Safety of Live-Attenuated Vaccines in Children Exposed to Biologic Response Modifiers in Utero.

Objectives:: To estimate the prevalence of biological response modifiers (BRM) use during pregnancy and compare clinical outcomes in infants, live-attenuated immunization coverage and adverse events of special interest (AESI) following immunization.

Methods:: We conducted a retrospective cohort study among pregnant people between 2006 – 2017 and children born from these pregnancies within the Vaccine Safety Datalink. We estimated the proportion of women who used BRM during pregnancy overall and by year of pregnancy onset. We compared clinical outcomes, live-attenuated vaccination coverage, and AESI occurring in specific risk intervals following immunization in children exposed and unexposed in utero to BRM.

Results:: Of the 1,205,416 pregnant people, 2,243 used BRM (19/10,000), which increased from 8/10,000 in 2006 to 46/10,000 pregnant people in 2017. The most frequently dispensed or prescribed BRM were etanercept (35.9%), anakinra (23.2%), adalimumab (21.4%) and infliximab (19.9%). Except for pneumonia, clinical outcomes of interest were rare among exposed and unexposed children to BRM. Proportions of clinical outcomes were similar between both groups. A lower proportion of children exposed to BRM receive rotavirus vaccines by age 12 months compared with unexposed children (79.5% vs. 85.4%). AESI with measles-containing vaccines or rotavirus vaccines were rare and proportions of these were similar among exposed and unexposed children.

Conclusion:: In utero exposure to BRM was not associated with an increased risk of clinically significant infections or adverse events following live-attenuated vaccines. These data provide reassurance that children exposed in utero to BRM can receive live-attenuated vaccines on the same schedule as other children.