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

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

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

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

Potential Misclassification of Blood Pressure Status in Children and Adolescents With Short or Tall Stature.

Blood pressure (BP) is measured in percentiles that are adjusted for sex, age, and height percentile in children and adolescents. Standard tables for the conversion of BP percentiles do not present exact BP percentile cutoffs for extremes in stature, either short (<5th percentile) or tall (>95th percentile). An algorithm can be used to calculate exact BP percentiles across a range of height z scores. We compared values from standard BP tables with exact calculations of BP percentiles to see which were better at identifying hypertension in more than 5,000 children with either short or tall stature. Study subjects were 3-17-year-old patients within HealthPartners Medical Group, an integrated health care delivery system in Minnesota, at any time between 2007 and 2012. Approximately half of the subjects who met the criteria for hypertension using exact calculation would be misclassified as normal using available thresholds in the published BP tables instead of the recommended algorithm, which was not included in the tables.

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

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

Initiation of oral contraceptives and changes in blood pressure and body mass index in healthy adolescents.

OBJECTIVES: To describe changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI) associated with initiation and continued use of combined oral contraceptives (COCs) in healthy adolescents. STUDY DESIGN: This observational, matched cohort study was conducted in 2 large health systems. Utilizing claims and electronic medical records, we identified adolescents 14-17.9 years of age initiating medium-dose COCs (containing 30 or 35 (µg of ethinyl estradiol or equivalent and a progestin) between July 1, 2007 and December 31, 2009 with a baseline and at least 1 follow-up blood pressure (BP) and BMI. COC-users were matched 1:2 by age, race/ethnicity, and site to controls (COC-nonusers). All BPs and BMIs recorded during outpatient visits starting 1 month prior to COC initiation (index date for controls), through December 31, 2010 were collected. Mixed model linear regression with random intercepts and slopes were then used to estimate changes in SBP, DBP, and BMI over time. RESULTS: The 510 adolescent COC-users and 912 controls did not differ significantly by age, race/ethnicity, insurance, and baseline SBP, DBP, or BMI. After adjusting for baseline values, over a median of 18 months follow-up, COC-users had an decrease in SBP of 0.07 mm Hg/mo, and controls had an increase of 0.02 mm Hg/mo (P = .65). Similarly, DBP decreased by 0.007 mm Hg/mo in COC-users vs 0.006 mm Hg/mo in controls (P = .99). BMI increased by 0.04 (kg/m(2))/mo in COC-users vs 0.025 (kg/m(2))/mo in controls (P = .09). CONCLUSIONS: These data should provide reassurance to patients and providers regarding the lack of significant associations between COC-use and BMI or BP changes in adolescents.

Influenza vaccine text message reminders for urban, low-income pregnant women: a randomized controlled trial.

OBJECTIVES: We evaluated the impact of influenza vaccine text message reminders in a low-income obstetric population. METHODS: We conducted a randomized controlled trial that enrolled 1187 obstetric patients from 5 community-based clinics in New York City. The intervention group received 5 weekly text messages regarding influenza vaccination starting mid-September 2011 and 2 text message appointment reminders. Both groups received standard automated telephone appointment reminders. The prespecified endpoints were receipt of either pre- or postpartum influenza vaccination calculated cumulatively at the end of each month (September-December 2011). RESULTS: After adjusting for gestational age and number of clinic visits, women who received the intervention were 30% more likely to be vaccinated as of December 2011 (adjusted odds ratio [AOR] = 1.30; 95% confidence interval [CI] = 1.003, 1.69 end of September: AOR = 1.34; 95% CI = 0.98, 1.85; October: AOR = 1.35; 95% CI = 1.05, 1.75; November: AOR = 1.27; 95% CI = 0.98, 1.65). The subgroup of women early in the third trimester at randomization showed the greatest intervention effect (December 31: 61.9% intervention vs 49.0% control; AOR = 1.88; 95% CI = 1.12, 3.15). CONCLUSIONS: In this low-income obstetric population, text messaging was associated with increased influenza vaccination, especially in those who received messages early in their third trimester.

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

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

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

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

Text4Health: impact of text message reminder-recalls for pediatric and adolescent immunizations.

OBJECTIVES: We conducted 2 studies to determine the impact of text message immunization reminder-recalls in an urban, low-income population. METHODS: In 1 study, text message immunization reminders were sent to a random sample of parents (n = 195) whose children aged 11 to 18 years needed either or both meningococcal (MCV4) and tetanus-diphtheria-acellular pertussis (Tdap) immunizations. We compared receipt of MCV4 or Tdap at 4, 12, and 24 weeks with age- and gender-matched controls. In the other study, we compared attendance at a postshortage Haemophilus influenzae B (Hib) immunization recall session between parents who received text message and paper-mailed reminders (n = 87) and those who only received paper-mailed reminders (n = 87). RESULTS: Significantly more adolescents with intervention parents received either or both MCV4 and Tdap at weeks 4 (15.4% vs 4.2%; P < .001), 12 (26.7% vs 13.9%; P < .005), and 24 (36.4% vs 18.1%; P < .001). Significantly more parents who received both Hib reminders attended a recall session compared with parents who only received a mailed reminder (21.8% vs 9.2%; P < .05). After controlling for age, gender, race/ethnicity, insurance status, and language, text messaging was still significantly associated with both studies' outcomes. CONCLUSIONS: Text messaging for reminder-recalls improved immunization coverage in a low-income, urban population.

Effect of a text messaging intervention on influenza vaccination in an urban, low-income pediatric and adolescent population: a randomized controlled trial.

CONTEXT: Influenza infection results in substantial costs, morbidity, and mortality. Vaccination against influenza is particularly important in children and adolescents who are a significant source of transmission to other high-risk populations, yet pediatric and adolescent vaccine coverage remains low. Traditional vaccine reminders have had a limited effect on low-income populations; however, text messaging is a novel, scalable approach to promote influenza vaccination. OBJECTIVE: To evaluate targeted text message reminders for low-income, urban parents to promote receipt of influenza vaccination among children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 9213 children and adolescents aged 6 months to 18 years receiving care at 4 community-based clinics in the United States during the 2010-2011 influenza season. Of the 9213 children and adolescents, 7574 had not received influenza vaccine prior to the intervention start date and were included in the primary analysis. INTERVENTION: Parents of children assigned to the intervention received up to 5 weekly immunization registry-linked text messages providing educational information and instructions regarding Saturday clinics. Both the intervention and usual care groups received the usual care, an automated telephone reminder, and access to informational flyers posted at the study sites. MAIN OUTCOME MEASURES: Receipt of an influenza vaccine dose recorded in the immunization registry via an electronic health record by March 31, 2011. Receipt was secondarily assessed at an earlier fall review date prior to typical widespread influenza activity. RESULTS: Study children and adolescents were primarily minority, 88% were publicly insured, and 58% were from Spanish-speaking families. As of March 31, 2011, a higher proportion of children and adolescents in the intervention group (43.6%; n = 1653) compared with the usual care group (39.9%; n = 1509) had received influenza vaccine (difference, 3.7% [95% CI, 1.5%-5.9%]; relative rate ratio [RRR], 1.09 [95% CI, 1.04-1.15]; P = .001). At the fall review date, 27.1% (n = 1026) of the intervention group compared with 22.8% (n = 864) of the usual care group had received influenza vaccine (difference, 4.3% [95% CI, 2.3%-6.3%]; RRR, 1.19 [95% CI, 1.10-1.28]; P < .001). CONCLUSIONS: Among children and adolescents in a low-income, urban population, a text messaging intervention compared with usual care was associated with an increased rate of influenza vaccination. However, the overall influenza vaccination rate remained low. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01146912.

Exploring pregnant women's views on influenza vaccination and educational text messages.

BACKGROUND: The influenza vaccine has the potential to reduce morbidity among pregnant women and newborns but immunization coverage remains low. Effective interventions are needed to promote vaccine uptake in this population. PURPOSE: The goal of this study was to explore attitudes toward influenza vaccination and interest in targeted educational text messages among urban pregnant women. METHODS: English and Spanish language focus groups were conducted with pregnant women in New York City in April 2010. Transcripts were independently coded using content analysis. RESULTS: The 40 participants ranged in age from 19-35 years (mean=26, SD=5). Their gestational age ranged from 8-40 weeks (mean=27, SD=8). Most were Latina (85%), had other children (70%), and were publicly insured (78%). Nearly half had received the seasonal influenza or influenza A (H1N1) 2009 monovalent vaccine. Barriers to vaccination included concerns regarding vaccine safety and efficacy, misperceptions regarding risks for influenza, and lack of provider recommendation. Pregnant women expressed interest in receiving educational text messages regarding influenza. Even women who had refused the influenza vaccine thought the text messages would encourage vaccine-related discussions during prenatal visits. CONCLUSION: Among urban pregnant women, educational text messages regarding influenza would be well received and may effectively address current barriers to vaccination.

Changes in Tdap and MCV4 vaccine coverage following enactment of a statewide requirement of Tdap vaccination for entry into sixth grade.

OBJECTIVES: We evaluated changes in tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap), and tetravalen meningococcal (MCV4) vaccine coverage following enactment of a New York State mandate requiring Tdap before entering sixth grade. METHODS: Using data from a hospital-based immunization registry, we measured Tdap and MCV4 coverage among youths aged 11 to 14 years in New York City at 3 time points: premandate, mandate year 1, and mandate year 2. RESULTS: Among overlapping cohorts of 4316 (premandate), 4131 (mandate year 1), and 3639 (mandate year 2) youths, Tdap coverage increased steadily over time (29%, 58%, and 83%, respectively). Increases were observed among all ages. Across the same time points, MCV4 coverage also increased (10%, 30%, and 60%, respectively). Most adolescents did not receive MCV4 during the same visit they received Tdap. CONCLUSIONS: A Tdap school-entry mandate was associated with substantial increases in immunization coverage, even in age groups not directly affected by the mandate. At the postmandate time points, MCV4 coverage remained lower than Tdap coverage. Provider education should emphasize the importance of reviewing vaccine records and administering all recommended vaccines at every clinical encounter.

Birth and early developmental screening outcomes associated with cannabis exposure during pregnancy.

OBJECTIVE: To compare birth and early developmental screening outcomes for infants with and without in utero cannabis exposures. STUDY DESIGN: Observational cohort of women receiving prenatal care within a large health system, live birth between October 1, 2015 and December 1, 2017, and at least one infant visit. Cannabis exposure was through routine urine toxicology screen. Preterm birth, small for gestational age (SGA) birth, birth defects, and early developmental screening outcomes were assessed from birth and electronic health record data. RESULTS: Of 3435 women, 283 (8.2%) had a positive urine toxicology screen. In utero cannabis exposure was associated with SGA birth, adjusted rate ratio (aRR) 1.69 (95% confidence interval [CI]: 1.22-2.34). Abnormal 12-month developmental screens occurred in 9.1% of infants with in utero cannabis exposure vs. 3.6% of those with negative maternal screens, aRR 1.90 (95% CI: 0.92-3.91). Additional birth outcomes were not associated with in utero cannabis exposure. CONCLUSIONS: Exposure to cannabis during pregnancy may adversely impact fetal growth.

Text4Health: a qualitative evaluation of parental readiness for text message immunization reminders.

We conducted focus groups and individual interviews in a diverse population of parents to qualitatively explore preferences and readiness for text message immunization reminders. We used content analysis to review and independently code transcripts. Text message reminders were well-accepted by parents; many thought they would be more effective than standard phone or mail reminders. Parents preferred text message reminders to be brief and personalized. Most parents were able to retrieve sample text messages but many had difficulty with interactive texting.

Evaluation of an Electronic Clinical Decision Support Tool for Incident Elevated BP in Adolescents.

OBJECTIVE: To evaluate, among adolescents 10 to 17 years of age with an incident hypertensive blood pressure (BP; ≥95th percentile) at a primary care visit, whether TeenBP, a novel electronic health record-linked clinical decision support tool (CDS), improved recognition of elevated BP, and return for follow-up BP evaluation. METHODS: We conducted a pragmatic cluster randomized trial in 20 primary care clinics in a large Midwestern medical group. Ten clinics received the TeenBP CDS, including an alert to remeasure a hypertensive BP at that visit, an alert that a hypertensive BP should be repeated in 1 to 3 weeks, and patient-specific order sets. In the 10 usual care (UC) clinics, elevated BPs were displayed in red font in the electronic health record. For comparisons between CDS and UC we used generalized linear mixed models. RESULTS: The study population included 607 CDS patients and 607 UC patients with an incident hypertensive BP. In adjusted analyses, at the index visit, CDS patients were more likely to have their hypertensive BP on the basis of ≥2 BP measurements (47.1% vs 27.6%; P = .007) and to have elevated BP (International Classification of Diseases, Ninth Revision code 796.2) diagnosed (28.2% vs 4.2%; P < .001). In a multivariate model adjusted for age, sex, systolic BP percentile, and visit type, rates for repeat BP measurement within 30 days were 14.3% at TeenBP CDS clinics versus 10.6% at UC clinics (P = .07). CONCLUSIONS: The TeenBP CDS intervention significantly increased repeat BP measurement at the index visit and recognition of a hypertensive BP. Rates for follow-up BP measurement at 30 days were low and did not differ between TeenBP and UC subjects.

Maternal Tdap vaccination: Coverage and acute safety outcomes in the vaccine safety datalink, 2007-2013.

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.

Helping mothers to get the message about influenza: are texts the future for increased immunization?

Pregnant women and children are at increased risk of severe influenza infections. Despite existing recommendations, uptake of influenza vaccine in these vulnerable groups remains low. Text message reminder-recalls are a feasible and scalable method for promoting influenza vaccination. In randomized controlled trials, text message interventions have demonstrated small but significant increases in influenza vaccine coverage. They should be considered one of many tools available for increasing vaccination and thus improving maternal and child health.

Impacting delayed pediatric influenza vaccination: a randomized controlled trial of text message reminders.

BACKGROUND: Influenza vaccination coverage is low, especially among low-income populations. Most doses are generally administered early in the influenza season, yet sustained vaccination efforts are crucial for achieving optimal coverage. The impact of text message influenza vaccination reminders was recently demonstrated in a low-income population. Little is known about their effect on children with delayed influenza vaccination or the most effective message type. PURPOSE: To determine the impact of educational plus interactive text message reminders on influenza vaccination of urban low-income children unvaccinated by late fall. DESIGN: Randomized controlled trial. SETTING/PARTICIPANTS: Parents of 5,462 children aged 6 months-17 years from four academically affiliated pediatric clinics who were unvaccinated by mid-November 2011. INTERVENTION: Eligible parents were stratified by their child's age and pediatric clinic site and randomized using a 1:1:1 allocation to educational plus interactive text message reminders, educational-only text message reminders, or usual care. Using an immunization registry-linked text messaging system, parents of intervention children received up to seven weekly text message reminders. One of the messages sent to parents in the educational plus interactive text message arm allowed selection of more information about influenza and influenza vaccination. MAIN OUTCOME MEASURES: Influenza vaccination by March 31, 2012. Data were collected and analyzed between 2012 and 2014. RESULTS: Most children were publicly insured and Spanish speaking. Baseline demographics were similar between groups. More children of parents in the educational plus interactive text message arm were vaccinated (38.5%) versus those in the educational-only text message (35.3%; difference=3.3%, 95% CI=0.02%, 6.5%; relative risk ratio (RRR)=1.09, 95% CI=1.002, 1.19) and usual care (34.8%; difference=3.8%, 95% CI=0.6%, 7.0%; RRR=1.11, 95% CI=1.02-1.21) arms. CONCLUSIONS: Text message reminders with embedded educational information and options for interactivity have a small positive effect on influenza vaccination of urban, low-income, minority children who remain unvaccinated by late fall.