Neonatal and infant mortality after maternal influenza and pertussis vaccination: Probabilistically linked cohort study

Maternal influenza and pertussis vaccination is an important strategy to reduce morbidity and mortality in infants. Previous vaccine safety studies have mostly focused on the association between maternal vaccination and fetal death. We conducted a probabilistically linked cohort study of mother-infant pairs in three Australian jurisdictions: Queensland, Northern Territory, and Western Australia, to evaluate the risk of all-cause neonatal and infant mortality associated with seasonal influenza and pertussis maternal vaccination. Vaccination records were obtained from regional immunization databases, and mortality information was obtained from perinatal databases and death registries from 2015 to 2017. Cox proportional hazard models with vaccination as time-varying exposure and weighted by the inverse probability of treatment were used to estimate adjusted hazard ratios (aHR). Among 252,924 mothers and 277,979 liveborn infants, 8,288 (3.0%) infants were exposed <i>in utero</i> to influenza vaccine only, 88,011 (31.7%) to pertussis vaccine only, and 67,036 (24.1%) to both vaccines. There were 741 all-cause infant deaths (crude mortality rate 2.67 deaths/1,000 live births). Influenza and pertussis vaccines were associated with a reduction in infant mortality when given alone (aHR [influenza]: 0.66, 95%CI 0.43, 0.99 and aHR [pertussis]: 0.69, 95%CI 0.54, 0.87), or in combination (aHR: 0.58; 95%CI 0.44, 0.77), predominantly attributed to reduction in early neonatal (0-7 d) death. No association was observed between influenza or pertussis vaccine and post-neonatal (8-28 d) mortality. We observed insufficient evidence of greater neonatal or infant mortality associated with maternal influenza or pertussis vaccination. These findings could be useful to healthcare professionals when counseling pregnant patients on maternal vaccination.