Dataset Information

Leukocyte telomere length in paediatric critical illness: effect of early parenteral nutrition.

ABSTRACT: BACKGROUND:Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. METHODS:Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. RESULTS:Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P

SUBMITTER: Verstraete S

PROVIDER: S-EPMC5820800 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Leukocyte telomere length in paediatric critical illness: effect of early parenteral nutrition.

Verstraete Sören S Vanhorebeek Ilse I van Puffelen Esther E Derese Inge I Ingels Catherine C Verbruggen Sascha C SC Wouters Pieter J PJ Joosten Koen F KF Hanot Jan J Guerra Gonzalo G GG Vlasselaers Dirk D Lin Jue J Van den Berghe Greet G

Critical care (London, England) 20180221 1

<h4>Background</h4>Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consump ...[more]

PMID: 29463275

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Project description:BACKGROUND:A genome-wide study identified de novo DNA methylation alterations in leukocytes of children at paediatric intensive care unit (PICU) discharge, offering a biological basis for their impaired long-term development. Early parenteral nutrition (early-PN) in PICU, compared with omitting PN in the first week (late-PN), explained differential methylation of 23% of the affected CpG-sites. We documented the time course of altered DNA methylation in PICU and the impact hereon of early nutritional management. RESULTS:We selected 36 early-PN and 36 late-PN matched patients, and 42 matched healthy children. We quantified DNA methylation on days 3, 5 and 7 for the 147 CpG-sites of which methylation was normal upon PICU admission in this subset and altered by critical illness at PICU discharge. Methylation in patients differed from healthy children for 64.6% of the 147 CpG-sites on day 3, for 72.8% on day 5 and for 90.5% on day 7 as revealed by ANOVA at each time point. Within-patients methylation time course analyses for each CpG-site identified different patterns based on paired t test p value and direction of change. Rapid demethylation from admission to day 3 occurred for 76.2% of the CpG-sites, of which 67.9% remained equally demethylated or partially remethylated and 32.1% further demethylated beyond day 3. From admission to day 3, 19.7% of the CpG-sites became hypermethylated, of which, beyond day 3, 34.5% remained equally hypermethylated or partially demethylated again and 65.5% further hypermethylated. For 4.1% of the CpG-sites, changes only appeared beyond day 3. Finally, for the CpG-sites affected by early-PN on the last PICU day, earlier changes in DNA methylation were compared for early-PN and late-PN patients, revealing that 38.9% were already differentially methylated by day 3, another 25.0% by day 5 and another 13.9% by day 7. CONCLUSIONS:Critical illness- and early-PN-induced changes in DNA methylation occurred mainly within 3 days. Most abnormalities were at least partially maintained or got worse with longer time in PICU. Interventions targeting aberrant DNA methylation changes should be initiated early.

Project description:OBJECTIVE:evaluation of telomere length change in acutely ill adult patients. DESIGN:Blood samples were drawn on the first and seventh day of intensive care unit (ICU) stay to assess telomere length using a polymerase chain reaction (PCR)-based technique. Demographic data collected included age, weight, admission diagnosis, baseline laboratory values (pH, C- reactive protein (CRP), serum albumin level, white blood cell count (WBC) count, platelet count), and baseline SOFA and APACHE II scores. Additional data collected during the ICU stay included a repeated WBC count, the presence of positive blood cultures and outcome data, including death in the ICU or following discharge, whether ventilated or not at ICU discharge, and destination following discharge, i.e., medical ward or rehabilitation. SETTING:General ICU in tertiary hospital. PATIENTS:Forty patients admitted to the ICU within 72 h of hospital admission suffering from an acute illness were included in this prospective, observational study. MAIN RESULTS:Of the 40 patients studied, telomere shortening was noted in 21, telomere lengthening in 11, and no significant change in the other eight. The age of patients demonstrating telomere shortening was statistically significantly younger (45.4 vs. 61.5 years, p < 0.023) compared to those showing increased telomere length. In addition, a significant correlation was observed between the difference in telomere length and the corresponding difference in WBC count (telomere shortening was associated with a decreased WBC count and vice versa). A trend toward shortening was seen in patients with sepsis (p = 0.07). No significant correlations were found for any other demographic or outcome parameter and changes in telomere length. CONCLUSION:Changes in telomere length, both shortening and lengthening, were evident in the acute setting, but no associations between such changes with outcome were noted. Further studies in more homogeneous groups of patients appear to be warranted.

Dataset Information

Leukocyte telomere length in paediatric critical illness: effect of early parenteral nutrition.

Publications

Leukocyte telomere length in paediatric critical illness: effect of early parenteral nutrition.

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