Analysis of the potential for immunosuppression of infants with in-utero and breast milk exposure to antitumor necrosis factor alpha agents: are all agents equally safe?

Objective: To assess the safety of tumor necrosis factor inhibitors (TNFi) during pregnancy, specifically in relation to infant infection rates, vaccine efficacy, and vaccine-associated adverse events in infants exposed to TNFi in utero and through breast milk. Data Sources: A comprehensive literature review was conducted using PubMed and Google Scholar. The review included retrospective studies, prospective studies, and systematic reviews published until June 2024, focusing on TNFi exposure during pregnancy and breastfeeding. Study Selections: Studies reporting on infant infection rates, vaccination outcomes, and adverse events following in-utero or breastfeeding exposure to TNFi agents, including certolizumab pegol, adalimumab, infliximab, etanercept, and golimumab. Narrative reviews were excluded, while systematic reviews were considered. Results: The review indicates that gestational exposure to TNFi does not increase the risk of severe infections in infants. Additionally, no significant rise in infections was found in infants exposed to TNFi through breast milk. Vaccination outcomes, including efficacy and adverse events, were comparable between exposed and unexposed infants. However, caution is advised when administering the Bacille Calmette-Guerin vaccine to infants exposed to TNFi, particularly within the first year of life. Conclusion: TNFi appear to be safe during pregnancy and breastfeeding. The data indicate that TNFi does not increase the risk of severe infections or vaccine complications in infants, with the exception of the Bacille Calmette-Guerin vaccine, for which a more cautious approach is recommended. These findings reinforce the use of TNFi in women with inflammatory conditions who are pregnant or breastfeeding, providing benefits to both maternal and fetal health.