Multidimensional Phenotype Classification in Grade 3 Bronchopulmonary Dysplasia
NCT Number: NCT06475976
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Bronchopulmonary Dysplasia
Interventions: DIAGNOSTIC_TEST: Chest computed tomography (CT) with angiography|DIAGNOSTIC_TEST: Bronchoscopy with bronchoalveolar lavage|DIAGNOSTIC_TEST: Echocardiography|DIAGNOSTIC_TEST: 24 hour esophageal pH ("potential of hydrogen") - multichannel intraluminal impedance (MII) monitoring (reflux testing)
Sponsor: Children's Hospital of Philadelphia
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Sex: ALL
Age: CHILD
Enrollment: 130
Study Design: Observational Model: |Time Perspective: p
Start Date: 2023-12-05
Completion Date: 2029-07-31
Locations: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, United States

Summary:
Bronchopulmonary Dysplasia (BPD), or chronic lung disease of prematurity, is the most consequential complication of preterm birth and is strong predictor of childhood pulmonary and neurodevelopmental disability, particularly in infants diagnosed with grade 3 BPD (ventilator dependence at 36 weeks' postmenstrual age), the most severe disease form. This study aims to (1) generate the first empirically defined phenotype classification system for grade 3 BPD developed using a rich array of objective and quantitative cardiopulmonary diagnostic, clinical, and biological data; and (2) define the association between phenotype subgroups and neurodevelopmental and respiratory outcomes through 2 years' corrected age.

Primary Outcome Measures: Empirically defined phenotype subgroup, The number and characteristics of phenotype subgroups will be empirically defined using cluster analyses applied to the collected cardiopulmonary diagnostic and clinical data. All recorded diagnostic and clinical information will be considered for inclusion in these analyses. Final study reports will indicate which diagnostic and clinical data were most associated with cluster classification. The strength of association between assigned cluster and neurodevelopmental and respiratory outcomes assessed through 26 months' corrected age will be defined., Up to 26 months' corrected age
Secondary Outcome Measures: Moderate to severe neurodevelopmental impairment (NDI), Moderate to severe NDI is a composite outcome that will be defined as the presence of one or more of the following outcomes at 22-26 month follow-up: Bayley Scale of Infant Development IV (BSID IV) cognitive score ≤84, Gross Motor Functional (GMF) level of 2-5, hearing deficit requiring amplification to understand commands or inability to understand commands despite amplification, blindness (\<20/200 vision) in one or both eyes based on visual acuity screening or medical history, and/or profound hearing loss (inability to understand commands despite amplification). The BSID is a standard series of developmental play tasks that are assessed by a trained clinician and takes between 45-60 minutes to complete. GMF is assessed using the 5-level Gross Motor Functional Classification System (GMFCS) that describes gross motor function on the basis of self initiated movement abilities., Up to 26 months' corrected age|Total problem behavior score, Behavior difficulties will be assessed using the Child Behavior Checklist (CBCL) at 22-26 month follow-up. Parents/caregivers complete 100 questions from observations of their child's behaviors, using a 3-point scale (this behavior is: "not true", "somewhat true", "very or often true"). The mean and standard deviation is 50 ±10. Higher scores indicate increased behavioral problems. Estimated time to administer the CBCL is 10-15 minutes. The questions are grouped into Diagnostic and Statistical Manual (DSM) oriented scales (affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant problems). These scales are grouped into empirically based composite scales measuring internalizing and externalizing. These values will be aggregated to derive the total problem behavior score which will be the primary measure of child behavior difficulties for this study., Up to 26 months' corrected age|Health related quality of life, Child health-related quality of life will be assessed using the Infant and Toddler Quality of Life Questionnaire Short Form (ITQOL-SF47). The ITQOL-SF47 has 47 questions and assesses domains such as the overall health, physical abilities, growth and development, bodily pain/discomfort, temperament and moods, general health perceptions, parent impact - emotional, parent impact - time and family cohesion with a score of 0 (worst) to 100 (best) for each of these domains., Up to 26 months' corrected age|Abnormal respiratory signs/symptoms, Recent history of wheezing/whistling, limitations of daily activities due to wheezing, and persistent cough. This will be assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) respiratory questionnaire which includes 6 questions based on the presence of wheeze, cough, night time respiratory signs, and limitations and activity., Up to 26 months' corrected age|Moderate to severe respiratory compromise, Moderate to severe respiratory compromise is a composite outcome that will be defined as one or more of the following:

* Tracheostomy placed any time between birth and 22-26 month follow-up
* home O2 therapy or positive airway pressure at 22-26 month follow-up
* ≥ 2 re-hospitalizations respiratory reasons - including viral respiratory infections through 22-26 month follow-up
* Respiratory medications (inhaled therapies, corticosteroids, diuretics) in the 3mo prior to 22-26 month follow-up.
* Home respiratory monitor (pulse oximeter, apnea monitor) use at 22-26 month follow-up., Up to 26 months' corrected age|Mortality, Death before anticipated 2 year follow-up, Up to 26 months' corrected age