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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Function; BPD - Bronchopulmonary Dysplasia
• Intervention / Treatment: Diagnostic test: Magnetic Resonance Imaging (MRI); Diagnostic test: Echocardiogram; Diagnostic test: Lung ultrasound

• Study Type: Observational
• Enrollment (Estimated): 319

Contacts and Locations

• Study Contact: Name: Sherri Katz; Phone Number: (613) 737-7600; Email: skatz@cheo.on.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Recruiting
      • The Children's Hospital of Eastern Ontario
      • Contact: Sherri Katz, Clinical Study Lead; Phone Number: 2956 (613) 737-7600; Email: skatz@cheo.on.ca
    • Toronto, Ontario, Canada, M5G 1X5
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Adel Mohamed, Site Lead; Phone Number: 7396 416-586-4800; Email: adel.mohamed@sinaihealth.ca
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Montreal Children's Hospital
      • Contact: Gabriel Altit, Co-Site Lead; Email: gabriel.altit@mcgill.ca
      • Contact: Larry Lands, Co-Site Lead; Email: larry.lands@mcgill.ca
    • Montréal, Quebec, Canada, H3T 1C5
      • Active, not recruiting
      • CHU-Sainte Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Babies will be recruited from four Canadian tertiary care pediatric centers: Children's Hospital of Eastern Ontario (CHEO), Ottawa, ON; Mount Sinai Hospital, Toronto, ON; Centre Hospitalier Universitaire Sainte-Justine, Montreal QC; and Montreal Children's Hospital, Montreal QC. MRI will occur at each site except Mount Sinai, whose babies will undergo MRI at The Hospital for Sick Children, Toronto, ON.

Description

Inclusion Criteria:

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

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Post-prematurity Respiratory Disease (PRD)	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental Impairment (NDI)	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.	Neurodevelopmental impairment will be determined at the 18-21 months corrected age visit

Collaborators and Investigators

• Sponsor: Children's Hospital of Eastern Ontario
• Collaborators: The Hospital for Sick Children; Hannover Medical School; MOUNT SINAI HOSPITAL; St. Justine's Hospital; Montreal Children's Hospital of the MUHC
• Investigators: Principal Investigator: Sherri Katz, Children's Hospital of Eastern Ontario

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia
• Other Study ID Numbers: 486713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No