(AS) Clinical Outcomes and Safety of Live-Attenuated Vaccines in Children Exposed to Biologics Response Modifiers in Utero

Publication Number: 1043

Background: Many countries recommend against immunization with live-attenuated vaccines during the first 6 months of life for infants exposed in utero to biological response modifiers (BRM). However, these recommendations were based on theoretical considerations rather than empirical data.

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

Methods: We conducted a retrospective cohort study among people pregnant between 2006 – 2017 and children born from these pregnancies in six integrated healthcare systems within the Vaccine Safety Datalink, in the US. We estimated the proportion of people who were prescribed BRM during pregnancy overall and by year of pregnancy onset. Among BRM-exposed and unexposed children, we compared clinical outcomes (neutropenia, immune thrombocytopenia, all-cause pneumonia, and infections from rotavirus, varicella, pertussis, and measles), live-attenuated vaccination coverage, and AESI (Acute disseminated encephalomyelitis, bloody stool, cerebellar ataxia, diarrhea, encephalitis, fever, febrile seizure, hepatitis, pneumonitis, myelitis, vomiting) occurring in specific risk intervals following immunization.

Results: Of the 1,205,416 pregnant people, 2243 were prescribed BRM (19/10,000). Prevalence increased from 8/10,000 in 2006 to 46/10,000 pregnant people in 2017. The most prescribed BRM were etanercept (35.9%), anakinra (23.2%), adalimumab (21.4%) and infliximab (19.9%). Among 960 BRM-exposed and 581,799 BRM-unexposed children, the proportions of assessed clinical outcomes at ages 12 months were small (0% - 4%) and were similar among in utero BRM-exposed and unexposed children. Coverage with rotavirus vaccine was lower among BRM-exposed than unexposed children at ages 12 months (81.00% vs. 85.20%, adjusted OR = 0.74, 95% CI 0.61 – 0.90). Coverage with measles-containing vaccines was higher at ages 24 months among BRM-exposed than unexposed (87.06% vs. 83.71%; OR = 1.30, 95% CI 1.10 – 1.69). AESI following measles-containing or rotavirus vaccines were rare and their proportions (0 – 4%) were similar among exposed and unexposed children. No cases of febrile seizure, cerebellar ataxia, hepatitis, pneumonitis, acute disseminated encephalomyelitis, or intussusception were diagnosed following vaccination among BRM-exposed children.

Conclusions: In utero exposure to BRM was not associated with increased risk of adverse events following live-attenuated vaccines, suggesting that children exposed in-utero to BRM can safely receive their live-attenuated vaccines without a delay.