Commentary
Since 1957, the International Atomic Energy Agency has recorded 128 significant radiation injuries or events involving different sources or locations, 62 in civilian environments, 66 in military environments, with 28 of the total involving nuclear reactors, according to the most up-to-date compilation of such incidents available from publicly accessible data sources.
1
-
3 Yet, with only 2 exceptions—one causing the deaths of some 200 individuals, another the early deaths of 28 individuals, but as many as 400 late deaths from cancer—deaths were exceedingly rare, especially among the pediatric population.
However, while death is clearly an important measure of impact, it is a limited measure, chiefly because it is difficult to ascribe causality to associated measures, such as increased cancer risk above baseline, when such effects are long-term and multifactorial. Moreover, though it is thought that the anatomic and physiologic differences between children and adults associated with children’s smaller body mass—including, but not limited to, their shorter height, larger relative body surface area, and thinner skin when compared with adults—renders them more vulnerable to radiation injury following exposure, especially with respect to thyroid neoplasia, for a multiplicity of reasons—dispersion of local effects across proximate organs, less overlying soft tissue protection, and greater groundshine exposure—radiation sensitivity in childhood is also related, at least in part, to ongoing growth and development and longer life expectancy, giving a larger window to manifest effects over time. That said, despite the many lessons learned on the long-term effects of ionizing radiation since the advent of the atomic age in 1945, in children as well as adults,
4 there remains little to guide clinical practitioners in the treatment of pediatric radiation injuries in their acute stages. This, of course, can be traced directly to the lack of reported clinical experience with such injuries, forcing clinical practitioners to rely on expert opinion.
The aim of this commentary is therefore to provide the reader with a basic sense of what is currently known or presumed in the management of such injuries, and to call for more research and education in this vital area of pediatric disaster medicine. Pediatric dose recommendations regarding potassium iodide, of course, are largely settled. By contrast, recent governmental investment in cytokine antidotes for the Strategic National Stockpile—following in part on increased governmental apprehension about the possible use of nuclear weapons—is based on evidence from animal studies. It is therefore critical to the health security of children in the United States, and worldwide, that the best available scientific evidence and expert guidance be made accessible as soon as possible to health providers everywhere.
Where We Are Now. Two separate reports, both from the American Academy of Pediatrics Committee on Environmental Health, published respectively in 1998 and 2003, describe the risks associated with radiation injury in children.
5
,
6 The first deals chiefly with exposure to diagnostic radiation, while the second focuses on the health effects and unique vulnerabilities of children from radiation injury, making preliminary recommendations regarding the administration of potassium iodide to children at risk of becoming internally contaminated with radioiodine following nuclear reactor release, although this only protects the child’s thyroid gland. Scant attention was then paid to the acute management of pediatric radiation injury in the scientific literature until 2018, when, in this journal, Gardner et al published a systematic review of medical countermeasures for radiation injuries and illnesses in children, identifying fifteen gaps in their application to the pediatric population (Table 1).Reference Gardner, Dziuban and Griese
7 These gaps were partially addressed later that year in a policy statement and technical report from the American Academy of Pediatrics, the former proffering 10 recommendations to pediatricians and the health sector, 6 recommendations to government, and 4 series of recommendations for families (Table 2), the latter providing the scientific basis for support of these recommendations.Reference Paulson
8
, Reference Linet, Kazzi and Paulson
9 While few, if any, of these recommendations directly addressed the gaps cited by Gardner et al, which focused its high and medium priority recommendations nearly entirely on cytokines as medical countermeasures for acute radiation syndrome, a review by Maciulewicz et al, published in this journal in 2024, partially addressed these concerns, although further research will be necessary to validate the recommendations made in this report.Reference Maciulewicz, Kazzi and Navis
10 However, the low priority recommendations cited by Gardner et al, in the view of the authors of this commentary, are arguably even more important—namely, public messaging and the need for additional subject matter experts in pediatric radiation emergencies, as well as guidelines and training in the use of pediatric radiation medical countermeasures for pharmacists and other clinicians. Additionally, information regarding the effects and toxicity of such countermeasures in infants and children, and the laboratory diagnostic and monitoring challenges associated with their use, are of equal importance. Unfortunately, since 2018, only one other article, a primer on the acute management of pediatric radiation injury designed to aid nonspecialist clinicians in recognition and early treatment of children with this condition, was published in the scientific literature. While the article does state that only pegfilgrastim, sargramostim, and romiplostim are approved by the Food and Drug Administration for use in children with acute radiation syndrome, it specifies neither the dosages to be used, nor the ideal methods for delivery, leaving definitive treatment to just-in-time consultation with specialists.Reference Feldman, Kazzi and Walter
11
Table 1.
Prioritized gaps in pediatric radiation Medical Countermeasures (MCMs)
6
Table 1. Long description
The table is organized into three main sections based on priority level.
High priority gaps include:
* Clinical guidelines for treating the hematopoietic subsyndrome of acute radiation syndrome in children with myeloid cytokines.
* Clinical guidelines for treating children who have internalized specific radioactive materials with M C Ms.
* Information for parents and families about treating the hematopoietic subsyndrome of acute radiation syndrome in children with myeloid cytokines.
* Indications, dosing, and recommendations for treating children less than 2 years of age with Prussian blue.
* Pre-established research protocols and processes to conduct studies and collect relevant data during radiation emergencies involving children to better inform the safe and effective use of radiation M C Ms in this population.
Medium priority gaps include:
* Preferred myeloid cytokine M C M for treating the hematopoietic subsyndrome of acute radiation syndrome in children.
* Information on the use of commercially available myeloid cytokine M C Ms that are not F D A-approved for the radiation indication in a large-scale radiation emergency involving children.
* Update to the most commonly used medical reference websites to include hematopoietic subsyndrome of acute radiation syndrome as an indication for currently available myeloid cytokines.
* Update to the most commonly used medical reference websites with information on diethylenetriamine pentaacetic acid and Prussian blue.
* Guidance for breastfeeding mothers taking radiation M C Ms during a radiation emergency.
Low priority gaps include:
* Guidelines and training in the use of pediatric radiation M C Ms for pharmacists.
* Information regarding the short- and long-term effects or toxicity of radiation M C Ms in infants and children.
* Laboratory diagnostic and monitoring challenges associated with the use of radiation M C Ms in children.
* Public health messaging about the long-term effects and risks of radiation exposure and contamination, as well as the psychological effects, in children.
* Few identified subject matter experts in pediatric radiation emergencies and M C Ms.
Table 2. Long description
The table is divided into three main sections:
1. Recommendations to pediatricians and the health sector:
• All hazards pediatric preparedness planning.
• Mental health assessment, treatment, referral.
• Designation of pediatric radiation centers.
• Potassium iodide distribution and administration.
• Maternal education regarding breastfeeding practices.
• Safe pediatric and family decontamination.
• Access to internal contamination guidelines.
• Access to appropriate governmental websites.
• Office training in potassium iodide.
• Universal psychological first aid training.
2. Recommendations to government:
• Include primary care providers P C Ps in preparedness planning.
• Train P C Ps in triage, treatment.
• Accessible stocks of potassium iodide.
• Standardized storage of potassium iodide.
• Funding for mental health services.
• Child and family decontamination guidelines.
3. Recommendations for families:
• Review governmental recommendations for a nuclear disaster.
• Make appropriate preparations for a nuclear disaster.
• Minimize radiation exposure during a nuclear disaster.
• Take appropriate steps after a nuclear disaster.
For example, one practical challenge in developing a medical countermeasure kit for civilian protection in Ukraine was difficulty in determining how to administer weight-based doses for children, as colony-stimulating factors like pegfilgrastim are only available in prefilled or autoinjector syringes for standard adult dosing. Even though standard dosing ranges are available for children 10-44 kg, the syringes are unmarked, so safe administration of smaller doses requires expelling liquid from the prefilled syringe into a sterile container and drawing it up in a new syringe. For infants <10 kg, weight-based dosing (0.1 mg/kg = 0.01 mL/kg) is recommended. This requires either the ability to dilute the medication or administer volumes <0.1 mL, which is challenging even when using a 1 mL syringe, and there is no safety data for administering a standard 1 mg dose (0.1 mL) for an infant <10 kg. This makes administration of a key acute radiation syndrome countermeasure exceedingly difficult, while it appears that national stockpiles and emergency planners have yet to include this level of practical considerations for children.
Recognizing the gaps in our current knowledge of effective countermeasures for acute radiation injury in children, the National Institute of Allergy and Infectious Diseases in 2024 hosted a National Institutes of Health-wide working meeting, “Understudied Populations in Radiation Exposure Research; Needs, Challenges, and Mitigation Strategies.” Speakers at this meeting provided updates related to recent developments in research related to health effects in children and discussed related challenges.Reference Taliaferro, Buchsbaum and DiCarlo
12
These important efforts notwithstanding, scientific evidence regarding the outcomes of emergency treatment of pediatric acute radiation injury is sparse. Yet, public awareness of the potential risk of nuclear attacks has continued to grow, though it has been focused on the population at large, rather than children per se. Articles have recently appeared in scientific and legacy media on both sides of the Atlantic, and on governmental websites, regarding the changing emergency preparedness challenges of nuclear attacks, public messaging on how to respond to nuclear attacks, and the expected locations and consequences of such attacks.Reference Dallas
13
-Reference O’Sullivan
18 Given the increasing concern worldwide that nuclear attacks are more likely to occur than has been thought for many decades, whether by state actors or dissident groups, it behooves all health providers to prepare themselves for such an eventuality, as massive numbers of patients will likely require care. Sadly, the state of knowledge about acute radiation injury, both pediatric and adult, among the great majority of health providers, even those who specialize in emergency, critical, and acute care medicine, surgery, and nursing, remains woefully inadequate.Reference Murray, Kim and Ralston
19
, Reference Veenema Goodwin, Moran and Kazzi
20
Where We Want to Be. All medical, nursing, and public health professionals, whether involved in acute care or not, should actively participate in awareness-level educational programs designed to offer foundational knowledge and behaviors in the acute management of radiation injury. Those involved in emergency, critical, and acute care medicine, surgery, nursing, and public health should be expected to possess the ability to respond to acute radiation injury at the operational level. Basic education and training for first responding prehospital providers and first receiving emergency department medical and nursing personnel should be competency based, include clear guidance on special considerations for pediatric patients and populations, be incorporated into functional and full-scale disaster exercises, and be updated at appropriate intervals, as new technologies become available. Just-in-time refresher training, offered via electronic media, will be deployed as needed, and readily accessible to all, as will expert consultation, also offered via electronic media, and again, must be readily accessible to all.
How to Get There. An overarching, multi-agency and multi-disciplinary working group should be created to ensure the strategic mitigation of identified gaps in preparedness and response to radiation injuries in children. As summarized above, the numerous gaps that have been identified call for a structured process to address them. Such a working group could also determine the priority level and timeline for every project, ensuring their effective and efficient execution. Examples of such projects include the creation of an acute radiation injury registry that includes children, large-scale screening of children after selected catastrophic radiation incidents, medical countermeasures research that addresses applicability to children, training curricula that include topics appropriate to pediatric patients, and public communication strategies that include guidance that is specific to the needs of children.
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Commentary
Since 1957, the International Atomic Energy Agency has recorded 128 significant radiation injuries or events involving different sources or locations, 62 in civilian environments, 66 in military environments, with 28 of the total involving nuclear reactors, according to the most up-to-date compilation of such incidents available from publicly accessible data sources. 1 - 3 Yet, with only 2 exceptions—one causing the deaths of some 200 individuals, another the early deaths of 28 individuals, but as many as 400 late deaths from cancer—deaths were exceedingly rare, especially among the pediatric population.
However, while death is clearly an important measure of impact, it is a limited measure, chiefly because it is difficult to ascribe causality to associated measures, such as increased cancer risk above baseline, when such effects are long-term and multifactorial. Moreover, though it is thought that the anatomic and physiologic differences between children and adults associated with children’s smaller body mass—including, but not limited to, their shorter height, larger relative body surface area, and thinner skin when compared with adults—renders them more vulnerable to radiation injury following exposure, especially with respect to thyroid neoplasia, for a multiplicity of reasons—dispersion of local effects across proximate organs, less overlying soft tissue protection, and greater groundshine exposure—radiation sensitivity in childhood is also related, at least in part, to ongoing growth and development and longer life expectancy, giving a larger window to manifest effects over time. That said, despite the many lessons learned on the long-term effects of ionizing radiation since the advent of the atomic age in 1945, in children as well as adults, 4 there remains little to guide clinical practitioners in the treatment of pediatric radiation injuries in their acute stages. This, of course, can be traced directly to the lack of reported clinical experience with such injuries, forcing clinical practitioners to rely on expert opinion.
The aim of this commentary is therefore to provide the reader with a basic sense of what is currently known or presumed in the management of such injuries, and to call for more research and education in this vital area of pediatric disaster medicine. Pediatric dose recommendations regarding potassium iodide, of course, are largely settled. By contrast, recent governmental investment in cytokine antidotes for the Strategic National Stockpile—following in part on increased governmental apprehension about the possible use of nuclear weapons—is based on evidence from animal studies. It is therefore critical to the health security of children in the United States, and worldwide, that the best available scientific evidence and expert guidance be made accessible as soon as possible to health providers everywhere.
Where We Are Now. Two separate reports, both from the American Academy of Pediatrics Committee on Environmental Health, published respectively in 1998 and 2003, describe the risks associated with radiation injury in children. 5 , 6 The first deals chiefly with exposure to diagnostic radiation, while the second focuses on the health effects and unique vulnerabilities of children from radiation injury, making preliminary recommendations regarding the administration of potassium iodide to children at risk of becoming internally contaminated with radioiodine following nuclear reactor release, although this only protects the child’s thyroid gland. Scant attention was then paid to the acute management of pediatric radiation injury in the scientific literature until 2018, when, in this journal, Gardner et al published a systematic review of medical countermeasures for radiation injuries and illnesses in children, identifying fifteen gaps in their application to the pediatric population (Table 1).Reference Gardner, Dziuban and Griese 7 These gaps were partially addressed later that year in a policy statement and technical report from the American Academy of Pediatrics, the former proffering 10 recommendations to pediatricians and the health sector, 6 recommendations to government, and 4 series of recommendations for families (Table 2), the latter providing the scientific basis for support of these recommendations.Reference Paulson 8 , Reference Linet, Kazzi and Paulson 9 While few, if any, of these recommendations directly addressed the gaps cited by Gardner et al, which focused its high and medium priority recommendations nearly entirely on cytokines as medical countermeasures for acute radiation syndrome, a review by Maciulewicz et al, published in this journal in 2024, partially addressed these concerns, although further research will be necessary to validate the recommendations made in this report.Reference Maciulewicz, Kazzi and Navis 10 However, the low priority recommendations cited by Gardner et al, in the view of the authors of this commentary, are arguably even more important—namely, public messaging and the need for additional subject matter experts in pediatric radiation emergencies, as well as guidelines and training in the use of pediatric radiation medical countermeasures for pharmacists and other clinicians. Additionally, information regarding the effects and toxicity of such countermeasures in infants and children, and the laboratory diagnostic and monitoring challenges associated with their use, are of equal importance. Unfortunately, since 2018, only one other article, a primer on the acute management of pediatric radiation injury designed to aid nonspecialist clinicians in recognition and early treatment of children with this condition, was published in the scientific literature. While the article does state that only pegfilgrastim, sargramostim, and romiplostim are approved by the Food and Drug Administration for use in children with acute radiation syndrome, it specifies neither the dosages to be used, nor the ideal methods for delivery, leaving definitive treatment to just-in-time consultation with specialists.Reference Feldman, Kazzi and Walter 11
Prioritized gaps in pediatric radiation Medical Countermeasures (MCMs) 6
Table 1. Long description
The table is organized into three main sections based on priority level.
High priority gaps include:
* Clinical guidelines for treating the hematopoietic subsyndrome of acute radiation syndrome in children with myeloid cytokines.
* Clinical guidelines for treating children who have internalized specific radioactive materials with M C Ms.
* Information for parents and families about treating the hematopoietic subsyndrome of acute radiation syndrome in children with myeloid cytokines.
* Indications, dosing, and recommendations for treating children less than 2 years of age with Prussian blue.
* Pre-established research protocols and processes to conduct studies and collect relevant data during radiation emergencies involving children to better inform the safe and effective use of radiation M C Ms in this population.
Medium priority gaps include:
* Preferred myeloid cytokine M C M for treating the hematopoietic subsyndrome of acute radiation syndrome in children.
* Information on the use of commercially available myeloid cytokine M C Ms that are not F D A-approved for the radiation indication in a large-scale radiation emergency involving children.
* Update to the most commonly used medical reference websites to include hematopoietic subsyndrome of acute radiation syndrome as an indication for currently available myeloid cytokines.
* Update to the most commonly used medical reference websites with information on diethylenetriamine pentaacetic acid and Prussian blue.
* Guidance for breastfeeding mothers taking radiation M C Ms during a radiation emergency.
Low priority gaps include:
* Guidelines and training in the use of pediatric radiation M C Ms for pharmacists.
* Information regarding the short- and long-term effects or toxicity of radiation M C Ms in infants and children.
* Laboratory diagnostic and monitoring challenges associated with the use of radiation M C Ms in children.
* Public health messaging about the long-term effects and risks of radiation exposure and contamination, as well as the psychological effects, in children.
* Few identified subject matter experts in pediatric radiation emergencies and M C Ms.
Pediatric considerations before, during, and after radiological or nuclear emergenciesReference Gardner, Dziuban and Griese 7 (abbreviated)
Table 2. Long description
The table is divided into three main sections:
1. Recommendations to pediatricians and the health sector:
• All hazards pediatric preparedness planning.
• Mental health assessment, treatment, referral.
• Designation of pediatric radiation centers.
• Potassium iodide distribution and administration.
• Maternal education regarding breastfeeding practices.
• Safe pediatric and family decontamination.
• Access to internal contamination guidelines.
• Access to appropriate governmental websites.
• Office training in potassium iodide.
• Universal psychological first aid training.
2. Recommendations to government:
• Include primary care providers P C Ps in preparedness planning.
• Train P C Ps in triage, treatment.
• Accessible stocks of potassium iodide.
• Standardized storage of potassium iodide.
• Funding for mental health services.
• Child and family decontamination guidelines.
3. Recommendations for families:
• Review governmental recommendations for a nuclear disaster.
• Make appropriate preparations for a nuclear disaster.
• Minimize radiation exposure during a nuclear disaster.
• Take appropriate steps after a nuclear disaster.
For example, one practical challenge in developing a medical countermeasure kit for civilian protection in Ukraine was difficulty in determining how to administer weight-based doses for children, as colony-stimulating factors like pegfilgrastim are only available in prefilled or autoinjector syringes for standard adult dosing. Even though standard dosing ranges are available for children 10-44 kg, the syringes are unmarked, so safe administration of smaller doses requires expelling liquid from the prefilled syringe into a sterile container and drawing it up in a new syringe. For infants <10 kg, weight-based dosing (0.1 mg/kg = 0.01 mL/kg) is recommended. This requires either the ability to dilute the medication or administer volumes <0.1 mL, which is challenging even when using a 1 mL syringe, and there is no safety data for administering a standard 1 mg dose (0.1 mL) for an infant <10 kg. This makes administration of a key acute radiation syndrome countermeasure exceedingly difficult, while it appears that national stockpiles and emergency planners have yet to include this level of practical considerations for children.
Recognizing the gaps in our current knowledge of effective countermeasures for acute radiation injury in children, the National Institute of Allergy and Infectious Diseases in 2024 hosted a National Institutes of Health-wide working meeting, “Understudied Populations in Radiation Exposure Research; Needs, Challenges, and Mitigation Strategies.” Speakers at this meeting provided updates related to recent developments in research related to health effects in children and discussed related challenges.Reference Taliaferro, Buchsbaum and DiCarlo 12
These important efforts notwithstanding, scientific evidence regarding the outcomes of emergency treatment of pediatric acute radiation injury is sparse. Yet, public awareness of the potential risk of nuclear attacks has continued to grow, though it has been focused on the population at large, rather than children per se. Articles have recently appeared in scientific and legacy media on both sides of the Atlantic, and on governmental websites, regarding the changing emergency preparedness challenges of nuclear attacks, public messaging on how to respond to nuclear attacks, and the expected locations and consequences of such attacks.Reference Dallas 13 -Reference O’Sullivan 18 Given the increasing concern worldwide that nuclear attacks are more likely to occur than has been thought for many decades, whether by state actors or dissident groups, it behooves all health providers to prepare themselves for such an eventuality, as massive numbers of patients will likely require care. Sadly, the state of knowledge about acute radiation injury, both pediatric and adult, among the great majority of health providers, even those who specialize in emergency, critical, and acute care medicine, surgery, and nursing, remains woefully inadequate.Reference Murray, Kim and Ralston 19 , Reference Veenema Goodwin, Moran and Kazzi 20
Where We Want to Be. All medical, nursing, and public health professionals, whether involved in acute care or not, should actively participate in awareness-level educational programs designed to offer foundational knowledge and behaviors in the acute management of radiation injury. Those involved in emergency, critical, and acute care medicine, surgery, nursing, and public health should be expected to possess the ability to respond to acute radiation injury at the operational level. Basic education and training for first responding prehospital providers and first receiving emergency department medical and nursing personnel should be competency based, include clear guidance on special considerations for pediatric patients and populations, be incorporated into functional and full-scale disaster exercises, and be updated at appropriate intervals, as new technologies become available. Just-in-time refresher training, offered via electronic media, will be deployed as needed, and readily accessible to all, as will expert consultation, also offered via electronic media, and again, must be readily accessible to all.
How to Get There. An overarching, multi-agency and multi-disciplinary working group should be created to ensure the strategic mitigation of identified gaps in preparedness and response to radiation injuries in children. As summarized above, the numerous gaps that have been identified call for a structured process to address them. Such a working group could also determine the priority level and timeline for every project, ensuring their effective and efficient execution. Examples of such projects include the creation of an acute radiation injury registry that includes children, large-scale screening of children after selected catastrophic radiation incidents, medical countermeasures research that addresses applicability to children, training curricula that include topics appropriate to pediatric patients, and public communication strategies that include guidance that is specific to the needs of children.
Author contribution
Iddins: Recruitment of coauthors, critical review of manuscript.
Dallas: Advocated the development of this commentary for inclusion in this special number of DMPHP, critical review of manuscript.
Kazzi: Critical review of manuscript.
Shapiro: Critical review of manuscript.
Boyle: Critical review of manuscript.
Cooper (corresponding/senior author): Conception/design, data acquisition/analysis/interpretation, drafting for intellectual content, final revision and approval following receipt of critical reviews from coauthors.
Competing interests
None.