Transient Hypothyroxinemia of PrematurityEEG-THOPNCT03493113
EEG Alterations in Preterm Infants With Thyroid Dysfunction
An observational study of Transient Hypothyroxinemia of Prematurity, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
The aim of this study is to investigate differences in electroencephalography (EEG) evolution between preterm infants with and without transient hypothyroxinemia of prematurity (THOP) in order to find differences in the interburst interval and the background pattern and in the maturation of the sleep-wake cycle. Read more about this study
- Who is it for?
- Ages 24 to 27 weeks
- Conditions the study is for
- Transient Hypothyroxinemia of Prematurity
- What is being tested?
- EEG
- How many people
- 87 participants
- Where
- 1 siteBelgium
- Study dates
- Oct 2011to Oct 2017
- 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 24 to 27 weeks
- All sexes
- No healthy volunteers
- Child
Study population: Preterm infants who had EEG recordings in the framework of the Resilience study and gestational age < 28 weeks.
Who may be able to join
- gestational age < 28 weeks
- serial EEG recordings available
- thyroid function test on the first day of life and at the end of the first week of life available
Who cannot join
- Presence of congenital abnormalities
Trial locations and contacts
1 site in 1 country.
Belgium1 site
UZ Leuven, Department of Neonatology
Leuven, Vlaams-Brabant, 3000
About this study
Official title: Transient Hypothyroxinemia of Prematurity: Electrophysiological Changes in the Preterm Infants' Brain, a Retrospective Study
The aim of this study is to investigate differences in electroencephalography (EEG) evolution between preterm infants with and without transient hypothyroxinemia of prematurity (THOP) in order to find differences in the interburst interval and the background pattern and in the maturation of the sleep-wake cycle.
Read the detailed description
- Definition of THOP The determination of thyroid hormones (TH) are assay-specific and related to the infants' gestational age (GA) and moment of determination. Immediately after birth, there will be a surge of TH, subsequently followed by a decrease to basal levels. Therefore, it is difficult to obtain reference values. The investigators plan to set out specific reference values for the preterm patient population, based on the TH laboratory results of cord blood, performed in the clinical laboratory of UZ Leuven and available over the last 4 years. The results will be linked to the gestational age. Dependent whether the data distribution is normal or not, the investigators are planning to use standard deviations or percentiles to classify patients.
- EEG findings In this retrospective study, quantitative EEG- sleep behavior at (near) term age (GA 36-44 weeks) in preterm infants born <28 weeks GA, will be analyzed (n = 87).
EEGs were taken in the framework of the Resilience study and hereby, parental informed consent was already obtained.
TH function is assessed in preterm infants ≤ 34 weeks as part of the clinical care protocol. No additional blood samples were taken.
Quantitative EEG measures will be compared between the preterm infants with THOP (circulating thyroxine levels< P10) and without THOP. Logisitic regression will be performed to determine the effect of thyroid function as well as other clinical and demographic variables, on functional brain development at term equivalent age. These results will also be linked to long-term neurodevelopment outcome.
In a subgroup of these preterm patients (n=42) sequential EEGs, recorded during their stay at the neonatal intensive care unit, are available. These EEGs will be analyzed in a fully automatic way to assess functional EEG- brain maturation.
In this way, the investigators want to investigate whether deviations of normal preterm EEG-brain maturation can be discerned in preterm neonates with THOP and without THOP.
In preterm infants with GA < 32 weeks, developmental follow up data are available at the corrected age of 9 months and 2 years (Follow up Convention). The investigators will use these results and link them to the EEG findings and THOP data.
- Being tested
- EEG
- Keywords
- EEG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EEGDiagnostic test
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in EEG measures in preterm infants with thyroid dysfunction
Quantitative EEG measures will be compared between the preterm infants with THOP (circulating T4 level< P10) and without THOP. In a subgroup of these preterm patients (n=42) sequential EEGs, recorded during their stay at the NICU, are available. These EEGs will be analyzed in a fully automatic way to assess functional EEG- brain maturation.
Measured: November 2011 - November 2017
Secondary outcomes (1)
Neurodevelopmental disturbances due to THOP and predicted by EEG alterations
In preterm infants with GA < 32 weeks, developmental follow up data are available at the corrected age of 9 months and 2 years (Follow up Convention). We will use these results and link them to the EEG findings and THOP data.
Measured: November 2011 - November 2019
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2018
- Study startOct 2011
- Primary completionOct 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Transient Hypothyroxinemia of PrematurityStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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
- Retrospective
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03493113
- Sponsor's protocol ID
- S61028
- Acronym
- EEG-THOP
- Status last verified
- Nov 2017
- First submitted
- 27 Nov 2017
- Last updated
- 10 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
La Gamma EF, Paneth N. Clinical importance of hypothyroxinemia in the preterm infant and a discussion of treatment concerns. Curr Opin Pediatr. 2012 Apr;24(2):172-80. doi: 10.1097/MOP.0b013e32835067cc.
PubMed 22273635Reuss ML, Paneth N, Pinto-Martin JA, Lorenz JM, Susser M. The relation of transient hypothyroxinemia in preterm infants to neurologic development at two years of age. N Engl J Med. 1996 Mar 28;334(13):821-7. doi: 10.1056/NEJM199603283341303.
PubMed 8596548Leviton A, Paneth N, Reuss ML, Susser M, Allred EN, Dammann O, Kuban K, Van Marter LJ, Pagano M. Hypothyroxinemia of prematurity and the risk of cerebral white matter damage. J Pediatr. 1999 Jun;134(6):706-11. doi: 10.1016/s0022-3476(99)70285-4.
PubMed 10356138Auso E, Lavado-Autric R, Cuevas E, Del Rey FE, Morreale De Escobar G, Berbel P. A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration. Endocrinology. 2004 Sep;145(9):4037-47. doi: 10.1210/en.2004-0274. Epub 2004 Apr 15.
PubMed 15087434Santisteban P, Bernal J. Thyroid development and effect on the nervous system. Rev Endocr Metab Disord. 2005 Aug;6(3):217-28. doi: 10.1007/s11154-005-3053-9. No abstract available.
PubMed 16151626Fisher DA. Thyroid system immaturities in very low birth weight premature infants. Semin Perinatol. 2008 Dec;32(6):387-97. doi: 10.1053/j.semperi.2008.09.003.
PubMed 19007675Shellhaas RA, Burns JW, Barks JD, Chervin RD. Quantitative sleep stage analyses as a window to neonatal neurologic function. Neurology. 2014 Feb 4;82(5):390-5. doi: 10.1212/WNL.0000000000000085. Epub 2014 Jan 2.
PubMed 24384644Scher MS, Loparo KA. Neonatal EEG/sleep state analyses: a complex phenotype of developmental neural plasticity. Dev Neurosci. 2009;31(4):259-75. doi: 10.1159/000216537. Epub 2009 Jan 2.
PubMed 19546563Koolen N, Dereymaeker A, Rasanen O, Jansen K, Vervisch J, Matic V, Naulaers G, De Vos M, Van Huffel S, Vanhatalo S. Early development of synchrony in cortical activations in the human. Neuroscience. 2016 May 13;322:298-307. doi: 10.1016/j.neuroscience.2016.02.017. Epub 2016 Feb 11.
PubMed 26876605Shellhaas RA, Burns JW, Hassan F, Carlson MD, Barks JDE, Chervin RD. Neonatal Sleep-Wake Analyses Predict 18-month Neurodevelopmental Outcomes. Sleep. 2017 Nov 1;40(11):zsx144. doi: 10.1093/sleep/zsx144.
PubMed 28958087Scher MS, Steppe DA, Banks DL. Prediction of lower developmental performances of healthy neonates by neonatal EEG-sleep measures. Pediatr Neurol. 1996 Feb;14(2):137-44. doi: 10.1016/0887-8994(96)00013-6.
PubMed 8703226Niemarkt HJ, Jennekens W, Maartens IA, Wassenberg T, van Aken M, Katgert T, Kramer BW, Gavilanes AW, Zimmermann LJ, Bambang Oetomo S, Andriessen P. Multi-channel amplitude-integrated EEG characteristics in preterm infants with a normal neurodevelopment at two years of corrected age. Early Hum Dev. 2012 Apr;88(4):209-16. doi: 10.1016/j.earlhumdev.2011.08.008. Epub 2011 Sep 15.
PubMed 21924567Niemarkt HJ, Jennekens W, Pasman JW, Katgert T, Van Pul C, Gavilanes AW, Kramer BW, Zimmermann LJ, Bambang Oetomo S, Andriessen P. Maturational changes in automated EEG spectral power analysis in preterm infants. Pediatr Res. 2011 Nov;70(5):529-34. doi: 10.1203/PDR.0b013e31822d748b.
PubMed 21772227Khedr EM, El Toony LF, Tarkhan MN, Abdella G. Peripheral and central nervous system alterations in hypothyroidism: electrophysiological findings. Neuropsychobiology. 2000 Jan;41(2):88-94. doi: 10.1159/000026638.
PubMed 10644929Fisher DA, Odell WD. Acute release of thyrotropin in the newborn. J Clin Invest. 1969 Sep;48(9):1670-7. doi: 10.1172/JCI106132.
PubMed 5822577
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transient Hypothyroxinemia of Prematurity: Electrophysiological Changes in the Preterm Infants' Brain, a Retrospective Study
- ClinicalTrials.gov ID
- NCT03493113
- Acronym / sponsor ID
- EEG-THOP / S61028
- Keywords
- EEG
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- KU Leuven
- Study start
- Oct 2011 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 10 Apr 2018 (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.
The aim of this study is to investigate differences in electroencephalography (EEG) evolution between preterm infants with and without transient hypothyroxinemia of prematurity (THOP) in order to find differences in the interburst interval and the background pattern and in the maturation of the sleep-wake cycle.
Detailed description
- Definition of THOP The determination of thyroid hormones (TH) are assay-specific and related to the infants' gestational age (GA) and moment of determination. Immediately after birth, there will be a surge of TH, subsequently followed by a decrease to basal levels. Therefore, it is difficult to obtain reference values. The investigators plan to set out specific reference values for the preterm patient population, based on the TH laboratory results of cord blood, performed in the clinical laboratory of UZ Leuven and available over the last 4 years. The results will be linked to the gestational age. Dependent whether the data distribution is normal or not, the investigators are planning to use standard deviations or percentiles to classify patients.
- EEG findings In this retrospective study, quantitative EEG- sleep behavior at (near) term age (GA 36-44 weeks) in preterm infants born <28 weeks GA, will be analyzed (n = 87).
EEGs were taken in the framework of the Resilience study and hereby, parental informed consent was already obtained.
TH function is assessed in preterm infants ≤ 34 weeks as part of the clinical care protocol. No additional blood samples were taken.
Quantitative EEG measures will be compared between the preterm infants with THOP (circulating thyroxine levels< P10) and without THOP. Logisitic regression will be performed to determine the effect of thyroid function as well as other clinical and demographic variables, on functional brain development at term equivalent age. These results will also be linked to long-term neurodevelopment outcome.
In a subgroup of these preterm patients (n=42) sequential EEGs, recorded during their stay at the neonatal intensive care unit, are available. These EEGs will be analyzed in a fully automatic way to assess functional EEG- brain maturation.
In this way, the investigators want to investigate whether deviations of normal preterm EEG-brain maturation can be discerned in preterm neonates with THOP and without THOP.
In preterm infants with GA < 32 weeks, developmental follow up data are available at the corrected age of 9 months and 2 years (Follow up Convention). The investigators will use these results and link them to the EEG findings and THOP data.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 24 to 27 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Preterm infants who had EEG recordings in the framework of the Resilience study and gestational age < 28 weeks.
Key inclusion criteria (3 listed)
- gestational age < 28 weeks
- serial EEG recordings available
- thyroid function test on the first day of life and at the end of the first week of life available
Key exclusion criteria (1 listed)
- Presence of 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.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EEG | Diagnostic test | – |
Primary outcome
Differences in EEG measures in preterm infants with thyroid dysfunction
Time frame: November 2011 - November 2017
Quantitative EEG measures will be compared between the preterm infants with THOP (circulating T4 level< P10) and without THOP. In a subgroup of these preterm patients (n=42) sequential EEGs, recorded during their stay at the NICU, are available. These EEGs will be analyzed in a fully automatic way to assess functional EEG- brain maturation.
1 secondary outcome
Neurodevelopmental disturbances due to THOP and predicted by EEG alterations
Time frame: November 2011 - November 2019
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 10 Apr 2018.
- Results publication: PubMed 22273635La Gamma EF, Paneth N. Clinical importance of hypothyroxinemia in the preterm infant and a discussion of treatment concerns. Curr Opin Pediatr. 2012 Apr;24(2):172-80. doi: 10.1097/MOP.0b013e32835067cc.
- Results publication: PubMed 8596548Reuss ML, Paneth N, Pinto-Martin JA, Lorenz JM, Susser M. The relation of transient hypothyroxinemia in preterm infants to neurologic development at two years of age. N Engl J Med. 1996 Mar 28;334(13):821-7. doi: 10.1056/NEJM199603283341303.
- Results publication: PubMed 10356138Leviton A, Paneth N, Reuss ML, Susser M, Allred EN, Dammann O, Kuban K, Van Marter LJ, Pagano M. Hypothyroxinemia of prematurity and the risk of cerebral white matter damage. J Pediatr. 1999 Jun;134(6):706-11. doi: 10.1016/s0022-3476(99)70285-4.
- Results publication: PubMed 15087434Auso E, Lavado-Autric R, Cuevas E, Del Rey FE, Morreale De Escobar G, Berbel P. A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration. Endocrinology. 2004 Sep;145(9):4037-47. doi: 10.1210/en.2004-0274. Epub 2004 Apr 15.
- Results publication: PubMed 16151626Santisteban P, Bernal J. Thyroid development and effect on the nervous system. Rev Endocr Metab Disord. 2005 Aug;6(3):217-28. doi: 10.1007/s11154-005-3053-9. No abstract available.
- Results publication: PubMed 19007675Fisher DA. Thyroid system immaturities in very low birth weight premature infants. Semin Perinatol. 2008 Dec;32(6):387-97. doi: 10.1053/j.semperi.2008.09.003.
- Results publication: PubMed 24384644Shellhaas RA, Burns JW, Barks JD, Chervin RD. Quantitative sleep stage analyses as a window to neonatal neurologic function. Neurology. 2014 Feb 4;82(5):390-5. doi: 10.1212/WNL.0000000000000085. Epub 2014 Jan 2.
- Results publication: PubMed 19546563Scher MS, Loparo KA. Neonatal EEG/sleep state analyses: a complex phenotype of developmental neural plasticity. Dev Neurosci. 2009;31(4):259-75. doi: 10.1159/000216537. Epub 2009 Jan 2.
- Results publication: PubMed 26876605Koolen N, Dereymaeker A, Rasanen O, Jansen K, Vervisch J, Matic V, Naulaers G, De Vos M, Van Huffel S, Vanhatalo S. Early development of synchrony in cortical activations in the human. Neuroscience. 2016 May 13;322:298-307. doi: 10.1016/j.neuroscience.2016.02.017. Epub 2016 Feb 11.
- Results publication: PubMed 28958087Shellhaas RA, Burns JW, Hassan F, Carlson MD, Barks JDE, Chervin RD. Neonatal Sleep-Wake Analyses Predict 18-month Neurodevelopmental Outcomes. Sleep. 2017 Nov 1;40(11):zsx144. doi: 10.1093/sleep/zsx144.
- Results publication: PubMed 8703226Scher MS, Steppe DA, Banks DL. Prediction of lower developmental performances of healthy neonates by neonatal EEG-sleep measures. Pediatr Neurol. 1996 Feb;14(2):137-44. doi: 10.1016/0887-8994(96)00013-6.
- Results publication: PubMed 21924567Niemarkt HJ, Jennekens W, Maartens IA, Wassenberg T, van Aken M, Katgert T, Kramer BW, Gavilanes AW, Zimmermann LJ, Bambang Oetomo S, Andriessen P. Multi-channel amplitude-integrated EEG characteristics in preterm infants with a normal neurodevelopment at two years of corrected age. Early Hum Dev. 2012 Apr;88(4):209-16. doi: 10.1016/j.earlhumdev.2011.08.008. Epub 2011 Sep 15.
- Individual participant dataSharing planned: No
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Transient Hypothyroxinemia of Prematurity, run by Universitaire Ziekenhuizen KU Leuven 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 3 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 10 Apr 2018. 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?
Differences in EEG measures in preterm infants with thyroid dysfunction (time frame: November 2011 - November 2017). 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 NCT03493113, which also lists 19 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 10 Apr 2018.