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T he past decades have witnessed a dramatic improvement in blood product safety due to a multifaceted approach including blood donor screening, sensitive infectious disease testing, and good manufacturing practice. Current residual risks of viral transmission range from one per 1 million to one per 2 million units transfused. These robust safeguards to the blood supply have been established in a reactive manner incrementally over time after evidence that certain pathogens can be transmitted via transfusion. For instance, the rapid national implementation of screening and laboratory detection for Chagas disease and, more recently, Zika virus in the United States were enormous undertakings that required substantial scientific effort, financial investment, and political pressure after it became clear that they posed a threat to blood safety. Despite these achievements, the blood supply remains at risk from emerging diseases and undiscovered pathogens. Increased mobility of the global population and expansion of tropical diseases into traditionally temperate areas have facilitated disease spread. Furthermore, even with current safety measures, morbidity and mortality due to transfusion of bacterially contaminated products (especially platelets [PLTs]) still occurs. Pathogen reduction (PR), also called pathogen inactivation (PI), is an all-encompassing term for a variety of methods, such as photochemical activation or solvent/ detergent (S/D) treatment, which may be applied to blood products after collection to confer broad protection against multiple infectious agents. Many of these technologies are effective across different classes of pathogens (e.g., viruses, bacteria, and parasites) by targeting their DNA or cell membranes. For example, preclinical data have shown that these systems are effective at preventing cytomegalovirus transmission in animal models. In addition to countering agents known to be transfusion transmissible, PR/PI systems also guard against emerging pathogens that pose uncertain risks to the blood supply. Some of the PR/PI technologies also inactivate residual donor white blood cells (WBCs) and thus are approved as an alternative to irradiation for the prevention of transfusion-associated graft-versus-host disease (GVHD), a product modification that is commonly needed in pediatric patients. Of note, photochemical activation of red blood cells (RBCs) and whole blood remains in the investigational stage. As RBCs are the most frequently transfused blood products, one can argue that PR/PI will not achieve its full potential in enhancing blood product safety until a viable methodology for RBCs exists. Overall, PR/PI systems are considered the next generation in blood safety technology, presenting a promising avenue for the future. For most medications, drugs and new treatments under study, we have limited experience in pediatric patients. Since children are a vulnerable population who may not be able to provide informed consent, institutional research boards require additional safeguards in place to protect their interests. These constraints make it more challenging to include children in investigational studies. PR/PI blood products have followed these norms; the data regarding blood product use in pediatric patients are limited (Table 1). On one hand, warnings about the use of blood products treated with psoralen compounds (the active ingredient in some PR/PI formulations) for infants have been put forward by prominent blood industry organizations. For example, the circular of information states that “[psoralen treated products] are also contraindicated for neonatal patients treated with phototherapy devices that emit a peak energy wavelength less than 425 nm, or have a lower bound of the emission bandwidth less than 375 nm, due to the potential for erythema resulting from the interaction between UV light and amotosalen.” Other nations have expressed similar reservations (Etablissement Français du