The Association of Prenatal Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccination With Attention-Deficit/Hyperactivity Disorder

Tracy A. Becerra-Culqui; Darios Getahun; Vicki Chiu; Lina S. Sy; Hung Fu Tseng


Am J Epidemiol. 2020;189(10):1163-1172. 

In This Article

Abstract and Introduction


As prenatal vaccinations become more prevalent, it is important to assess potential safety events. In a retrospective cohort study of Kaiser Permanente Southern California (Pasadena, California) mother-child pairs with birth dates during January 1, 2011–December 31, 2014, we investigated the association between prenatal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Information on Tdap vaccination during pregnancy was obtained from electronic medical records. ADHD was defined by International Classification of Diseases codes (Ninth or Tenth Revision) and dispensed ADHD medication after age 3 years. Children were followed to the date of their first ADHD diagnosis, the end of Kaiser Permanente membership, or the end of follow-up (December 31, 2018). In Cox proportional hazards models, we estimated unadjusted and adjusted hazard ratios for the association between maternal Tdap vaccination and ADHD, with inverse probability of treatment weighting (IPTW) used to adjust for confounding. Of 128,756 eligible mother-child pairs, 85,607 were included in the final sample. The ADHD incidence rate was 3.41 per 1,000 person-years in the Tdap-vaccinated women and 3.93 per 1,000 person-years in the unvaccinated (hazard ratio = 1.01, 95% confidence interval: 0.88, 1.16). The IPTW-adjusted analyses showed no association between prenatal Tdap vaccination and ADHD in offspring (hazard ratio = 1.00, 95% confidence interval: 0.88, 1.14). In this study, prenatal Tdap vaccination was not associated with ADHD risk in offspring, supporting recommendations to vaccinate pregnant women.


Young infants are at highest risk of hospitalization and death following pertussis infection, a highly contagious respiratory disease (whooping cough) caused by the bacterium Bordetella pertussis.[1] In 2018, infants younger than 6 months of age had the highest incidence rate: 72.8 per 100,000.[2] Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination is recommended prenatally between 27 and 36 weeks' gestation by the Advisory Committee on Immunization Practices (ACIP) for the prevention of pertussis in infants.[3] One retrospective study of newborns demonstrated that the effectiveness of maternal Tdap vaccine against polymerase chain reaction-confirmed pertussis was 91.4%.[3] Antibodies are passed along to newborns, providing some immunity until the infants reach 2 months of age, the age at which they are expected to receive their first dose of diphtheria, tetanus, and acellular pertussis (DTaP) vaccine.[4,5] Given the increasing practice of vaccinating pregnant women with Tdap and potentially other vaccines, it is important to monitor the safety of vaccines administered during pregnancy and the potential link to neurodevelopmental outcomes in children, such as attention-deficit/hyperactivity disorder (ADHD).[6–8] Continuous assessment of the risks and benefits of new vaccine recommendations, especially during a sensitive period of human development, can guide public perception of vaccines not only during the prenatal period but in early childhood.[9]

Since the 2012 ACIP recommendation, prenatal Tdap vaccination and maternal-infant outcomes have been studied, but examination of longer-term childhood neurodevelopmental outcomes is limited.[10–12] Only 1 previous study, to our knowledge, has examined the longer-term association following in utero exposure to Tdap vaccination, finding no increased risk of the neurodevelopmental outcome of autism.[13]

ADHD is a neurodevelopmental disorder characterized by inattention and/or hyperactivity-impulsivity that interferes with development and everyday functioning, such as socialization and academic performance.[14] In preschool children, the main manifestation is hyperactivity.[14] The prevalence of childhood ADHD (≤18 years) is estimated to be 7.2% (95% confidence interval: 6.7, 7.8), based on a pooled prevalence estimate calculated from 175 studies.[15] It is estimated that 10%–40% of the variance associated with ADHD is probably accounted for by environmental factors, and exposures during the prenatal period are implicated.[16,17] Prenatal exposure to inflammation is associated with offspring brain development, alteration in cortical gray matter volume, and neurotransmitter systems observed in ADHD populations.[17]

Though there is consistent evidence supporting the view that vaccines administered in childhood and their preservatives do not cause neurodevelopmental disorders.[18–22] there is limited research on the safety of vaccines administered during pregnancy and ADHD. In this study, we aimed to evaluate the association between Tdap vaccine administered during pregnancy and ADHD risk in a cohort of children born at Kaiser Permanente Southern California (KPSC) hospitals.