Safety assessment of intravenous immunoglobulins in pediatric population: A systematic review of adverse events

Abstract

BACKGROUND: Intravenous immunoglobulin (IVIG) is a therapeutic intervention utilized in various disorders due to its antimicrobial, antiinflammatory, and immunomodulatory properties. The market offers a range of IVIG products, leading to variations in efficacy and safety profiles. This study aimed to systematically evaluate the safety profile of IVIG administration in pediatric patients. METHODS: A systematic search was conducted on PubMed, Embase, and Cochrane databases using predetermined MeSH terms, covering the period from January 1, 2000, to October 15, 2022. Two independent reviewers performed relevance screening. Inclusion criteria encompassed English-language studies involving patients below 18 years of age who received IVIG treatment. Included studies were limited to peer-reviewed full-text publications with a minimum of 5 patients. A total of 8 studies met the inclusion criteria, encompassing 1088 pediatric patients. RESULTS: Eight studies met the inclusion criteria (total 1088 pediatric patients). Five studies reported patient-level adverse event data suitable for pooling (688 patients). Among these 688 patients, 267 (38.8%) experienced adverse events (AEs). Among reported AEs, the most frequent were headache 68/267 (25.5%) and fever 47/267 (17.6%). Less common AEs included nausea 12/267 (4.5%) and fatigue 12/267 (4.5%). Four studies recorded a total of 2960 IVIG infusions, with 12.6% of infusions accompanied by AEs. The predominant AEs during infusions were headache (54.3%) and fever (29.4%). Cough (0.8%) and nausea (1.6%) were the least commonly observed AEs. Other AEs such as rash, vomiting, and abdominal pain were also reported. Of the 23 full-text articles reviewed, 8 were included. The remaining 15 were excluded due to the following reasons: 6 for duplicate data, 4 for inappropriate study design, 3 for not meeting the minimum number of patients, and 2 for incomplete adverse event reporting. These reasons are now detailed in the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. CONCLUSION: IVIG therapy demonstrates good tolerability in pediatric patients, with an overall favorable safety profile, aside from mild AEs associated with its administration. Serious AEs were infrequent and mainly observed in high-risk patients. Headache was the most prevalent AE, which seldom required hospitalization and could be effectively managed with acetaminophen. Other AEs were generally mild systemic reactions. Notably, AEs appear to be more frequent during the initial exposure to IVIG.