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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 aged18 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 aged18 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 aged18 years. Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety.

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.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.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-values ≥ 0.05). 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-Barré 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).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.

Objective To measure the risk of influenza under-vaccination in children of vaccine-hesitant parents, referent to children of nonhesitant parents, in a sample of disadvantaged families in one influenza season. Study Design A prospective observational cohort study of English- and Spanish-speaking parents of 2-year-olds presenting at random for well, sick, or specialty visit care from August 1, 2019 to February 28, 2020. Parents answered demographic questions and the Parent Attitudes about Childhood Vaccines survey. We followed children until season's end, extracting vaccination data on April 30, 2020. We dichotomized vaccination status as unvaccinated or partially/fully vaccinated, analyzing data with multivariable Poisson regression; in secondary analyses, we conducted adjusted time-to-event analyses. Results Overall, 263 parents consented (response rate: 90%); our final sample included 255 dyads. Thirty-three (13%) parents were vaccine hesitant. In adjusted analyses, children of hesitant parents (n = 33) had a 195% increased risk (adjusted Risk Ratio 2.95; 95% confidence interval 1.91, 4.56) of being unvaccinated at season's end, referent to children of nonhesitant parents (n = 222). In time-to-event analyses, children of vaccine-hesitant parents were also more likely to be unvaccinated before influenza activity peaked (P = .02). Conclusions Parental vaccine hesitancy tripled the risk of pediatric influenza nonvaccination in a sample of poor and minority families during the 2019 to 2020 influenza season. As parental vaccine hesitancy appears to exacerbate pediatric influenza vaccination disparities, future work should explore parental hesitancy with poor and minority stakeholders and tailor evidence-based interventions to benefit children from these communities who receive care at all practice sites.

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 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

The self-controlled case series (SCCS) and the matched cohort are two frequently used study designs to adjust for known and unknown con- founding effects in epidemiological studies. Count data arising from these two designs may not be independent. While conditional Poisson regres- sion models have been used to take into account the dependence of such data, these models have not been available in some standard statistical soft- ware packages (e.g., SAS). This article demonstrates 1) the relationship of the likelihood function and parameter estimation between the conditional Poisson regression models and Cox's proportional hazard models in SCCS and matched cohort studies; 2) that it is possible to fit conditional Pois- son regression models with procedures (e.g., PHREG in SAS) using Cox's partial likelihood model. We tested both conditional Poisson likelihood and Cox's partial likelihood models on data from studies using either SCCS or a matched cohort design. For the SCCS study, we fitted both parametric and semi-parametric models to model age effects, and described a simple way to apply the parametric and complex semi-parametric analysis to case series data.

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.

Background: Promising approaches for reduction of childhood obesity include interventions such as Connect for Health, a scalable, primary care-based intervention to improve family-centered outcomes for children ages 2-12 years. Substantial gaps remain in the adoption of proven-effective interventions particularly in settings that care for low-income children. Methods: We used the Consolidated Framework for Implementation Research to examine contextual determinants of implementation of Connect for Health in four organizations that deliver primary care to low-income children in Boston, MA, Denver, CO, and Greenville, SC. The Connect for Health program includes (1) electronic health record (EHR)-based clinical decision support tools to guide clinicians; (2) family educational materials; and (3) text messages for parents to support behavior change. We used the RE-AIM framework to guide our mixed-methods evaluation. Using a quasi-experimental design, we will examine the effectiveness of stakeholder-informed strategies in supporting program adoption and child outcomes. At baseline, we abstracted EHR data from the organizations to describe characteristics of children ages 2-12 years with a BMI ≥ 85th percentile.Results: During the 15-month period prior to implementation, 26,161 children with a BMI ≥ 85th percentile ages 2-12 years were seen for a primary care visit. Across the organizations, 79% of children with a BMI ≥ 85th percentile had public insurance, 49% were Hispanic, and 18% were Black. Approximately 37% of children had a BMI ≥ 95th percentile and 15% had a BMI in the severe obesity category. Childhood obesity ICD-10 diagnostic codes were used more for children with obesity (44%) and severe obesity (60%) than children with overweight (17%); nutrition (7%) and physical activity (6%) counseling codes were seldom used. Referrals for weight management programs were less than 17% and less than 16% for nutrition services. Laboratory evaluations were ordered more often for children with obesity (39%) and severe obesity (64%) than children with overweight (29%)Discussion: A majority of children with overweight and obesity lacked recommended diagnosis codes, referrals, and laboratory evaluations for assessment and management of obesity and related co-morbidities. These findings suggest the need to augment current approaches to increase uptake of proven-effective weight management programs. Trial Registration: Clinicaltrials.gov, NCT04042493, Registered on August 2, 2019; https://clinicaltrials.gov/ct2/show/NCT04042493

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.

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.

To assess the association between cumulative aluminum exposure from vaccines before age 24 months and persistent asthma at age 24 to 59 months.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.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).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.

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.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.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.This study evaluated UTD status among children reaching specific ages in February, May, and September 2020, compared with those reaching these ages in 2019.Weekly vaccination rates for routine age-specific vaccines and the proportion of children UTD for all age-specific recommended vaccines.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).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.

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.

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.

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.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.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.SARS-CoV-2 infection.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.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).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.

* Abbreviations: NJNPlay — : No Jab No Play NJNPay — : No Jab No Pay In this issue of Pediatrics , Attwell et al1 assess the impact of two policy changes on childhood vaccination coverage in Australia. Conducting an interrupted time series analysis, the authors measure vaccination coverage of Australian children at 12 and 60 months at federal, state, and community levels after the implementation of (1) “No Jab, No Play” (NJNPlay), state-level policies denying unvaccinated children enrollment in preschool starting in 2014; and (2) “No Jab, No Pay” (NJNPay), a federal-level policy linking vaccination receipt to government family assistance payments enacted in 2016. This study is an important contribution to the vaccination policy literature and an intriguing study of behavioral theory and health equity. Psychology is an essential part of vaccine intervention design. In an exhaustive review, Brewer et al2 summarized the vaccination and psychology literature in 2017, finding 3 ways researchers have leveraged psychology to increase vaccination: (1) understanding and changing thoughts and feelings about infectious diseases and vaccines via direct communication, (2) leveraging social processes and norms to alter vaccination behaviors, and (3) facilitating direct behavior change … Address correspondence to Joshua T. B. Williams, MD, Denver Health Medical Center, 301 W 6th Ave, MC #1911, Denver, CO 80204. E-mail: joshua.williams{at}dhha.org

* Abbreviations: ADU — : average days undervaccinated PACV — : Parent Attitudes about Childhood Vaccines VH — : vaccine hesitancy Poor and minority children still lag behind wealthier, white children in vaccination coverage.1,2 Structural, logistic, cultural, and attitudinal barriers contribute to vaccination disparities.3,4 Vaccine hesitancy (VH) is an important attitudinal barrier and a growing challenge.5 We measured VH and its association with child average days undervaccinated (ADU) in English- and Spanish-speaking parents of children aged 2 years in 3 safety-net clinics, describing associations by language, race, and ethnicity. We surveyed English- and Spanish-speaking parents bringing children aged 2 years to 3 pediatric clinics for well or sick care from August 2019 … Address correspondence to Joshua T.B. Williams, MD, Denver Health Medical Center, 301 W 6th Ave, MC #1911, Denver, CO 80204. E-mail: joshua.williams{at}dhha.org

OBJECTIVE: To evaluate whether quadrivalent human papillomavirus vaccine (4vHPV) administered during the periconceptional period or during pregnancy was associated with increased risks for adverse obstetric events, adverse birth outcomes, or selected major structural birth defects. METHODS: We conducted a retrospective, observational cohort study using administrative and health care data from the Vaccine Safety Datalink. Insured women 13–27 years old with singleton pregnancies and a live birth from January 1, 2007, through September 1, 2013, who received 4vHPV during the periconceptional period (2 weeks before to 2 weeks after their last menstrual period), during pregnancy, or during both periods combined were compared with women who had a live birth during the same time period and received 4vHPV 4–18 months before their last menstrual period. We examined risks of gestational diabetes, hypertensive disorders of pregnancy, chorioamnionitis, preterm birth, small-for-gestational-age birth, and selected major structural birth defects in offspring. We estimated relative risks associated with receipt of 4vHPV during the periconceptional period, during pregnancy, and both exposure periods combined using a generalized linear model with Poisson distribution including a propensity score that included relevant maternal demographic and pregnancy characteristics. RESULTS: Of 92,579 potentially eligible pregnant women, 720 received 4vHPV during the periconceptional period, 638 received 4vHPV during pregnancy, and 8,196 received 4vHPV during the comparison period. Administration of 4vHPV during pregnancy was not associated with increased risk of adverse obstetric events, birth outcomes. Preterm birth occurred in 7.9% of pregnancies with vaccine exposures during pregnancy compared with 7.6% of pregnancies with vaccination in the comparison period (adjusted relative risk 0.97, 95% CI 0.72–1.3). Major structural birth defects were diagnosed in 2.0% of pregnancies with vaccine exposure during pregnancy compared with 1.8% of pregnancies with vaccine exposure during the comparison period (adjusted prevalence ratio 1.0, 95% CI 0.52–1.9). Results were similar for 4vHPV exposure during the periconceptional period. CONCLUSION: Quadrivalent HPV vaccine inadvertently administered in pregnancy or during the periconceptional period was not associated with adverse pregnancy or birth outcomes.

Objectives. To assess an oral health promotion (OHP) intervention for medical providers’ impact on early childhood caries (ECC). Methods. We implemented a quasiexperimental OHP intervention in 8 federally qualified health centers that trained medical providers on ECC risk assessment, oral examination and instruction, dental referral, and fluoride varnish applications (FVAs). We measured OHP delivery by FVA count at medical visits. We measured the intervention’s impact on ECC in 3 unique cohorts of children aged 3 to 4 years in 2009 (preintervention; n = 202), 2011 (midintervention; n = 420), and 2015 (≥ 4 FVAs; n = 153). We compared numbers of decayed, missing, and filled tooth surfaces using adjusted zero-inflated negative binomial models. Results. Across 3 unique cohorts, the FVA mean (range) count was 0.0 (0), 1.1 (0–7), and 4.5 (4–7) in 2009, 2011, and 2015, respectively. In adjusted zero-inflated negative binomial models analyses, children in the 2015 cohort had significantly fewer decayed, missing, and filled tooth surfaces than did children in previous cohorts. Conclusions. An OHP intervention targeting medical providers reduced ECC when children received 4 or more FVAs at a medical visit by age 3 years.

Background Connect for Health is an evidence-based weight management program with clinical- and family-facing components for delivery in pediatric primary care for families of children ages 2 to 12 years. We used the Consolidated Framework for Implementation Research (CFIR) to guide formative work prior to national implementation. The purpose of this study was to describe the process and results of stakeholder engagement and program adaptation. Methods We used mixed qualitative and quantitative methods to iteratively adapt and optimize the program by assessing needs and perspectives of clinicians and parents, as well as contextual barriers, facilitators, and organizational readiness for the uptake of the proposed program tools and implementation strategies. We conducted interviews with primary care clinicians from four health care organizations in Boston, MA; Denver, CO; and Greenville, SC, and used principles of immersion-crystallization for qualitative analyses. We also conducted surveys of parents of children with a body mass index ≥ 85th percentile. Results We reached thematic saturation after 52 clinician interviews. Emergent themes representing the CFIR domains of intervention characteristics, outer and inner setting, and process included (1) importance of evidence-based clinical decision support tools that integrate into the workflow and do not extend visit time, (2) developing resources that respond to family’s needs, (3) using multimodal delivery options for family resources, (4) addressing childhood obesity while balancing competing demands, (5) emphasizing patient care rather than documentation and establishing sustainability plans, and (6) offering multiple training methods that incorporate performance feedback. Of the parents surveyed (n = 400), approximately 50% were Spanish-speaking and over 75% reported an annual income < $50,000. Parents affirmed the importance of addressing weight management during well-child visits, being provided with referrals and resources, and offering multiple methods for resource delivery. Decisions about program modifications were made at the program and healthcare-system level and based on stakeholder engagement findings. Modifications included cultural, geographic, and target audience adaptations, as well as varied resource delivery options. Conclusions To ensure the fit between the Connect for Health program and national implementation settings, adaptations were systematically made through engagement of clinician and parent stakeholders to support adoption, sustainability, and health outcomes. Trial registration NCT04042493

Background Early Intervention (EI) is a federally mandated, state-administered system of care for children with developmental delays and disabilities under the age of three. Gaps exist in the process of accessing EI through pediatric primary care, and low rates of EI access are well documented and disproportionately affect poor and minority children. The aims of this paper are to examine child characteristics associated with gaps in EI (1) referral, (2) access and (3) service use. To our knowledge, this is the first study to leverage linked safety net health system pediatric primary care and EI records data to follow EI-referred children longitudinally to understand EI service use gaps from EI referral to EI service utilization. Methods In a retrospective cohort design (14,710 children with developmental disability or delay), we linked pediatric primary care records between a large, integrated safety net health system in metro Denver and its corresponding EI program (2014–2016). Using adjusted marginal effects [ME, (95% CI)], we estimated gaps in EI referral, access, and service type (i.e., physical [PT], occupational [OT], speech therapy [ST] and developmental intervention [DI]). Analyses accounted for child characteristics including socio-demographics, diagnosis, condition severity, and baseline function. Results Only 18.7% of EI-eligible children (N = 2726) received a referral; 26% of those (N = 722) received services for a net enrollment rate of 5% among EI-eligible children. Having the most severe developmental condition was positively associated with EI referral [ME = 0.334 [0.249, 0.420]) and Individualized Family Services Plan (IFSP) receipt [ME = 0.156 [0.088, 0.223]). Children less likely to be EI-referred were Black, non-Hispanic (BNH) [ME = -0.029 (− 0.054, − 0.004)] and had a diagnosed condition ([ME = − 0.046 (− 0.087, − 0.005)]. Children with a diagnosis and those with higher income were more likely to receive PT or OT. Higher baseline cognitive and adaptive skills were associated with lower likelihood of PT [ME = -0.029 (− 0.054, − 0.004)], OT [ME = -0.029 (− 0.054, − 0.004)], and ST [ME = -0.029 (− 0.054, − 0.004)]. Conclusions We identified and characterized gaps in EI referral, access, and service use in an urban safety-net population of children with high rates of developmental delay. Interventions are needed to improve integrated systems of care affecting primary care and EI processes and coordination.

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 suboptimal 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. This research was approved by the HealthPartners Institutional Review Board, by all participating VSD sites, and by the CDC, with a waiver of informed consent. 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 2 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.

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 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.

Introduction Pregnant women are at risk for influenza-related complications and have been recommended for vaccination by the Advisory Committee on Immunization Practices (ACIP) since 1990. Annual rates of influenza coverage of pregnant women have been consistently low. The Vaccine Safety Datalink was used to assess influenza vaccine coverage over 10 consecutive years (2002–2012); assess patterns related to changes in ACIP recommendations; identify predictors of vaccination; and compare the results with those published by national U.S. surveys. Methods Retrospective cohort study of 721,898 pregnancies conducted in 2014. Coverage rates were assessed for all pregnancies and for live births only. Multivariate regression analysis identified predictors associated with vaccination. Results Coverage increased from 8.8% to 50.9% in 2002–2012. Seasonal coverage rates increased slowly following the 2004 ACIP influenza vaccine recommendation (to remove the first trimester restriction), but spiked significantly during the 2009 H1N1 influenza pandemic. Significant predictors of vaccination during pregnancy included older age; vaccination in a previous season; high-risk conditions in addition to pregnancy; pregnancy during either the 2004–2005 or 2009–2010 seasons; entering the influenza season after the first trimester of pregnancy; and a pregnancy with longer overlap with the influenza season ( p Conclusions Influenza vaccination coverage among pregnant women increased between the 2002–2003 and 2011–2012 seasons, although it was still below the developmental Healthy People 2020 goal of 80%. The 2004 ACIP language change positively impacted first-trimester vaccination uptake. Vaccine Safety Datalink data estimates were consistent with U.S. estimates.

Background Varicella (VAR) and measles-mumps-rubella (MMR) vaccines are recommended for children at ages 12–15 months and 4–6 years. These are administered as separate MMR and VAR vaccines (MMR+VAR) or as combined measles-mumps-rubella-varicella (MMRV) vaccine. Herpes zoster (HZ), caused by wild-type or vaccine-strain varicella-zoster virus, can occur in children after varicella vaccination. It is unknown whether HZ incidence after varicella vaccination varies by vaccine formulation or simultaneous receipt of MMR. Methods Using data from six integrated health systems, we examined HZ incidence among children who turned 12 months old during 2003–2008 and received varicella and MMR vaccines according to routine recommendations. All HZ cases ≥ 21 days after first varicella vaccination were identified using ICD-9 codes from inpatient, outpatient, emergency room encounters, and claims data, through 2014. HZ incidence was examined by vaccine formulation (MMR+VAR, MMRV, or VAR without same-day MMR) and doses received and compared using incidence rate ratios (IRR). Results Among 199,797 children, we identified 601 HZ cases. Crude HZ incidence after first-dose MMR+VAR (18.6 [95% CI 11.1–29.2] cases/100,000 person-years) was similar to the rate after first-dose MMRV (17.9 [95% CI 10.6–28.3] cases/100,000 person-years), but approximately double the rate among those with first-dose VAR without same-day MMR (7.5 [95% CI 3.1–15.0] cases/100,000 person-years); see Table 1. The IRR for HZ after first-dose MMR+VAR or MMRV, compared with VAR, was 2.5 (95% CI 1.4–4.4; P = 0.002). When examining any first or second dose formulation, crude HZ incidence was lower after the second varicella vaccine dose (13.9 cases/100,000 person-years), than in the period before the second dose (i.e., between first and second doses or after the first dose in children with only one dose; 21.8 cases/100,000 person-years, P < 0.0001). HZ incidence was also lower after two varicella vaccine doses in each of the three first-dose formulation groups. Conclusion HZ incidence among children varied by first-dose varicella vaccine formulation and number of varicella vaccine doses. Regardless of the first-dose varicella vaccine formulation, children who received two vaccine doses had lower HZ incidence after the second dose. Disclosures All authors: No reported disclosures.

Introduction Since October 2012, the combined tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine (Tdap) has been recommended in the United States during every pregnancy. Methods In this observational study from the Vaccine Safety Datalink, we describe receipt of Tdap during pregnancy among insured women with live births across seven health systems. Using a retrospective matched cohort, we evaluated risks for selected medically attended adverse events in pregnant women, occurring within 42 days of vaccination. Using a generalized estimating equation, we calculated adjusted incident rate ratios (AIRR). Results Our vaccine coverage cohort included 438,487 live births between January 1, 2007 and November 15, 2013. Across the coverage cohort, 14% received Tdap during pregnancy. By 2013, Tdap was administered during pregnancy in 41.7% of live births, primarily in the 3rd trimester. Our vaccine safety cohort included 53,885 vaccinated and 109,253 matched unvaccinated pregnant women. There was no increased risk for a composite outcome of medically attended acute adverse events within 3 days of vaccination. Similarly, across the safety cohort, over a 42 day window, incident neurologic events, thrombotic events, and new onset proteinuria did not differ by maternal receipt of Tdap. Among women receiving Tdap at 20 weeks gestation or later, as compared to their matched controls, there was no increased risk for gestational diabetes or cardiac events while venous thromboembolic events and thrombocytopenia were diagnosed within 42 days of vaccination at slightly decreased rates. Conclusion Tdap coverage during pregnancy increased from 2007 through 2013, but was still below 50%. No acute maternal safety signals were detected in this large cohort.

OBJECTIVE:To evaluate the safety of coadministering tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during pregnancy by comparing adverse events after concomitant and sequential vaccination.METHODS:We conducted a retrospective cohort study of pregnant

Objective To identify which English and Spanish terms Latino parents consider motivating, as well as culturally and linguistically appropriate, for provider use during weight counseling of overweight and obese Latino youth. Methods Latino parent perceptions of common Spanish and English terms for overweight were discussed with 54 parents in 6 focus groups (3 English, 3 Spanish). Atlas.ti software was used for qualitative analysis. An initial codebook was used to code passages for English and Spanish terminology separately. Subsequent changes to the coded passages and creation of new codes were made by team consensus. Results "Demasiado peso para su salud" (too much weight for his/her health) was the only phrase for excess weight that was consistently identified as motivating and inoffensive by Spanish-speaking parents. "Sobrepeso" (overweight), a commonly used term among health care providers, was motivating to some parents but offensive to others. English-speaking parents had mixed reactions to "unhealthy weight," "weight problem," and "overweight," finding them motivating, confusing, or insulting. Parents found "fat" "gordo" and "obese" "obeso" consistently offensive. Most participants found growth charts and the term "BMI" confusing. Parents consistently reported that providers could enhance motivation and avoid offending families by linking a child's weight to health risks, particularly diabetes. Conclusions "Demasiado peso para su salud" (too much weight for his/her health) was motivating to many Spanish-speaking Latino parents. Among English-speaking Latino parents, no single English term emerged as motivating, well-understood, and inoffensive. Linking a child's excess weight with increased health risks was motivating and valuable to many parents regardless of language spoken.

BACKGROUND AND OBJECTIVES:All measles-containing vaccines are associated with several types of adverse events, including seizure, fever, and immune thrombocytopenia purpura (ITP). Because the measles-mumps-rubella-varicella (MMRV) vaccine compared with the separate measles-mumps-rubella (MMR) and varicella (MMR + V) vaccine increases a toddler’s risk for febrile seizures, we investigated whether MMRV is riskier than MMR + V and whether either vaccine elevates the risk for additional safety outcomes.METHODS:Study children were aged 12 to 23 months in the Vaccine Safety Datalink from 2000 to 2012. Nine study outcomes were investigated: 7 main outcomes (anaphylaxis, ITP, ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease), seizure, and fever. Comparing MMRV with MMR + V, relative risk was estimated by using stratified exact binomial tests. Secondary analyses examined post-MMRV or MMR + V risk versus comparison intervals; risk and comparison intervals were then contrasted for MMRV versus MMR+V.RESULTS:We evaluated 123 200 MMRV and 584 987 MMR + V doses. Comparing MMRV with MMR + V, risks for the 7 main outcomes were not significantly different. Several outcomes had few or zero postvaccination events. Comparing risk versus comparison intervals, ITP risk was higher after MMRV (odds ratio [OR]: 11.3 [95% confidence interval (CI): 1.9 to 68.2]) and MMR + V (OR: 10 [95% CI: 4.5 to 22.5]) and ataxia risk was lower after both vaccines (MMRV OR: 0.8 [95% CI: 0.5 to 1]; MMR + V OR: 0.8 [95% CI: 0.7 to 0.9]). Compared with MMR + V, MMRV increased risk of seizure and fever 7 to 10 days after vaccination.CONCLUSIONS:This study did not identify any new safety concerns comparing MMRV with MMR + V or after either the MMRV or the MMR + V vaccine. This study provides reassurance that these outcomes are unlikely after either vaccine.

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.

Introduction An increased risk of diagnosed chorioamnionitis in women vaccinated with Tdap during pregnancy was previously detected at two Vaccine Safety Datalink (VSD) sites. The clinical significance of this finding related to infant outcomes remains uncertain. Methods Retrospective cohort study of singleton live births born to women who were continuously insured from 6 months prior to their last menstrual period through 6 weeks postpartum, with ≥1 outpatient visit during pregnancy from January 1, 2010 to November 15, 2013 at seven integrated United States health care systems part of the VSD. We re-evaluated the association between maternal Tdap and chorioamnionitis and evaluated whether specific infant morbidities differ among infants born to mothers who did and did not receive Tdap during pregnancy. We focused on 2 Tdap exposure windows: the recommended 27–36 weeks gestation or anytime during pregnancy. We identified inpatient diagnostic codes for transient tachypnea of the newborn (TTN), neonatal sepsis, neonatal pneumonia, respiratory distress syndrome (RDS), and newborn convulsions associated with an infant's first hospitalization. A generalized linear model with Poisson distribution and log-link was used to estimate propensity score adjusted rate ratios (ARR) with 95% confidence intervals (CI). Results The analyses included 197,564 pregnancies. Chorioamnionitis was recorded in 6.4% of women who received Tdap vaccination any time during pregnancy and 5.2% of women who did not (ARR [95% CI]: 1.23 [1.17, 1.28]). Compared with unvaccinated women, there were no significant increased risks (ARR [95% CI]) for TTN (1.04 [0.98, 1.11]), neonatal sepsis (1.06 [0.91, 1.23]), neonatal pneumonia (0.94 [0.72, 1.22]), RDS (0.91 [0.66, 1.26]), or newborn convulsions (1.16 [0.87, 1.53]) in infants born to Tdap-vaccinated women. Conclusions and Relevance Despite an observed association between maternal Tdap vaccination and maternal chorioamnionitis, we did not find increased risk for clinically significant infant outcomes associated with maternal chorioamnionitis.

Objective To describe childhood weight gain using body mass index (BMI) z-score trajectories in a low-income urban safety-net population and identify among gender- and race/ethnicity-specific groups any trends for increased risk. Methods A retrospective cohort study was conducted among 2- to 12-year-old patients (2006–2013) visiting a safety-net provider. BMI z-score trajectories were calculated overall, for gender- and race/ethnicity-specific groups, and for peak BMI percentile subgroups to describe weight gain longitudinally. Results From 2006 to 2013, a total of 26,234 eligible children were followed for an average of 3.7 years. At baseline (mean age, 4.2 years), 74% of patients were at a normal weight compared to 65% at most recent observation (mean age, 7.8 years). All gender and race/ethnicity subgroups showed increasing average BMI z-scores during childhood. Children consistently under the 50th percentile and those of white race had the most stable BMI z-score trajectories. BMI z-score increased with increasing age in all subgroups. Hispanic boys and black girls had the most significant increase in BMI z-score during this observation period. Children observed in early childhood and whose BMI exceeded the 95th percentile at any time were often already overweight (20%) or obese (36%) by 3 years of age. Conclusions The entire population demonstrated an upward trend in BMI z-score trajectory. This trend was most notable among black girls and Hispanic boys. Many obese children were already overweight by age 3, and persistence of obesity after 3 years of age was high, suggesting that intervention before age 3 may be essential to curbing unhealthy weight trajectories.

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.

BACKGROUND: Little is known regarding the timing of childhood vaccination and postvaccination seizures. METHODS: In a cohort of 323 247 US children from the Vaccine Safety Datalink born from 2004 to 2008, we analyzed the association between the timing of childhood vaccination and the first occurrence of seizure with a self-controlled case series analysis of the first doses of individual vaccines received in the first 2 years of life. RESULTS: In infants, there was no association between the timing of infant vaccination and postvaccination seizures. In the second year of life, the incident rate ratio (IRR) for seizures after receipt of the first measles-mumps-rubella vaccine (MMR) dose at 12 to 15 months was 2.65 (95% confidence interval [CI] 1.99–3.55); the IRR after an MMR dose at 16 to 23 months was 6.53 (95% CI 3.15–13.53). The IRR for seizures after receipt of the first measles-mumps-rubella-varicella vaccine (MMRV) dose at 12 to 15 months was 4.95 (95% CI 3.68–6.66); the IRR after an MMRV dose at 16 to 23 months was 9.80 (95% CI 4.35 –22.06). CONCLUSIONS: There is no increased risk of postvaccination seizure in infants regardless of timing of vaccination. In year 2, delaying MMR vaccine past 15 months of age results in a higher risk of seizures. The strength of the association is doubled with MMRV vaccine. These findings suggest that on-time vaccination is as safe with regard to seizures as delayed vaccination in the first year of life, and that delayed vaccination in the second year of life is associated with more postvaccination seizures than on-time vaccination.

Background In 2008, a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combined vaccine (DTaP–IPV) was licensed for use in children 4 through 6 years of age. While pre-licensure studies did not demonstrate significant safety concerns, the number vaccinated in these studies was not sufficient to examine the risk of uncommon but serious adverse events. Objective To assess the risk of serious adverse events following DTaP–IPV vaccination. Methods The study was conducted from January 2009 through September 2012 in the Vaccine Safety Datalink (VSD) project. In the VSD, electronic vaccination and encounter data are updated and aggregated weekly as part of ongoing surveillance activities. Based on previous reports and biologic plausibility, eight potential adverse events were monitored: meningitis/encephalitis; seizures; stroke; Guillain–Barre syndrome; Stevens–Johnson syndrome; anaphylaxis; serious allergic reactions other than anaphylaxis; and serious local reactions. Adverse event rates in DTaP–IPV recipients were compared to historical incidence rates in the VSD population prior to 2009. Sequential probability ratio testing was used to analyze the data on a weekly basis. Results During the study period, 201,116 children received DTaP–IPV vaccine. Ninety-seven percent of DTaP–IPV recipients also received other vaccines on the same day, typically measles–mumps–rubella and varicella vaccines. There was no statistically significant increased risk of any of the eight pre-specified adverse events among DTaP–IPV recipients when compared to historical incidence rates. Conclusions In this safety surveillance study of more than 200,000 DTaP–IPV vaccine recipients, there was no evidence of increased risk for any of the pre-specified adverse events monitored. Continued surveillance of DTaP–IPV vaccine safety may be warranted to monitor for rare adverse events, such as Guillain–Barre syndrome.

Objective School-located influenza vaccination (SLIV) may be instrumental in achieving high vaccination rates among children. Sustainability of SLIV programs may require third-party billing. This study assessed, among parents of elementary school students, the attitudes about SLIV and billing at school, as well as factors associated with being supportive of SLIV. Methods We conducted a survey (April 2010 to June 2010) of parents of 1000 randomly selected primarily low-income children at 20 elementary schools at which SLIV with billing had occurred. Results Response rate was 70% (n = 699). Eighty-one percent agreed (61% strongly) they "would be okay" with SLIV for their child. Many agreed it was better to get vaccinated at their child's doctor's office because they could take care of other health issues (72%) and the doctor knows the child's medical history (65%). However, an equal percentage (47%) thought the best place for influenza vaccination was the child's doctor's office and the child's school. Twenty-five percent did not want to give health insurance information necessary for billing at school. Factors independently associated with strongly supporting SLIV included parental education of high school or less (relative risk 1.30; 95% confidence interval 1.09–1.58), Hispanic ethnicity (1.25; 1.08–1.45); believing the vaccine is efficacious (1.49; 1.23–1.84); and finding school delivery more convenient (2.37; 1.82–3.45). Having concerns about the safety of influenza vaccine (0.80; 0.72–0.88) and not wanting their child to be vaccinated without a parent (0.74; 0.64–0.83) were negatively associated. Conclusions The majority of parents were supportive of SLIV, although parental concerns about not being present for vaccination and about the safety and efficacy of the vaccine will need to be addressed.

BACKGROUND: Home oxygen has been incorporated into the emergency department management of bronchiolitis in high-altitude settings. However, the outpatient course on oxygen therapy and factors associated with subsequent admission have not been fully defined. METHODS: We conducted a retrospective cohort study in consecutive patients discharged on home oxygen from the pediatric emergency department at Denver Health Medical Center from 2003 to 2009. The integration of inpatient and outpatient care at our study institution allowed comprehensive assessment of follow-up rates, outpatient visits, time on oxygen, and subsequent admission. Admitted and nonadmitted patients were compared by using a χ2 test and multivariable logistic regression. RESULTS: We identified 234 unique visits with adequate follow-up for inclusion. The median age was 10 months (interquartile range [IQR]: 7–14 months). Eighty-three percent of patients were followed up within 24 hours and 94% within 48 hours. The median length of oxygen use was 6 days (IQR: 4–9 days), and the median number of associated encounters was 3 (range: 0–9; IQR: 2–3). Ninety-three percent of patients were on room air at 14 days. Twenty-two patients (9.4%) required subsequent admission. Fever at the initial visit (>38.0°C) was associated with admission (P < .02) but had a positive predictive value of 15.4%. Age, prematurity, respiratory rate, oxygen saturation, and history of previous bronchiolitis or wheeze were not associated with admission. CONCLUSIONS: There is a significant outpatient burden associated with home oxygen use. Although fever was associated with admission, we were unable to identify predictors that could modify current protocols.

Background A number of studies have described influenza vaccination coverage during pregnancy but few publications have described rates of other vaccinations. Purpose To describe vaccination rates during pregnancy in the Vaccine Safety Datalink (VSD), with particular focus on vaccinations contraindicated during pregnancy. Methods Pregnancies ending in 2002 through 2009 and vaccinations administered during these pregnancies were identified in the VSD. Vaccination rates per 1000 pregnancies during the study period were calculated by vaccine type, recommendation category, pregnancy year, maternal age, and trimester. Analyses were conducted in 2012–2013. Results In the VSD, 669,695 pregnancies and 141,389 vaccinations were identified. Trivalent inactivated influenza (TIV) was the most commonly administered vaccination (174.1 doses per 1000 pregnancies) and was most often administered during the 2nd and 3rd trimesters. The most common vaccines in the “consider if indicated” category were tetanus–diphtheria (6.1 per 1000) and hepatitis B (3.7 per 1000). Contraindicated vaccination was infrequent, and the majority of these were measles–mumps–rubella (MMR) (1.2 per 1000); varicella (1.0 per 1000); and live-attenuated influenza vaccine (LAIV) (0.3 per 1000). Both “consider if indicated” and contraindicated vaccines were more frequently administered during early pregnancy. Conclusions TIV was the most commonly administered vaccine. With the exception of TIV, other vaccines were most frequently administered during early pregnancy and among younger women, suggesting that vaccination may occur when the woman and/or provider are unaware of the pregnancy. Contraindicated vaccines were infrequently administered during pregnancy; however, given that some women received contraindicated vaccines later in pregnancy, clearer recommendations and improved provider education may be needed.

Background Previously published studies reported an increased risk of gastrointestinal illness in the 14 days following trivalent influenza vaccination (TIV) in young children. While gastrointestinal illness may be a true adverse effect of TIV, other factors may influence this observed association, such as seasonal illness patterns and children being exposed to gastrointestinal pathogens at medical visits. The objective of this study was to examine factors influencing the association between TIV and gastrointestinal illness. Specifically, using data from a previous influenza vaccine safety study, we examined the association between medical encounters without TIV and gastrointestinal illness. Methods Using electronic health record (EHR) data from 6 managed care organizations (MCOs), we identified medically attended gastrointestinal illness cases among children 24–59 months in the 2002–2006 influenza seasons. We matched each case to four controls on sex, birthdate (month/year), MCO, influenza season, and presence of a chronic condition. We then looked 1–14 days prior to the index date (gastrointestinal illness diagnosis date) to determine whether the child had a medical encounter. We excluded previous medical encounters with gastrointestinal-related diagnoses or TIV. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Results We identified 2062 gastrointestinal illness cases and matched them to 8248 controls. We observed increased odds of gastrointestinal illness within 14 days after a medical encounter (odds ratio = 1.9; 95% confidence interval [CI]: 1.7–2.2) among children without chronic conditions. Among children with chronic conditions, the odds ratio was 3.9 (95% CI: 2.5–6.2). Conclusions We demonstrated that another exposure related to vaccination, medical visits, is also associated with increased odds for gastrointestinal illness. This study highlights challenges of interpreting results from observational vaccine safety studies when there are co-occurring exposures, and the importance of investigating confounding in EHR data, which are an essential resource for vaccine safety research.

OBJECTIVE:To estimate the risks for medically attended events occurring within 42 days of receiving trivalent inactivated influenza vaccine and to evaluate specific risks of first-trimester vaccination.METHODS:This retrospective observational cohort study compared rates of medically attended adverse

OBJECTIVE: Our objective was to assess whether the occurrence of medically attended local reactions to intramuscularly administered vaccines varies by injection site (arm versus thigh) in children 1 to 6 years of age. METHODS: This is a retrospective cohort study of children in the Vaccine Safety Datalink population from 2002 to 2009. Site of injection and the outcome of medically attended local reactions were identified from administrative data. RESULTS: The study cohort of 1.4 million children received 6.0 million intramuscular (IM) vaccines during the study period. The primary analyses evaluated the IM vaccines most commonly administered alone, which included inactivated influenza, hepatitis A, and diphtheria-tetanus-acellular pertussis (DTaP) vaccines. For inactivated influenza and hepatitis A vaccines, local reactions were relatively uncommon, and there was no difference in risk of these events with arm versus thigh injections. The rate of local reactions after DTaP vaccines was higher, and vaccination in the arm was associated with a significantly greater risk of this outcome compared with vaccination in the thigh, both for children 12 to 35 months (relative risk: 1.88 [95% confidence interval: 1.34–2.65]) and 3 to 6 years of age (relative risk: 1.41 [95% confidence interval: 0.84–2.34]), although this difference was not statistically significant in the older age group. CONCLUSIONS: Injection in the thigh is associated with a significantly lower risk of a medically attended local reaction to a DTaP vaccination among children 12 to 35 months of age, supporting current recommendations to administer IM vaccinations in the thigh for children younger than 3 years of age.

BACKGROUND AND OBJECTIVE: Despite national recommendations for adolescent human papillomavirus (HPV) vaccination, rates have lagged behind those of other adolescent vaccines. We implemented interventions and examined rates of vaccination coverage in a large, urban, safety net health care system to understand whether our tactics for achieving high rates of adolescent vaccination were successful. METHODS: Denver Health is an integrated urban safety net health system serving >17 000 adolescents annually. The process for achieving high vaccination rates in our health system includes “bundling” of vaccines, offering vaccines at every visit, and standard orders. Data from vaccine registry and utilization statistics were used to determine vaccination rates in adolescents aged 13 to 17 years from 2004 to 2014, and these findings were compared with state and national rates for 2013. Regression analysis was used to identify characteristics associated with vaccination. RESULTS: In 2013 (N = 11 463), HPV coverage of ≥1 dose was 89.8% (female subjects) and 89.3% (male subjects), compared with national rates of 57.3% and 34.6%. Rates of HPV coverage (≥3 doses) were 66.0% for female subjects and 52.5% for male subjects, versus 37.6% and 13.9% nationally. For both sexes, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed, vaccine coverage was 95.9% (86.0% nationally), and meningococcal conjugate vaccine coverage was 93.5% (77.8% nationally). Female subjects, Hispanic subjects, non-English speakers, and teenagers CONCLUSIONS: Through low-cost, system-wide standard procedures, Denver Health achieved adolescent vaccination rates well above national coverage rates. Avoiding missed opportunities for vaccination and normalizing the HPV vaccine were key procedures that contributed to high coverage rates.

BACKGROUND AND OBJECTIVE: An increased risk of febrile seizure (FS) was identified with concomitant administration of trivalent inactivated influenza vaccine (IIV3) and pneumococcal conjugate vaccine (PCV) 13-valent during the 2010–2011 influenza season. Our objective was to determine whether concomitant administration of IIV3 with other vaccines affects the FS risk. METHODS: We examined the risk of FS 0 to 1 day postvaccination for all routinely recommended vaccines among children aged 6 through 23 months during a period encompassing 5 influenza seasons (2006–2007 through 2010–2011). We used a population-based self-controlled risk interval analysis with a control interval of 14 to 20 days postvaccination. We used multivariable regression to control for receipt of concomitant vaccines and test for interaction between vaccines. RESULTS: Only PCV 7-valent had an independent FS risk (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.00 to 3.91). IIV3 had no independent risk (IRR, 0.46; 95% CI, 0.21 to 1.02), but risk was increased when IIV3 was given with either PCV (IRR, 3.50; 95% CI, 1.13 to 10.85) or a diphtheria-tetanus-acellular-pertussis (DTaP)-containing vaccine (IRR, 3.50; 95% CI, 1.52 to 8.07). The maximum estimated absolute excess risk due to concomitant administration of IIV3, PCV, and DTaP-containing vaccines compared with administration on separate days was 30 FS per 100 000 persons vaccinated. CONCLUSIONS: The administration of IIV3 on the same day as either PCV or a DTaP-containing vaccine was associated with a greater risk of FS than when IIV3 was given on a separate day. The absolute risk of postvaccination FS with these vaccine combinations was small.