Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?

Ilse Vanhorebeek; Govindan Malarvannan; Fabian Güiza; Giulia Poma; Inge Derese; Pieter J. Wouters; Koen Joosten; Sascha Verbruggen; Philippe G. Jorens; Adrian Covaci; Greet Van den Berghe

doi:10.1016/j.envint.2021.106962

Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?

Ilse Vanhorebeek^*, Govindan Malarvannan, Fabian Güiza, Giulia Poma, Inge Derese, Pieter J. Wouters, Koen Joosten, Sascha Verbruggen, Philippe G. Jorens, Adrian Covaci, Greet Van den Berghe

^*Corresponding author for this work

Pediatric Surgery

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Children who have been critically ill face long-term developmental impairments. Iatrogenic expo-
sure to di(2-ethylhexyl)phthalate (DEHP), a plasticizer leaching from plastic indwelling medical devices used in
the pediatric intensive care unit (PICU), has been associated with the pronounced attention deficit observed in
children 4 years after critical illness. As concerns about DEHP toxicity increased, governmental authorities urged
the phase out of DEHP in indwelling medical devices and replacement with alternative plasticizers. We hy-
pothesized that exposure to DEHP decreased over the years, attenuating the pronounced long-term attention
deficit of these vulnerable children.
Methods: We compared plasma concentrations of 3 oxidative DEHP metabolites (5cx-MEPP, 5OH-MEHP, 5oxo-
MEHP) on the last PICU day in 216 patients who participated in the Tight Glucose Control study (2004–2007)
and 334 patients who participated in the PEPaNIC study (2012–2015) and survived PICU stay. Corresponding
minimal exposures to these metabolites (plasma concentration multiplied with number of days in PICU) were
also evaluated. In patients with 4-year follow-up data, we compared measures of attention (standardized reaction
times and consistency). Comparisons were performed with univariable analyses and multivariable linear
regression analyses adjusted for baseline risk factors.
Results: In the PEPaNIC patients, last PICU day plasma concentrations of 5cx-MEPP, 5OH-MEHP, 5oxo-MEHP and
their sum, and corresponding minimal exposures, were reduced to 17–69% of those in the Tight Glucose Control
study (p < 0.0001). Differences remained significant after multivariable adjustment (p ≤ 0.001). PEPaNIC pa-
tients did not show better attention than patients in the Tight Glucose Control study, also not after multivariable
adjustment for risk factors.
Conclusion: Exposure of critically ill children to DEHP in the PICU decreased over the years, but the lower
exposure did not translate into improved attention 4 years later. Whether the residual exposure may still be toxic
or whether the plasticizers replacing DEHP may not be safe for neurodevelopment needs further investigation.

Original language	English
Article number	106962
Journal	Environment international
Volume	158
Early online date	2 Nov 2021
DOIs	https://doi.org/10.1016/j.envint.2021.106962 https://doi.org/10.1016/j.envint.2021.106962
Publication status	Published - Jan 2022

Bibliographical note

Funding Information:
This study was supported by the European Research Council ( AdvG-2012-321670 and AdvG-2017-785809 to GVdB), the Methusalem program of the Flemish government ( METH14/06 to IV and GVdB), Flanders Institute for Science and Technology ( IWT-TBM110685 , IWT-TBM150181 to GVdB), the Sophia Research Foundation (to SV), Stichting Agis Zorginnovatie (to SV), Erasmus Trustfonds (to SV), and the European Society for Clinical Nutrition and Metabolism (ESPEN research grant to SV). The study sponsors had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Publisher Copyright:
© 2021 The Authors

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Phasing out DEHP from plastic indwelling medical devices used for intensive careFinal published version, 632 KBLicence: CC BY-NC-ND

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Vanhorebeek, I., Malarvannan, G., Güiza, F., Poma, G., Derese, I., Wouters, P. J., Joosten, K., Verbruggen, S., Jorens, P. G., Covaci, A., & Van den Berghe, G. (2022). Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children? Environment international, 158, Article 106962. https://doi.org/10.1016/j.envint.2021.106962, https://doi.org/10.1016/j.envint.2021.106962

@article{26e7cf9369d54e849af48f248c17866e,

title = "Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?",

abstract = "Background: Children who have been critically ill face long-term developmental impairments. Iatrogenic expo-sure to di(2-ethylhexyl)phthalate (DEHP), a plasticizer leaching from plastic indwelling medical devices used inthe pediatric intensive care unit (PICU), has been associated with the pronounced attention deficit observed inchildren 4 years after critical illness. As concerns about DEHP toxicity increased, governmental authorities urgedthe phase out of DEHP in indwelling medical devices and replacement with alternative plasticizers. We hy-pothesized that exposure to DEHP decreased over the years, attenuating the pronounced long-term attentiondeficit of these vulnerable children.Methods: We compared plasma concentrations of 3 oxidative DEHP metabolites (5cx-MEPP, 5OH-MEHP, 5oxo-MEHP) on the last PICU day in 216 patients who participated in the Tight Glucose Control study (2004–2007)and 334 patients who participated in the PEPaNIC study (2012–2015) and survived PICU stay. Correspondingminimal exposures to these metabolites (plasma concentration multiplied with number of days in PICU) werealso evaluated. In patients with 4-year follow-up data, we compared measures of attention (standardized reactiontimes and consistency). Comparisons were performed with univariable analyses and multivariable linearregression analyses adjusted for baseline risk factors.Results: In the PEPaNIC patients, last PICU day plasma concentrations of 5cx-MEPP, 5OH-MEHP, 5oxo-MEHP andtheir sum, and corresponding minimal exposures, were reduced to 17–69% of those in the Tight Glucose Controlstudy (p < 0.0001). Differences remained significant after multivariable adjustment (p ≤ 0.001). PEPaNIC pa-tients did not show better attention than patients in the Tight Glucose Control study, also not after multivariableadjustment for risk factors.Conclusion: Exposure of critically ill children to DEHP in the PICU decreased over the years, but the lowerexposure did not translate into improved attention 4 years later. Whether the residual exposure may still be toxicor whether the plasticizers replacing DEHP may not be safe for neurodevelopment needs further investigation.",

author = "Ilse Vanhorebeek and Govindan Malarvannan and Fabian G{\"u}iza and Giulia Poma and Inge Derese and Wouters, {Pieter J.} and Koen Joosten and Sascha Verbruggen and Jorens, {Philippe G.} and Adrian Covaci and {Van den Berghe}, Greet",

note = "Funding Information: This study was supported by the European Research Council ( AdvG-2012-321670 and AdvG-2017-785809 to GVdB), the Methusalem program of the Flemish government ( METH14/06 to IV and GVdB), Flanders Institute for Science and Technology ( IWT-TBM110685 , IWT-TBM150181 to GVdB), the Sophia Research Foundation (to SV), Stichting Agis Zorginnovatie (to SV), Erasmus Trustfonds (to SV), and the European Society for Clinical Nutrition and Metabolism (ESPEN research grant to SV). The study sponsors had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2022",

month = jan,

doi = "10.1016/j.envint.2021.106962",

language = "English",

volume = "158",

journal = "Environment international",

issn = "0160-4120",

publisher = "Elsevier Ltd.",

}

Vanhorebeek, I, Malarvannan, G, Güiza, F, Poma, G, Derese, I, Wouters, PJ, Joosten, K , Verbruggen, S, Jorens, PG, Covaci, A & Van den Berghe, G 2022, 'Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?', Environment international, vol. 158, 106962. https://doi.org/10.1016/j.envint.2021.106962, https://doi.org/10.1016/j.envint.2021.106962

TY - JOUR

T1 - Phasing out DEHP from plastic indwelling medical devices used for intensive care

T2 - Does it reduce the long-term attention deficit of critically ill children?

AU - Vanhorebeek, Ilse

AU - Malarvannan, Govindan

AU - Güiza, Fabian

AU - Poma, Giulia

AU - Derese, Inge

AU - Wouters, Pieter J.

AU - Joosten, Koen

AU - Verbruggen, Sascha

AU - Jorens, Philippe G.

AU - Covaci, Adrian

AU - Van den Berghe, Greet

N1 - Funding Information: This study was supported by the European Research Council ( AdvG-2012-321670 and AdvG-2017-785809 to GVdB), the Methusalem program of the Flemish government ( METH14/06 to IV and GVdB), Flanders Institute for Science and Technology ( IWT-TBM110685 , IWT-TBM150181 to GVdB), the Sophia Research Foundation (to SV), Stichting Agis Zorginnovatie (to SV), Erasmus Trustfonds (to SV), and the European Society for Clinical Nutrition and Metabolism (ESPEN research grant to SV). The study sponsors had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: © 2021 The Authors

PY - 2022/1

Y1 - 2022/1

N2 - Background: Children who have been critically ill face long-term developmental impairments. Iatrogenic expo-sure to di(2-ethylhexyl)phthalate (DEHP), a plasticizer leaching from plastic indwelling medical devices used inthe pediatric intensive care unit (PICU), has been associated with the pronounced attention deficit observed inchildren 4 years after critical illness. As concerns about DEHP toxicity increased, governmental authorities urgedthe phase out of DEHP in indwelling medical devices and replacement with alternative plasticizers. We hy-pothesized that exposure to DEHP decreased over the years, attenuating the pronounced long-term attentiondeficit of these vulnerable children.Methods: We compared plasma concentrations of 3 oxidative DEHP metabolites (5cx-MEPP, 5OH-MEHP, 5oxo-MEHP) on the last PICU day in 216 patients who participated in the Tight Glucose Control study (2004–2007)and 334 patients who participated in the PEPaNIC study (2012–2015) and survived PICU stay. Correspondingminimal exposures to these metabolites (plasma concentration multiplied with number of days in PICU) werealso evaluated. In patients with 4-year follow-up data, we compared measures of attention (standardized reactiontimes and consistency). Comparisons were performed with univariable analyses and multivariable linearregression analyses adjusted for baseline risk factors.Results: In the PEPaNIC patients, last PICU day plasma concentrations of 5cx-MEPP, 5OH-MEHP, 5oxo-MEHP andtheir sum, and corresponding minimal exposures, were reduced to 17–69% of those in the Tight Glucose Controlstudy (p < 0.0001). Differences remained significant after multivariable adjustment (p ≤ 0.001). PEPaNIC pa-tients did not show better attention than patients in the Tight Glucose Control study, also not after multivariableadjustment for risk factors.Conclusion: Exposure of critically ill children to DEHP in the PICU decreased over the years, but the lowerexposure did not translate into improved attention 4 years later. Whether the residual exposure may still be toxicor whether the plasticizers replacing DEHP may not be safe for neurodevelopment needs further investigation.

AB - Background: Children who have been critically ill face long-term developmental impairments. Iatrogenic expo-sure to di(2-ethylhexyl)phthalate (DEHP), a plasticizer leaching from plastic indwelling medical devices used inthe pediatric intensive care unit (PICU), has been associated with the pronounced attention deficit observed inchildren 4 years after critical illness. As concerns about DEHP toxicity increased, governmental authorities urgedthe phase out of DEHP in indwelling medical devices and replacement with alternative plasticizers. We hy-pothesized that exposure to DEHP decreased over the years, attenuating the pronounced long-term attentiondeficit of these vulnerable children.Methods: We compared plasma concentrations of 3 oxidative DEHP metabolites (5cx-MEPP, 5OH-MEHP, 5oxo-MEHP) on the last PICU day in 216 patients who participated in the Tight Glucose Control study (2004–2007)and 334 patients who participated in the PEPaNIC study (2012–2015) and survived PICU stay. Correspondingminimal exposures to these metabolites (plasma concentration multiplied with number of days in PICU) werealso evaluated. In patients with 4-year follow-up data, we compared measures of attention (standardized reactiontimes and consistency). Comparisons were performed with univariable analyses and multivariable linearregression analyses adjusted for baseline risk factors.Results: In the PEPaNIC patients, last PICU day plasma concentrations of 5cx-MEPP, 5OH-MEHP, 5oxo-MEHP andtheir sum, and corresponding minimal exposures, were reduced to 17–69% of those in the Tight Glucose Controlstudy (p < 0.0001). Differences remained significant after multivariable adjustment (p ≤ 0.001). PEPaNIC pa-tients did not show better attention than patients in the Tight Glucose Control study, also not after multivariableadjustment for risk factors.Conclusion: Exposure of critically ill children to DEHP in the PICU decreased over the years, but the lowerexposure did not translate into improved attention 4 years later. Whether the residual exposure may still be toxicor whether the plasticizers replacing DEHP may not be safe for neurodevelopment needs further investigation.

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DO - 10.1016/j.envint.2021.106962

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SN - 0160-4120

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JO - Environment international

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ER -

Phasing out DEHP from plastic indwelling medical devices used for intensive care: Does it reduce the long-term attention deficit of critically ill children?

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