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

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.

Study Overview

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

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 Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Erin Smith Lonergan; Phone Number: 312-227-3300; Email: ersmith@luriechildrens.org
• Study Contact Backup: Name: Casey Rand; Phone Number: 312-227-3300; Email: crand@luriechildrens.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Contact: Erin Lonergan, RRT, MS
      • Contact: Casey Rand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 5 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will be drawn from surviving, previously consented children in the existing Pre-Vent study cohort or in any IRB protocol of the Pre-Vent study that authorized re-contact for future research, which was drawn from Neonatal Intensive Care Unit Populations in Chicago, IL; Cleveland, OH; Birmingham, AB; or Miami, FL, USA.

Up to 500 children will be enrolled after parent/guardian provides informed consent.

Parents, guardians or primary caretakers will act as proxies for providing information about the children.

Description

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 Plan

How is the study designed?

What is the study measuring?

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. Scores >0.33 are considered positive and suggestive of high-risk for a pediatric sleep-related breathing disorder.	5 years ± 6 months of age
Neurodevelopmental Impairment (NDI)	≤10th percentile in any of the National Institutes of Health (NIH) Toolbox domains may indicate neurodevelopmental impairment.	5 years ± 6 months of age

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Miami; Northwestern University; University of Alabama at Birmingham; University of Virginia; Case Western Reserve University
• Investigators: Principal Investigator: Debra Weese-Mayer, MD, Ann & Robert H Lurie Children's Hospital of Chicago; Principal Investigator: Anna Maria Hibbs, MD, Case Western Reserve University; Principal Investigator: Ambalavanan Namasivayam, MD, University of Alabama at Birmingham; Principal Investigator: Randall Moorman, MD, University of Virginia; Principal Investigator: Nelson Claure, MSc, PhD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Nervous System Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Premature Birth; Neurodevelopmental Disorders; Hypoxia; Sleep Apnea Syndromes
• Other Study ID Numbers: HSR210359; 1R01HL157256-01A1 (U.S. NIH Grant/Contract)

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