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.

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.

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.

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.

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.

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.

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.

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.

Monovalent H1N1 influenza vaccine safety in pregnant women, risks for acute adverse events.

OBJECTIVE: To assess risks for acute adverse events and pregnancy complications in pregnant women following monovalent 2009 H1N1 inactivated influenza (MIV) vaccination. METHODS: Within the Vaccine Safety Datalink, we compared rates of pre-specified medically attended events (MAE) occurring within 42 days of MIV vaccination to those occurring in matched cohorts that at the same gestational age were either unvaccinated or received seasonal trivalent inactivated influenza (TIV) vaccine. Using generalized estimating equation method, with a Poisson distribution and log link, we calculated adjusted incident rate ratios (AIRR). RESULTS: Among 9349 women receiving MIV in any trimester, only one MAE occurred 0-3 days following MIV, an allergic reaction. No cases of Guillain-Barré syndrome, Bell's palsy, or transverse myelitis occurred 1-42 days after MIV. Compared to women receiving TIV and to unvaccinated women, risks for acute MAEs were not increased following MIV for any outcome. Hyperemesis was the most common adverse event in the MIV, TIV, and unvaccinated groups, occurring at a rate of about 4% over a 42-day period in all groups. Over a 42-day window, among all groups, incident gestational diabetes occurred at a rate of 3% and thrombocytopenia occurred at a rate of approximately 0.3%. Among women receiving MIV during pregnancy, increased risks for these and other less common obstetric events were not detected. CONCLUSION: In this large cohort of pregnant women no acute safety signals were identified within 6 weeks of receipt of MIV.

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.

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.

Adolescent consent for vaccination: a position paper of the Society for Adolescent Health and Medicine.

Vaccines currently recommended for adolescents by the Advisory Committee on Immunization Practices have the potential to improve the health of youth by preventing conditions such as: tetanus, pertussis, meningococcal disease, influenza, and genital warts, as well as later adult outcomes such as cervical and other human papillomavirus-related cancers. Adolescent vaccine coverage lags behind that for younger age groups. A requirement to obtain parental consent for vaccination can present a significant barrier to improving adolescent vaccine uptake across all health care settings in which adolescents access care. The ability of minors to consent to vaccination can influence whether adolescents receive indicated vaccines during adolescent health care visits when parents are absent and when adolescents are seen for confidential services. State laws govern consent for the delivery of health care to minors. All states have some laws that allow minors to consent to health care based either on their status or on the services they are seeking. Some of these laws would allow them to consent to vaccination. It is the Position of the Society for Adolescent Health and Medicine that, within ethical and legal guidelines, it will be important to develop strategies that maximize opportunities for minors to receive vaccinations when parents are not physically present, including opportunities for them to give their own consent.

Inactivated influenza vaccine during pregnancy and risks for adverse obstetric events.

OBJECTIVE: To compare risks for adverse obstetric events between females who did and did not receive trivalent inactivated influenza vaccine during pregnancy. METHOD: This retrospective, observational cohort study was conducted at seven Vaccine Safety Datalink sites. Pregnancies were identified from administrative and claims data using a validated algorithm. Females vaccinated while pregnant from 2002 to 2009 were matched one-to-two with replacement to unvaccinated pregnant females. Using a generalized estimating equation method with a Poisson distribution and log link, we evaluated the association of trivalent inactivated influenza vaccine with 13 outcomes. Given our large sample size and multiple comparisons (19 contrasts), a cutoff for significance of P<.005 was selected a priori. RESULTS: Our cohort included 74,292 vaccinated females matched on age, site, and pregnancy start date with 144,597 unvaccinated females. We did not observe increased risks within 42 days of vaccination for hyperemesis, chronic hypertension, gestational hypertension, gestational diabetes, proteinuria, or urinary tract infection. Using a risk window from vaccination through pregnancy end, we did not observe increased risks after vaccination for proteinuria, urinary tract infection, gestational hypertension, preeclampsia or eclampsia, chorioamnionitis, puerperal infection, venous complications, pulmonary embolism, or peripartum cardiomyopathy. A reduced risk for gestational diabetes after vaccination was detected (adjusted hazard rate ratio 0.88, 95% confidence interval 0.83-0.93), likely as a result of healthy vaccine bias or earlier detection among vaccinees. CONCLUSION: In this large cohort, influenza vaccination during pregnancy was not associated with increased risks for medically attended adverse obstetric events. LEVEL OF EVIDENCE: II.

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.

Maternal safety of trivalent inactivated influenza vaccine in pregnant women.

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 events in trivalent inactivated influenza-vaccinated and unvaccinated pregnant women in the Vaccine Safety Datalink. Using a Poisson distribution and log link, we calculated maternal adjusted incident rate ratios for composite safety outcomes for the full cohort and the subset vaccinated during the first trimester. RESULTS: The cohort included 75,906 vaccinated (28.4% in the first trimester) and 147,992 unvaccinated women matched by age, site, and pregnancy start date. In the first 3 days after vaccination, trivalent inactivated influenza vaccine was not associated with increased risk of specified medically attended events, including allergic reactions, cellulitis, and seizures (full cohort adjusted incident rate ratio 1.12, 95% confidence interval [CI] 0.81-1.55; P=.48; first-trimester adjusted incident rate ratio .97, 95% CI 0.53-1.78; P=.93). In the first 42 days, no incident cases of Guillain-Barré syndrome, optic neuritis, transverse myelitis, or Bells palsy were identified. Trivalent inactivated influenza vaccine was not associated with thrombocytopenia (full cohort adjusted incident rate ratio 0.90, 95% CI 0.68--1.19; P=.45; first-trimester adjusted incident rate ratio 0.56, 95% CI 0.22-1.39; P=.21) or an acute neurologic event (full cohort adjusted incident rate ratio 0.92, 95% CI 0.54-1.6; P=.75; first-trimester adjusted incident rate ratio 1.05, 95% CI 0.46-2.38; P=.91). CONCLUSIONS: Receipt of trivalent inactivated influenza vaccine during pregnancy was not associated with increased risk of adverse events in the 42 days after vaccination, supporting its safety for the mother.

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.