Inflammation associated with cerebral palsy appears to persist beyond the period around birth and into childhood and later life, according to a systematic review of the available studies. The authors interpret the evidence as indicating that this inflammatory activity remains present beyond the perinatal period. The review also reports a correlation with disease severity, particularly higher GMFCS scores across cerebral palsy subtypes. That is an association, not evidence that inflammation causes cerebral palsy or makes it more severe.
The review set out to examine whether systemic inflammation linked to cerebral palsy persists into childhood and beyond, and whether the pattern points to potential therapeutic targets. Its central message is therefore about persistence: inflammatory markers were still being reported after the earliest period of life. It names possible targets, but it reports no treatment results.
The signal appears in several samples
Studies looked for inflammation in several biological materials: blood, saliva, cerebrospinal fluid, or CSF, and muscle. Commonly assessed biomarkers included TNF-alpha, IL-6, IL-10 and IL-8. The review also reports associations with TNF-alpha, IL-1 beta, IL-6 and IL-10, as well as higher baseline levels of certain immune cells.
That spread of samples makes the result broader than a finding from a single test, but it also makes comparisons harder. The supplied analysis reports no pooled biomarker estimates or assay comparisons, so it does not show how large the inflammatory differences were across the studies.
A link to severity, without a causal answer
Ten of the 17 included studies reported higher cytokine or immune-cell levels in children with cerebral palsy than in controls. The review links persistent inflammation with elevated cytokines and with higher baseline levels of certain immune cells. It does not report the size of these differences, participant counts or uncertainty intervals.
The severity finding follows the same cautious pattern. Persistent inflammation was reported to correlate with disease severity, particularly higher GMFCS scores, across cerebral palsy subtypes. The review does not provide subtype-specific estimates or correlation coefficients, leaving the strength and consistency of that relationship unclear.
A broad search, but a small final evidence base
To gather the evidence, the researchers conducted a systematic review that adhered to PRISMA guidelines. They used specified keywords to search PubMed, the Cochrane Library, Embase, the Neuroscience journal published by Science Direct, and Ovid on 27 February 2024. Study quality was assessed with the Newcastle-Ottawa Scale, and relevant data were extracted into a Google Sheets spreadsheet for analysis.
The review identified 1,064 studies and included 17. That final group is a study count, not a count of participants, and the supplied analysis does not report participant-level sample sizes or pooled estimates. The evidence therefore shows a direction of findings across studies, but not a single numerical measure of the overall effect.
The authors say the evidence is difficult to combine because samples and biomarkers varied, reported aetiologies differed, and small sample sizes could confound the conclusions. They call for consensus to reduce that heterogeneity and improve the search for universal therapeutic targets.
Another problem is that many studies did not use a standardised consensus definition and classification of cerebral palsy. Without common definitions and measurement approaches, a result described as persistent inflammation may not be directly comparable from one study to the next.
Possible treatments remain research targets
The review names magnesium sulphate, melatonin, immunotherapy and stem-cell treatments as potential therapeutic targets. It does not estimate whether any of them improve outcomes or what risks they may carry, so the list should be read as research directions rather than treatment advice.
The authors' next step is a more consistent evidence base: shared definitions, less variation in samples and biomarkers, and studies large enough to clarify how inflammation relates to severity. They argue that this consensus is needed to identify therapeutic targets that could apply across cerebral palsy subtypes.
The citation lists the article as accepted on 20 June 2026 and published, with its version of record, on 21 August 2026. The disclosure says the authors have no competing interests; it does not report funding.
Paper data and sources
Original title: Persistent dysregulated inflammation in cerebral palsy: a systematic review.
Authors: Sara Betzhold, Mariam Cender, Mustafa Dhuhaibawi et al.
Journal/Repository: Pediatric research
Status: Peer-reviewed
First online: 2026-08-21
DOI: 10.1038/s41390-026-05319-3
Original paper · Full text