Preterm BirthPLASTIC-NICUNCT05404815
Exposure to Plasticisers in the Neonatal Intensive Care Unit
An observational study of Preterm Birth and Premature Birth, run by University Hospital, Antwerp at 1 site in Belgium.
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. Read more about this study
- Who is it for?
- Ages Up to 3 daysHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth, Premature Birth, Neurodevelopmental Disorders
- How many people
- 132 participants
- Where
- 1 siteBelgium
- Study dates
- 2 Jun 2020to 30 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 3 days
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- Preterm NICU neonates: Gestational Age < 31 weeks and/or birth weight < 1500 gram
- Healthy controls: term neonates
Who cannot join
- Major congenital abnormalities
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Antwerp University Hospital - Neonatal Intensive Care Unit
Edegem, Antwerp, 2650
About this study
Official title: 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.
Read the 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
- Keywords
- Plasticizers, Phthalates, Alternative Plasticizers, Respiratory development, Neurodevelopmental outcome, Preterm birth, Neonatal Intensive Care Unit, NICU
- Medical subject headings
- Premature Birth, Neurodevelopmental Disorders, Lung Diseases, Bronchopulmonary Dysplasia, Harm Reduction
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Scalp hair samples are being collected at term age (37-40 weeks post menstrual age).
Perinatal Morbidity
Prospective data collection
Measured: NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Perinatal Survival
Prospective data collection
Measured: NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Respiratory development - 3 months
Respiratory questionnaire
Measured: 3 months corrected for gestational age
Respiratory development - 12 months
Respiratory questionnaire
Measured: 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
Measured: 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
Measured: 12 months corrected for gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2022
- Study start2 Jun 2020
- Primary completion30 Dec 2023
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Research Foundation Flanders, Universiteit Antwerpen
- Responsible party
- Sponsor
- Investigators
- Philippe G Jorens, MD, PhD, Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05404815
- Sponsor's protocol ID
- 20/23/022
- Acronym
- PLASTIC-NICU
- Status last verified
- Aug 2023
- First submitted
- 13 May 2022
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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
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.
PubMed 36526146Cleys 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.
PubMed 37482128Vercauteren 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.
PubMed 38506503Panneel 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.
PubMed 38569425
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exposure to Plasticizers in the Neonatal Intensive Care Unit and Long- Term Neurodevelopmental and Pulmonary Toxicity
- ClinicalTrials.gov ID
- NCT05404815
- Acronym / sponsor ID
- PLASTIC-NICU / 20/23/022
- Conditions
- Preterm Birth, Premature Birth, Neurodevelopmental Disorders, Pulmonary Disease, Bronchopulmonary Dysplasia, Harm Reduction
- Keywords
- Plasticizers, Phthalates, Alternative Plasticizers, Respiratory development, Neurodevelopmental outcome, Preterm birth, Neonatal Intensive Care Unit, NICU
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Research Foundation Flanders, Universiteit Antwerpen
- Study start
- 2 Jun 2020 (actual)
- Primary completion
- 30 Dec 2023 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 3 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 3 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (2 listed)
- Preterm NICU neonates: Gestational Age < 31 weeks and/or birth weight < 1500 gram
- Healthy controls: term neonates
Key exclusion criteria (1 listed)
- Major congenital abnormalities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
Perinatal Morbidity
Time frame: NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Prospective data collection
Perinatal Survival
Time frame: NICU Discharge (or death, assessed up to 40 weeks post menstrual age)
Prospective data collection
Respiratory development - 3 months
Time frame: 3 months corrected for gestational age
Respiratory questionnaire
Respiratory development - 12 months
Time frame: 12 months corrected for gestational age
Respiratory questionnaire
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
- Results publicationLucas 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
- Results publication: PubMed 36526146Panneel 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.
- Results publication: PubMed 37482128Cleys 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.
- Results publication: PubMed 38506503Vercauteren 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.
- Results publication: PubMed 38569425Panneel 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe G Jorens, MD, PhD principal investigator
University Hospital, Antwerp
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Preterm Birth and Premature Birth, run by University Hospital, Antwerp at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05404815, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.