Ferritin in pediatric critical illness: a scoping review

Abstract

This scoping review aimed to elucidate and summarize the predictive role of serum ferritin in critical pediatric illness. The Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was employed to conduct a scoping review of 5 databases (MEDLINE, CENTRAL, ProQuest, ScienceDirect, and Epistemonikos) from the date of inception through January 24, 2022. Primary research studies involving subjects aged <18 years and serum ferritin levels were screened and reviewed independently following an a priori defined protocol. Of the 1,580 retrieved studies, 66 were analyzed. Summary statistics of serum ferritin levels for overall and condition-specific studies were reported in 30 (45.4%) and 47 studies (71.2%), respectively. The normal range was defined in 16 studies (24.2%), whereas the threshold was determined in 43 studies (65.1%). A value of <500 ng/mL was most often the upper limit of the normal range. Serum ferritin as a numerical variable (78.9%) was usually significantly higher (80.8%) in the predicted condition than in controls, while as a categorical variable with preset thresholds, ferritin was a significant predictor in 84.6% of studies. A total of 22 predictive thresholds predicted mortality (12 of 46 [26.1%]), morbidity (18 of 46 [39.1%]), and specific (16 of 46 [34.8%]) outcomes in 15 unique conditions. Increased precision in serum ferritin measures followed by close attention to the threshold modeling strategy and reporting can accelerate the translation from evidence to clinical practice.

Keywords: Clinical laboratory techniques; Critical illness; Ferritins; Hyperferritinemia; Pediatric intensive care unit.

Fig. 1.

Flow diagram of the study selection process.

Fig. 2.

Boxplots of overall serum ferritin summary statistics. HLH, hemophagocytic lymphohistiocytosis; MODS, multiple organ dysfunction syndrome; MAS, macrophage activation syndrome; COVID-19, coronavirus disease 2019; PIMS-TS, pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2; MIS-C, multisystem inflammatory syndrome in children; IEI, inborn errors of immunity; IPH, idiopathic pulmonary hemosiderosis.

Fig. 3.

Boxplots of serum ferritin summary statistics in the case or intervention group. HLH, hemophagocytic lymphohistiocytosis; VL, visceral leishmaniasis; MOF, multiorgan failure; MODS, multiple organ dysfunction syndrome; MAS, macrophage activation syndrome; COVID-19, coronavirus disease 2019; KD, Kawasaki disease; sJIA, systemic juvenile idiopathic arthritis; MIS-C, multisystem inflammatory syndrome in children; AKI, acute kidney injury; TPE, therapeutic plasma exchange; ICU, intensive care unit; IEI, inborn errors of immunity; IPH, idiopathic pulmonary hemosiderosis.