Exposure to Plasticisers in the Neonatal Intensive Care Unit

Preterm Birth Clinical Trial

— PLASTIC-NICU  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05404815
• Other study ID #: 20/23/022
• Status: Active, not recruiting
• Start date: June 2, 2020
• Est. completion date: December 30, 2023

Study information

• Verified date: August 2023
• Source: University Hospital, Antwerp
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 132
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 3 Days

Eligibility

Inclusion Criteria:

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

• Healthy controls: term neonates

Exclusion Criteria:

• Major congenital abnormalities

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital - Neonatal Intensive Care Unit	Edegem	Antwerp

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Antwerp	Research Foundation Flanders, Universiteit Antwerpen

Country where clinical trial is conducted

Belgium, 

References & Publications (3)

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. Enviro — View Citation

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, DO

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.2022.122 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).
Primary	Perinatal Morbidity	Prospective data collection	NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Primary	Perinatal Survival	Prospective data collection	NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Primary	Respiratory development - 3 months	Respiratory questionnaire	3 months corrected for gestational age
Primary	Respiratory development - 12 months	Respiratory questionnaire	12 months corrected for gestational age
Primary	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
Primary	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