Ines Verlinden1, Karolijn Dulfer2, Ilse Vanhorebeek1, Fabian Güiza1, José A Hordijk2, Pieter J Wouters1, Gonzalo Garcia Guerra3, Koen F Joosten2, Sascha C Verbruggen2, Greet Van den Berghe4. 1. Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. 2. Intensive Care Unit, Department of Paediatrics and Paediatric Surgery, Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, the Netherlands. 3. Department of Paediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada. 4. Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. Electronic address: greet.vandenberghe@kuleuven.be.
Abstract
BACKGROUND & AIMS: Early use of parenteral nutrition (early-PN), as compared with withholding it for one week (late-PN), in the PICU, has shown to slow down recovery from critical illness and impair long-term development of 6 neurocognitive/behavioural/emotional functions assessed 2 years later. Given that key steps in brain maturation occur at different times during childhood, we hypothesised that age at time of exposure determines long-term developmental impact of early-PN. METHODS: The 786 children who were neurocognitively tested 2 years after participation in the PEPaNIC-RCT were included in this study. First, for each studied long-term outcome, interaction between randomisation to early-PN versus late-PN and age was assessed with multivariable linear regression analysis. Subsequently, for outcomes with an interaction p ≤ 0.15, the impact of early-PN versus late-PN was analysed, after adjustment for risk factors, for 4 subgroups defined based on developmentally-relevant age at time of exposure [≤28 days (n = 121), 29 days to 11 months (n = 239), 11 months to <5 years (n = 223) and ≥5 years (n = 203)]. RESULTS: Interaction between randomisation and age was present for weight, and parent-reported inhibitory control, cognitive flexibility, working memory, planning/organisation, metacognition, total executive functioning, and internalising and total behavioural/emotional problems. Subgroup analyses revealed that none of the age-groups revealed benefit, whereas children aged 29 days to <11 months were most vulnerable to harm by early-PN for development of inhibitory control (p = 0.008), working memory (p = 0.009), planning/organisation (p = 0.004), metacognition (p = 0.008), and total executive functioning (p = 0.004), and for internalising (p = 0.005) and total behavioural/emotional problems (p = 0.01). Children aged 11 months to <5 years revealed harm by early-PN for development of inhibitory control (p = 0.003). In contrast, children aged ≥5 years and neonates aged ≤28 days appeared less vulnerable. CONCLUSIONS: Critically ill children aged 29 days to 11 months at time of exposure were identified as most vulnerable to developmental harm evoked by early-PN. CLINICAL TRIALS.GOV: NCT01536275.
BACKGROUND & AIMS: Early use of parenteral nutrition (early-PN), as compared with withholding it for one week (late-PN), in the PICU, has shown to slow down recovery from critical illness and impair long-term development of 6 neurocognitive/behavioural/emotional functions assessed 2 years later. Given that key steps in brain maturation occur at different times during childhood, we hypothesised that age at time of exposure determines long-term developmental impact of early-PN. METHODS: The 786 children who were neurocognitively tested 2 years after participation in the PEPaNIC-RCT were included in this study. First, for each studied long-term outcome, interaction between randomisation to early-PN versus late-PN and age was assessed with multivariable linear regression analysis. Subsequently, for outcomes with an interaction p ≤ 0.15, the impact of early-PN versus late-PN was analysed, after adjustment for risk factors, for 4 subgroups defined based on developmentally-relevant age at time of exposure [≤28 days (n = 121), 29 days to 11 months (n = 239), 11 months to <5 years (n = 223) and ≥5 years (n = 203)]. RESULTS: Interaction between randomisation and age was present for weight, and parent-reported inhibitory control, cognitive flexibility, working memory, planning/organisation, metacognition, total executive functioning, and internalising and total behavioural/emotional problems. Subgroup analyses revealed that none of the age-groups revealed benefit, whereas children aged 29 days to <11 months were most vulnerable to harm by early-PN for development of inhibitory control (p = 0.008), working memory (p = 0.009), planning/organisation (p = 0.004), metacognition (p = 0.008), and total executive functioning (p = 0.004), and for internalising (p = 0.005) and total behavioural/emotional problems (p = 0.01). Children aged 11 months to <5 years revealed harm by early-PN for development of inhibitory control (p = 0.003). In contrast, children aged ≥5 years and neonates aged ≤28 days appeared less vulnerable. CONCLUSIONS:Critically illchildren aged 29 days to 11 months at time of exposure were identified as most vulnerable to developmental harm evoked by early-PN. CLINICAL TRIALS.GOV: NCT01536275.
Authors: Tom Fivez; Dorian Kerklaan; Dieter Mesotten; Sascha Verbruggen; Pieter J Wouters; Ilse Vanhorebeek; Yves Debaveye; Dirk Vlasselaers; Lars Desmet; Michael P Casaer; Gonzalo Garcia Guerra; Jan Hanot; Ari Joffe; Dick Tibboel; Koen Joosten; Greet Van den Berghe Journal: N Engl J Med Date: 2016-03-15 Impact factor: 91.245
Authors: Esther van Puffelen; Ilse Vanhorebeek; Koen F M Joosten; Pieter J Wouters; Greet Van den Berghe; Sascha C A T Verbruggen Journal: Lancet Child Adolesc Health Date: 2018-05-11
Authors: Sören Verstraete; Sascha C Verbruggen; José A Hordijk; Ilse Vanhorebeek; Karolijn Dulfer; Fabian Güiza; Esther van Puffelen; An Jacobs; Sandra Leys; Astrid Durt; Hanna Van Cleemput; Renate D Eveleens; Gonzalo Garcia Guerra; Pieter J Wouters; Koen F Joosten; Greet Van den Berghe Journal: Lancet Respir Med Date: 2018-09-14 Impact factor: 30.700
Authors: Ines Verlinden; Fabian Güiza; Karolijn Dulfer; Hanna Van Cleemput; Pieter J Wouters; Gonzalo Garcia Guerra; Koen F Joosten; Sascha C Verbruggen; Ilse Vanhorebeek; Greet Van den Berghe Journal: Pediatr Crit Care Med Date: 2022-05-09 Impact factor: 3.971