Pertussis Immunisation in Pregnancy Safety (PIPS) Study: A retrospective cohort study of safety outcomes in pregnant women vaccinated with Tdap vaccine

BackgroundNew Zealand has funded the administration of tetanus, diphtheria and acellular pertussis (Tdap) vaccine during pregnancy to prevent infant pertussis since 2013. The aim of this study was to assess the safety of Tdap vaccine administered to pregnant women as part of a national maternal immunisation programme.MethodsWe conducted a national retrospective observational study using linked administrative New Zealand datasets. The study population consisted of pregnant women eligible to receive funded Tdap vaccination from 28 to 38 weeks gestation in 2013. Primary study outcomes were based on prioritised adverse events for the assessment of vaccine safety in pregnant women, as defined by WHO and Brighton Collaboration taskforces. We examined the effect of Tdap vaccination on prioritised maternal outcomes using Cox proportional hazard models. Adjusted hazard ratios controlled for key confounding variables.ResultsIn the cohort of 68,550 women eligible to receive funded antenatal Tdap vaccination during 2013, 8178 (11.9%) were vaccinated and 60,372 (88.1%) were unvaccinated. The use of Tdap in pregnancy was not associated with an increase in the rate of primary outcomes, including preterm labour; pre-eclampsia; pre-eclampsia with severe features; eclampsia; gestational hypertension; fetal growth restriction; or post-partum haemorrhage. Tdap also did not increase secondary outcomes, including gestational diabetes mellitus; antenatal bleeding; placental abruption; premature rupture of membranes; preterm delivery; fetal distress; chorioamnionitis; or, maternal fever during or after labour. Lactation disorders was the only secondary maternal outcome with a significantly increased hazard ratio. Tdap vaccine had a protective effect on pre-eclampsia with severe features, preterm labour, preterm delivery, and antenatal bleeding.ConclusionWe did not detect any biologically plausible adverse maternal outcomes following Tdap vaccination during pregnancy. This study provides further assurance that Tdap administration during pregnancy is not associated with unexpected safety risks.     

Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System

BackgroundIn October 2012, the Advisory Committee on Immunization Practices (ACIP) recommended a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) during each pregnancy, irrespective of the woman's prior history of receiving Tdap. A retrospective cohort study to assess the safety of Tdap vaccination in pregnant women in two Vaccine Safety Datalink (VSD) sites during 2010–2012 found a small but statistically significant increased risk of chorioamnionitis.ObjectiveWe conducted a review of the VAERS database to describe reports of chorioamnionitis following receipt of any vaccines.MethodsWe searched the VAERS database for reports of chorioamnionitis after any vaccine in the United States during the period from July 1, 1990 through February 2, 2014.ResultsVAERS received 31 reports of chorioamnionitis out of 3389 pregnancy reports in 24 years. The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight percent of reports had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were reported.ConclusionChorioamnionitis was found to be uncommonly reported, representing 1% of pregnancy reports to VAERS. A majority of reports had at least one risk factor for chorioamnionitis.     

Safety of tetanus,diphtheria, and acellular pertussis vaccination among pregnant active duty U.S. military women

BackgroundThe tetanus, diphtheria, and acellular pertussis (Tdap) vaccine was approved for U.S. adults in 2005 and recommended for administration in every pregnancy in 2012, with optimal timing between 27 and 36 weeks’ gestation. In the military, however, a current Tdap vaccination status is compulsory for service, and active duty women may be inadvertently exposed in early pregnancy. Safety data in this population are limited.ObjectivesTo assess safety of inadvertent (0–13 weeks’ gestation) and recommended (27–36 weeks’ gestation) exposure to the Tdap vaccine in pregnancy.MethodsPregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to determine pregnancy Tdap vaccine exposure among active duty women, 2006–2014. Multivariable Cox and generalized linear regression models estimated associations between Tdap vaccine exposure and adverse pregnancy or infant outcomes.ResultsOf 145,883 pregnancies, 1272 were exposed to the Tdap vaccine in the first trimester and 9438 between 27 and 36 weeks’ gestation. Neither inadvertent nor recommended vaccine exposure were associated with spontaneous abortion, preeclampsia, or preterm labor. Among 117,724 live born infants, 984 were exposed to the Tdap vaccine in the first trimester and 9352 between 27 and 36 weeks’ gestation. First trimester exposure was not associated with birth defects, growth problems in utero, growth problems in infancy, preterm birth, or low birth weight. Tdap vaccine exposure between 27 and 36 weeks’ gestation was not associated with any adverse infant outcome.ConclusionsAmong a population of active duty women in the U.S. military who received the Tdap vaccine during pregnancy, we detected no increased risks for adverse maternal, fetal, or infant outcomes. Our findings corroborate existing literature on the safety of exposure to the Tdap vaccine in pregnancy.     

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

IntroductionSince October 2012, the combined tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine (Tdap) has been recommended in the United States during every pregnancy.MethodsIn 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).ResultsOur 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.ConclusionTdap coverage during pregnancy increased from 2007 through 2013, but was still below 50%. No acute maternal safety signals were detected in this large cohort.     

Enhanced surveillance of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011–2015

BackgroundIn October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.ObjectivesWe characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011–2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005–2010).MethodsWe searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011–6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005–06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation.ResultsWe found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5–2.8%) and injection site reactions/arm pain (4.5–11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7–1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports.ConclusionsNo new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester.     

Maternal Tdap vaccination and risk of infant morbidity

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

Evaluation of two vaccine education interventions to improve pertussis vaccination among pregnant African American women: A randomized controlled trial

BackgroundVaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in pregnancy or immediately postpartum has been low. Limited data exist on rigorously evaluated interventions to increase maternal vaccination, including Tdap. Tailored messaging based on the Elaboration Likelihood Model (ELM) framework has been successful in improving uptake of some public health interventions. We evaluated the effect of two ELM-based vaccine educational interventions on Tdap vaccination among pregnant African American women, a group of women who tend to have lower vaccine uptake compared with other groups.MethodsWe conducted a prospective randomized controlled trial to pilot test two interventions – an affective messaging video and a cognitive messaging iBook – among pregnant African American women recruited during routine prenatal care visits. We measured Tdap vaccination during the perinatal period (during pregnancy and immediately postpartum), reasons for non-vaccination, and intention to receive Tdap in the next pregnancy.ResultsAmong the enrolled women (n = 106), 90% completed follow-up. Tdap vaccination in the perinatal period was 18% in the control group; 50% in the iBook group (Risk Ratio [vs. control group]: 2.83; 95% CI, 1.26–6.37), and 29% in the video group (RR: 1.65; 95% CI, 0.66–4.09). From baseline to follow-up, women’s reported intention to receive Tdap during the next pregnancy improved in all three groups. Among unvaccinated women, the most common reason reported for non-vaccination was lack of a recommendation for Tdap by the woman’s physician.ConclusionsEducation interventions that provide targeted information for pregnant women in an interactive manner may be useful to improve Tdap vaccination during the perinatal period. However, larger studies including multiple racial and ethnic groups are needed to evaluate robustness of our findings.Trial Registration: clinicaltrials.gov Identifier: NCT01740310.     

Tetanus,diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections

BackgroundTo protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36 weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants <2 months of age.MethodsThis retrospective cohort study included 99,434 infants born to active duty military women in the Department of Defense Birth and Infant Health Registry from 2006 through 2013. Multivariable log-binomial regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at <2 months of age.ResultsInfants of mothers who received Tdap vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at <2 months of age (RR, 0.91; 95% CI, 0.84–0.99), and the risk was 17% lower if vaccination was received between 27 and 36 weeks of pregnancy (RR, 0.83; 95% CI, 0.74–0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36 weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74–0.98).ConclusionsMaternal Tdap vaccination between 27 and 36 weeks of pregnancy was consistently protective against infant ARI in the first 2 months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy.     

Safety of maternal pertussis vaccination on pregnancy and birth outcomes: A prospective cohort study

ObjectiveTo evaluate the safety of maternal pertussis vaccination on pregnancy and birth outcomes.MethodsThe study population comprised 1272 healthy nulliparous pregnant women who participated in Screening Tests to identify poor Outcomes in Pregnancy (STOP) study at two obstetric hospitals in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination (confirmed by medical records), extensive amounts of pregnancy and birth outcome data collected by research midwives. Adjusted relative risks (aRRs) and hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and the temporal nature of each outcome.ResultsOf the 1272 women included in this study, 80.1% (n = 1019) received maternal pertussis vaccination. Vaccinated women had an average 0.22 weeks (95% CI 0.001, 0.44) longer gestation at delivery compared to unvaccinated women. Maternal pertussis vaccination was not associated with chorioamnionitis (aRR 0.71, 95% CI 0.27,1.82), gestational hypertension (aHR 1.24, 95% CI, 0.66, 2.30), preeclampsia (aHR 0.75, 95% CI 0.47, 1.18) nor preterm birth (aHR 0.99, 95% CI 0.47, 2.07). Neither risk of low birth weight (aHR 0.72, 95% CI 0.41, 1.27) nor small for gestational age infants (aHR 0.67,95% CI 0.29, 1.55) were increased following maternal pertussis vaccination. No associations between pertussis vaccination during pregnancy and adverse birth outcomes including admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for maternal influenza vaccination.ConclusionOur study provides reassuring evidence of the safety of maternal pertussis vaccination with no increased risk of adverse pregnancy and birth outcomes. These findings support recommendations for pertussis vaccination during pregnancy to prevent morbidity and mortality associated with early-infant pertussis disease.     

Levels of antibodies specific to diphtheria toxoid,tetanus toxoid,and Haemophilus influenzae type b in healthy children born to Tdap-vaccinated mothers

IntroductionVaccination of pregnant women protects both women and their newborns against some infectious diseases. Thailand implemented tetanus toxoid (TT) vaccination of pregnant women in 1977, which was replaced by tetanus–diphtheria toxoid (dT) vaccination in 2005. The tetanus–diphtheria–acellular pertussis (Tdap) vaccine has been recommended for pregnant women at 27–36 weeks of gestation since 2012 in several countries. Data on antibody responses to diphtheria toxoid (DT), TT, and Hemophilus influenzae type b (Hib) induced by combined vaccines in children born to TT-vaccinated and/or Tdap-vaccinated mothers are limited.Material and methodsWe investigated anti-DT, anti-TT, and anti-Hib IgG responses in a cohort of Thai children (ClinicalTrial.gov NCT02408926) born to mothers who received a TT-containing and/or the Tdap vaccine during pregnancy. Children born to Tdap-vaccinated mothers were randomized to receive either a hexavalent (Infanrix-hexa) or pentavalent (Quinvaxem) vaccine, whereas children born to TT-vaccinated mothers received only Quinvaxem vaccine at 2, 4, 6, and 18 months of age. IgG levels were evaluated at birth (cord blood), 2 (pre-primary), 7 (post-primary), 18 (pre-booster), and 19 months of age (post-booster) using a commercially available enzyme-linked immunoassay.ResultsSeroprotective concentrations of anti-DT, anti-TT, and anti-Hib IgG were achieved in >90% and >99% of children following primary and booster vaccination, respectively. Among children born to Tdap-vaccinated mothers, the pentavalent vaccine induced higher levels of anti-Hib IgG than the hexavalent vaccine after primary and booster vaccination. Significantly higher anti-Hib IgG levels were observed among children receiving the pentavalent vaccine and who were born to TT-vaccinated mothers than among children receiving the pentavalent vaccine and born to Tdap-vaccinated mothers after primary and booster vaccination.ConclusionsVaccination with a TT-containing and/or the Tdap vaccine during pregnancy did not compromise the seroprotection rate achieved following primary and booster immunization in individuals receiving either the pentavalent or hexavalent vaccine.     

Birth outcomes for Australian mother-infant pairs who received an influenza vaccine during pregnancy, 2012–2014: The FluMum study

IntroductionIn Australia, influenza vaccination is recommended for all women who will be pregnant during the influenza season. Vaccine safety and effectiveness are key concerns and influencers of uptake for both vaccine providers and families. We assessed the safety of receiving an influenza vaccination during any trimester of pregnancy with respect to preterm births and infant birthweight.MethodsWe conducted a nested retrospective cohort study of ‘FluMum’ participants (2012–2014). Our primary exposure of interest was influenza vaccination during pregnancy. The primary outcomes of interest were infant birthweight and weeks’ gestation at birth for live singleton infants. Analyses included comparisons of these birth outcomes by vaccination status and trimester of pregnancy an influenza vaccine was given. We calculated means, proportions, and relative risks and performed multivariable logistic regression for potential confounding factors.ResultsIn the 7126 mother-infant pairs enrolled in this study, mean maternal age at infant birth was 31.7 years. Influenza vaccine uptake in pregnancy was 34%. Most mothers with a known date of vaccination received a vaccine in the second trimester (51%). Those mothers with a co-morbidity or risk factor were 13% more likely to have influenza vaccine during pregnancy compared to other mothers (RR 1.13, 95% CI 1.04–1.24, p = 0.007). Mean weeks’ gestation at birth was 38.7 for the vaccinated and 38.8 for the unvaccinated group (p = 0.051). Infants in the vaccinated group weighed 15 g less in birthweight compared to the unvaccinated infants (95% CI −12.8 to 42.2, p = 0.29).ConclusionResults arising from this large Australian cohort study are reassuring with respect to two critical safety outcomes; preterm births and low infant birthweights. Studies examining a broader range of birth outcomes following influenza vaccination during pregnancy are required, particularly now that maternal vaccination in pregnancy has expanded to include pertussis as well as influenza.     

Maternal and infant outcomes following exposure to quadrivalent human papillomavirus vaccine during pregnancy

IntroductionThe Department of Defense encourages service members ≤26 years of age to receive the human papillomavirus (HPV) vaccine. Although this vaccine is not recommended in pregnancy, inadvertent vaccination may occur. The objective of this study was to assess whether active duty US military women who received the quadrivalent HPV vaccine (4vHPV) during pregnancy were at increased risk for adverse maternal or infant outcomes.MethodsThe study population included active duty US military women aged 17–28 years with at least one pregnancy between 2007 and 2014, and the infants resulting from those pregnancies. Pregnancies, live births, and outcomes were identified using medical codes in administrative medical records. Exposure to 4vHPV during pregnancy was ascertained from personnel immunization records. Multivariable regression models were used to calculate risk estimates and 95% confidence intervals for the maternal outcomes of spontaneous abortion, preeclampsia/eclampsia and preterm labor, and the infant outcomes of preterm birth, birth defects, growth problems in infancy or in utero, and infant sex.ResultsOverall, 90,600 pregnancies and 75,670 singleton infants were identified. Approximately 2% of pregnancies and infants were exposed to 4vHPV during pregnancy. After adjustments, no positive associations were detected between inadvertent exposure to 4vHPV during pregnancy and any adverse pregnancy or infant outcomes.DiscussionOur findings add to an established body of literature demonstrating the safety of 4vHPV when inadvertently administered during pregnancy. Although 4vHPV is no longer administered in the US, its use continues overseas; therefore, safety studies remain important. Furthermore, such studies can provide reassurance to women inadvertently exposed to nonavalent HPV vaccine (9vHPV) in pregnancy, which protects against four of the same antigens as 4vHPV, since safety of 9vHPV has not yet been established in pregnant women.     

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

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

Prenatal Tdap immunization and risk of maternal and newborn adverse events

Many countries recommend combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis immunization (Tdap) during pregnancy to stimulate transplacental transmission of pertussis antibodies to newborns. The immune system can be altered during pregnancy, potentially resulting in differing immunization risks in pregnant women. The safety of widespread Tdap immunization during pregnancy needs to be established. Our objective was to assess whether prenatal Tdap immunization was associated with adverse birth outcomes, and to evaluate the effect of timing of Tdap administration on these outcomes.We identified pregnancies at delivery in a large insurance claims database (2010–2014). Tdap immunization was categorized as optimal prenatal (27 + weeks), early prenatal (<27 weeks), postpartum (≤7 days post-delivery), or none. Medical claims were searched to identify maternal adverse immunization reactions (e.g. anaphylaxis, fever, Guillian-Barre syndrome [GBS]), adverse birth outcomes (e.g. preeclampsia/eclampsia, premature rupture or membranes, chorioamnionitis) and newborn outcomes (e.g. respiratory distress, pulmonary hypertension, neonatal jaundice). Women with optimal or early prenatal Tdap were compared to those not immunized in pregnancy, using propensity score-weighted log-binomial regression and Cox proportional hazards models to estimate risk ratios (RR) and hazard ratios (HR). We identified 1,079,034 deliveries and 677,075 linked newborns; 11.5% were immunized optimally and 2.3% immunized early. There were 1 case of post-immunization anaphylaxis, and 12 cases of maternal encephalopathy (all post- delivery); there were no cases of GBS. Optimally-timed immunization was associated with small increased relative risks of: chorioamnionitis [RR = 1.11, (95% CI: 1.07–1.15), overall risk = 2.8%], and postpartum hemorrhage [RR = 1.23 (95% DI: 1.18–1.28), overall risk = 2.4%]; however, these relative increases corresponded to low absolute risk increases. Tdap was not associated with increased risk of any adverse newborn outcome. Overall, prenatal Tdap immunization was not associated with newborn adverse events, but potential associations with chorioamnionitis consistent with one previous study and postpartum hemorrhage require further investigation.     

Assessing the reactogenicity of Tdap vaccine administered during pregnancy and antibodies to Bordetella pertussis antigens in maternal and cord sera of Thai women

IntroductionPregnant Thai women have low antibody titers against B. pertussis antigens, which coincide with an increasing incidence of pertussis among Thai infants. Thus, there exists a potential benefit of a booster dose of tetanus- diphtheria-acellular pertussis (Tdap) vaccine administered during pregnancy. Here, we report the vaccine reactogenicity profile and birth outcomes in Tdap-vaccinated pregnant women who have or have not had prior immunization with tetanus vaccine, and the IgG levels to B. pertussis antigens in maternal and cord sera at delivery.Materials and methodsPregnant women (N = 370) aged 18–40 years were administered the Tdap vaccine (Boostrix®, GlaxoSmithKline, Rixensart, Belgium) at 26–36 weeks gestation. Adverse events following vaccination were identified by follow-up telephone call and medical record review. IgG against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA) and pertactin (anti-PRN) in both maternal and umbilical cord blood obtained at delivery were quantitatively evaluated using enzyme-linked immunosorbent assay (EUROIMMUN®, Lübeck, Germany).ResultsThere was no reported increase in the severity or duration of adverse events associated with the administration of an extra tetanus-containing vaccine within the previous five years (N = 181) or multiple doses of tetanus-containing vaccines during the current pregnancy (N = 98). Vaccination at least eight weeks prior to delivery resulted in high antibody titers to all B. pertussis antigens studied.ConclusionsThe reactogenicity of Tdap vaccine administered during pregnancy was not affected by prior tetanus toxoid immunization. High transplacental antibody against B. pertussis antigens in the cord blood provides evidence of antibody transfer and should thus help to protect newborns from pertussis during early life.     

Patient attitudes toward influenza and tetanus,diphtheria and acellular pertussis vaccination in pregnancy

BackgroundRoutine influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccination of pregnant women to prevent poor maternal, fetal and neonatal outcomes is recommended practice; however, actual rates of influenza vaccine acceptance are typically well below the (Healthy People 2020, 2015) goal of 80%.ObjectiveWe sought to identify barriers to accepting either vaccination.Materials and MethodsFrom December 2014 to April 2015 women were given a questionnaire eliciting their experiences, attitudes and history of influenza and Tdap vaccination in pregnancy during their routine prenatal care appointments at a tertiary care center. Patient demographics were included in the questionnaire. A similar questionnaire was administered to prenatal care providers. Patient influenza and Tdap vaccination acceptance rates were compared and predictors of vaccine acceptance were analyzed with bivariate logistic regression.ResultsOut of the 400 patient questionnaires distributed, 338 (84.5%) were completed and returned; 24 of 45 (53.3%) provider questionnaires were returned. Vaccination acceptance rates were 70.7% for the influenza vaccine and 76.3% for the Tdap vaccine. The logistic regression model indicated that predictors of acceptance for either vaccine in pregnancy are patient attitude and previous vaccination history. Patient attitudes were more favorable towards Tdap than influenza vaccination. The combination of healthcare provider recommendation and educational materials was significantly predictive of both Tdap and influenza vaccine acceptance. The most common reasons given for declining the influenza vaccine were safety concerns; the most common reasons given for declining the Tdap vaccine were that patients did not think it was required again when they received the vaccine before pregnancy.ConclusionsOur study suggests that providers can improve Tdap and influenza vaccination acceptance in pregnancy by recommending the vaccination in combination with provision of educational materials on the vaccines.     

Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial

BackgroundPertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization.MethodsThis phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6–14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (27^0/7–36^6/7 weeks’ gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination.Results601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5–77.1%) versus placebo (90.0–99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related.ConclusionsPertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant’s ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience.Clinical Trial Registration: ClinicalTrials.gov: NCT02422264.     

Immunogenicity,transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized,placebo-controlled trial

BackgroundPertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach.MethodsThis phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27–36 weeks’ gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded.Results687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5–19.2) for anti-filamentous hemagglutinin, 20.7 (15.9–26.9) for anti-pertactin and 8.5 (7.0–10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination.ConclusionsTdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease.Clinical Trial Registration. ClinicalTrials.gov: NCT02377349.     

Seroprevalence of Bordetella pertussis antibodies and anti-pertussis antibody response after a single dose of reduced-antigen combined diphtheria,tetanus, and acellular pertussis vaccine (Tdap) in pregnant Thai women

BackgroundMaternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) has recently been implemented to prevent infant pertussis. Tdap is still not routinely recommended in Thailand, and there are limited data to support or challenge this strategy.ObjectivesThe primary aim was to determine the seroprevalence of anti-pertussis toxin antibodies (anti-PT IgG) among pregnant Thai women. The secondary aims were to evaluate antibodies response after Tdap vaccination between seronegative and seropositive mothers and to compare the different antibody titers at delivery among seropositive mothers who received Tdap to those who received tetanus-diphtheria vaccine (Td).MethodsThis randomized clinical trial was conducted during April 2018 to April 2019 at Siriraj Hospital, Bangkok, Thailand. A total of 129 pregnant women were included. Paired blood samples for anti-PT IgG levels were obtained during the first antenatal visit and at delivery. A baseline cut-off value of <5 IU/ml indicated seronegativity. There were 29 exclusions from the original 129 enrollment. All seronegative participants (n = 69) received Tdap, while the seropositive group were randomized 1:1 to receive either Tdap (n = 18) or Td (n = 13) during 27–36 weeks’ gestation. The antibody levels from both sera were compared between groups.ResultsThe seroprevalence of maternal anti-PT IgG was 33.3% (43/129). There was no significant difference in the increment of antibody levels after Tdap vaccination between the seronegative and seropositive groups (30.2 vs. 42 IU/ml; p = 0.183). Among seropositive groups, all Tdap recipients had increased antibody titers at delivery, while all Td recipients showed waning of immunity throughout gestation. (42 IU/ml vs. −7.4 IU/ml; p < 0.001).ConclusionMost pregnant Thai women have seronegative against pertussis. Most seropositive mothers had initial low antibody titers and their immunity significantly decreased before delivery. Our findings highlight the need for universal pertussis immunization in pregnancy regardless of individual baseline immunity.