Table 1.

Summary of meta-analyses on the safety profile of brainstem biopsy in children.

Meta- Analysis Study	Details of component studies	Key Findings	Comments
Kickingereder 2013 (27)	Included both adult and children, mean age 29 years. N = 1480 total cases. All stereotactic, 68% transfrontal approach.	96.2% diagnostic success, 7.8% overall morbidity (95% CI 5.6-10.2), 1.7% permanent morbidity (95% CI 0.9-2.7), 0.9% mortality (95% CI 0.5-1.4). Biopsy trajectory had no influence on outcome measures.	Widely cited due to large pooled sample size but with the significant limitation that adults and children are combined for analysis.
Hamisch 2017 (28)	N = 735 children, mean age 8 years, all stereotactic, 60% transfrontal. Included studies from 1993-2015.	96.1 diagnostic success, 6.7% overall morbidity (95% CI 4.2-9.6), 0.6% permanent morbidity (95% CI 0.2-1.4), 0.6% mortality (95% CI 0.2-1.3). Biopsy trajectory had no influence on outcome measures.	Large pediatric-only cohort, about a third of studies are from 1980s-1990s so unclear if they reflect contemporary practice. No clear description of what the specific morbidities encountered in component studies and aggregated in the meta-analysis were.
Fu 2023 (29)	N = 381 cases, all patients <21 years of age, only included patients with suspected diffuse midline glioma.	For biopsies in general: 11% overall morbidity (95% CI 4.8-18.9), 0.3% permanent morbidity (95% CI 0-2.2), 3 mortalities in the total cohort (0.8%). For stereotactic biopsies: 5.3% overall morbidity (95 CI: 1.5 – 10.7), 0% permanent morbidity (95% CI 0-1.1), no deaths	Highly selective inclusion criteria resulting in a focused analysis for pediatric suspected DMG cases, though with smaller pooled sample size.
Lu 2023 (30)	N = 99 cases, all children with mean age 9 years, all patients had stereotactic, frameless, robot-assisted biopsy	Transient complications: 10% (95% CI: 4-19%), permanent complications 0% (95% CI 0-2%), no deaths	This study describes a pediatric-only population undergoing brainstem biopsy with a cutting-edge technique (frameless, robotic stereotaxy).
Sheikh 2024 (31)	N=1002 children, 87% stereotactic.	Transient complications: 6% (95% CI 4-8), permanent complications 1% (95% CI 0.5-2). 5 mortalities in total.	Largest pooled cohort of pediatric cases. Included only contemporary series (2003-2023). Most common transient neurological complications were: 1) cranial nerve dysfunction, 2) worsening or new ataxia, 3) limb weakness. Most common permanent complications were: 1) cranial nerve dysfunction, 2) limb weakness.