Safety of pertussis vaccination in pregnancy and effectiveness in infants: a Danish national cohort study 2019-2023

Abstract

Objectives: Recent surges in pertussis spread have renewed focus on pertussis vaccination strategies. Denmark implemented pertussis vaccination during pregnancy in 2019 to protect infants under 3 months. This nationwide study assessed the real-world safety and effectiveness of acellular pertussis vaccination during pregnancy.

Methods: Using nationwide Danish registers, we included all pregnancies beyond 24 gestational weeks and all liveborn children from November 1, 2019, to June 1, 2023, with follow-up until December 31, 2023. Maternal safety outcomes included hypertension, preeclampsia, chorioamnionitis, preterm birth, and stillbirth. Infant safety outcomes included neonatal mortality, neonatal intensive care unit admission, and sepsis. Vaccine effectiveness was evaluated against laboratory-confirmed pertussis and related hospital contacts. For maternal safety, vaccinated individuals were matched 1:1 to unvaccinated individuals based on gestational days, calendar week, and region. Infant outcomes were assessed among the cohort of all liveborn children with follow-up until 3 months of age. Analyses were adjusted for a range of demographic, socioeconomic and medical characteristics.

Results: Among 50 851 vaccinated and 50 851 unvaccinated individuals during pregnancy, initial analyses showed an increased risk of hypertension and preeclampsia after pertussis vaccination. However, after adjusting for influenza and COVID-19 vaccination during pregnancy, pertussis vaccination was not associated with increased risks of any maternal safety outcomes including hypertension (incidence rate ratio 0.98, 0.94-1.02), mild preeclampsia (0.97, 0.92-1.02), and severe preeclampsia or haemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome (0.95, 0.86-1.05). Among 215 974 liveborn children, 108 350 were exposed to the vaccine. Vaccination was not associated with adverse infant outcomes and yielded a 72% (42-87%) effectiveness against laboratory-confirmed pertussis (9 vs. 32 events).

Discussion: Pertussis vaccination in pregnancy was effective in preventing infant pertussis and was not associated with adverse pregnancy or infant outcomes. Future studies should, however, examine whether other vaccines or the administration of multiple vaccines during pregnancy pose an increased maternal risk of hypertensive disorders in pregnancy.

Keywords: Effectiveness; Infant; Pertussis; Preeclampsia; Pregnancy; Safety; Tdap; Vaccine; chorioamnionitis; preterm birth.