# Protocols and safety profile of convection enhanced delivery in pediatric patients: a systematic review

## TL;DR

This study reviews the safety and protocols of a drug delivery method called CED in children, finding that while mild side effects are common, severe ones are rare.

## Contribution

The first systematic review of convection-enhanced delivery (CED) in pediatric patients, providing a benchmark for safety and protocols.

## Key findings

- CED was primarily used for unresectable high-grade glioma in pediatric patients.
- Most adverse events were mild (Grade 1 or 2), with no severe (Grade 4 or 5) events reported.
- The trans-frontal approach was the most common delivery method in pediatric CED.

## Abstract

Convection-enhanced delivery (CED) is a developmental drug delivery system enabling direct, intraparenchymal placement of therapeutics that bypass the blood-brain barrier. This systematic review aggregates and outlines the available data surrounding current applications and adverse events of pediatric CED to benchmark safety as protocols expand. A comprehensive search through CINAHL, Cochrane, OVID Medline, and Scopus databases was conducted using a modified PRISMA analysis. After deduplication and screening, final articles were selected for data extraction. Of 108 unique articles, 12 studies met the inclusion criteria, including 162 patients (51% males, 44% females, and 5% not reported). The average age was 8.64 years (range 5–14.1 years). The most common indication for CED was for unresectable high-grade glioma (92%), predominantly diffuse intrinsic pontine glioma (83%). CED also addressed genetic enzyme deficiency (8%). The trans-frontal approach was most common (58%), with single catheter systems employed in 50% of studies. A total of 285 adverse events were reported. The most common included headache (20%), limb weakness (18.2%), Grade 1 cranial nerve deficits (6.3%), and general pain (4.9%). Of 132 CTCAE-graded events, 125 were Grade 1 or Grade 2 (94.7%) and 7 were Grade 3 (5.3%). No Grade 4 or Grade 5 adverse events occurred. This first systematic review of CED of pediatric patients demonstrates that while mild side effects are common, severe adverse events are rare. Multi-institutional and longitudinal data are needed to further define CED’s role in pediatric applications. These findings support CED as a viable platform for investigational therapies in treatment-resistant pediatric pathologies.

The online version contains supplementary material available at 10.1007/s00381-025-07121-8.