The Long-term Consequences of Neonatal Encephalopathy in the Hypothermia Era
NCT ID: NCT05756296
Last Updated: 2023-10-23
Study Results
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Basic Information
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NOT_YET_RECRUITING
198 participants
OBSERVATIONAL
2023-11-01
2028-12-31
Brief Summary
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1. Compare executive function, attention, social cognition, behaviour, anxiety, self-esteem, and peer problems between children with NE-TH and matched peers without NE.
2. Compare brain volumes, cortical and subcortical morphology, white matter microstructure, and myelination between children with NE-TH and matched peers without NE.
3. Evaluate the associations of perinatal risk factors and structural brain integrity with neuropsychological deficits to inform about the potential aggravating and protective factors for neuropsychological functioning.
Participants will complete one study visit to perform standardized evaluations and a brain MRI. Parents of participants will be invited to complete a series of questionnaires during this study visit or at a moment of their choice virtually.
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Detailed Description
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Therapeutic hypothermia (TH) became the standard of care treatment for neonates with moderate and severe neonatal encephalopathy (NE) in most industrialized countries about 10 years ago. Although TH is effective in reducing mortality and the incidence of severe developmental disabilities, various morbidities are still frequent in survivors. Moreover, because the focus of previous follow-up studies has been restricted to mortality rates and the most severe forms of morbidities, it is wrong to conclude that TH minimizes all developmental deficits. In fact, recent literature reports frequent cognitive and behavioural difficulties at school entry in children with NE-TH without severe disabilities. Although these difficulties can be less impressive than cerebral palsy and intellectual disability, their negative impacts on a child's self-determination and family well-being are not less important and their nature and extend need to be comprehensively assessed.
Aims and Hypotheses:
1. To compare higher-order cognitive, socialization, and psycho-emotional abilities using comprehensive standardized assessments of outcomes between 9-year-old children with NE-TH and age- and sex-matched peers without NE.
Hypothesis 1: Children with NE-TH will display lower IQ, executive functioning, attention, social cognition, and self-esteem, but more anxiety and behavioural and peer problems than age- and sex-matched peers without NE-TH.
2. To compare structural brain integrity using quantitative MRI between 9-year-old children with NE-TH and age- and sex-matched peers without NE.
Hypothesis 2: Children with NE-TH will present with smaller total and regional (basal ganglia, hippocampus, cerebellum) brain volumes, altered cortical and subcortical morphometry, and widespread white matter microstructural and myelination alterations when compared to age- and sex-matched peers without NE-TH.
3. To evaluate the relationships between cognitive, psycho-emotional and motor skills at 9 years and (1) individual and perinatal risk factors and (2) structural brain integrity at 9 years.
Hypothesis 3: A combination of individual (e.g., socio-economic), perinatal factors (e.g., neonatal brain injury) and markers of aberrant brain integrity (e.g., volume, microstructure) will be associated with domain-specific deficits at 9 years in children with NE-TH.
Population:
Children born between 2014 and 2018, who received whole-body cooling to an esophageal temperature of 33.5°C initiated within the first 6 hours of life, continued for 72 hours, and then they were slowly rewarmed for moderate or severe NE at one of the two centers will be approached. Eligibility for TH at our institutions followed those established in previous TH trials. Participants with a history of (1) congenital infections, (2) genetic or metabolic disorders, or (3) major brain malformations (e.g., lissencephaly), as well as (4) any contraindication for MRI (e.g., metal implant, claustrophobia), are ineligible.
For each of two same-sex and same-age NE-TH participants, a matched control for age (+/- 6 months of mean age) and sex will be recruited. Participants born at term (gestational age ≥37 weeks), without neonatal complication, will be considered as ineligible controls. Inclusion criteria for the controls include the same were similar to the NE-TH group, and a previous history of neurodevelopmental delay or disorder, or a traumatic brain injury were the specific exclusion cirteria for the comparison group.
Assessment procedure:
For this study, enrollees will complete one study visit to perform standardized evaluations and a brain MRI. Children will have the opportunity to familiarize themselves with the MRI environment on a mock scanner before the MRI and to watch a movie or listen to the music of their choice during the acquisition. Parents will be invited to complete a series of questionnaires during their child's testing or at a moment of their choice via a provided secure link. The visit will start with the outcome evaluations that are the most cognitively demanding and breaks will be provided as necessary. Outcome evaluations will be conducted by trained research staff or trainees blinded to the details of the child's neonatal and developmental history, and group allocation (i.e., NE-TH vs. control) to the extent possible. The choice of outcome measures has been made based on their clinical significance, psychometric properties, and availability in both French and English, considering the bilingual context of Quebec, Canada.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Intervention group
Children aged 9 years old with NE-TH meeting study inclusion criteria.
Therapeutic hypothermia
whole-body cooling to an esophageal temperature of 33.5°C initiated within the first 6 hours of life, continued for 72 hours, and then they were slowly rewarmed for moderate or severe NE
Control group
A comparison group of sex and age matched children with no NE-TH meeting similar study inclusion criteria to intervention group. Specific exclusion criteria for matched control group include a previous history of neurodevelopmental delay or disorder, or a traumatic brain injury, and born at term (gestational age ≥37 weeks), or born without neonatal complication.
No interventions assigned to this group
Interventions
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Therapeutic hypothermia
whole-body cooling to an esophageal temperature of 33.5°C initiated within the first 6 hours of life, continued for 72 hours, and then they were slowly rewarmed for moderate or severe NE
Eligibility Criteria
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Inclusion Criteria
* received whole-body cooling to an esophageal temperature of 33.5°C initiated within the first 6 hours of life, continued for 72 hours, and then they were slowly rewarmed received TH for moderate or severe NE
Exclusion Criteria
* congenital infections
* genetic or metabolic disorders
* major brain malformations (e.g., lissencephaly) and
* any contraindication for MRI (e.g., metal implant, claustrophobia)
8 Years
11 Years
ALL
No
Sponsors
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Canadian Institutes of Health Research (CIHR)
OTHER_GOV
McGill University Health Centre/Research Institute of the McGill University Health Centre
OTHER
Responsible Party
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Marie Brossard-Racine
Associate Professor
Locations
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Centre Hospitalier Universitaire Ste-Justine (CHUSJ).
Montreal, Quebec, Canada
the Montreal Children's Hospital (MCH) of the McGill University Health Centre
Montreal, Quebec, Canada
Countries
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Central Contacts
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Facility Contacts
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References
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Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005 Oct 13;353(15):1574-84. doi: 10.1056/NEJMcps050929.
Levine DS. Neuroexecutive Function. In: Encyclopedia of Human Behavior.2012:701-706
Scarpina F, Tagini S. The Stroop Color and Word Test. Front Psychol. 2017 Apr 12;8:557. doi: 10.3389/fpsyg.2017.00557. eCollection 2017.
Deli DC, Kaplan E, Kramer JH. Delis-Kaplan Executive Function System. Pearson Publication Inc; 2001
Rey A. L'examen psychologique dans les cas d'encéphalopathie traumatique. (Les problems.). [The psychological examination in cases of traumatic encepholopathy. Problems.]. Archives de Psychologie. 1941;28:215-285
Conners CK. Conner Continuous Performance Test - 3rd Ed Pearson Publication Inc.; 2014.
Hunt C, Borgida E, Lavine H. Social Cognition. In: Encyclopedia of Human Behavior.2012:456-462
Korjman M, Kirk U, Kemp S. NEPSY Second Edition (NEPSY-II): A developmental NEuroPSYchological Assessment. Pearson Publication Inc; 2007
Roid GH, Miller LJ. Leither Internaltional Performance Scale - Revised. Wod Dale, IL: Stoelting; 1997
Thompson EJ, Beauchamp MH, Darling SJ, Hearps SJC, Brown A, Charalambous G, Crossley L, Darby D, Dooley JJ, Greenham M, Jaimangal M, McDonald S, Muscara F, Turkstra L, Anderson VA. Protocol for a prospective, school-based standardisation study of a digital social skills assessment tool for children: The Paediatric Evaluation of Emotions, Relationships, and Socialisation (PEERS) study. BMJ Open. 2018 Feb 8;8(2):e016633. doi: 10.1136/bmjopen-2017-016633.
Beck J, S., Beck A, T., Jolly J, B. . Beck Youth Inventories - Second Edition. San Antonio, TX: Peason; 2005
Spence SH. Spence Children's Anxiety Scale. Washington, DC: American Psychology Association; 1997
March JS, Parker JD, Sullivan K, Stallings P, Conners CK. The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability, and validity. J Am Acad Child Adolesc Psychiatry. 1997 Apr;36(4):554-65. doi: 10.1097/00004583-199704000-00019.
Gratz KL, Roemer L. Multidimensional Assessment of Emotion Regulation and Dysregulation: Development, Factor Structure, and Initial Validation of the Difficulties in Emotion Regulation Scale. Journal of Pyschopathology and Behavioral Assessment. 2004;26(1):41-54
Russel DJ, Rosenbaum P, Wright M, Avery LM. Gross Motor Function Measure (GMFM-66 & GMFM-88) User's Manual, 2nd Edition. 2nd ed: Mac Keith Press; 2013
Harrison P, Oakland T. Adaptive Behavior Assessment Systems 3rd Ed. Pearson Publication Inc; 2015.
Brossard-Racine M, Rampakakis E, Tardif CL, Gilbert G, White A, Luu TM, Gallagher A, Pinchefsky E, Montreuil T, Simard MN, Wintermark P. Long-term consequences of neonatal encephalopathy in the hypothermia era: protocol for a follow-up cohort study at 9 years of age. BMJ Open. 2023 Apr 13;13(4):e073063. doi: 10.1136/bmjopen-2023-073063.
Other Identifiers
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MP-37-2023-9320
Identifier Type: -
Identifier Source: org_study_id
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