OBJECTIVES: Transplacental passage of certain biologic and targeted synthetic DMARDs leads to detectable levels in the neonate, which may impact on the safety of live vaccines. Guidelines advise delaying live vaccine administration in biologic-exposed infants until they are 7 months old. METHODS: A systematic review of Embase, Medline and Cochrane identified live vaccine outcomes in infants exposed to biologic or targeted synthetic DMARDs in utero. RESULTS: Studies included 276 in utero exposures to adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and ustekinumab. Live vaccine exposures at <12 months of age included Bacille Calmette-Guérin (BCG) (n = 215), rotavirus (n = 46), and measles, mumps and rubella (MMR) (n = 12). We identified no reactions following MMR, seven mild reactions to rotavirus vaccination and eight reactions to BCG, including one death. All infants with an adverse reaction to BCG had been exposed to infliximab in utero, and six had received BCG in the first month of life. A freedom of information request to the Medicines and Healthcare products Regulatory Agency revealed four fatal disseminated BCG infections in infants exposed to TNF inhibitors in utero, including infliximab, adalimumab and one unspecified TNF inhibitor. CONCLUSION: Most evidence for a clinically harmful effect was for early administration of the BCG vaccine to infants exposed in utero to TNF inhibitors with high transplacental transfer rates.
- Newborn
- Safety
- Tuberculosis
- Rotavirus
