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


There were 128,756 women with continuous KPSC enrollment at least since the beginning of their 27th week of pregnancy and with nonassisted conceptions who gave birth to live singletons during January 1, 2011–December 31, 2014. Of these singletons, 101,025 children (78.5%) were enrolled after 3 years of age. We further excluded 10,330 children (8.0%) because they had less than 90 days of continuous enrollment after turning 3 years of age, 3,383 children (2.6%) who were diagnosed with chromosomal or congenital anomalies, and 1,705 children (1.3%) with no evidence of outpatient visits during the follow-up period. These exclusions resulted in a final cohort of 85,607 mother-child pairs for analysis (Figure 1).

Figure 1.

Selection of children born at Kaiser Permanente Southern California hospitals for a study of the association of prenatal tetanus, diphtheria, and acellular pertussis vaccination with attention-deficit/hyperactivity disorder, 2011–2014. Livebirths were from nonassisted pregnancies and from mothers who were continuously enrolled in Kaiser Permanente Southern California at and after 27 weeks of pregnancy.

Uptake of prenatal Tdap vaccination ranged from 28.2% (6,007/21,322) among women who gave birth in 2012 to 79.5% (17,918/22,552) for those who delivered in 2014. The mean and median gestational ages at vaccination were 28 weeks (standard deviation (SD), 7.2) and 29 weeks (interquartile range, 27–33 weeks), respectively. Approximately 71% of women were vaccinated during the recommended pregnancy period, at 27–36 weeks (data not shown in tables). Compared with Tdap-unvaccinated women, those who were vaccinated during pregnancy were more likely to be Asians/Pacific Islanders, to have a bachelor's degree or more, to be nulliparous, to have received the influenza vaccine prenatally, and to have given birth at term (≥37 weeks' gestation) (Table 1).

The children's follow-up times ranged between 0.1 year and 5.0 years and was longer in the unvaccinated group, on average (Table 2). There was an average difference of about 7 months in follow-up between the 2 groups (unvaccinated: mean = 3.08 (SD, 1.05) years; vaccinated: mean = 2.46 (SD, 1.22) years). ADHD was diagnosed in 882 children (1.0%). Among the children diagnosed with ADHD, the first diagnosis occurred most often at 5 years of age in both groups (36.5%).

The ADHD incidence rate was 3.41 per 1,000 person-years in the vaccinated group and 3.93 per 1,000 person-years in the unvaccinated group (Table 3). The unadjusted hazard ratio was 1.01 (95% confidence interval: 0.88, 1.16). After propensity score weighting, the standardized difference scores for all variables were less than 0.1, suggesting a good covariate balance (Figure 2). In the IPTW-adjusted analyses, Tdap vaccination during pregnancy was not associated with ADHD risk (hazard ratio = 1.00, 95% confidence interval: 0.88, 1.14), and results were consistent across study birth years and among nulliparous women. Results from the sensitivity analysis including maternal smoking, alcohol drinking, and prepregnancy body mass index in the propensity score model were consistent with the main results (Table 3).

Figure 2.

Standardized difference scores for maternal and child characteristics before and after inverse probability of treatment weighting (IPTW) in a study of the association of prenatal tetanus, diphtheria, and acellular pertussis vaccination with attention-deficit/hyperactivity disorder (ADHD), Kaiser Permanente Southern California, 2011–2014. Flu, influenza.