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

Sponsor

University Hospital, Antwerp (Other)

Overall Status

Recruiting

CT.gov ID

NCT05404815

Collaborator

Research Foundation Flanders (Other), Universiteit Antwerpen (Other)

130

Enrollment

Location

42.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Preterm Birth Premature Birth Neurodevelopmental Disorders Pulmonary Disease Bronchopulmonary Dysplasia Harm Reduction Environmental Exposure Development, Infant

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 Design

Study Type:

Observational

Anticipated Enrollment :

130 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jun 2, 2020

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 30, 2023

Outcome Measures

Primary Outcome Measures

Level and sources of NICU exposure to phthalates and alternative plasticizers, measured by liquid chromatography coupled to tandem mass spectrometry in urine samples. [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.
Level and sources of NICU exposure to phthalates and alternative plasticizers, measured by liquid chromatography coupled to tandem mass spectrometry in hair samples. [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.
Perinatal Morbidity [NICU Discharge (or death, assessed up to 40 weeks post menstrual age)]
Prospective data collection
Perinatal Survival [NICU Discharge (or death, assessed up to 40 weeks post menstrual age)]
Prospective data collection
Respiratory development - 3 months [3 months corrected for gestational age]
Respiratory questionnaire
Respiratory development - 12 months [12 months corrected for gestational age]
Respiratory questionnaire
Neurodevelopmental outcome - 3 months [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
Neurodevelopmental outcome - 12 months [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