Assessing Obstetrical and Perinatal Outcomes Associated with Maternal Tdap Immunization

Abstract

Background: In February 2018, Canada’s National Advisory Committee on Immunization (NACI) began recommending maternal immunization with pertussis-containing vaccine (Tetanus-diphtheria-acellular pertussis [Tdap]) during every pregnancy as a strategy to prevent pertussis infection in young infants. As a baseline for future evaluation of the NACI policy, this thesis aimed to describe the characteristics of women who received Tdap immunization during pregnancy in the pre-policy time period and assess the relationship between maternal Tdap immunization with obstetrical and perinatal outcomes. Methods: We performed a population-based retrospective cohort study of all live births in Ontario, from April 2012 to March 2017 using multiple linked provincial health administrative databases. Tdap immunization during pregnancy was ascertained using Tdap-specific immunization fee codes. We used an extended Cox regression model with a time-dependent exposure variable to estimate adjusted hazards ratios (aHR) for preterm and very preterm birth. All other outcomes (gestational hypertension, chorioamnionitis, small-for-gestational-age birth, neonatal intensive care unit admissions >24 hours, composite outcome for neonatal morbidity) were assessed using log-binomial regression to generate adjusted risk ratios (aRR). All estimates were adjusted using inverse probability of treatment weights derived from propensity scores. Results: Of the 621,903 pregnancies ending in a live birth, 11,750 (1.9%) women received Tdap during pregnancy. The maternal Tdap vaccination rate increased by 8-fold across the study time period, from 4.6 per 1000 women in fiscal-year 2012 to 39.1 per 1000 women in fiscal-year 2016. Women who were nulliparous, residing in a higher-income neighbourhood, and receiving adequate or intensive prenatal care had the highest vaccination rates. There were no significant increased risks (aHR/aRR [95% CI]) for preterm birth (0.99 [0.87-1.12]), very preterm birth (1.03 [0.71-1.50]), or small-for-gestational-age birth (0.95 [0.90-1.02]) in Tdap-exposed infants. A significant reduction in risk for neonatal hospitalization and morbidity (measured by a composite outcome) was found among exposed infants; however, these associations were attenuated following sensitivity analyses. Among Tdap-vaccinated women, compared to unvaccinated women, there was no association with chorioamnionitis (0.95 [0.79-1.15]), but a 19% lower risk of gestational hypertension was observed (0.81 [0.74-0.90]). Conclusions: We did not detect any adverse obstetrical or perinatal outcomes following Tdap vaccination during pregnancy. These results complement existing evidence that maternal Tdap vaccination is not associated with adverse outcomes in either the mother or infant. On-going evaluation in Canada is needed as Tdap coverage among pregnant women increases in the coming years.