Exposure to Plasticisers in the Neonatal Intensive Care Unit

NCT05404815 | Completed

• 1 other identifier: 20/23/022
• Study Type: observational
• Target: 132
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Plasticizers; Phthalates; Alternative Plasticizers; Respiratory development; Neurodevelopmental outcome; Preterm birth; Neonatal Intensive Care Unit; NICU

Outcome Measures

Primary Outcomes (8)

• Level and sources of NICU exposure to phthalates and alternative plasticizers, measured by liquid chromatography coupled to tandem mass spectrometry in urine samples.

  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.

  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

  Prospective data collection

  NICU Discharge (or death, assessed up to 40 weeks post menstrual age)

• Perinatal Survival

  Prospective data collection

  NICU Discharge (or death, assessed up to 40 weeks post menstrual age)

• Respiratory development - 3 months

  Respiratory questionnaire

  3 months corrected for gestational age

• Respiratory development - 12 months

  Respiratory questionnaire

  12 months corrected for gestational age

• Neurodevelopmental outcome - 3 months

  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

  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

Eligibility Criteria

• Age: Up to 3 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

You may not qualify if:

• Major congenital abnormalities

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• Research Foundation Flanders: collaborator
• Universiteit Antwerpen: collaborator

Study Sites (1)

Antwerp University Hospital - Neonatal Intensive Care Unit

Edegem, Antwerp, 2650, Belgium

Location

Related Publications (5)

• 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

  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.

  PMID: 36526146 RESULT

• 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.

  PMID: 37482128 RESULT

• 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.

  PMID: 38506503 RESULT

• 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.

  PMID: 38569425 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine, hair, breast milk

MeSH Terms

Conditions

Premature Birth; Neurodevelopmental Disorders; Lung Diseases; Bronchopulmonary Dysplasia; Harm Reduction

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Mental Disorders; Respiratory Tract Diseases; Ventilator-Induced Lung Injury; Lung Injury; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior

Study Officials

• Philippe G Jorens, MD, PhD

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: June 3, 2022
• Study Start: June 2, 2020
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: August 19, 2024

Record last verified: 2023-08

Locations

BE (1)