and estimated cumulative vaccine exposure from birth through 23 months. Conditional logistic regression was used to estimate matched odds ratios representing the odds of non-vaccine-targeted infections for every 30-unit increase in estimated cumulative number of antigens received. Results: Among the 944 patients (193 cases and 751 controls), the mean (SD) age was 32.5 (6.3) months, 422 (45%) were female, and 61 (7%) had a complex chronic condition. Through the first 23 months, the estimated mean (SD) cumulative vaccine antigen exposure was 240.6 (48.3) for cases and 242.9 (51.1) for controls. The between-group difference for estimated cumulative antigen exposure was -2.3 (95% CI, -10.1 to 5.4; P = .55). Among children with vs without non-vaccine-targeted infections from 24 through 47 months of age, the matched odds ratio for estimated cumulative antigen exposure through age 23 months was not significant (matched odds ratio, 0.94; 95% CI, 0.84 to 1.07). Conclusions and Relevance: Among children from 24 through 47 months of age with emergency department and inpatient visits for infectious diseases not targeted by vaccines, compared with children without such visits, there was no significant difference in estimated cumulative vaccine antigen exposure through the first 23 months of life.

First Trimester Influenza Vaccination and Risks for Major Structural Birth Defects in Offspring.

OBJECTIVE: To examine risks for major structural birth defects in infants after first trimester inactivated influenza vaccine (IIV) exposures. STUDY DESIGN: In this observational study, we used electronic health data from 7 Vaccine Safety Datalink sites to examine risks for selected major structural defects in infants after maternal IIV exposure. Vaccine exposures for women with continuous insurance enrollment through pregnancy who delivered singleton live births between 2004 and 2013 were identified from standardized files. Infants with continuous insurance enrollment were followed to 1 year of age. We excluded mother-infant pairs with other exposures that potentially increased their background risk for birth defects. Selected cardiac, orofacial or respiratory, neurologic, ophthalmologic or otologic, gastrointestinal, genitourinary and muscular or limb defects were identified from diagnostic codes in infant medical records using validated algorithms. Propensity score adjusted generalized estimating equations were used to estimate prevalence ratios (PRs). RESULTS: We identified 52 856 infants with maternal first trimester IIV exposure and 373 088 infants whose mothers were unexposed to IIV during first trimester. Prevalence (per 100 live births) for selected major structural birth defects was 1.6 among first trimester IIV exposed versus 1.5 among unexposed mothers. The adjusted PR was 1.02 (95% CI 0.94-1.10). Organ system-specific PRs were similar to the overall PR. CONCLUSION: First trimester maternal IIV exposure was not associated with an increased risk for selected major structural birth defects in this large cohort of singleton live births.

Identifying birth defects in automated data sources in the Vaccine Safety Datalink.

PURPOSE: The Vaccine Safety Datalink (VSD), a collaboration between the Centers for Disease Control and Prevention and several large healthcare organizations, aims to monitor safety of vaccines administered in the USA. We present definitions and prevalence estimates for major structural birth defects to be used in studies of maternal vaccine safety. METHODS: In this observational study, we created and refined algorithms for identifying major structural birth defects from electronic healthcare data, conducted formal chart reviews for severe cardiac defects, and conducted limited chart validation for other defects. We estimated prevalence for selected defects by VSD site and birth year and compared these estimates to those in a US and European surveillance system. RESULTS: We developed algorithms to enumerate >50 major structural birth defects from standardized administrative and healthcare data based on utilization patterns and expert opinion, applying criteria for number, timing, and setting of diagnoses. Our birth cohort included 497 894 infants across seven sites. The period prevalence for all selected major birth defects in the VSD from 2004 to 2013 was 1.7 per 100 live births. Cardiac defects were most common (65.4 per 10 000 live births), with one-fourth classified as severe, requiring emergent intervention. For most major structural birth defects, prevalence estimates were stable over time and across sites and similar to those reported in other population-based surveillance systems. CONCLUSIONS: Our algorithms can efficiently identify many major structural birth defects in large healthcare datasets and can be used in studies evaluating the safety of vaccines administered to pregnant women. Copyright © 2017 John Wiley & Sons, Ltd.

Rates and risk factors associated with hospitalization for pneumonia with ICU admission among adults.

BACKGROUND: Pneumonia poses a significant burden to the U.S. health-care system. However, there are few data focusing on severe pneumonia, particularly cases of pneumonia associated with specialized care in intensive care units (ICU). METHODS: We used administrative and electronic medical record data from six integrated health care systems to estimate rates of pneumonia hospitalizations with ICU admissions among adults during 2006 through 2010. Pneumonia hospitalization was defined as either a primary discharge diagnosis of pneumonia or a primary discharge diagnosis of sepsis or respiratory failure with a secondary diagnosis of pneumonia in administrative data. ICU admissions were collected from internal electronic medical records from each system. Comorbidities were identified by ICD-9-CM codes coded during the current pneumonia hospitalization, as well as during medical visits that occurred during the year prior to the date of admission. RESULTS: We identified 119,537 adult hospitalizations meeting our definition for pneumonia. Approximately 19% of adult pneumonia hospitalizations had an ICU admission. The rate of pneumonia hospitalizations requiring ICU admission during the study period was 76 per 100,000 population/year; rates increased for each age-group with the highest rates among adults aged ≥85 years. Having a co-morbidity approximately doubled the risk of ICU admission in all age-groups. CONCLUSIONS: Our study indicates a significant burden of pneumonia hospitalizations with an ICU admission among adults in our cohort during 2006 through 2010, especially older age-groups and persons with underlying medical conditions. These findings reinforce current strategies aimed to prevent pneumonia among adults.

Risk of Preterm or Small-for-Gestational-Age Birth After Influenza Vaccination During Pregnancy: Caveats When Conducting Retrospective Observational Studies.

Vaccines are increasingly targeted toward women of reproductive age, and vaccines to prevent influenza and pertussis are recommended during pregnancy. Prelicensure clinical trials typically have not included pregnant women, and when they are included, trials cannot detect rare events. Thus, postmarketing vaccine safety assessments are necessary. However, analysis of observational data requires detailed assessment of potential biases. Using data from 8 Vaccine Safety Datalink sites in the United States, we analyzed the association of monovalent H1N1 influenza vaccine (MIV) during pregnancy with preterm birth (<37 weeks) and small-for-gestational-age birth (birth weight < 10th percentile). The cohort included 46,549 pregnancies during 2009-2010 (40% of participants received the MIV). We found potential biases in the vaccine-birth outcome association that might occur due to variable access to vaccines, the time-dependent nature of exposure to vaccination within pregnancy (immortal time bias), and confounding from baseline differences between vaccinated and unvaccinated women. We found a strong protective effect of vaccination on preterm birth (relative risk = 0.79, 95% confidence interval: 0.74, 0.85) when we ignored potential biases and no effect when accounted for them (relative risk = 0.91; 95% confidence interval: 0.83, 1.0). In contrast, we found no important biases in the association of MIV with small-for-gestational-age birth. Investigators conducting studies to evaluate birth outcomes after maternal vaccination should use statistical approaches to minimize potential biases.

Maternal influenza vaccine and risks for preterm or small for gestational age birth.

OBJECTIVE: To study the impact of influenza vaccine administered to pregnant women during all trimesters on the rates of preterm and small for gestational age (SGA) births, evaluating both increased and decreased risk. STUDY DESIGN: This retrospective observational matched cohort study involved 7 Vaccine Safety Datalink sites across the US for the 2004-05 through 2008-09 influenza seasons. Cohort eligibility and outcomes were determined from administrative, claims, medical records, and birth data. In propensity score- and vaccine exposure time-matched analyses, ORs for preterm and SGA births were calculated. RESULTS: Among 57 554 matched vaccinated and unvaccinated pregnant women, including 16 240 women in the first trimester, maternal vaccination was not associated with increased or decreased risk for preterm birth (OR for delivery at <37 weeks gestation, 0.97 [95% CI, 0.93-1.02]; for delivery at ≤32 weeks gestation, 0.98 [95% CI, 0.86-1.12]; and for delivery at ≤34 weeks gestation, 0.96 [95% CI, 0.88-1.04]) or SGA birth (OR for <5th percentile weight for gestational age, 1.02 [95% CI, 0.96-1.09], and for <10th percentile weight for gestational age, 1.00 [95% CI, 0.96-1.04]). Similarly, first trimester vaccination was not associated with increased or decreased risk for preterm or SGA birth. CONCLUSION: Receipt of trivalent inactivated influenza vaccine during pregnancy was not associated with increased or decreased risk of preterm or SGA birth. These findings support the safety of vaccinating pregnant women against influenza during the first, second, and third trimesters, and suggest that a nonspecific protective effect of the influenza vaccine for these outcomes does not exist.

Receipt of pertussis vaccine during pregnancy across 7 Vaccine Safety Datalink sites.

OBJECTIVE: In response to widespread pertussis outbreaks and infant deaths, in 2010, the California Department of Health (CDPH) and in 2011 the Advisory Committee on Immunization Practices (ACIP) advised that the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine be administered during pregnancy. The goals of this study were to describe Tdap coverage among pregnant women following these recommendations. METHODS: In this observational cohort study, we utilized electronic medical record and claims data from seven Vaccine Safety Datalink sites to identify pregnancies and Tdap administrations. All Tdap doses were classified as pre-pregnancy, during pregnancy or post-pregnancy/postpartum. For pregnancies ending in a live birth, we evaluated factors associated with Tdap vaccination. RESULTS: Among 289,141 live births at the California VSD sites, receipt of Tdap during pregnancy increased substantially in the years 2010, 2011, and 2012, when coverage was 15.9, 30.0 and 19.5%, respectively. Among 82,398 women with live births at the Oregon, Washington, Colorado, Wisconsin and Minnesota VSD sites, receipt of Tdap during pregnancy first increased in 2012, at 16.0%. Women receiving early prenatal care and other vaccine(s) during pregnancy had higher Tdap coverage. CONCLUSION: We observed substantial increases in Tdap coverage during pregnancy following CDPH and ACIP recommendations.

Absence of associations between influenza vaccines and increased risks of seizures, Guillain-Barré syndrome, encephalitis, or anaphylaxis in the 2012-2013 season.

PURPOSE: We conducted weekly surveillance for pre-specified adverse events following receipt of the 2012-2013 influenza vaccines in the Vaccine Safety Datalink (VSD). METHODS: For each outcome, risk intervals (i.e., period after vaccination with a potentially increased risk) were defined on the basis of biologic plausibility and prior literature. Seizures following inactivated influenza vaccine (IIV) were monitored in children in three age groups (6-23 months, 24-59 months, and 5-17 years) using a self-controlled risk interval design. We also monitored for Guillain-Barré syndrome, encephalitis, and anaphylaxis following IIV in patients ≥6 months of age using a cohort design with historical controls. In the risk intervals following live attenuated influenza vaccine (LAIV), we collected weekly counts of Guillain-Barré syndrome, encephalitis, and anaphylaxis in patients ages 2-49. Among LAIV vaccinees, numbers of expected events based on rates in historical controls were calculated, adjusted for age and site. RESULTS: At the end of surveillance, approximately 3.6 million first doses of IIV and 250 000 first doses of LAIV had been administered in the VSD. No elevated risks were identified in risk intervals following 2012-2013 IIV, as compared with a self-matched control interval or to historical controls. For each outcome, fewer than three events occurred in the risk interval following 2012-2013 LAIV, and we thus were unable to estimate measures of relative risks. CONCLUSIONS: No increased risk was identified for any of the pre-specified outcomes following 2012-2013 influenza vaccinations in the VSD. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outcomes.

IMPORTANCE: In 2010, due to a pertussis outbreak and neonatal deaths, the California Department of Health recommended that the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) be administered during pregnancy. Tdap is now recommended by the Advisory Committee on Immunization Practices for all pregnant women, preferably between 27 and 36 weeks' gestation. Limited data exist on Tdap safety during pregnancy. OBJECTIVE: To evaluate whether maternal Tdap vaccination during pregnancy is associated with increased risks of adverse obstetric events or adverse birth outcomes. DESIGN AND SETTING: Retrospective, observational cohort study using administrative health care databases from 2 California Vaccine Safety Datalink sites. PARTICIPANTS AND EXPOSURES: Of 123,494 women with singleton pregnancies ending in a live birth between January 1, 2010, and November 15, 2012, 26,229 (21%) received Tdap during pregnancy and 97,265 did not. MAIN OUTCOMES AND MEASURES: Risks of small-for-gestational-age (SGA) births (<10th percentile), chorioamnionitis, preterm birth (<37 weeks' gestation), and hypertensive disorders of pregnancy were evaluated. Relative risk (RR) estimates were adjusted for site, receipt of another vaccine during pregnancy, and propensity to receive Tdap during pregnancy. Cox regression was used for preterm delivery, and Poisson regression for other outcomes. RESULTS: Vaccination was not associated with increased risks of adverse birth outcomes: crude estimates for preterm delivery were 6.3% of vaccinated and 7.8% of unvaccinated women (adjusted RR, 1.03; 95% CI, 0.97-1.09); 8.4% of vaccinated and 8.3% of unvaccinated had an SGA birth (adjusted RR, 1.00; 95% CI, 0.96-1.06). Receipt of Tdap before 20 weeks was not associated with hypertensive disorder of pregnancy (adjusted RR, 1.09; 95% CI, 0.99-1.20); chorioamnionitis was diagnosed in 6.1% of vaccinated and 5.5% of unvaccinated women (adjusted RR, 1.19; 95% CI, 1.13-1.26). CONCLUSIONS AND RELEVANCE: In this cohort of women with singleton pregnancies that ended in live birth, receipt of Tdap during pregnancy was not associated with increased risk of hypertensive disorders of pregnancy or preterm or SGA birth, although a small but statistically significant increased risk of chorioamnionitis diagnosis was observed.

Receipt of human papillomavirus vaccine among privately insured adult women in a U.S. Midwestern Health Maintenance Organization.

OBJECTIVES: To describe human papillomavirus (HPV) vaccine coverage among adult privately insured women including variation in coverage by race/ethnicity. METHODS: This cross-sectional, observational study included women 18-26 years of age with continuous enrollment in a U.S. Midwestern health insurance plan and at least one visit to a plan affiliated practice. Vaccination data came from insurance claims and the electronic medical record. Primary outcomes were: receipt of at least 1 HPV vaccine (HPV1) and completion of the 3-dose HPV vaccine series (HPV3). Coverage was described for the entire cohort and stratified by race/ethnicity. For a subset of women, automated data was compared to personal recall. RESULTS: As of June 2010, among 2546 privately insured women 18-26 years, 72.7% had received their first HPV vaccine and 57.9% completed the 3-dose series. Compared to white women, African American and Asian women had significantly lower coverage for HPV1 and HPV3. There was 94.5% (95% CI: 88.5-100%) agreement between personal recall and claims/EMR for receiving HPV1. CONCLUSIONS: In this cohort of privately insured women, a majority received HPV1 and more than half completed the 3-dose vaccine series. Marked disparities in receipt of HPV vaccine by race/ethnicity were observed.

Risk of adverse events following oseltamivir treatment in influenza outpatients, Vaccine Safety Datalink Project, 2007-2010.

PURPOSE: An association between the influenza antiviral medication oseltamivir and neuropsychiatric events has been suggested by post-marketing case reports in Japan. This possible association was not supported by cohort studies in the U.S. conducted prior to the 2009 influenza A (H1N1) pandemic, when usage rates were comparatively low. We assessed oseltamivir safety before and during the pandemic using biologically plausible risk intervals, particularly focusing on psychiatric events. METHODS: Outpatients with influenza episodes from January 2007 through June 2010 were identified using diagnosis codes and positive tests at eight health care systems (sites) in the Vaccine Safety Datalink Project. Oseltamivir-treated and untreated patients were matched according to calendar week, age, sex, site, and propensity for treatment. Within this matched cohort, conditional logistic regression models were used to estimate the risk of four neuropsychiatric and five other adverse events (AEs) during pre-specified risk intervals. RESULTS: Among 27,684 matched pairs, no associations were identified between oseltamivir treatment and any pre-defined AE. The absolute risks of incident psychiatric events in the 1-7 day risk interval were 0.126% for oseltamivir-treated and 0.105% for untreated patients (odds ratio = 1.21, 95% confidence interval [CI]: 0.74, 1.97; risk difference = 0.022%, 95% CI: -0.035%, 0.078%); the most common diagnosis was unspecified anxiety state. Results were similar for 1-14 and 1-2 day risk intervals and for pediatric/adolescent subgroups. CONCLUSIONS: Consistent with prior U.S. cohort studies, no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment. Safety should be prospectively monitored to inform antiviral medication usage recommendations.

Influenza and pertussis vaccination coverage among privately insured women of reproductive age.

An increasing number of vaccines are now designated as maternal vaccines, recommended prior to, during, or immediately following pregnancy. The influenza and pertussis (Tdap) vaccines have the potential to improve the health of women and their offspring. Among privately insured women of reproductive age, goals of this study were to describe influenza and Tdap vaccination coverage and to explore variation in coverage by age and race/ethnicity. This cross-sectional, observational study included women 18-44 years of age with continuous enrollment from 1 January 2007-31 March 2011 in a single, Midwestern health insurance plan and at least one visit to a plan affiliated practice. Data on vaccine coverage came from insurance claims, supplemented by electronic medical record data. Primary outcomes were: receipt of Tdap ever, receipt of Tdap or Tetanus vaccination (Td) in the past 10 years, and receipt of influenza vaccination during the 2010-2011 influenza season. Coverage was compared by race/ethnicity. Among 12,657 women with continuous private insurance, 45.5 % had received Tdap ever, 82.5 % had received Td or Tdap in the past 10 years, and 39.8 % received the influenza vaccine in the 2010-2011 season. Marked disparities in influenza vaccination coverage by race/ethnicity were observed, only 30.0 % of African American women received influenza vaccine compared to 40.7 % of white, non-Hispanic women (p < .0001). Among insured women of reproductive age, there is a need for interventions to increase Tdap and influenza vaccination uptake. Further research is needed to understand and address disparities in influenza vaccination coverage in this population.

Association Between Aluminum Exposure From Vaccines Before Age 24 Months and Persistent Asthma at Age 24 to 59 Months.

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 aluminum exposure was 4.07 mg (SD 0.60) and 3.98 mg (SD 0.72), 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.

Assessing the safety of influenza immunization during pregnancy: the Vaccine Safety Datalink.

The influenza vaccine can reduce maternal and neonatal morbidity and mortality and thus is recommended for all pregnant women. However, concerns regarding safety of influenza vaccine remain a barrier to vaccination. We describe ongoing analyses of influenza vaccine safety during pregnancy within the Vaccine Safety Datalink that includes the evaluation of acute events, adverse pregnancy and birth outcomes, and congenital anomalies. In addition, we highlight unique challenges and strategies for the study of vaccine safety among pregnant women with the use of large linked databases.

Association of the COVID-19 Pandemic With Routine Childhood Vaccination Rates and Proportion Up to Date With Vaccinations Across 8 US Health Systems in the Vaccine Safety Datalink.

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.

Near real-time surveillance for influenza vaccine safety: proof-of-concept in the Vaccine Safety Datalink Project.

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06-2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillain-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety.

Effectiveness of influenza vaccine in the community-dwelling elderly.

BACKGROUND: Reliable estimates of the effectiveness of influenza vaccine among persons 65 years of age and older are important for informed vaccination policies and programs. Short-term studies may provide misleading pictures of long-term benefits, and residual confounding may have biased past results. This study examined the effectiveness of influenza vaccine in seniors over the long term while addressing potential bias and residual confounding in the results. METHODS: Data were pooled from 18 cohorts of community-dwelling elderly members of one U.S. health maintenance organization (HMO) for 1990-1991 through 1999-2000 and of two other HMOs for 1996-1997 through 1999-2000. Logistic regression was used to estimate the effectiveness of the vaccine for the prevention of hospitalization for pneumonia or influenza and death after adjustment for important covariates. Additional analyses explored for evidence of bias and the potential effect of residual confounding. RESULTS: There were 713,872 person-seasons of observation. Most high-risk medical conditions that were measured were more prevalent among vaccinated than among unvaccinated persons. Vaccination was associated with a 27% reduction in the risk of hospitalization for pneumonia or influenza (adjusted odds ratio, 0.73; 95% confidence interval [CI], 0.68 to 0.77) and a 48% reduction in the risk of death (adjusted odds ratio, 0.52; 95% CI, 0.50 to 0.55). Estimates were generally stable across age and risk subgroups. In the sensitivity analyses, we modeled the effect of a hypothetical unmeasured confounder that would have caused overestimation of vaccine effectiveness in the main analysis; vaccination was still associated with statistically significant--though lower--reductions in the risks of both hospitalization and death. CONCLUSIONS: During 10 seasons, influenza vaccination was associated with significant reductions in the risk of hospitalization for pneumonia or influenza and in the risk of death among community-dwelling elderly persons. Vaccine delivery to this high-priority group should be improved.