Exposure to Plasticisers in the Neonatal Intensive Care Unit

NCT ID: NCT05404815

Last Updated: 2024-08-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 132 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-06-02
• Study Completion Date: 2023-12-30

Brief Summary

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.

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).

Conditions

Preterm Birth; Premature Birth; Neurodevelopmental Disorders; Pulmonary Disease; Bronchopulmonary Dysplasia; Harm Reduction; Environmental Exposure; Development, Infant

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Major congenital abnormalities

• Maximum Eligible Age: 3 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Research Foundation Flanders

OTHER

Sponsor Role: collaborator

Universiteit Antwerpen

OTHER

Sponsor Role: collaborator

University Hospital, Antwerp

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe G Jorens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Antwerp

Locations

Antwerp University Hospital - Neonatal Intensive Care Unit

Edegem, Antwerp, Belgium

Countries

Belgium

References

Lucas Panneel, Govindan Malarvannan, Philippe G. Jorens, Adrian Covaci & Antonius Mulder (2021) Plasticizers in the neonatal intensive care unit: A review on exposure sources and health hazards, Critical Reviews in Environmental Science and Technology, DOI: 10.1080/10643389.2021.1970455

Reference Type: RESULT

Panneel L, Cleys P, Breugelmans C, Christia C, Malarvannan G, Poma G, Jorens PG, Mulder A, Covaci A. Neonatal exposure to phthalate and alternative plasticizers via parenteral nutrition. Int J Pharm. 2023 Jan 25;631:122472. doi: 10.1016/j.ijpharm.2022.122472. Epub 2022 Dec 13.

Reference Type: RESULT

PMID: 36526146 (View on PubMed)

Cleys P, Panneel L, Bombeke J, Dumitrascu C, Malarvannan G, Poma G, Mulder A, Jorens PG, Covaci A. Hair as an alternative matrix to assess exposure of premature neonates to phthalate and alternative plasticizers in the neonatal intensive care unit. Environ Res. 2023 Nov 1;236(Pt 2):116712. doi: 10.1016/j.envres.2023.116712. Epub 2023 Jul 22.

Reference Type: RESULT

PMID: 37482128 (View on PubMed)

Vercauteren M, Panneel L, Jorens PG, Covaci A, Cleys P, Mulder A, Janssen CR, Asselman J. An Ex Vivo Study Examining Migration of Microplastics from an Infused Neonatal Parenteral Nutrition Circuit. Environ Health Perspect. 2024 Mar;132(3):37703. doi: 10.1289/EHP13491. Epub 2024 Mar 20. No abstract available.

Reference Type: RESULT

PMID: 38506503 (View on PubMed)

Panneel L, Cleys P, Poma G, Ait Bamai Y, Jorens PG, Covaci A, Mulder A. Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients. Environ Int. 2024 Apr;186:108605. doi: 10.1016/j.envint.2024.108605. Epub 2024 Mar 28.

Reference Type: RESULT

PMID: 38569425 (View on PubMed)

Other Identifiers

20/23/022

Identifier Type: -

Identifier Source: org_study_id