ArticleClinical epigenetics2024
Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness.
Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Aberrant DNA methylation within circadian entrainment and clock genes two years after pediatric critical illness is associated with impaired physical and neurocognitive development.Clinical epigenetics · 2025Trial
- Factors associated with constipation in critically ill children: A retrospective study.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2026Article
- Article
- Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics.Frontiers in psychiatry · 2026Review
- Association between chronic stress and the epigenome: Exploration of psychological and biological stress.PloS one · 2026Article
- Overweight and POMC methylation: epigenetic associations with adolescent depression.BMC psychiatry · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- On how to feed critically ill children in intensive care: A slowly shifting paradigm.Clinical nutrition (Edinburgh, Scotland) · 2025Review
- Sex-dependent biobehavioural responses to transgenerational maternal stress: evidence of stress resilience and vulnerability in the F3 generation.Environmental epigenetics · 2025Article
- Delving Into the Interaction Between Exercise and Diabetes on Methylation of the FKBP5 Gene.Journal of diabetes research · 2025Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCritically ill children suffer from impaired physical/neurocognitive development 2 years later. Glucocorticoid treatment alters DNA methylation within the hypothalamus-pituitary-adrenal (HPA) axis which may impair normal brain development, cognition and behaviour. We tested the hypothesis that paediatric-intensive-care-unit (PICU) patients, sex- and age-dependently, show long-term abnormal DNA methylation within the HPA-axis layers, possibly aggravated by glucocorticoid treatment in the PICU, which may contribute to the long-term developmental impairments.
resultsIn a pre-planned secondary analysis of the multicentre PEPaNIC-RCT and its 2-year follow-up, we identified differentially methylated positions and differentially methylated regions within HPA-axis genes in buccal mucosa DNA from 818 former PICU patients 2 years after PICU admission (n = 608 no glucocorticoid treatment; n = 210 glucocorticoid treatment) versus 392 healthy children and assessed interaction with sex and age, role of glucocorticoid treatment in the PICU and associations with long-term developmental impairments. Adjusting for technical variation and baseline risk factors and correcting for multiple testing (false discovery rate < 0.05), former PICU patients showed abnormal DNA methylation of 26 CpG sites (within CRHR1, POMC, MC2R, NR3C1, FKBP5, HSD11B1, SRD5A1, AKR1D1, DUSP1, TSC22D3 and TNF) and three DNA regions (within AVP, TSC22D3 and TNF) that were mostly hypomethylated. These abnormalities were sex-independent and only partially age-dependent. Abnormal methylation of three CpG sites within FKBP5 and one CpG site within SRD5A1 and AKR1D1 was partly attributable to glucocorticoid treatment during PICU stay. Finally, abnormal methylation within FKBP5 and AKR1D1 was most robustly associated with long-term impaired development.
conclusionsTwo years after critical illness in children, abnormal methylation within HPA-axis genes was present, predominantly within FKBP5 and AKR1D1, partly attributable to glucocorticoid treatment in the PICU, and explaining part of the long-term developmental impairments. These data call for caution regarding liberal glucocorticoid use in the PICU.
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