Received Tdap Vaccine Research Articles

Maternal Pertussis Immunization and Immunoglobulin G Levels in Early- to Late-Term and Preterm Infants

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination protects newborns against severe pertussis. Data on transplacental antibody transfer on Tdap vaccination before 24 weeks' gestation remain scarce and are particularly relevant for preterm infants to increase the time interval for maternal antibody transfer. To assess noninferiority of anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) antibody levels at age 2 months in early- to late-term infants following Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation and compared with preterm infants. This prospective, multicenter cohort study included pregnant women aged 18 years or older in birthing centers and hospitals in the Netherlands between August 2019 and November 2021 who received Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation. Women with imminent premature birth were recruited if they had received maternal Tdap vaccination between 20 and 24 weeks' gestation. Blood samples were collected from mothers at delivery, from the umbilical cord, and from infants at age 2 months. Data from infants' blood samples at age 2 months were compared with a reference cohort (recruited between January 2014 and February 2016) of early- to late-term infants of the same age whose mothers had received Tdap vaccination between 30 0/7 and 33 0/7 weeks' gestation. Maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation or 30 0/7 and 33 0/7 weeks' gestation. The primary outcome was the geometric mean concentration (GMC) of anti-PT IgG antibodies in early- to late-term infants (≥37 0/7 weeks' gestation) at age 2 months, comparing maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' vs 30 0/7 and 33 0/7 weeks' gestation (reference cohort). Anti-PT GMC in 2-month-old infants born preterm (<35 0/7 weeks' gestation) compared with early- to late-term infants after maternal Tdap vaccination between 20 and 24 weeks' gestation was a secondary outcome. In total, 221 women who delivered 239 offspring were enrolled in the study; 66 early- to late-term infants (median gestational age [GA], 40.6 weeks [IQR, 39.8-41.0 weeks]; 38 [57.6%] male) and 73 preterm infants (median GA, 32.1 weeks [IQR, 29.5-33.0 weeks]; 42 [54.5%] female) had blood samples collected at 2 months of age. Anti-PT GMC was 14.7 IU/mL (95% CI, 10.6-20.4 IU/mL) in early- to late-term infants following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 27.3 IU/mL (95% CI, 20.1-37.1 IU/mL) in 55 infants in the reference group (median GA, 40.3 [IQR, 39.1-41.0]; 33 [60.0%] female). The mean anti-PT GMC in preterm infants in the study group was 11.2 IU/mL (95% CI, 8.1-15.3 IU/mL) (P = .23 compared with early- to late-term infants). In this cohort study, 2-month-old preterm and early- to late-term infants showed significantly lower anti-PT antibody levels following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation; preterm and early- to late-term infants had similar anti-PT antibody levels, but both groups showed significantly lower antibody levels compared with the reference group. Epidemiological research should investigate whether maternal Tdap vaccination before 24 weeks' gestation provides sufficient protection against clinical pertussis, particularly in preterm infants, as long as no correlate of protection is available.

Influenza, Tdap, and COVID-19 Vaccination Coverage and Hesitancy Among Pregnant Women - United States, April 2023.

Influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), and COVID-19 vaccines can reduce the risk for influenza, pertussis, and COVID-19 among pregnant women and their infants. To assess influenza, Tdap, and COVID-19 vaccination coverage among women pregnant during the 2022-23 influenza season, CDC analyzed data from an Internet panel survey conducted during March 28-April 16, 2023. Among 1,814 survey respondents who were pregnant at any time during October 2022-January 2023, 47.2% reported receiving influenza vaccine before or during their pregnancy. Among 776 respondents with a live birth by their survey date, 55.4% reported receiving Tdap vaccine during pregnancy. Among 1,252 women pregnant at the time of the survey, 27.3% reported receipt of a COVID-19 bivalent booster dose before or during the current pregnancy. Data from the same questions included in surveys conducted during influenza seasons 2019-20 through 2022-23 show that the proportion of pregnant women who reported being very hesitant about influenza and Tdap vaccinations during pregnancy increased from 2019-20 to 2022-23. Pregnant women who received a provider recommendation for vaccination were less hesitant about influenza and Tdap vaccines. Promotion of efforts to improve vaccination coverage among pregnant women, such as provider recommendation for vaccination and informative conversations with patients to address vaccine hesitancy, might reduce vaccine hesitancy and increase coverage with these important vaccines to protect mothers and their infants against severe respiratory diseases.

Tdap vaccination during pregnancy and risk of chorioamnionitis and related infant outcomes.

An increased risk of chorioamnionitis in people receiving tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy has been reported. The importance of this association is unclear as additional study has not demonstrated increased adverse infant outcomes associated with Tdap vaccination in pregnancy. We conducted a retrospective observational cohort study of pregnant people ages 15-49years with singleton pregnancies ending in live birth who were members of 8 Vaccine Safety Datalink (VSD) sites during October 2016-September 2018. We used a time-dependent covariate Cox model with stabilized inverse probability weights applied to evaluate associations between Tdap vaccination during pregnancy and chorioamnionitis and preterm birth outcomes. We used Poisson regression with robust variance with stabilized inverse probability weights applied to evaluate the association of Tdap vaccination with adverse infant outcomes. We performed medical record reviews on a random sample of patients with ICD-10-CM-diagnosed chorioamnionitis to determine positive predictive values (PPV) of coded chorioamnionitisfor "probable clinical chorioamnionitis," "possible clinical chorioamnionitis," or "histologic chorioamnionitis." We included 118,211 pregnant people; 103,258 (87%) received Tdap vaccine during pregnancy; 8098 (7%) were diagnosed with chorioamnionitis. The adjusted hazard ratio for chorioamnionitis in the Tdap vaccine-exposed group compared to unexposed was 0.96 (95% CI 0.90-1.03). There was no association between Tdap vaccine and preterm birth or adverse infant outcomes associated with chorioamnionitis. Chart reviews were performed for 528 pregnant people with chorioamnionitis. The PPV for clinical (probable or possible clinical chorioamnionitis) was 48% and 59% for histologic chorioamnionitis. The PPV for the combined outcome of clinical or histologic chorioamnionitis was 81%. Tdap vaccine exposure during pregnancy was not associated with chorioamnionitis, preterm birth, or adverse infant outcomes. ICD-10 codes for chorioamnionitis lack specificity for clinical chorioamnionitis and should be a recognized limitation when interpreting results.

Reactogenicity and safety of second trimester maternal tetanus, diphtheria and acellular pertussis vaccination in the Netherlands

BackgroundMaternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination is offered to all pregnant women during their second trimester in the Netherlands since December 2019. We assessed second trimester Tdap vaccination reactogenicity and compared with third trimester data from a similar study. For safety assessment, adverse pregnancy outcomes were compared with national data from 2018, before Tdap vaccine-introduction. MethodsPregnant women were included between August 2019-December 2021 and received Tdap vaccination between 20 and 24w gestational age (GA). Participants completed a questionnaire on solicited local reactions and systemic adverse events (AEs) within one week after vaccination. Results were compared with historical data on reactogenicity from women vaccinated between 30 and 33w GA (n = 58). Regarding safety-related outcomes, each participant was matched to four unvaccinated pregnant women from the Dutch Perinatal Registry, based on living area, parity and age. ResultsAmong 723 participants who completed the questionnaire, 488 (67.5 %) experienced ≥ 1 local reaction with pain at the injection site as most reported reaction (62.3 %), and 460 (63.6 %) experienced ≥ 1 systemic AE with stiffness in muscles/joints (38.9 %), fatigue (28.9 %), headache (14.5 %) and common cold-like symptoms (11.0 %) most frequently reported. 4 women (0.6 %) reported fever (≥38.0˚C). Symptoms were considered mild and transient within days. No difference in AEs were found between vaccination at 20-24w versus 30-33w GA. 723 participants were matched to 2,424 unvaccinated pregnant women with no increased rates of premature labor, small-for-gestational-age, or other adverse pregnancy outcomes. ConclusionsSecond trimester maternal Tdap vaccination appears safe and well-tolerated. Comparison between second versus third trimester vaccination yielded no reactogenicity concerns.

Safety of tetanus, diphtheria, acellular pertussis (Tdap) vaccination during pregnancy

The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among pregnant members at Kaiser Permanente Southern California (KPSC). The exposed cohort consisted of women who received Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019. The unexposed cohort consisted of matched women who were pregnant between January 2012 and December 2014 and were not vaccinated with any Tdap vaccine throughout their pregnancy. Maternal and infant characteristics and pre-specified endpoints were collected through automated data and review of the electronic health records. Unadjusted and adjusted relative risks (aRRs) with confidence intervals (CIs) were estimated by Poisson regression. Non-inferiority testing (i.e., to rule out a two-fold increase) was conducted for primary endpoints with adjustment for multiplicity. Superiority testing was conducted without multiplicity adjustment for secondary endpoints. The analysis consisted of 16,606 pairs of Tdap recipients and unexposed pregnant women. For the primary endpoints, the aRR for preeclampsia/eclampsia was 1.38 (98.75% CI:1.21–1.58) and the aRR for intrauterine infection was 1.28 (98.75% CI:1.12–1.47). These increases were consistent with the background increasing trend of these diagnoses among all pregnant women at KPSC since 2011, and the upper limit of the 98.75% CI of both aRRs did not exceed the pre-specified threshold of 2. No increased risks of small for gestational age (aRR = 1.04, 98.75% CI:0.94–1.16) or preterm delivery (aRR = 0.71, 98.75% CI:0.64–0.78) were observed. No evidence of increased risks for secondary endpoints, including poor fetal growth, preterm pre-labor rupture of membranes, stillbirth/fetal death, placental abruption, transfusion during delivery hospitalization, and neonatal death, was observed. Prenatal Tdap vaccination after the 27th week of pregnancy was not associated with increased risks of pre-specified maternal and infant outcomes, supporting the safety of Tdap vaccination during pregnancy.

Pertussis antibody levels in infants and their mothers receiving combined tetanus-diphtheria toxoid and acellular pertussis vaccine during pregnancy in Turkey

ObjectivePertussis is an important cause of morbidity and mortality in infants under two months of age and these high risk babies are dependent on maternally derived antibodies until completion of their first immunization series. This study aimed to evaluate the vaccine response of late preterm and term newborns as well as their mothers who underwent combined tetanus-diphtheria toxoid and acellular pertussis (Tdap) vaccination during pregnancy. Study designA total of 70 pregnant women were administered Tdap vaccine (Boostrix®, GSK) between 27 and 33 gestational weeks of pregnancy. The IgG antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) in maternal blood before vaccination and in both maternal and umbilical cord blood after vaccination were evaluated using the in-house ELISA method. The geometric mean concentrations (GMC) and placental transfer ratios of antibodies were measured. ResultsParticipants’ with a mean age of 29.59 ± 4.70 years received Tdap vaccine at an average 28.6 ± 1.31 gestational weeks. Average pre and post vaccination levels of anti-PT IgG GMCs and anti-FHA IgG GMCs were 8.01 IU/ml vs 39.48 IU/ml (p = 0.001) and 122.24 IU/ml vs 183.97 IU/ml (p < 0.001), respectively. The anti-PT and anti-FHA IgG GMCs of cord blood after vaccination was 25.15 IU/ml and 118.77 IU/ml, respectively (p < 0.001 and p = 0.064). Placental transfer ratios of anti-PT ve anti-FHA IgG antibodies were detected as 0.65 and 0.62, respectively. ConclusionImmunization of pregnant women with Tdap at the third trimester results in high maternal and infant antibody levels. Maternal immunization during each pregnancy seems to be the best strategy in revealing the highest maternal and infant antibodies and in narrowing the gap between birth and immune system maturation in infants. Pregnant women in our country should also get the Tdap vaccine during pregnancy especially in the early third trimester.

Breast Milk Antibody Levels in Tdap-Vaccinated Women After Preterm Delivery.

Enrichment of breast milk (BM) with immunoglobulin (Ig) A and IgG through maternal vaccination could help infants combat targeted pathogens. However, evidence on this effect after preterm delivery is lacking. In this study, we investigated the total and anti-pertussis toxin (anti-PT)-specific IgA and IgG production in BM after term and preterm delivery in the presence of maternal Tdap (tetanus, diphtheria, acellular pertussis) vaccination. Serum and BM samples of lactating women who delivered at term or prematurely and did or did not receive Tdap vaccine (Boostrix, GSK Biologicals) during pregnancy were collected as part of a clinical study (N = 234). Anti-PT IgA/IgG (IBL assay; Meso Scale Discovery assay) and total IgA/IgG (Thermofisher, on BM samples only) immunosorbent assays were performed on all samples collected at 72 hours and 4, 8, and 12 weeks postpartum. BM after preterm delivery contained anti-PT IgA and IgG geometric mean concentrations (GMCs) comparable to those after term delivery (eg, colostrum anti-PT IgA, 5.39 IU/mL vs 6.69 IU/mL, respectively). Maternal Tdap vaccination induced significantly higher anti-PT IgG GMCs in colostrum of vaccinated compared with unvaccinated women who delivered at term (0.110 IU/mL vs 0.027 IU/mL, P = .009). Anti-PT antibodies persisted up to 12 weeks postpartum. This study provides evidence that maternal Tdap vaccination induces high Ig levels in BM after both term and preterm delivery and that these antibodies remain abundantly present throughout lactation, possibly offering additional mucosal protection during the most vulnerable period in early life. NCT02511327.

Maternal Self-Report of Tetanus Diphtheria Pertussis Vaccination during Pregnancy Correlates with Patient-Specific Electronic Medical Records

To evaluate the concordance between maternal report of antepartum tetanus, diphtheria, pertussis (Tdap) vaccination and vaccination status documented in the electronic medical record (EMR), as well as factors associated with discordance. A survey was completed by a convenience sample of postpartum patients in a New York metropolitan hospital. The survey collected patients' demographic information, health beliefs, and whether they received Tdap vaccine during this pregnancy. The patient's Tdap vaccination status was abstracted from the EMR, a combination of data gathered from the obstetrician and patient's hospital record. Kappa statistics measured the agreement between maternal report and EMR on antepartum Tdap vaccination. Univariate and multivariable logistic regression analyses were performed to identify maternal characteristics associated with discordance. Of the 1571 patients with Tdap status available in the EMR, 1549 patients (92%) reported on receipt status for Tdap vaccination during pregnancy; 1328 maternal reports (86%) agreed with the EMR for Tdap status (kappa=0.72, 95% CI 0.68-0.75). Several factors were statistically significant in multivariable analyses: lower income was associated with greater discordance (ie, overreporting; P=.02), as well as certain health beliefs including "Pregnant women should be concerned about the possibility of pertussis in their babies" (aOR 2.86, 95% CI 1.02-8.04) and "My friends would probably think getting a Tdap vaccine is a good idea" (aOR 2.36, 95% CI 1.11-4.99). Maternal recall of Tdap vaccination during pregnancy is consistent with the EMR. This supports the value of maternal report in determining Tdap vaccination status, which is especially important when vaccination records are not available.

Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Pertussis in the Newborn in Publicly and Privately Insured Mother-infant Pairs in the United States.

In the United States, pertussis circulation persists and primarily infects infants and children, despite routine vaccinations. To minimize infant morbidity and mortality from the disease before the first DTaP dose, the Advisory Committee on Immunization Practices recommends maternal Tdap vaccination in weeks 27-36 of pregnancy. Cohorts of mother-infant pairs in the Medicaid Analytic eXtract (MAX) (2010-2014) and IBM MarketScan (2011-2015) databases were analyzed to estimate the effectiveness of prenatal Tdap vaccination compared with no vaccination to prevent infant pertussis in the first 6 months. Hazard ratios were estimated with Cox proportional hazards models and adjusted for potential confounders via inverse probability weights. The impact of preterm delivery on the risk of pertussis was analyzed. Results from the 2 databases were pooled. In MarketScan, women received Tdap vaccination before delivery in 114,067 (25.6%) of 445,638 pregnancies and in MAX, 33,286 (4.8%) of 695,262 pregnancies. Among pregnancies with preterm delivery, only 21.2% and 3.8% in MarketScan and MAX had been vaccinated. The risk of pertussis in unvaccinated term infants was 3.5 (MarketScan) and 17 (MAX) per 10,000; and in preterm infants, it was 8.4 (MarketScan) and 19.8 (MAX) per 10,000. The pooled hazard ratio for Tdap vaccination any time before delivery versus no vaccination was 0.64 [95% confidence interval (CI): 0.41-1.00]. The hazard ratio was 0.11 (95% CI: 0.03-0.36) for preterm and 0.78 (95% CI: 0.48-1.29) for term infants vaccinated before 37 weeks. The incidence of pertussis was higher and the protective hazard ratio stronger during pertussis outbreaks. Prenatal Tdap vaccination reduces the risk of pertussis infections in the infants' first 6 months by 36%. Vaccination soon after 27 weeks of pregnancy, before when deliveries began, ensures vaccination includes those born preterm, who are at highest risk for pertussis and benefit particularly from this vaccination.

Effect of educational and financial incentive-based interventions on immunization attitudes, beliefs, intentions and receipt among close contacts of pregnant women

IntroductionCocooning, the vaccination of close contacts of a newborn, is a strategy to limit the risk of pertussis and influenza infection among vulnerable infants. MethodsPregnant women in Colorado and Georgia referred close contacts to an app that provided tailored educational videos about vaccines along with a small pharmacy-based financial incentive for vaccine receipt. The primary objective of this study was to determine the feasibility of implementing this app-based cocooning intervention. ResultsTwo hundred seventy seven contacts were enrolled in this study. Of those who received the educational videos, 96% found them interesting, 100% found them clear to understand, 97% found them helpful, and 99% trusted them. Completion of the videos led to significant increases in influenza vaccine knowledge (p = 0.025), Tdap vaccine knowledge (p < 0.001), and intention to receive these vaccines (p = 0.046). Of the 136 participants who reported receiving influenza vaccine, 41 (30%) reported receiving it at a pharmacy, and of the 66 who reported receiving Tdap vaccine, 15 (23%) reported receiving it at a pharmacy. Of all participants, 80% reported being comfortable receiving vaccines at a pharmacy instead of a doctor’s office. The provision of small pharmacy-based financial incentives combined with individually-tailored educational videos about vaccines led to 6.97 (95%CI: 2.25–21.64) times higher odds of self-reported receipt of influenza vaccine than providing small pharmacy-based financial incentives without these videos. No significant difference was found for Tdap vaccine. ConclusionsTailored vaccine education can positively impact vaccine knowledge and intentions among adults. An app-based referral program providing education and financial incentives for cocooning vaccination at pharmacies is feasible.

Safety of pertussis vaccines for adolescents

Aim: to investigate the safety of acellular pertussis vaccines for adolescents.Materials and methods. The clinical tolerability of revaccination against pertussis (cell-free component), diphtheria and tetanus was analyzed in 107 children aged 13,5–14 years. Group 1 consisted of children revaccinated with DTacP-IPV combined vaccine (Tetraxim), group 2 – vaccinated with Td and group 3 – children who received Tdap vaccine (Adacel).Results. Statistically significant differences in the frequency of local reactions between the group that received Tdap and the other two (DTacP-IPV and Td) were detected (p = 0.001and p = 0.04, respectively). Analysis of the structure of local reactions revealed a difference only in the occurrence of the hyperemia at the site of injection, with the most frequent registration in the groups of children vaccinated with DTacPIPV (29,4%) and Td (14,7%), whereas in patients vaccinated with Tdap – only in 5,9% (χ2 = 6,8 p = 0,03). Systemic reactions occurred with the same frequency in all studied groups and did not require medical correction, as well as local reactions. Thus, revaccination against pertussis, diphtheria and tetanus of adolescents using Tdap, containing the acellular pertussis component, does not exceed the frequency of systemic reactions and the number of local reactions is significantly lower in comparison with the vaccine with a reduced content of diphtheria and tetanus toxoids (Td) that is used in practice for a long time.

Using the North Dakota IIS to Assess the Response of Health Care Providers to the ACIP Recommendation for Tdap Vaccination During Pregnancy.

To evaluate the response of North Dakota health care providers to follow the recommendation set forth by the Advisory Committee on Immunization Practices (ACIP) to administer a dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine to women during each pregnancy using the North Dakota Immunization Information System (NDIIS). Data from the NDIIS for North Dakota infants born during calendar years 2013-2018 were extracted. Mother's name was taken from the newborn records and matched to NDIIS female client records to identify the population of mothers of newborns who would have been recommended to receive Tdap during their pregnancy. Doses of Tdap vaccine administered after October 1, 2012, were extracted from the NDIIS, and the dose records were matched back to the mother's record. The time from baby's birthdate back to the doses of Tdap vaccine administered to the mother was measured to find any doses that would have been administered during pregnancy. The percentage of women receiving Tdap vaccine during pregnancy increased from 31.5% in 2013 to 60.6% in 2018. Of those women who received Tdap during pregnancy, 94% received the vaccine during the ACIP-recommended interval of 27 to 36 weeks' gestation, using the assumption that all babies were born at 40 weeks' gestation. North Dakota health care providers have responded positively to the recommendation of the ACIP to administer a dose of Tdap vaccine to women during each pregnancy and have increased their administration of the vaccine to their patients.

Effectiveness of a Pharmacist-Directed Tdap Immunization Program for a University Campus

Background/Objectives: Despite a slight increase in Tdap immunization rates, the total numbers are still low among adults. The purpose of this study is to determine the impact of a pharmacist-directed immunization program. The primary objective was to assess the increase in vaccination rates among the subjects indicated to receive the Tdap vaccine. The secondary objective was to assess changes in pre and post vaccine knowledge scores.Methods: Employees enrolled in the pharmacist-directed employee wellness clinic on a university campus in Ohio were screened forTdap vaccination at the annual employee health fair during Fall of 2016. Results were cross-referenced with the state vaccination database. Subjects were recruited via email to an educational program. Indicated patients were asked to schedule an appointment with a pharmacist. Assessment data on the educational program was collected before the presentation and after the appointment when the vaccine was administered. The efficacy endpoint for the primary objective was a 20% increase in baseline vaccination rates.Results: Of the 198 subjects recruited, a total of 54 received Tdap vaccination. The baseline vaccination rate of the study populationwas 37.4% and increased by 27.2% after the intervention to a total vaccination rate of 64.6% (p&lt; 0.001). Six knowledge assessmentswere utilized for the secondary objective; however, these results did not show significance.Conclusions: A pharmacist-directed Tdap immunization program is effective at increasing vaccination rates. Even though the changein education assessment data proved more observational, the education provided will empower subjects to make informed healthcaredecisions.

Effectiveness of a multimodal intervention to increase vaccination in obstetrics/gynecology settings

ObjectiveTo test the effectiveness of a multimodal intervention in obstetrics/gynecology (ob-gyn) clinics to increase uptake of influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines in pregnant women and these vaccines plus human papillomavirus (HPV) vaccine in non-pregnant women. MethodsA cluster randomized controlled trial among 9 private ob-gyn practices in Colorado from 9/2011 to 5/2014. The intervention consisted of: designation of immunization champions, staff/provider trainings, assistance with vaccine purchasing/management, identification of eligible patients, standing order implementation, chart review/feedback, and patient education materials. Control practices continued usual care. Primary outcomes were receipt of influenza and Tdap vaccines among pregnant women and these vaccines plus HPV vaccine among non-pregnant women, comparing a Baseline period (Year 0/Year 1) to Year 2, intervention versus control. With an estimated sample size of 32,590 per arm, there would be >80% power to detect a 10% difference between groups. ResultsIn the Baseline period, 27% of pregnant women in both intervention and control practices received influenza vaccine. In Year 2, 29% of pregnant women in intervention practices received influenza vaccine versus 41% in control practices. In the Baseline period, 18% of pregnant women in intervention practices received Tdap vaccine versus 22% in control practices. Both intervention and control practices increased to 51% in Year 2, representing an increase of 33% for intervention practices and 29% for control practices, consistent with a change in Tdap recommendations. Relatively few HPV, influenza or Tdap vaccines (≤6% of eligible patients) were given to non-pregnant patients in either intervention or control practices at any time during the study. ConclusionIn this cluster randomized trial designed to increase vaccination uptake, both intervention and control practices showed improved vaccination of pregnant but not non-pregnant patients. Future work should focus on tailoring evidence-based immunization practices or developing new approaches to specifically fit busy ob-gyn offices.

Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination offers protection for neonates against clinical pertussis until primary vaccinations, but maternal antibodies also interfere with infants' immune responses to primary vaccinations. We investigated the effect of maternal Tdap vaccination on the pertussis antibody responses of infants starting primary vaccinations at age 3 months. In an open-label, parallel, randomised, controlled trial, pregnant women aged 18-40 years with a low risk of pregnancy complications were recruited through independent midwives at 36 midwife clinics in the Netherlands and received Tdap vaccination either at 30-32 weeks of pregnancy (maternal Tdap group) or within 48 h after delivery (control group). All term-born infants were vaccinated with the diphtheria, tetanus, and pertussis-inactivated poliomyelitis-Haemophilus influenzae type B-hepatitis B six-in-one vaccine and a ten-valent pneumococcal vaccine at 3 months, 5 months, and 11 months. Randomisation was done using a number generator in a 1:1 ratio and with sealed envelopes. Participants and clinical trial staff were not masked, but laboratory technicians were unaware of study group assignments. The primary endpoint was serum IgG pertussis toxin antibody concentrations at age 3 months. Cord blood and infant blood samples were collected at age 2 months, 3 months, 6 months, 11 months, and 12 months. Analysis was done by modified intention to treat with all randomly assigned participants in case a laboratory result was available. This trial is registered with ClinicaltTrialsRegister.eu (EudraCT 2012-004006-9) and trialregister.nl (NTR number NTR4314). The trial is now closed to new participants. Between Jan 16, 2014, and March 4, 2016, 118 pregnant women were enrolled into our study, with 58 in the maternal Tdap group and 60 in the control group. The geometric mean concentration (GMC) of pertussis toxin antibodies were higher in infants in the maternal Tdap group than in the control group infants at age 3 months (GMC ratio 16·6, 95% CI 10·9-25·2) and also significantly higher compared with control infants at age 2 months. After primary vaccinations, antibody concentrations for pertussis toxin, filamentous haemagglutinin, and pertactin were significantly lower at all timepoints in infants of the maternal Tdap group than in infants in the control group. No safety issues after maternal Tdap vaccination were encountered. In view of the high pertussis toxin antibody concentrations at age 3 months, maternal vaccination supports a delay of the first pertussis vaccination in infants until at least age 3 months. Maternal antibody interference affects antibody concentrations after primary and booster vaccinations. The clinical consequences of this interference remain to be established. The Dutch Ministry of Health, Welfare, and Sport.

Trends in Tdap vaccination among privately insured pregnant women in the United States, 2009–2016

BackgroundInfants younger than 6 months are at increased risk of complications and mortality from pertussis infection. In October 2012, the Advisory Committee on Immunization Practices revised its recommendation to include a Tdap dose during each pregnancy, ideally between 27 and 36 weeks gestation. ObjectiveAssess trends in Tdap vaccination coverage among privately insured pregnant women from 2009 to 2016 including timing of Tdap vaccination (before, during, or after pregnancy), trimester of vaccination for women vaccinated during pregnancy, and missed vaccination opportunities for unvaccinated women. Identify factors associated with vaccination during the optimal period of 27–36 weeks gestation. Study designRetrospective analysis of privately insured women 15–49 years who delivered live births during 2009–2016 conducted using 2009–2016 MarketScan data. Tdap vaccination coverage and the timing of Tdap vaccine administration were assessed for women continuously enrolled from 6 months before pregnancy to 1 month after delivery. Multivariable logistic regression was performed to identify factors independently associated with receipt of Tdap vaccine at 27–36 weeks gestation. ResultsTdap vaccination coverage during pregnancy increased from 0.4% in 2009 to 6.2% in 2012 and to 53.2% in 2016. The proportion of vaccinated women receiving Tdap at 27–36 weeks gestation increased from <10% in 2009 to nearly 90% in 2016, with most vaccination occurring at 27–32 weeks gestation. Women of older age, residing in a metropolitan statistical area, residing outside the South, and having a capitated health insurance plan were more likely to receive Tdap at 27–36 weeks gestation than their counterparts. Among women not vaccinated during pregnancy, 77.7% had a pregnancy-related medical claim between 27 and 36 weeks gestation. ConclusionTdap vaccination coverage during pregnancy increased significantly from 2009 to 2016, with the greatest increase occurring after the revised Advisory Committee on Immunization Practices recommendation. Most women who did not receive Tdap vaccine had a missed vaccination opportunity during pregnancy, indicating potential for much higher vaccination coverage and consequent infant protection against pertussis.

2278. Maternal Immunization Rates With Tetanus–Diphtheria–Acellular Pertussis and Influenza Vaccines in the United States: A Retrospective Claims Database Analysis

BackgroundThe Advisory Committee on Immunization Practices (ACIP) recommends maternal immunization (MI) with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during every pregnancy, preferably between 27–36 weeks of gestation, as well as influenza vaccination for all women who are pregnant or who might be pregnant in the influenza season.MethodsThis retrospective cohort analysis characterizes the rate of Tdap and influenza vaccination among large national samples of pregnant women in the United States using administrative claims data. The MarketScan® Commercial Claims and Encounters (“Commercial”) and the Multi-State Medicaid Databases (“Medicaid”) were used to identify pregnancies between January 1, 2010 and April 30, 2017. Diagnosis and procedure codes that describe gestational age at pregnancy end were used to estimate the date of last menstrual period (LMP) or the index date (Figure 1). Eligible pregnancies had ≥6 months of continuous enrollment prior to index date (“baseline”) through 60 days after pregnancy end (“follow-up”). Maternal Tdap and influenza immunization rates are described by calendar year of pregnancy end. Analyses are reported separately for Commercial and Medicaid cohorts.ResultsA total of 1,862,705 and 628,079 eligible pregnancies in the Commercial and Medicaid databases, respectively, were identified. After the 2013 ACIP recommendation to administer Tdap vaccination during each pregnancy, the proportion of pregnancies vaccinated against Tdap was 39% in 2014 and increased to 54% in 2016 for the Commercial cohort (Figure 2). A similar trend for Tdap MI was observed for the Medicaid cohort (Figure 3). In 2016, 41% and 25% of all pregnancies received influenza vaccination in the Commercial and Medicaid cohorts, respectively. Tdap and influenza MI rates also varied by several factors, including maternal age group, geographic region, urban/rural location, and race/ethnicity. ConclusionIn this analysis of large claims databases, for pregnancies ending in 2016 in the Commercial cohort, over 50% received Tdap vaccination and over 40% received influenza vaccination, whereas, in the Medicaid cohort, 30% of all pregnancies were vaccinated against Tdap and 25% received influenza vaccination.Disclosures P. Ghaswalla, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary. J. E. Poirrier, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary. E. Packnett, GSK: Research Contractor, Research support. D. Irwin, GSK: Research Contractor, Research support. S. Gray, GSK: Research Contractor, Research support. P. Buck, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary.

Association Between Third-Trimester Tdap Immunization and Neonatal Pertussis Antibody Concentration

Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]). Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

Immunogenicity and safety of a second booster dose of an acellular pertussis vaccine combined with reduced antigen content diphtheria-tetanus toxoids 10 years after a first booster in adolescence: An open, phase III, non-randomized, multi-center study

ABSTRACTPertussis is a highly contagious disease, for which periodic peaks in incidence and an increasing number of outbreaks have been observed over the last decades. The reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine (Tdap) can be used to boost individuals aged ≥10 years, vaccinated in infancy with a diphtheria-tetanus-acellular pertussis vaccine (DTaP), to reduce pertussis morbidity and maintain protection against diphtheria and tetanus throughout adolescence and adulthood. This phase III, open-label, non-randomized, multicenter follow-up study (NCT01738477) enrolled 19–30-year-old participants from the United States who had received booster vaccination 10 years earlier with either Tdap (Tdap group) or Td (Td group). In total, 128 (Tdap group) and 37 (Td group) participants received Tdap vaccination. After administration of Tdap, all participants were seroprotected (antibody concentrations ≥0.1 international units [IU]/ml) against diphtheria and tetanus. Immune responses to a second Tdap dose in the Tdap group were shown to be non-inferior to responses elicited by a first Tdap dose in the Td group for diphtheria and tetanus and to a 3-dose DTaP vaccination during infancy for pertussis antigens (primary objectives). Post-booster vaccination, all participants in both groups had antibody concentrations above assay cut-offs and antibody geometric mean concentrations increased by 3.8–15.5-fold compared to pre-booster levels for all antigens. The incidence of adverse events was similar in the Td (80.6%) and Tdap (85.6%) groups (no serious adverse events reported). A Tdap dose administered after previous Td or Tdap vaccination was shown to be immunogenic and well-tolerated in young adults, supporting repeated vaccination with Tdap at 10-year intervals.

Tdap Vaccination Coverage During Pregnancy - Selected Sites, United States, 2006-2015.

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended during the third trimester of each pregnancy to provide protection to newborns, who are at risk for pertussis-related morbidity and mortality (1). As part of its case-control surveillance study of medications and birth defects, the Birth Defects Study of the Slone Epidemiology Center at Boston University (the Birth Defects Study) has recorded data on vaccinations received during pregnancy since 2006. Among 5,606 mothers of infants without structural birth defects in this population (control group), <1% had received Tdap vaccine before 2009. By 2012, the percentage of mothers of infants in the control group (control infants) who had received Tdap increased to approximately 9%, and then in 2013 and continuing through 2015, increased markedly, to 28% and 54%, respectively. As the prevalence of maternal Tdap vaccination increased, so did the proportion of pregnant women who received Tdap in the third trimester, as recommended (94%-100% from 2010 to 2015). The vast majority of Tdap vaccinations (96%) were received in a traditional health care setting (e.g., the office of the woman's obstetrician or primary care physician or her prenatal clinic). Increasing vaccination coverage during pregnancy could help reduce the impact of pertussis on infant morbidity and mortality.