Aberrant DNA methylation within circadian entrainment and clock genes two years after pediatric critical illness is associated with impaired physical and neurocognitive development
Abstract
Background: Pediatric critical illness can disrupt circadian rhythms, potentially leading to long-term deficits in growth, neurocognition, and behavior. Disturbances in circadian rhythms have been associated with altered gene expression and DNA methylation. We investigated long-term DNA methylation alterations in circadian entrainment and clock genes in children previously admitted to the pediatric intensive care unit (PICU), the influence of parenteral nutrition (PN) timing hereon and their associations with long-term health outcomes.
Methods: This study is a secondary analysis of the PEPaNIC randomized controlled trial (RCT) and its two-year follow-up. The PEPaNIC-RCT randomized critically ill children to early initiation of supplemental PN within the first 24 h or its omission in the first week of PICU admission. DNA methylation of 127 circadian entrainment and clock genes was studied in buccal mucosa DNA of former PICU patients (n = 818) and matched healthy children (n = 392) at the two-year follow-up using Infinium® HumanMethylation EPIC BeadChips. Multivariable linear models were used to identify differential methylation between former patients and controls and their association with randomization group and outcomes at two-year follow-up.
Results: Former PICU patients showed 61 differentially methylated CpG sites (DMPs) within 34 of the genes, with 60 (98.4%) showing hypomethylation as compared with healthy children. Omitting early PN during PICU stay did not affect…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 818 participants or records.
Read the paper
Related studies
- Tryptophan Metabolism and Gut-Brain Homeostasis
- Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review
- Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit
- Relationship between sleep disorders and gut dysbiosis: what affects what?
- The role of CLOCK gene in psychiatric disorders: Evidence from human and animal research
- Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.