Exposure to Plasticisers in the Neonatal Intensive Care Unit (PLASTIC-NICU)

November 28, 2023 updated by: University Hospital, Antwerp

Exposure to Plasticizers in the Neonatal Intensive Care Unit and Long- Term Neurodevelopmental and Pulmonary Toxicity

Neonatal intensive care relies on indwelling plastic medical devices fundamental in respiratory support, intravenous catheterization, and nutrition. While being in a critical developmental period, constant exposure to these invasive medical devices puts premature neonates at risk of plasticizers' potential toxicity. Despite novel regulations and development of alternative plasticizers (AP), reference to guide manufacturers and an overview of the prevailing exposure levels to DEHP or alternatives in the neonatal intensive care unit (NICU) are still missing. The three main objectives of this project are: (1) to assess current exposure to plasticizers in the NICU, (2) to identify the sources of exposure and (3) to study the resultant long-term health risk in premature neonates. These objectives are addressed in three work packages (WP). In work package 1, in vivo exposure of premature neonates to phthalates and alternative plasticizers is assessed by determining their metabolites in biological matrices (urine and hair). Work package 2 explores ex vivo leaching characteristics of different plasticizers from medical devices used in the NICU. Finally, Work package 3 studies the long-term neurocognitive and lung development in relation to plasticizer exposure in the NICU.

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

RESEARCH HYPOTHESIS: Leaching of plasticizers (DEHP and APs) from indwelling medical devices used in the neonatal intensive care unit (NICU) may expose premature neonates to these chemicals and their metabolites. The resulting exposure may contribute to medical risks and to impaired (neurocognitive) development of the children after hospital discharge.

This project aims to explore scalp hair and urine as a diagnostic tool for exposure to plasticizers in the extremely vulnerable population of premature neonates. The use of scalp hair to detect past exposure is by itself a novel approach and is expected to provide fresh insights into the role of plasticizers in post NICU morbidity. Within this project, we intend to address the following goals to be pursued:

Objective 1. Exploring the use of a non-invasive matrix (scalp hair) to determine past exposure to plasticizers in neonates. By measuring the levels of DEHP and AP metabolites A/ soon after birth in urine and neonatal scalp hair to determine intra-uterine exposure and B/ during follow-up after NICU discharge in infant scalp hair to determine past exposure in NICU (3 months) and early life (12 months).

Objective 2. To study the extent of leaching of plasticizers from indwelling medical devices used in NICU, by A/ determining the ex vivo leaching from the devices in ambient conditions and taking into account acidity and lipid content with relevance for neonatal care and B/ quantifying levels of plasticizers and metabolites in neonatal urine, collected on daily basis upon NICU admission until discharge.

Objective 3. To study the contribution of exposure to plasticizers leaching from indwelling medical devices used in the NICU, to neurocognitive and pulmonary development during the first year of life.

Importance and impact: NICU saves many lives of premature babies, but the long-term consequences of NICU may jeopardize the quality of life. Hence, finding strategies to prevent or attenuate this legacy is crucial. The completion of this project will lead to a comprehensive characterization of the potential health effects arising from leaching of plasticizers currently used in medical devices in NICU.

The study will be carried out in the NICU of the Antwerp University Hospital (UZA), a 28-beds ICU serving as a tertiary reference centre. We will include neonates with a gestational age under 31 weeks and/or birth weight under 1500 grams. We focus on this group of extreme premature neonates, because of their high and prolonged exposure. Board certified neonatologists will prospectively follow up the neonates. All are exposed to a variable number (range 1-6) of a diversity of indwelling medical devices, leading to a variable degree of exposure in the individual neonate. Term born neonates with age, gender and socio-economic status (not admitted to the NICU, n=100) comparable with those of the patients will be recruited as a control group for non-NICU exposure. The study protocol and informed consent forms have already been approved by the UZA Ethical Committee (Ref. 2003022).

Study Type

Observational

Enrollment (Actual)

132

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
    • Antwerp
      • Edegem, Antwerp, Belgium, 2650
        • Antwerp University Hospital - Neonatal Intensive Care Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 3 days (Child)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study will be carried out in the NICU of the Antwerp University Hospital (UZA), a 28-beds ICU serving as a tertiary reference centre. We will include neonates with a gestational age under 31 weeks and/or birth weight under 1500 grams. We focus on this group of extreme premature neonates, because of their high and prolonged exposure. Board certified neonatologists will prospectively follow up the neonates. All are exposed to a variable number (range 1-6) of a diversity of indwelling medical devices, leading to a variable degree of exposure in the individual neonate. Term born neonates with age, gender and socio-economic status (not admitted to the NICU, n=100) comparable with those of the patients will be recruited as a control group for non-NICU exposure.

Description

Inclusion Criteria:

  • Preterm NICU neonates: Gestational Age < 31 weeks and/or birth weight < 1500 gram
  • Healthy controls: term neonates

Exclusion Criteria:

  • Major congenital abnormalities

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level and sources of NICU exposure to phthalates and alternative plasticizers, measured by liquid chromatography coupled to tandem mass spectrometry in urine samples.
Time Frame: Starting at day 1 postnatal, we collect weekly urine samples, until term age (40 weeks post-menstrual age) or NICU discharge (whatever comes first, up to 120 days postnatally).
Urine samples are analysed for phthalate and alternative plasticizers' metabolites by liquid chromatography coupled to tandem mass spectrometry at the Antwerp Toxicological Centre. Results will be described as ng/mL.
Starting at day 1 postnatal, we collect weekly urine samples, until term age (40 weeks post-menstrual age) or NICU discharge (whatever comes first, up to 120 days postnatally).
Level and sources of NICU exposure to phthalates and alternative plasticizers, measured by liquid chromatography coupled to tandem mass spectrometry in hair samples.
Time Frame: Scalp hair samples are being collected at term age (37-40 weeks post menstrual age).
Hair samples are analysed for phthalate and alternative plasticizers' metabolites by liquid chromatography coupled to tandem mass spectrometry at the Antwerp Toxicological Centre. Results will be described as ng/mg.
Scalp hair samples are being collected at term age (37-40 weeks post menstrual age).
Perinatal Morbidity
Time Frame: NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Prospective data collection
NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Perinatal Survival
Time Frame: NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Prospective data collection
NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Respiratory development - 3 months
Time Frame: 3 months corrected for gestational age
Respiratory questionnaire
3 months corrected for gestational age
Respiratory development - 12 months
Time Frame: 12 months corrected for gestational age
Respiratory questionnaire
12 months corrected for gestational age
Neurodevelopmental outcome - 3 months
Time Frame: 3 months corrected for gestational age
Bayley Scales of Infant and Toddler Development (BSID III) - Mean score 100 points, standard deviation 15 points. Higher score corresponds to better outcome
3 months corrected for gestational age
Neurodevelopmental outcome - 12 months
Time Frame: 12 months corrected for gestational age
Bayley Scales of Infant and Toddler Development (BSID III) - Mean score 100 points, standard deviation 15 points. Higher score corresponds to better outcome
12 months corrected for gestational age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Antwerp

Collaborators

Universiteit Antwerpen
Research Foundation Flanders

Investigators

  • Principal Investigator: Philippe G Jorens, MD, PhD, University Hospital, Antwerp

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 2, 2020

Primary Completion (Estimated)

December 30, 2023

Study Completion (Estimated)

December 30, 2023

Study Registration Dates

First Submitted

May 13, 2022

First Submitted That Met QC Criteria

June 1, 2022

First Posted (Actual)

June 3, 2022

Study Record Updates

Last Update Posted (Estimated)

December 5, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20/23/022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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