Is the Tdap Vaccine Administered during Pregnancy Associated with Autism Spectrum Disorder in Offspring?

Background: Prenatal infections and fever are associated with increased autism spectrum disorder (ASD) risk. The increasing practice to vaccinate pregnant women to protect mother and child makes it important to assess not only short-term but also longer-term safety events potentially linked to prenatal vaccination. Except for influenza vaccination, no study to our knowledge has investigated the association between the Tetanus, diphtheria, acellular pertussis vaccine (Tdap) during pregnancy and ASD.

Objectives: To investigate the association between prenatal Tdap vaccination and ASD risk in offspring.

Methods: This retrospective cohort study included 81,993 children born at Kaiser Permanente Southern California (KPSC) from January 1, 2011 to December 31, 2014. Information on maternal Tdap vaccination from pregnancy start to delivery date and children’s clinical diagnoses of ASDs were obtained from the KPSC electronic medical record (EMR). ASD was identified by International Classification of Diseases, 9^th edition codes 299.0, 299.8, or 299.9 and 10^th edition codes F84.0, F84.5, F84.8, F84.9 recorded after age one. They were followed from birth to first ASD diagnosis, end of membership, or end of follow-up (June 30, 2017), whichever came first. Cox hazards models were used to estimate the unadjusted and adjusted hazard ratios (HR) to assess the association between maternal Tdap vaccination and ASD. We used propensity score analyses with inverse probability of treatment weighting to adjust for confounding.

Results: Prenatal Tdap vaccination ranged from 26% to 79% during the study years. The 2012 year had the lowest uptake and 2014 had the highest. Women vaccinated during pregnancy were more likely to be Asian/Pacific Islander, have a bachelors or higher educational degree, be pregnant for the first time, also have received the flu vaccine prenatally, and give birth at term.

Follow-up time ranged between 1.2 and 6.5 years. ASD was diagnosed in 1,341 children (1.6%). Diagnosis ranged from 1.9% in children born in 2011 to 1.2% in children born in 2014. ASD incidence rate was 4.05 per 1,000 person-years in the unexposed and 3.78 per 1,000 person-years in the Tdap exposed group. The unadjusted hazard ratio was 0.98 [95% confidence interval (CI): 0.88, 1.09].

The propensity score adjusted analyses showed that prenatal Tdap vaccination was not associated with increased ASD risk (HR: 0.85, CI: 0.77, 0.95). Results were consistent among women who were pregnant with their first child (HR: 0.87, CI: 0.75, 1.01) and across children born in the 2011-2014 study years (HR: 0.87, CI: 0.70, 1.07; HR: 0.79, CI: 0.62, 1.02; HR: 0.98, CI: 0.79, 1.22; HR: 0.86, CI: 0.65, 1.14; respectively).

Conclusions: Getting vaccinated with Tdap during pregnancy was not associated with increased risk of ASD in offspring, and the association was consistent among women pregnant for the first time and by year of birth. Indication of decreased ASD risk in the overall results could be due to unmeasured confounding, such as evolving practices in Tdap vaccine and ASD service implementation during the study years. Future studies with updated data are warranted to further evaluate potential associations between Tdap and ASD.