OR04-6 Circulating Phthalates during Critical Illness in Children and Their Long-Term Attention Deficit Legacy: An Association Study of a Development and a Validation Cohort

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR04-Endocrine Disrupting Chemicals
Friday, April 1, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 1:00 PM
Room 258 (BCEC)
Sören Verstraete*1, Ilse Vanhorebeek2, Adrian Covaci3, Fabian Güiza1, Govindan Malarvannan3, Philippe G Jorens4 and Greet Van den Berghe1
1Katholieke Universiteit Leuven, Leuven, Belgium, 2KU Leuven, Leuven, Belgium, 3University of Antwerp, Antwerp, Belgium, 4Antwerp University Hospital, Edegem, Belgium

Background: The long-term legacy of pediatric critical illness comprises a severe and unexplained attention deficit.1 Phthalates, which may be neurotoxic, are used to soften plastic indwelling medical devices and can leach into the circulation.2, 3

Hypothesis: 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, that 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 elevated 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 and Relevance: Exposure to phthalates leaching from indwelling medical devices used for intensive medical care in children was independently and robustly associated with their long-term attention deficit. Development of alternative plasticizers for this application may be indicated.

1. Mesotten et al., JAMA. 2012;308:1641:1650.2. Green et al., Environ Health Perspect. 2005;113:1222-1225.3. Chopra et al., Environ Res. 2014;128:64-69.

Nothing to Disclose: SV, IV, AC, FG, GM, PGJ, GV

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting/pr-resources-for-endo

Sources of Research Support: This work was supported by the Research Foundation-Flanders (FWO), Belgium (FWO fellowship to SV); by the Methusalem program of the Flemish government (through the University of Leuven to GVdB, METH/08/07 and to GVdB and IV, METH14/06); by an ERC Advanced Grant (AdvG-2012-321670) from the Ideas Program of the European Union 7th framework program to GVdB; and by the Institute for Science and Technology, Flanders, Belgium (through the University of Leuven to GVdB, IWT/070695/TBM).