Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

Beyond Vaccination Coverage: Population-Based Measurement of Early Childhood Immunization Schedule Adherence.

The immunization schedule recommended by the U.S. Advisory Committee on Immunization Practices (ACIP) provides a structure for how 10 different vaccine series should be administered to children in the first 18 months of life. Progress toward US early childhood immunization goals has largely focused on measuring vaccination coverage at age 24 months. However, standard vaccination coverage measures do not reflect whether children received vaccine doses by recommended ages, or whether vaccines were given concomitantly, per the schedule. In this paper, we describe innovations in population-level measurement of immunization schedule adherence through quantifying vaccination timeliness and undervaccination patterns. Measuring vaccination timeliness involves comparing when children received vaccine doses relative to ACIP age recommendations. To assess undervaccination patterns, children's vaccination histories are analyzed to determine whether they were vaccinated consistent with the ACIP schedule. Some patterns, such as spreading out vaccines across visits, are indicative of parental hesitancy. Other patterns, such as starting all recommended series but missing doses, are largely indicative of other immunization services delivery challenges. Since 2003, at least 12 studies have used National Immunization Survey-Child, immunization information system, or integrated health plan data to measure vaccination timeliness or undervaccination patterns at national or state levels. Moving forward, these novel measures can be leveraged for population-based surveillance of vaccine confidence, and for distinguishing undervaccination due to parental vaccine hesitancy from undervaccination due to other causes. Broader adoption of these measures can facilitate identification of targeted strategies for improving timely and routine early childhood vaccination uptake across the United States.

Health Care Utilization in the 6 Months Following SARS-CoV-2 Infection.

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

Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth - Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021.

COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).

Monitoring vaccine safety using the vaccine safety Datalink: Assessing capacity to integrate data from Immunization Information systems.

BACKGROUND: The Vaccine Safety Datalink (VSD) uses vaccination data from electronic health records (EHR) at eight integrated health systems to monitor vaccine safety. Accurate capture of data from vaccines administered outside of the health system is critical for vaccine safety research, especially for COVID-19 vaccines, where many are administered in non-traditional settings. However, timely access and inclusion of data from Immunization Information Systems (IIS) into VSD safety assessments is not well understood. METHODS: We surveyed the eight data-contributing VSD sites to assess: 1) status of sending data to IIS; 2) status of receiving data from IIS; and 3) integration of IIS data into the site EHR. Sites reported separately for COVID-19 vaccination to capture any differences in capacity to receive and integrate data on COVID-19 vaccines versus other vaccines. RESULTS: All VSD sites send data to and receive data from their state IIS. All eight sites (100%) routinely integrate IIS data for COVID-19 vaccines into VSD research studies. Six sites (75%) also routinely integrate all other vaccination data; two sites integrate data from IIS following a reconciliation process, which can result in delays to integration into VSD datasets. CONCLUSIONS: COVID-19 vaccines are being administered in a variety of non-traditional settings, where IIS are commonly used as centralized reporting systems. All eight VSD sites receive and integrate COVID-19 vaccine data from IIS, which positions the VSD well for conducting quality assessments of vaccine safety. Efforts to improve the timely receipt of all vaccination data will improve capacity to conduct vaccine safety assessments within the VSD.

COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy - Eight Integrated Health Care Organizations, United States, December 14, 2020-May 8, 2021.

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

Incidence of pediatric inflammatory bowel disease within the Vaccine Safety Datalink network and evaluation of association with rotavirus vaccination.

BACKGROUND: Recent studies have reported an increase in Inflammatory bowel disease (IBD) incidence in young children, highlighting the need to better understand risk factors for the development of IBD. Licensed for use in infants in 2006, the oral, live-attenuated rotavirus vaccine has biologic plausibility for instigating inflammation of the gut mucosa as a pathway to immune dysregulation. METHODS: Over a ten-year period, we evaluated incidence of IBD within a cohort of children under the age of ten, enrolled in seven integrated healthcare delivery systems. We conducted a nested case-control study to evaluate the association between rotavirus vaccination and IBD using conditional logistic regression. Cases were confirmed via medical record review and matched to non-IBD controls on date of birth, sex, and study site. RESULTS: Among 2.4 million children under the age of 10 years, 333 cases of IBD were identified with onset between 2007 and 2016. The crude incidence of IBD increased slightly over the study period (p-value for trend = 0.046). Of the 333 cases, 227 (68%) were born prior to 2007. Forty-two cases born in 2007 or later, with continuous enrollment since birth were included in the case-control study and matched to 210 controls. The adjusted odds ratio for any rotavirus vaccination in IBD cases, compared to matched controls, was 0.72 (95% confidence interval 0.19-2.65). CONCLUSIONS: Data from this large pediatric cohort demonstrate a small overall increase in IBD incidence in young children over a ten-year period. The data suggest that rotavirus vaccination is not associated with development of IBD.

Commitment to Change Statements and Actual Practice Change After a Continuing Medical Education Intervention.

INTRODUCTION: Continuing medical education (CME) interventions often evaluate participant commitment to change (CTC) clinical practice. Evidence linking CTC to actual practice change is limited. METHODS: In an intervention that combined live CME with changes to the electronic health record to promote judicious antibiotic use for children with urinary tract infections (UTIs), we evaluated CTC and subsequent prescribing behavior in Kaiser Permanente Colorado, an integrated health care system. CTC was assessed immediately after the session using closed-ended questions about session learning objectives and open-ended questions to elicit specific practice changes. Perceived barriers to implementing recommended changes were also assessed. RESULTS: Among 179 participants, 80 (45%) completed postsession evaluations and treated one or more child with a UTI in the subsequent 17 months (856 UTIs in total). In closed-ended responses about session learning objectives, 45 clinicians (56%) committed to changing practice for antibiotic choice and duration, whereas 37 (46%) committed to implementing new practice guidelines. When asked open-ended questions to identify specific practice changes, 32 (40%) committed to antibiotic choice change and 29 (36%) committed to treatment duration change. Participants who made specific CTC statements had greater improvement in antibiotic choice (relative rate ratio 1.56, 95% CI 1.16-2.09) and duration (relative rate ratio 1.59, 95% CI 1.05-2.41) than participants who did not make specific commitments. Few perceived barriers affected subsequent prescribing. DISCUSSION: Commitments to changing specific clinical behaviors were associated with sustained changes in prescribing for children with UTIs. Linking self-evaluations with clinical data in integrated health care systems is an important tool for CME evaluators.

Racial/Ethnic Disparities in the Prevalence of Diabetes and Prediabetes by BMI: Patient Outcomes Research To Advance Learning (PORTAL) Multisite Cohort of Adults in the U.S.

OBJECTIVE: To examine racial/ethnic disparities in the prevalence of diabetes and prediabetes by BMI category. RESEARCH DESIGN AND METHODS: In a consortium of three U.S. integrated health care systems, 4,906,238 individuals aged ≥20 years during 2012-2013 were included. Diabetes and prediabetes were ascertained by diagnosis and laboratory results; antihyperglycemic medications were also included for diabetes ascertainment. RESULTS: The age-standardized diabetes and prediabetes prevalence estimates were 15.9% and 33.4%, respectively. Diabetes but not prediabetes prevalence increased across BMI categories among all racial/ethnic groups (P for trend < 0.001). Racial/ethnic minorities reached a given diabetes prevalence at lower BMIs than whites; Hawaiians/Pacific Islanders and Asians had a diabetes prevalence of 24.6% (95% CI 24.1-25.2%) in overweight and 26.5% (26.3-26.8%) in obese class 1, whereas whites had a prevalence of 23.7% (23.5-23.8%) in obese class 2. The age-standardized prediabetes prevalence estimates in overweight among Hispanics (35.6% [35.4-35.7%]), Asians (38.1% [38.0-38.3%]), and Hawaiians/Pacific Islanders (37.5% [36.9-38.2%]) were similar to those in obese class 4 among whites (35.3% [34.5-36.0%]), blacks (36.8% [35.5-38.2%]), and American Indians/Alaskan Natives (34.2% [29.6-38.8%]). In adjusted models, the strength of association between BMI and diabetes was highest among whites (relative risk comparing obese class 4 with normal weight 7.64 [95% CI 7.50-7.79]) and lowest among blacks (3.16 [3.05-3.27]). The association between BMI and prediabetes was less pronounced. CONCLUSIONS: Racial/ethnic minorities had a higher burden of diabetes and prediabetes at lower BMIs than whites, suggesting the role of factors other than obesity in racial/ethnic disparities in diabetes and prediabetes risk and highlighting the need for tailored screening and prevention strategies.

Uptake and safety of Hepatitis B vaccination during pregnancy: A Vaccine Safety Datalink study.

INTRODUCTION: Hepatitis B virus (HBV) infection acquired during pregnancy can pose a risk to the infant at birth that can lead to significant and lifelong morbidity. Hepatitis B vaccine (HepB) is recommended for anyone at increased risk for contracting HBV infection, including pregnant women. Limited data are available on the safety of HepB administration during pregnancy. OBJECTIVES: To assess the frequency of maternal HepB receipt among pregnant women and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. METHODS: We examined a retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live birth outcomes from 2004 through 2015. Eligible pregnancies in women aged 12-55 years who were continuously enrolled from 6 months pre-pregnancy to 6 weeks postpartum in VSD integrated health systems were included. We compared pregnancies with HepB exposure to those with other vaccine exposures, and to those with no vaccine exposures. High-risk conditions for contracting HBV infection were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were also evaluated according to maternal HepB exposure status. RESULTS: Among over 650,000 pregnancies in the study period, HepB was administered at a rate of 2.1 per 1000 pregnancies (n = 1399), commonly within the first 5 weeks of pregnancy. Less than 3% of the HepB-exposed group had a high-risk ICD-9 code indicating need for HepB; this was similar to the rate among HepB unvaccinated groups. There were no significant associations between HepB exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, low birthweight or small for gestational age infants. CONCLUSIONS: Most women who received maternal HepB did not have high-risk indications for vaccination. No increased risk for the adverse events that were examined were observed among women who received maternal HepB or their offspring.

Risk of Spontaneous Abortion After Inadvertent Human Papillomavirus Vaccination in Pregnancy.

OBJECTIVE: To evaluate the risk of spontaneous abortion after quadrivalent human papillomavirus (4vHPV) vaccination before and during pregnancy across seven integrated health systems within the Vaccine Safety Datalink. METHODS: Within a retrospective observational cohort, we compared risks for spontaneous abortion after 4vHPV in three exposure windows: distal (16-22 weeks before the last menstrual period [LMP]), peripregnancy (within 6 weeks before the LMP), and during pregnancy (LMP through 19 weeks of gestation). Women 12-27 years of age with a pregnancy between 2008 and 2014, with continuous insurance enrollment 8 months before and through pregnancy end, and with a live birth, stillbirth, or spontaneous abortion were included. Pregnancies were identified through validated algorithms. Spontaneous abortions and stillbirths were verified by chart review with spontaneous abortions adjudicated by clinical experts. We excluded multiple gestations, spontaneous abortions before 6 weeks of gestation, and women using medications increasing risk of spontaneous abortion. Spontaneous abortion risk after 4vHPV during pregnancy was compared with distal vaccination using time-dependent covariate Cox models. Spontaneous abortion risk for peripregnancy compared with distal vaccination was evaluated with standard Cox models. RESULTS: We identified 2,800 pregnancies with 4vHPV exposure in specified risk windows: 919 (33%) distal, 986 (35%) peripregnancy, and 895 (32%) during pregnancy. Mean age was 22.4 years in distal and peripregnancy groups compared with 21.4 years among women vaccinated during pregnancy. Among women with distal 4vHPV exposure, 96 (10.4%) experienced a spontaneous abortion. For peripregnancy and during pregnancy exposures, spontaneous abortions occurred in 110 (11.2%) and 77 (8.6%), respectively. The risk of spontaneous abortion was not increased among women who received 4vHPV during pregnancy (adjusted hazard ratio 1.10, 95% CI 0.81-1.51) or peripregnancy 1.07 (0.81-1.41). CONCLUSION: Inadvertent 4vHPV exposure during or peripregnancy was not significantly associated with an increased risk of spontaneous abortion.

Addressing Parents' Vaccine Concerns: A Randomized Trial of a Social Media Intervention.

INTRODUCTION: Successful strategies are needed to address parental vaccine hesitancy, a significant public health issue. The study objective was to assess whether an Internet-based platform with vaccine information and interactive social media components improved parents' vaccine-related attitudes. STUDY DESIGN: A three-arm RCT. SETTING/PARTICIPANTS: The study was conducted in a large Colorado integrated healthcare organization. Parents were enrolled during September 2013 through October 2015 and followed through November 2016; data were analyzed in 2017. Parents, recruited during pregnancy, were given a survey about vaccine-related attitudes at enrollment (i.e., baseline) and when their child was aged 3-5 months and 12-15 months (Timepoints 1 and 2, respectively). Parental vaccine hesitancy was assessed at baseline. INTERVENTION: Study participants were randomized to the following: a study website with vaccine information and social media components (VSM arm); a website with vaccine information only (VI); or usual care. MAIN OUTCOME MEASURES: Change in parental vaccine attitudes over time by baseline degree of vaccine hesitancy. RESULTS: Among 1,093 study participants, 945 (86.5%) completed all three surveys. Comparing baseline with Timepoint 1 among vaccine-hesitant parents, the VSM and VI arms were associated with significant improvements in attitudes regarding vaccination benefits compared to usual care (VSM mean change 0.23 on a 5-point scale, 95% CI=0.05, 0.40, VI mean change 0.22, 95% CI=0.04, 0.40). Comparing baseline with Timepoint 2 among hesitant parents, the VSM and VI arms were also associated with significant reductions in parental concerns about vaccination risks compared to usual care (VSM mean change -0.37, 95% CI= -0.60, -0.14, VI mean change -0.31, 95% CI= -0.55, -0.07). Self-efficacy around vaccine decision making also improved among vaccine-hesitant parents. No intervention effect was observed among parents not vaccine-hesitant at baseline. CONCLUSIONS: Among vaccine-hesitant parents, an Internet-based intervention improved parents' attitudes about vaccines. TRIAL REGISTRATION: This study was registered at www.clinicaltrials.gov NCT01873040.

Vaccination Patterns in Children After Autism Spectrum Disorder Diagnosis and in Their Younger Siblings.

Importance: In recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown. Objectives: To investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD. Design, Setting, and Participants: This investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015. Exposures: Recommended childhood vaccines between ages 1 month and 12 years. Main Outcome and Measure: The proportion of children who received all of their vaccine doses according to ACIP recommendations. Results: The study included 3729 children with ASD (676 [18.1%] female), 592 907 children without ASD, and their respective younger siblings. Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child's younger sibling and to limit the number of vaccines administered during the younger sibling's first year of life. Conclusions and Relevance: Children with ASD and their younger siblings were undervaccinated compared with the general population. The results of this study suggest that children with ASD and their younger siblings are at increased risk of vaccine-preventable diseases.

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.

Cardiometabolic Risk Factors Among 1.3 Million Adults With Overweight or Obesity, but Not Diabetes, in 10 Geographically Diverse Regions of the United States, 2012-2013.

INTRODUCTION: Various phenotypes of overweight and obesity pose various health risks. The objective of this study was to determine the prevalence of 4 commonly measured cardiometabolic risk factors (CRFs) among adults with overweight or obesity, but not diabetes, at the time of the study. METHODS: We analyzed data for 1,294,174 adults (aged ≥20 y) who were members of one of 4 integrated health systems. Each cohort member had a body mass index in 2012 or 2013 that indicated overweight or obesity. We determined the presence of 4 CRFs within 1 year of the first BMI measurement: elevated blood pressure (systolic ≥130 mm Hg or diastolic >85 mm Hg or ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification] diagnosis code 401.0-405.9); elevated triglycerides (≥150 mg/dL or ICD-9-CM 272.1); low high-density lipoprotein cholesterol (<40 mg/dL for men or <50 mg/dL for women or ICD-9-CM 272.5); and prediabetes (fasting glucose 100-125 mg/dL or HbA1c 5.7%-6.4% or ICD-9-CM 790.2x). We tested the risk of having 1 or more CRFs after adjusting for obesity class and demographic characteristics with multivariable logistic regression. RESULTS: Among participants with overweight (52.5% of the sample), 18.6% had none of the 4 CRFs. Among the 47.5% of participants with obesity, 9.6% had none; among participants with morbid obesity, 5.8% had none. Age was strongly associated with CRFs in multivariable analysis. CONCLUSION: Almost 10% of participants with obesity had no CRFs. Overweight or obesity increases cardiometabolic risk, but the number and type of CRFs varied substantially by age, even among participants with morbid obesity.

Effectiveness and cost of influenza vaccine reminders for adults with asthma or chronic obstructive pulmonary disease.

OBJECTIVES: To assess the effectiveness and cost of interactive voice response (IVR) reminders for influenza vaccination compared with postcards, among adults with asthma or chronic obstructive pulmonary disease (COPD). STUDY DESIGN: Pragmatic, 3-arm, randomized control trial. METHODS: The trial was conducted in an integrated healthcare organization during 2012 and 2013, using an existing IVR system. All adults aged 19 through 64 years with asthma or COPD (n = 12,285) were randomized to receive 1 of the following vaccination reminders: 1) postcard reminder only, 2) IVR reminder only, or 3) postcard plus IVR reminder. The primary outcome was influenza vaccination by October 31, 2012; the secondary outcomes were influenza vaccination by December 31, 2012, and by March 31, 2013. RESULTS: For subjects receiving an IVR call, 57% received a message on their answering machine; 27% answered the call; and 16% were not reached. Influenza vaccination rates were 29.5%, 31.1%, and 30.6% in the postcard-only, IVR-only, and postcard-plus-IVR study arms, respectively. After controlling for relevant covariates, IVR reminders were not significantly more or less effective than postcard reminders. Program costs were $0.78, $1.23, and $1.93 per subject for postcard-only, IVR-only, and postcard-plus-IVR reminders, respectively. Extrapolating costs to the entire population at the study site that typically receives influenza vaccination reminders (approximately 100,000 individuals), reminder costs would have been $0.55, $0.05, and $0.60 per subject for postcard-only, IVR-only, and postcard-plus-IVR reminders, respectively. CONCLUSIONS: IVR reminders are not more effective at promoting influenza vaccination than postcard reminders, but IVR reminders may be less expensive for large patient populations.

Severe obesity in children: prevalence, persistence and relation to hypertension.

BACKGROUND: Newer approaches for classifying gradations of pediatric obesity by level of body mass index (BMI) percentage above the 95th percentile have recently been recommended in the management and tracking of obese children. Examining the prevalence and persistence of severe obesity using such methods along with the associations with other cardiovascular risk factors such as hypertension is important for characterizing the clinical significance of severe obesity classification methods. METHODS: This retrospective study was conducted in an integrated healthcare delivery system to characterize obesity and obesity severity in children and adolescents by level of body mass index (BMI) percentage above the 95th BMI percentile, to examine tracking of obesity status over 2-3 years, and to examine associations with blood pressure. Moderate obesity was defined by BMI 100-119% of the 95th percentile and severe obesity by BMI ≥120% × 95th percentile. Hypertension was defined by 3 consecutive blood pressures ≥95th percentile (for age, sex and height) on separate days and was examined in association with obesity severity. RESULTS: Among 117,618 children aged 6-17 years with measured blood pressure and BMI at a well-child visit during 2007-2010, the prevalence of obesity was 17.9% overall and was highest among Hispanics (28.9%) and blacks (20.5%) for boys, and blacks (23.3%) and Hispanics (21.5%) for girls. Severe obesity prevalence was 5.6% overall and was highest in 12-17 year old Hispanic boys (10.6%) and black girls (9.5%). Subsequent BMI obtained 2-3 years later also demonstrated strong tracking of severe obesity. Stratification of BMI by percentage above the 95th BMI percentile was associated with a graded increase in the risk of hypertension, with severe obesity contributing to a 2.7-fold greater odds of hypertension compared to moderate obesity. CONCLUSION: Severe obesity was found in 5.6% of this community-based pediatric population, varied by gender and race/ethnicity (highest among Hispanics and blacks) and showed strong evidence for persistence over several years. Increasing gradation of obesity was associated with higher risk for hypertension, with a nearly three-fold increased risk when comparing severe to moderate obesity, underscoring the heightened health risk associated with severe obesity in children and adolescents.

Pharmacotherapy for incident attention-deficit/hyperactivity disorder: practice patterns and quality metrics.

INTRODUCTION: This study examines incident treatment patterns for attention-deficit/hyperactivity disorder (ADHD) in children seen in eight integrated healthcare delivery systems and identifies factors associated with adherence to Healthcare Effectiveness Data and Information Set (HEDIS) quality measures developed by the National Committee for Quality Assurance (NCQA). METHOD: A retrospective cohort analysis using electronic healthcare data from children aged 3 through 17 years with newly diagnosed ADHD between January 1, 2009 and December 31, 2010 was conducted. NCQA quality definitions for initiation and for continuation and maintenance (C&M) of ADHD medications were expanded to include preschoolers and adolescents. Poisson regression models with robust error variance were used to evaluate the association between NCQA HEDIS adherence measures, provider type, patient characteristics and care process measures. RESULTS: Of 6864 children aged 3-17 years old qualifying for incident treatment analyses, 5538 (80.7%) were started on ADHD medication within a year of diagnosis. Adherence to NCQA HEDIS measures was 49.8% for initiation and 45.8% for C&M, with adherence rates higher for mental health than non-mental health providers, school-aged children than adolescents, and for patients concurrently on other psychotropic medications than those who were not. Of those started on ADHD medication, 62.3% were not eligible for C&M analyses according to HEDIS guidelines, because they did not receive continuous (210 of 300 days) ADHD medication treatment, with adolescents less likely than school-aged children to persist with medications. CONCLUSION: Study limitations must be considered, including reliance on electronic medical record data, absence of patient race and sociodemographic data, and limited generalizability to other care contexts. Nevertheless, findings suggest novel strategies are needed to improve the quality of ADHD care processes for children of all ages, because even within integrated delivery systems less than half of children with ADHD received care consistent with NCQA HEDIS standards for initiation and C&M care. RESULTS suggest the need to refine quality measures by including follow-up care in those children not receiving or discontinuing medication treatment, a considerable quality concern not currently captured in NCQA HEDIS standards.

Prehypertension and hypertension in community-based pediatric practice.

OBJECTIVE: To examine the prevalence of prehypertension and hypertension among children receiving well-child care in community-based practices. METHODS: Children aged 3 to 17 years with measurements of height, weight, and blood pressure (BP) obtained at an initial (index) well-child visit between July 2007 and December 2009 were included in this retrospective cohort study across 3 large, integrated health care delivery systems. Index BP classification was based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents: normal BP, <90th percentile; prehypertension, 90th to 94th percentile; hypertension, 3 BP measurements ≥95th percentile (index and 2 subsequent consecutive visits). RESULTS: The cohort included 199 513 children (24.3% aged 3-5 years, 34.5% aged 6-11 years, and 41.2% aged 12-17 years) with substantial racial/ethnic diversity (35.9% white, 7.8% black, 17.6% Hispanic, 11.7% Asian/Pacific Islander, and 27.0% other/unknown race). At the index visit, 81.9% of participants were normotensive, 12.7% had prehypertension, and 5.4% had a BP in the hypertension range (≥95th percentile). Of the 10 848 children with an index hypertensive BP level, 3.8% of those with a follow-up BP measurement had confirmed hypertension (estimated 0.3% prevalence). Increasing age and BMI were significantly associated with prehypertension and confirmed hypertension (P < .001 for trend). Among racial/ethnic groups, blacks and Asians had the highest prevalence of hypertension. CONCLUSIONS: The prevalence of hypertension in this community-based study is lower than previously reported from school-based studies. With the size and diversity of this cohort, these results suggest the prevalence of hypertension in children may actually be lower than previously reported.