Risk of anaphylaxis after vaccination in children and adults.

BACKGROUND: Anaphylaxis is a potentially life-threatening allergic reaction. The risk of anaphylaxis after vaccination has not been well described in adults or with newer vaccines in children. OBJECTIVE: We sought to estimate the incidence of anaphylaxis after vaccines and describe the demographic and clinical characteristics of confirmed cases of anaphylaxis. METHODS: Using health care data from the Vaccine Safety Datalink, we determined rates of anaphylaxis after vaccination in children and adults. We first identified all patients with a vaccination record from January 2009 through December 2011 and used diagnostic and procedure codes to identify potential anaphylaxis cases. Medical records of potential cases were reviewed. Confirmed cases met the Brighton Collaboration definition for anaphylaxis and had to be determined to be vaccine triggered. We calculated the incidence of anaphylaxis after all vaccines combined and for selected individual vaccines. RESULTS: We identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after 25,173,965 vaccine doses. The rate of anaphylaxis was 1.31 (95% CI, 0.90-1.84) per million vaccine doses. The incidence did not vary significantly by age, and there was a nonsignificant female predominance. Vaccine-specific rates included 1.35 (95% CI, 0.65-2.47) per million doses for inactivated trivalent influenza vaccine (10 cases, 7,434,628 doses given alone) and 1.83 (95% CI, 0.22-6.63) per million doses for inactivated monovalent influenza vaccine (2 cases, 1,090,279 doses given alone). The onset of symptoms among cases was within 30 minutes (8 cases), 30 to less than 120 minutes (8 cases), 2 to less than 4 hours (10 cases), 4 to 8 hours (2 cases), the next day (1 case), and not documented (4 cases). CONCLUSION: Anaphylaxis after vaccination is rare in all age groups. Despite its rarity, anaphylaxis is a potentially life-threatening medical emergency that vaccine providers need to be prepared to treat.

Risk of Preterm or Small-for-Gestational-Age Birth After Influenza Vaccination During Pregnancy: Caveats When Conducting Retrospective Observational Studies.

Vaccines are increasingly targeted toward women of reproductive age, and vaccines to prevent influenza and pertussis are recommended during pregnancy. Prelicensure clinical trials typically have not included pregnant women, and when they are included, trials cannot detect rare events. Thus, postmarketing vaccine safety assessments are necessary. However, analysis of observational data requires detailed assessment of potential biases. Using data from 8 Vaccine Safety Datalink sites in the United States, we analyzed the association of monovalent H1N1 influenza vaccine (MIV) during pregnancy with preterm birth (<37 weeks) and small-for-gestational-age birth (birth weight < 10th percentile). The cohort included 46,549 pregnancies during 2009-2010 (40% of participants received the MIV). We found potential biases in the vaccine-birth outcome association that might occur due to variable access to vaccines, the time-dependent nature of exposure to vaccination within pregnancy (immortal time bias), and confounding from baseline differences between vaccinated and unvaccinated women. We found a strong protective effect of vaccination on preterm birth (relative risk = 0.79, 95% confidence interval: 0.74, 0.85) when we ignored potential biases and no effect when accounted for them (relative risk = 0.91; 95% confidence interval: 0.83, 1.0). In contrast, we found no important biases in the association of MIV with small-for-gestational-age birth. Investigators conducting studies to evaluate birth outcomes after maternal vaccination should use statistical approaches to minimize potential biases.

Adverse Events Following Measles, Mumps, and Rubella Vaccine in Adults Reported to the Vaccine Adverse Event Reporting System (VAERS), 2003-2013.

BACKGROUND: Limited data exist on the safety of the measles, mumps, and rubella (MMR) vaccine in adults. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in this previously understudied group. METHODS: VAERS is the national spontaneous vaccine safety surveillance system coadministered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adults aged ≥19 years who received the MMR vaccine from 1 January 2003 to 31 July 2013. We clinically reviewed reports and available medical records for serious AEs, pregnancy reports, and reports for selected prespecified outcomes. RESULTS: During this period, VAERS received 3175 US reports after MMR vaccine in adults. Of these, 168 (5%) were classified as serious, including 7 reports of death. Females accounted for 77% of reports. The most common signs and symptoms for all reports were pyrexia (19%), rash (17%), pain (13%), and arthralgia (13%). We did not detect any new safety findings in empirical Bayesian data mining. We identified 131 reports of MMR vaccine administered to a pregnant woman; the majority of these vaccinations were in the first trimester and in 83 (62%), no AE was reported. CONCLUSIONS: In our review of VAERS data, we did not detect any new or unexpected safety concerns for MMR vaccination in adults. We identified reports of pregnant women exposed to MMR, which is a group in whom the vaccine is contraindicated, suggesting the need for continued provider education on vaccine recommendations and screening.

Association of Tdap Vaccination With Acute Events and Adverse Birth Outcomes Among Pregnant Women With Prior Tetanus-Containing Immunizations.

IMPORTANCE: The Advisory Committee on Immunization Practices (ACIP) recommends the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for pregnant women during each pregnancy, regardless of prior immunization status. However, safety data on repeated Tdap vaccination in pregnancy is lacking. OBJECTIVE: To determine whether receipt of Tdap vaccine during pregnancy administered in close intervals from prior tetanus-containing vaccinations is associated with acute adverse events in mothers and adverse birth outcomes in neonates. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study in 29,155 pregnant women aged 14 through 49 years from January 1, 2007, through November 15, 2013, using data from 7 Vaccine Safety Datalink sites in California, Colorado, Minnesota, Oregon, Washington, and Wisconsin. EXPOSURES: Women who received Tdap in pregnancy following a prior tetanus-containing vaccine less than 2 years before, 2 to 5 years before, and more than 5 years before. MAIN OUTCOMES AND MEASURES: Acute adverse events (fever, allergy, and local reactions) and adverse birth outcomes (small for gestational age, preterm delivery, and low birth weight) were evaluated. Women who were vaccinated with Tdap in pregnancy and had a prior tetanus-containing vaccine more than 5 years before served as controls. RESULTS: There were no statistically significant differences in rates of medically attended acute adverse events or adverse birth outcomes related to timing since prior tetanus-containing vaccination. [table: see text]. CONCLUSIONS AND RELEVANCE: Among women who received Tdap vaccination during pregnancy, there was no increased risk of acute adverse events or adverse birth outcomes for those who had been previously vaccinated less than 2 years before or 2 to 5 years before compared with those who had been vaccinated more than 5 years before. These findings suggest that relatively recent receipt of a prior tetanus-containing vaccination does not increase risk after Tdap vaccination in pregnancy.

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

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

Infant Hospitalizations and Mortality After Maternal Vaccination.

BACKGROUND: The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. There are limited studies of the long-term safety in infants for vaccines administered during pregnancy. We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life. METHODS: We included singleton, live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014. Outcomes were infant hospitalizations and mortality in the first 6 months of life. We performed a case-control study matching case patients and controls 1:1 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza and/or Tdap vaccines in pregnancy. RESULTS: There were 413 034 live births in our population. Of these, 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life. We found no association between infant hospitalization and maternal influenza (adjusted odds ratio: 1.00; 95% confidence interval [CI]: 0.96-1.04) or Tdap (adjusted odds ratio: 0.94; 95% CI: 0.88-1.01) vaccinations. We found no association between infant mortality and maternal influenza (adjusted odds ratio: 0.96; 95% CI: 0.54-1.69) or Tdap (adjusted odds ratio: 0.44; 95% CI: 0.17-1.13) vaccinations. CONCLUSIONS: We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life. These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy.

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

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

Risk of Guillain-Barré Syndrome following quadrivalent human papillomavirus vaccine in the Vaccine Safety Datalink.

OBJECTIVE: Describe the Vaccine Safety Datalink's (VSD) Guillain Barré Syndrome (GBS) surveillance following quadrivalent HPV vaccine (4vHPV) from 2006 through 2015. METHODS: Among 4vHPV vaccinated persons aged 9-26, ICD-9 coded GBS was identified in VSD's electronic data. Medical records were reviewed and adjudicated to confirm GBS. We calculated incidence rates of confirmed GBS within 1-42days following 4vHPV with a one-sided 95% confidence interval. RESULTS: Following 2,773,185 4vHPV doses, we confirmed 1 case of GBS in a male and no cases among females. The incidence rate of medical record confirmed GBS within 42days following 4vHPV vaccine was 0.36 cases per million 4vHPV doses administered (1-sided 95% CI 1.71), which was less than the background rate. CONCLUSION: We found no evidence of an increased risk of GBS following 4vHPV. With an upper 95% confidence limit, we estimate that, if an increased risk exists, we would expect at most 1.08 additional cases of GBS per million people vaccinated with 4vHPV.

Major Birth Defects after Vaccination Reported to the Vaccine Adverse Event Reporting System (VAERS), 1990 to 2014.

BACKGROUND: Major birth defects are important infant outcomes that have not been well studied in the postmarketing surveillance of vaccines given to pregnant women. We assessed the presence of major birth defects following vaccination in the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system used to monitor the safety of vaccines in the United States. METHODS: We searched VAERS for reports of major birth defects during January 1, 1990, through December 31, 2014. We excluded birth defects from vaccines that had been studied in pregnancy registries or other epidemiological studies (e.g., human papilloma virus, varicella, measles/mumps/rubella, and anthrax vaccines). Birth defects were categorized into trimester of vaccination and classified based on the organs and/or systems affected. If several birth defects affecting different systems were described, we classified those as multiple body systems. Empirical Bayesian data mining was used to assess for disproportionate reporting. RESULTS: We identified 50 reports of major birth defects; in 28 reports, the vaccine was given during the first trimester; 25 were reports with single vaccines administered. Birth defects accounted for 0.03% of all reports received by VAERS during the study period and 3.2% of pregnancy reports; reported defects affected predominately the musculoskeletal (N = 10) or nervous (N = 10) systems. No unusual clusters or specific birth defects were identified. CONCLUSION: This review of the VAERS database found that major birth defects were infrequently reported, with no particular condition reported disproportionally. Birth defects after routine maternal vaccination will continue to be monitored in VAERS for signals to prompt future studies. Birth Defects Research 109:1057-1062, 2017. © 2017 Wiley Periodicals, Inc.

Patterns of childhood immunization and all-cause mortality.

BACKGROUND: Evidence supports the safety of the recommended childhood immunization schedule as a whole. However, additional research is warranted as parents' refusing or delaying vaccinations has increased in recent years. All-cause mortality has been identified as a priority outcome to study in the context of the recommended immunization schedule. METHODS: We included children born January 1, 2004 through December 31, 2009, enrolled in the Vaccine Safety Datalink (VSD) from birth through 18 months of age. We examined vaccination patterns during the first 18 months of life among 8 vaccines, and identified deaths occurring between 19 and 48 months of age. We excluded children with complex chronic conditions, contraindications to vaccination, and deaths due to injuries, congenital anomalies, or diseases with onset prior to 19 months of age. We calculated mortality rates among children with different patterns of immunization, and incidence rate ratios (IRR) using the Cox proportional hazards model for children vaccinated according to the schedule versus undervaccinated children, adjusting for outpatient healthcare utilization, influenza vaccination, sex, and VSD site. RESULTS: Among 312,388 children in the study, 199,661 (64%) were vaccinated according to the schedule, and 112,727 (36%) were delayed or not vaccinated for at least one vaccine dose. Of 18 deaths eligible for analysis, 11 occurred in children following the schedule (2.28 per 100,000 person-years), and seven occurred in undervaccinated children (2.57 per 100,000 person-years). Mortality rates among children following the schedule were not significantly different from those of undervaccinated children when excluding deaths with unknown causes (IRR = 1.29, 95% CI = 0.33-4.99), as well as when including deaths with unknown causes (IRR = 0.84, 95% CI = 0.32-2.99). CONCLUSION: Although there were few deaths, our results do not indicate a difference in risk of all-cause mortality among fully vaccinated versus undervaccinated children. Our findings support the safety of the currently recommended immunization schedule with regard to all-cause mortality.

Maternal and Infant Outcomes After Human Papillomavirus Vaccination in the Periconceptional Period or During Pregnancy.

OBJECTIVE: To evaluate whether quadrivalent human papillomavirus vaccine (4vHPV) administered during the periconceptional period or during pregnancy was associated with increased risks for adverse obstetric events, adverse birth outcomes, or selected major structural birth defects. METHODS: We conducted a retrospective, observational cohort study using administrative and health care data from the Vaccine Safety Datalink. Insured women 13-27 years old with singleton pregnancies and a live birth from January 1, 2007, through September 1, 2013, who received 4vHPV during the periconceptional period (2 weeks before to 2 weeks after their last menstrual period), during pregnancy, or during both periods combined were compared with women who had a live birth during the same time period and received 4vHPV 4-18 months before their last menstrual period. We examined risks of gestational diabetes, hypertensive disorders of pregnancy, chorioamnionitis, preterm birth, small-for-gestational-age birth, and selected major structural birth defects in offspring. We estimated relative risks associated with receipt of 4vHPV during the periconceptional period, during pregnancy, and both exposure periods combined using a generalized linear model with Poisson distribution including a propensity score that included relevant maternal demographic and pregnancy characteristics. RESULTS: Of 92,579 potentially eligible pregnant women, 720 received 4vHPV during the periconceptional period, 638 received 4vHPV during pregnancy, and 8,196 received 4vHPV during the comparison period. Administration of 4vHPV during pregnancy was not associated with increased risk of adverse obstetric events, birth outcomes. Preterm birth occurred in 7.9% of pregnancies with vaccine exposures during pregnancy compared with 7.6% of pregnancies with vaccination in the comparison period (adjusted relative risk 0.97, 95% CI 0.72-1.3). Major structural birth defects were diagnosed in 2.0% of pregnancies with vaccine exposure during pregnancy compared with 1.8% of pregnancies with vaccine exposure during the comparison period (adjusted prevalence ratio 1.0, 95% CI 0.52-1.9). Results were similar for 4vHPV exposure during the periconceptional period. CONCLUSION: Quadrivalent HPV vaccine inadvertently administered in pregnancy or during the periconceptional period was not associated with adverse pregnancy or birth outcomes.

Quadrivalent HPV vaccine safety review and safety monitoring plans for nine-valent HPV vaccine in the United States.

Quadrivalent human papillomavirus (4vHPV) vaccine was licensed for use in the United States in 2006 and through 2015 was the predominate HPV vaccine used. With the exception of syncope, a known preventable adverse event after any injected vaccination, both pre-licensure and post-licensure 4vHPV safety data have been reassuring with no confirmed safety signals identified. Nine-valent HPV vaccine (9vHPV) was licensed in 2014. This review includes post-licensure 4vHPV safety findings published to date that have informed the US vaccination program; these data will inform US safety monitoring and evaluation for 9vHPV.

Vaccination and 30-Day Mortality Risk in Children, Adolescents, and Young Adults.

OBJECTIVE: This study evaluates the potential association of vaccination and death in the Vaccine Safety Datalink (VSD). METHODS: The study cohort included individuals ages 9 to 26 years with deaths between January 1, 2005, and December 31, 2011. We implemented a case-centered method to estimate a relative risk (RR) for death in days 0 to 30 after vaccination.Deaths due to external causes (accidents, homicides, and suicides) were excluded from the primary analysis. In a secondary analysis, we included all deaths regardless of cause. A team of physicians reviewed available medical records and coroner's reports to confirm cause of death and assess the causal relationship between death and vaccination. RESULTS: Of the 1100 deaths identified during the study period, 76 (7%) occurred 0 to 30 days after vaccination. The relative risks for deaths after any vaccination and influenza vaccination were significantly lower for deaths due to nonexternal causes (RR 0.57, 95% confidence interval [CI] 0.38-0.83, and RR 0.44, 95% CI 0.24-0.80, respectively) and deaths due to all causes (RR 0.72, 95% CI 0.56-0.91, and RR 0.44, 95% CI 0.28-0.65). No other individual vaccines were significantly associated with death. Among deaths reviewed, 1 cause of death was unknown, 25 deaths were due to nonexternal causes, and 34 deaths were due to external causes. The causality assessment found no evidence of a causal association between vaccination and death. CONCLUSIONS: Risk of death was not increased during the 30 days after vaccination, and no deaths were found to be causally associated with vaccination.

Neonatal infections: Case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

Maternal vaccination is an important area of research and requires appropriate and internationally comparable definitions and safety standards. The GAIA group, part of the Brighton Collaboration was created with the mandate of proposing standardised definitions applicable to maternal vaccine research. This study proposes international definitions for neonatal infections. The neonatal infections GAIA working group performed a literature review using Medline, EMBASE and the Cochrane collaboration and collected definitions in use in neonatal and public health networks. The common criteria derived from the extensive search formed the basis for a consensus process that resulted in three separate definitions for neonatal blood stream infections (BSI), meningitis and lower respiratory tract infections (LRTI). For each definition three levels of evidence are proposed to ensure the applicability of the definitions to different settings. Recommendations about data collection, analysis and presentation are presented and harmonized with the Brighton Collaboration and GAIA format and other existing international standards for study reporting.

The Centers for Disease Control and Prevention's public health response to monitoring Tdap safety in pregnant women in the United States.

In 2010, in response to a widespread pertussis outbreak and neonatal deaths, California became the first state to recommend routine administration of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy. In 2011, the Advisory Committee on Immunization Practices (ACIP) followed with a similar recommendation for Tdap vaccination during pregnancy for previously unvaccinated women. In 2012, this recommendation was expanded to include Tdap vaccination of every pregnant woman during each pregnancy. These recommendations were based on urgent public health needs and available evidence on the safety of other inactivated vaccines during pregnancy. However, there were limited data on the safety of Tdap during pregnancy. In response to the new ACIP recommendations, the Centers for Disease Control and Prevention (CDC) implemented ongoing collaborative studies to evaluate whether vaccination with Tdap during pregnancy adversely affects the health of mothers and their offspring and provide the committee with regular updates. The current commentary describes the public health actions taken by CDC to respond to the ACIP recommendation to study and monitor the safety of Tdap vaccines in pregnant women and describes the current state of knowledge on the safety of Tdap vaccines in pregnant women. Data from the various monitoring activities support the safety of Tdap use during pregnancy.

Demographic characteristics of members of the Vaccine Safety Datalink (VSD): A comparison with the United States population.

BACKGROUND: The Vaccine Safety Datalink (VSD) is a collaboration between CDC and nine integrated health care systems that serves as a cornerstone of US post-licensure vaccine safety monitoring. Given concerns that potential differences between the insured VSD population and the US population could limit the generalizability of VSD study findings, we performed a comparison of the demographic characteristics between the two populations. METHODS: We collected data from medical records and administrative files at VSD sites in 2010 to compare sex, age, race, ethnicity, income, and educational attainment to the 2010 US Census population. We also compared data on the 2012 VSD Medicaid population to 2012 US Medicaid data. RESULTS: The VSD population included over eight million individuals in 2010, which represented 2.6% of the total US population. All major demographic groups were represented in the VSD. We found no major differences in comparing sex, race, ethnicity, and educational attainment between the VSD and the US population. Middle income populations were comparable between the VSD and the US. While the percentage of lower income populations was less in the VSD compared to the US, the VSD had over two million individuals in this group. Additionally, there were over 600,000 Medicaid members in the VSD in 2012, which represented 1.1% of the US Medicaid population. CONCLUSIONS: We found that the VSD population is representative of the general US population on several key demographic and socioeconomic variables. Despite a few specific groups being underrepresented in the VSD compared to the US, the absolute number of VSD members is large enough to ensure significant representation of these groups in vaccine safety studies that use VSD data.

Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis and Influenza Vaccinations in Pregnancy.

OBJECTIVE: To evaluate the safety of coadministering tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during pregnancy by comparing adverse events after concomitant and sequential vaccination. METHODS: We conducted a retrospective cohort study of pregnant women aged 14-49 years in the Vaccine Safety Datalink from January 1, 2007, to November 15, 2013. We compared medically attended acute events (fever, any acute reaction) and adverse birth outcomes (preterm delivery, low birth weight, small for gestational age) in women receiving concomitant Tdap and influenza vaccination and women receiving sequential vaccination. RESULTS: Among 36,844 pregnancies in which Tdap and influenza vaccines were administered, the vaccines were administered concomitantly in 8,464 (23%) pregnancies and sequentially in 28,380 (77%) pregnancies. Acute adverse events after vaccination were rare. We found no statistically significant increased risk of fever or any medically attended acute adverse event in pregnant women vaccinated concomitantly compared with sequentially. When analyzing women at 20 weeks of gestation or greater during periods of influenza vaccine administration, there were no differences in preterm delivery, low-birth-weight, or small-for-gestational-age neonates between women vaccinated concomitantly compared with sequentially in pregnancy. CONCLUSION: Concomitant administration of Tdap and influenza vaccines during pregnancy was not associated with a higher risk of medically attended adverse acute outcomes or birth outcomes compared with sequential vaccination. LEVEL OF EVIDENCE: II.