Early-life MRI Biomarkers of Longer-term Respiratory Morbidity in Infants Born Extremely Preterm (EMBLEM)

Recruiting

• Conditions: Lung Function; BPD - Bronchopulmonary Dysplasia

• Registration Number: NCT06065215
• Lead Sponsor: Children's Hospital of Eastern Ontario

Brief Summary

Bronchopulmonary dysplasia (BPD) is a common, major complication of premature birth, associated with developmental and health consequences that continue into adulthood. Prediction of who will have these problems is challenging using traditional definitions of disease. It is believed that underdevelopment and injury occur in both lung tissue and the blood vessels in the lungs, with a sophisticated interplay between them that contributes to lung disease seen in prematurity. New magnetic resonance imaging (MRI) techniques can delineate tissue structure with unprecedented granularity, assessing lung tissue, blood vessels, and their interplay. The ability to identify, at an early stage, those infants destined for chronic lung disease with greater certainty will be useful in counseling families and critical for the effective introduction of promising new BPD therapies. 319 infants born less than 29 weeks gestation will be recruited from 4 centres, including 5 babies who received stem cell therapy in a clinical trial. Babies will be evaluated at 36 weeks post-conception with lung MRI, oscillometry (lung function), echocardiogram (heart ultrasound), and oscillometry. Lung health will be assessed every 3 months by phone questionnaire and chart review. At 18-21 months post-conception, babies will undergo neurodevelopmental assessment and lung function testing. The investigators will look at how well baseline MRI markers predict subsequent lung health and development, independently and combined with echocardiogram, lung ultrasound, and traditional markers of BPD. The investigators anticipate that these new MRI markers will measure lung health safely and longitudinally in babies born extremely preterm. By identifying predictors of longer-term lung disease, clinicians will be able to allocate resources to babies at the highest risk of severe disease. Further, The investigators envision that MRI will help identify babies who would benefit most from interventions like stem cell therapy and be useful for evaluation of future treatments.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-27
• Study First Submitted QC: 2023-09-27
• Study First Posted: 2023-10-03
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-07
• Last Update Posted: 2024-03-08
• Study Start: 2024-03-30
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 319

Inclusion Criteria

1. Infants born at <29 weeks gestation;
2. currently <36 weeks PMA.

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Exclusion Criteria

1. Known interstitial lung disease, congenital lung anomaly, ciliary dysfunction, immunodeficiency, cystic fibrosis, neuromuscular disease, or structural heart disease (other than atrial septal defect/hemodynamically insignificant ventricular septal defect/patent ductus arteriosus);
2. genetic syndrome or congenital anomaly;
3. contraindications for MRI or transport;
4. invasive or non-invasive ventilation that cannot be safely removed for MRI;
5. current respiratory infection;
6. family cannot speak English/French;
7. transferred to another hospital prior to baseline study visit
8. not receiving follow-up at one of the study centres.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Severe Post-prematurity Respiratory Disease (PRD)	The evaluation will be conducted at regular intervals of every 3 months, commencing at 36 weeks PMA and continuing until the child reaches 18 months corrected age	PRD will be defined based on the consensus definition of the Prematurity and Respiratory Outcomes Program. This composite outcome characterizes clinically relevant persistent respiratory morbidity in early life. It will be evaluated every 3 months from 36 weeks PMA to 18 months corrected age through parent questionnaire and chart review. Severe PRD is defined as a positive response to any of the following: ≥2 respiratory-related hospitalizations, home oxygen at 3 months corrected age or any home respiratory support, systemic corticosteroid or pulmonary vasodilators after discharge home, chronic respiratory symptoms (cough without cold or wheeze at least once per week) despite concurrent inhaled corticosteroids in ≥ 2 questionnaires, or death secondary to a cardiopulmonary cause. PRD has been used as a clinical outcome in cohort studies and an American Thoracic Society guideline on optimal neonatal care pathways and predictive perinatal characteristics.

Secondary Outcome Measures

Name	Time	Method
Neurodevelopmental Impairment (NDI)	Neurodevelopmental impairment will be determined at the 18-21 months corrected age visit	Per the Canadian Neonatal Follow-Up Network protocol, NDI will be determined at the 18-21 months corrected age visit. Children will be administered the Bayley Scales of Infant and Toddler Development, 4th edition (Bayley-4), assessing infant developmental functioning across five domains. Cognition, language, and motor subtests are directly assessed by a blinded, trained assessor regarding neonatal history. The social-emotional and adaptive behavior components are assessed via parental questionnaires. The Bayley-4 yields standard mean scores of 100±15. A pediatrician performs a neurological examination to identify signs of cerebral palsy and determine functional level using the Gross Motor Functional Classification System (GMFCS). Visual and hearing function data are retrieved from the chart. NDI will be defined as the presence of any of the following: Bayley-4 score \<85, cerebral palsy with GMFCS ≥ 2, the requirement for hearing aids/cochlear implants, and bilateral blindness.

Trial Locations

Locations (4)

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

Montreal Children's Hospital; 🇨🇦 Montréal, Quebec, Canada

CHU-Sainte Justine; 🇨🇦 Montréal, Quebec, Canada

The Children's Hospital of Eastern Ontario; 🇨🇦 Ottawa, Ontario, Canada