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HERO ID
3070930
Reference Type
Journal Article
Title
Circulating phthalates during critical illness in children are associated with long-term attention deficit: a study of a development and a validation cohort
Author(s)
Verstraete, S; Vanhorebeek, I; Covaci, A; Güiza, F; Malarvannan, G; Jorens, PG; Van den Berghe, G
Year
2016
Is Peer Reviewed?
Yes
Journal
Intensive Care Medicine
ISSN:
0342-4642
EISSN:
1432-1238
Publisher
Springer Verlag
Volume
42
Issue
3
Page Numbers
379-392
Language
English
PMID
26667027
DOI
10.1007/s00134-015-4159-5
Web of Science Id
WOS:000370198700009
URL
https://search.proquest.com/docview/1764339569?accountid=171501
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Abstract
PURPOSE:
Environmental phthalate exposure has been associated with attention deficit disorders in children. We hypothesized that in children treated in the pediatric intensive care unit (PICU), circulating phthalates leaching from indwelling medical devices contribute to their long-term attention deficit.
METHODS:
Circulating plasma concentrations of di(2-ethylhexyl)phthalate (DEHP) metabolites were quantified in 100 healthy children and 449 children who had been treated in PICU and were neurocognitively tested 4 years later. In a development patient cohort (N = 228), a multivariable bootstrap study identified stable thresholds of exposure to circulating DEHP metabolites above which there was an independent association with worse neurocognitive outcome. Subsequently, in a second patient cohort (N = 221), the observed independent associations were validated.
RESULTS:
Plasma concentrations of DEHP metabolites, which were virtually undetectable [0.029 (0.027-0.031) µmol/l] in healthy children, were 4.41 (3.76-5.06) µmol/l in critically ill children upon PICU admission (P < 0.001). Plasma DEHP metabolite concentrations decreased rapidly but remained 18 times higher until PICU discharge (P < 0.001). After adjusting for baseline risk factors and duration of PICU stay, and further for PICU complications and treatments, exceeding the potentially harmful threshold for exposure to circulating DEHP metabolites was independently associated with the attention deficit (all P ≤ 0.008) and impaired motor coordination (all P ≤ 0.02). The association with the attention deficit was confirmed in the validation cohort (all P ≤ 0.01). This phthalate exposure effect explained half of the attention deficit in post-PICU patients.
CONCLUSIONS:
Iatrogenic exposure to DEHP metabolites during intensive care was independently and robustly associated with the important attention deficit observed in children 4 years after critical illness. Clinicaltrials.gov identifier: NCT00214916.
Keywords
PICU; Critical illness; Sepsis; Phthalate; Attention; Neurocognitive development; Plasticizers
Tags
IRIS
•
Dibutyl Phthalate (DBP)
Database Searches
Litsearch Jan 2016 - July 2016
Pubmed
Studies with Health Effects Data
Human health effects studies
Litsearch June 2015 - Jan 2016
Pubmed
•
Phthalates – Targeted Search for Epidemiological Studies
Source – all searches
Pubmed
WOS
Included
DEHP
Source - Jun 2016 Update (Private)
Pubmed
WOS
Source - Dec 2016 Update (Private)
Pubmed
WOS
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