Post-Vent, the Sequelae: Personalized Prognostic Modeling for Consequences of Neonatal Intermittent Hypoxemia in Preterm Infants at Pre-School Age

Study Overview
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Brief Summary
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Despite improved survival of extremely premature infants in recent decades, neonatal intensive care unit (NICU) graduates are diagnosed with asthma, sleep disordered breathing (SDB) in childhood, and neurodevelopmental impairments (NDI) at significant rates, disproportionate to their term peers. Early detection and intervention are critical to mitigate the impact of these impairments. Mechanisms leading from premature birth to these undesirable outcomes remain unclear, and accurate prognostic measures are lacking. This study wants to learn if these problems are related to certain patterns of breathing that babies had while they were in the NICU.

Detailed Description
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Asthma, SDB, and NDI are common consequences of preterm birth with significant impact on child and family quality of life and public health. To date, the mechanisms leading to these outcomes remain unclear, and improvements in neonatal care have not improved these outcomes. While early detection and intervention can reduce the burden of these outcomes, methods for early identification of infants destined for these morbidities is currently lacking. Utilizing the Pre-Vent cohort to investigate potential underlying causes and identify predictors for these conditions as we propose here is essential to inform future prevention and intervention strategies that promote optimal health and development. Recent compelling data indicate that early postnatal intermittent hypoxemia (IH) events may play a role in undesirable outcomes. Early postnatal IH events in extremely preterm infants are associated with bronchopulmonary dysplasia (BPD), asthma medication at 2 years, and NDI at 18 months. The ability of IH to perturb maturation of long-term respiratory control has been demonstrated in neonatal rodents consistent with preterm infants being at heightened risk for childhood SDB. Although evidence is emerging that IH events are linked to poor outcomes in premature infants, the specific relationship between distinct IH patterns (e.g. duration, timing, frequency, and nadir) and longer-term respiratory and neurologic function remains to be elucidated.

Official Title
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Post-Vent, the Sequelae: Personalized Prognostic Modeling for Consequences of Neonatal Intermittent Hypoxemia in Preterm Infants at Pre-School Age

Conditions
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Premature Birth, Asthma in Children, Sleep-Disordered Breathing, Neurodevelopmental Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled in any IRB protocol of the Pre-Vent Study that had signed consent, or in any IRB protocol of the Pre-Vent Study that authorized re-contact for future research Born <29 weeks gestational age Age at enrollment less than or equal to 60 +6 months Exclusion Criteria: Subject was withdrawn from the Pre-Vent study after signing Pre-Vent consent form, for any reason Subject had no physiological data recorded as part of Pre-Vent Lack of regulatory approval from local IRB or DCFS to recontact subjects Adopted by non-consenting family Parent refused further contact, prior to approach for Post-Vent Infant enrolled in Pre-Vent at Washington University St Louis, which is not a Post-Vent participating site.

Ages Eligible for Study
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Minimum Age: 30 Weeks
Maximum Age: 66 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma | Doctor diagnosed asthma as assessed in the International Study on Asthma and Allergies in Childhood questionnaire (ISAAC) | 5 years ± 6 months of age | 
| Sleep Disordered Breathing (SDB) | Sleep-Related Breathing Disorder (SRBD) score >= 0.33 | 5 years ± 6 months of age | 
| Neurodevelopmental Impairment (NDI) | ≤10th percentile in any of the National Institutes of Health (NIH) Toolbox domains | 5 years ± 6 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Symptoms by ISAAC Questionnaire |  | 5 yr. (+/- 6 months) | 
| Medically attended respiratory illnesses |  | 5 yr. (+/- 6 months) | 
| Asthma Severity by Modified Composite Asthma Severity Score (MCASI) |  | 5 yr. (+/- 6 months) | 
| SDB: by SRBD score as Continuous variable |  | 5 yr. (+/- 6 months) | 
| Motor Function based on NIH Toolbox Motor Battery |  | 5 yr. (+/- 6 months) | 
| Motor Function based on Gross Motor Functional Classification System |  | 5 yr. (+/- 6 months) | 
| Cognitive Function based on NIH Toolbox Cognitive Battery |  | 5 yr. (+/- 6 months) | 
| Executive Function based on Behavior rating inventory of executive function |  | 5 yr. (+/- 6 months) | 
| Social, Emotional and Behavioral Outcomes based on NIH Toolbox Parent Proxy Emotion Battery |  | 5 yr. (+/- 6 months) | 
| Sensory Outcomes based on NIH Toolbox Odor Identification Test |  | 5 yr. (+/- 6 months) | 
| Sensory Outcomes based on NIH Toolbox Visual Acuity Test |  | 5 yr. (+/- 6 months) | 
| Quality of life as assessed by the Pediatric Quality of Life questionnaire |  | 5 yr. (+/- 6 months) | 
| Asthma Severity using Global Initiative for Asthma (GINA) criteria, based on parent questionnaire |  | 5 yr. (+/- 6 months) | 
| Health utilization, based on parent questionnaire |  | 5 yr. (+/- 6 months) | 
| Medications, based on parent questionnaire |  | 5 yr. (+/- 6 months) | 
| Medications, based on parent questionnaire |  | 6 mo through 5 yr. +6 months | 
| Doctor Diagnosed Asthma based on ISAAC |  | 6 mo through 5 yr. +6 months | 
| Respiratory Symptoms based on ISAAC |  | 6 mo through 5 yr. +6 months | 
| Medically attended respiratory illnesses in past year |  | 6 mo through 5 yr. +6 months | 
| Asthma Severity by MCASI |  | 6 mo through 5 yr. +6 months | 
| Asthma Severity using GINA criteria |  | 6 mo through 5 yr. +6 months | 
| Health utilization, based on parent questionnaire |  | 6 mo through 5 yr. +6 months |