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

Recruiting

• Conditions: Premature Birth; Asthma in Children; Sleep-Disordered Breathing; Neurodevelopmental Disorders

• Registration Number: NCT05336890
• Lead Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-04-14
• Study First Submitted QC: 2022-04-14
• Study First Posted: 2022-04-20
• Study Start: 2022-11-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-05
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Enrolled in any Institutional Review Board (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 7 years old

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 Department of Children and Family Services (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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Asthma	5 years ± 6 months of age	Doctor diagnosed asthma as assessed in the International Study on Asthma and Allergies in Childhood questionnaire (ISAAC)
Sleep Disordered Breathing (SDB)	5 years ± 6 months of age	Sleep-Related Breathing Disorder (SRBD) score \>= 0.33. Scores \>0.33 are considered positive and suggestive of high-risk for a pediatric sleep-related breathing disorder.
Neurodevelopmental Impairment (NDI)	5 years ± 6 months of age	≤10th percentile in any of the National Institutes of Health (NIH) Toolbox domains may indicate neurodevelopmental impairment.

Secondary Outcome Measures

Name	Time	Method
Motor Function	5 yr. (+/- 6 months)	Motor Function based on NIH Toolbox Motor Battery
Sensory Outcomes: Odor Identification	5 yr. (+/- 6 months)	Sensory Outcomes based on NIH Toolbox Odor Identification Test
Respiratory Symptoms	6 mo through 5 yr. +6 months	Respiratory Symptoms based on ISAAC
Medically attended respiratory illnesses	6 mo through 5 yr. +6 months	Medically attended respiratory illnesses in past year based on broad health parent questionnaire
Asthma Severity	5 yr. (+/- 6 months)	Asthma Severity by Modified Composite Asthma Severity Score (MCASI). Minimum value = 0. Max value = 21. Higher scores mean a worse outcome.
Sleep Disordered Breathing (SDB)	5 yr. (+/- 6 months)	Score on SDB questionnaire. Scores \>0.33 are considered positive and suggestive of high-risk for a pediatric sleep-related breathing disorder.
Gross Motor Function	5 yr. (+/- 6 months)	Motor Function based on Gross Motor Functional Classification System
Cognitive Function	5 yr. (+/- 6 months)	Cognitive Function based on NIH Toolbox Cognitive Battery
Executive Function	5 yr. (+/- 6 months)	Executive Function based on Behavior rating inventory of executive function
Sensory Outcomes: Acuity	5 yr. (+/- 6 months)	Sensory Outcomes based on NIH Toolbox Visual Acuity Test
Pediatric Quality of life	5 yr. (+/- 6 months)	Quality of life as assessed by the Pediatric Quality of Life parent proxy questionnaire
Health utilization	6 mo through 5 yr. +6 months	Health utilization, based on parent broad health questionnaire
Medications	5 yr. (+/- 6 months)	Medications based on broad health parent questionnaire
Doctor Diagnosed Asthma	6 mo through 5 yr. +6 months	Doctor Diagnosed Asthma based on ISAAC
Asthma Severity: Modified Composite Asthma Severity Index(MCASI)	6 mo through 5 yr. +6 months	Asthma Severity by MCASI score. Minimum value = 0. Max value = 21. Higher scores mean a worse outcome.
Asthma Severity: Global Initiative for Asthma criteria (GINA)	6 mo through 5 yr. +6 months	Asthma Severity using GINA criteria based on broad health parent questionnaire. A score of 19 or less indicates poorly controlled asthma, while a score greater than 19 indicates well-controlled asthma.
Social, Emotional and Behavioral Outcomes	5 yr. (+/- 6 months)	Social, Emotional and Behavioral Outcomes based on NIH Toolbox Parent Proxy Emotion Battery

Trial Locations

Locations (1)

Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States