Etiologies of Pancytopenia in Children: A Systematic Review with Meta-Analysis of 3,768 Subjects

Abstract Pancytopenia, defined as concurrent deficiency of red blood cells, white blood cells, and platelets, poses a significant diagnostic challenge in pediatrics due to its wide ranging etiologies. Management focuses on addressing the underlying cause, which makes an accurate diagnosis crucial for effective treatment. This systematic review with meta-analysis aims to characterize the etiologic distribution of pediatric pancytopenia to aid clinical decision-making. A comprehensive search of PubMed, EMBASE, and SCOPUS was conducted for observational studies, cross-sectional case series, or clinical trials with ≥ 10 pediatric patients (ages 0 – 21) diagnosed with pancytopenia. Inclusion required clinical confirmation and English-language abstracts. Data were synthesized using a Bayesian model to estimate pooled frequencies of etiologies. From 6,188 unique citations, 37 studies met inclusion criteria, encompassing 3,768 patients. Diagnoses were grouped into malignant, infectious, non malignant/non-infectious (NM/NI), and other/unknown categories. NM/NI etiologies predominated (2,315 patients; 61.4%; 95% CI: 60% – 63%), followed by malignant (848; 22.5%; 95% CI: 21– 24%), infectious (511; 13.6%; 95% CI: 13% – 15%), and other/unknown (94; 2.5%; 95% CI: 2% –3%). The overall most common individual diagnoses were aplastic anemia (787; 34%; 95% CI: 32% – 36%) and megaloblastic anemia (765; 33%; 95% CI: 31% – 35%). Additionally, a statistically significant difference was found in the most common etiologies in South Asia and the USA. This systematic review of 3,768 pediatric patients offers a comprehensive probabilistic, evidence based etiologic framework for diagnosing pancytopenia, improving efficiency and accuracy in clinical evaluation.