Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness.

"Declarations Ethics approval and consent to participateThe institutional review boards at each participating site approved this follow-up study (Ethische Commissie Onderzoek UZ Leuven/KU Leuven: ML8052; Medische Ethische Toetsingscommissie Erasmus MC: NL49708.078). The study was performed in accordance with the 1964 Declaration of Helsinki and its amendments. Written informed consent was obtained from the parents or legal guardians, or from the children if 18 years or older. Consent for publicationNot applicable. Competing interestsWe declare no competing interest. Competing interests We declare no competing interest."

"Funding This work was supported by European Research Council Advanced Grants (AdvG-2012-321670 and AdvG-2017-785809) to Greet Van den Berghe; by the Methusalem program of the Flemish government (through the University of Leuven to Greet Van den Berghe and Ilse Vanhorebeek, METH14/06) and by the Institute for Science and Technology, Flanders, Belgium (through the University of Leuven to Greet Van den Berghe, IWT/110685/TBM and IWT/150181/TBM); by the Sophia Research Foundation (SSWO) to Sascha Verbruggen; by the ‘Stichting Agis Zorginnovatie’ to Sascha Verbruggen and by a European Society for Clinical Nutrition and Metabolism (ESPEN) research grant to Sascha Verbruggen."

"This study is a pre-planned secondary analysis of the multicentre PEPaNIC-RCT (registered at ClinicalTrials.gov NCT01536275, 2012-2015) and its 2-year follow-up study (2014–2018) [, ]. The PEPaNIC-RCT included 1440 consecutive critically ill children aged 0–17 years admitted to the PICUs of Leuven (Belgium), Rotterdam (The Netherlands) or Edmonton (Canada), who had an expected PICU stay of at least 24 h, were at risk of malnutrition, and did not meet any of the exclusion criteria []. All patients, who survived and for whom written informed consent was obtained, were eligible for a follow-up study 2 years after PICU admission, to assess physical, neurocognitive and emotional/behavioural development []. Healthy children with comparable sex and age distribution as the former PICU patients were included as controls. These were either siblings and relatives of the patients or unrelated children from the same geographical area, attempting to adjust as much as possible for genetic and socio-economic/environmental background []. The number of healthy children to be recruited as control group was based on power to detect relevant differences in developmental outcomes []."