Altered Cerebral Growth and Development in Infants With Congenital Heart Disease

Congenital Heart Disease Clinical Trial

Official title:

Altered Cerebral Growth and Development in Infants With Congenital Heart Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04233775
• Other study ID #: Knirsch 01
• Status: Recruiting
• Start date: January 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: University Children's Hospital, Zurich
• Contact: Walter H Knirsch, MD
• Phone: +41442667617
• Email: walter.knirsch[@]kispi.uzh.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: Congenital heart disease (CHD) is the most frequent inborn defect with an incidence of 1 in 100 newborns per year, i.e. 800 children born in Switzerland per year. 10% to 15% of cases are born with single ventricle (SV), the most complex type of CHF requiring immediate surgical intervention after birth. Infants with SV CHD are treated in three surgical staged procedures over the first three years of life. However, cerebral injuries occur in around 40% of those children and impact neurocognitive abilities. As more than 90% of all infants with CHD survive to adulthood, scientific concern is focussed on patient-individual course brain growth and development within the relative contribution of fetal, perinatal, cardiac and surgical risk factors. Therefore, serial cerebral MRI examinations are needed, starting (1) at the third trimester during fetal life proceeding to (2) pre- and postoperative time points at the stage I surgery after birth and (3) before stage II surgery at 4 months of age. We will compare the cerebral MRI findings with a healthy control population, recruited at the same time points, and correlate brain growth and development with the neurodevelopmental outcome assessed at one year of age. Three Pediatric Heart Centers in Switzerland and Germany will participate.

The overall aims are:

1. To analyse the patient-individual cerebral developmental trajectories, brain growth and determine the time course of brain abnormalities in infants with single ventricle CHD by serial cerebral MRI during fetal life, after birth and at an age of 4 months (primary endpoints).

2. To determine the neurodevelopmental outcome at one year of age using the Bayley III and will be correlated with the brain growth and brain development in the third trimester of fetal life and at the age of 4 months (secondary endpoints).

3. To analyse fetal, neonatal, surgery-related and intensive care associated factors determining the patient-individual course for altered cerebral growth and impaired neurodevelopmental outcome at one year of age.

Methodology: We will prospectively enroll fetuses and neonates with single ventricle CHD at the three Pediatric Heart Centers in Switzerland (Zurich, Bern) and Germany (Giessen). Advanced MR imaging will assess cerebral volumes, microstructural and hemodynamic changes at repeated time points during the third trimester of fetal life (32. week of gestation), the perioperative neonatal period before and after stage I surgery and before stage II surgery at 4 months of age. Biomechanical analysis of longitudinal changes of brain morphology will be applied to longitudinal fetal and neonatal MRI data. Outcome is determined with the Bayley-III at one year of age.

Significance: Using a population-based sample of children with single ventricle CHD, we will be able to determine cerebral growth from the third fetal trimester until the first 4 months after birth, when the brain is most rapidly growing. By performing serial brain imaging, the knowledge of etiological pattern affecting cerebral growth, development and brain injury will increase. Morphometric and biomechanical analysis of brain growth patterns will be performed that may capture fine-grained changes associated with CHD. By correlating these data with the neurodevelopmental outcome at one year of age it will be possible to identify specific risk constellations leading to impaired brain development and categories of brain injuries that confer a higher risk of adverse outcome. The better understanding of the pathophysiological mechanisms will serve as the basis for neuroprotective studies and pharmacological trials aiming to improve outcomes in children with CHD in the future.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Days to 6 Months

Eligibility

Inclusion Criteria:

All fetuses and neonates with the diagnosis complex type of CHD undergoing open-heart surgery are prospectively enrolled

Exclusion Criteria:

a) Clinical evidence or suspicion of a congenital malformation or syndrome, b) brain malformation, c) congenital infection and d) preterms before 37 weeks. These criteria will exclude fetuses and newborns with other conditions that will impact neurodevelopmental outcome.

Related Conditions & MeSH terms

• Brain Injuries
• Congenital Heart Disease
• Fetal Growth Retardation
• Heart Defects, Congenital
• Heart Diseases
• Neurodevelopmental Disorders

Locations

Country	Name	City	State
Switzerland	University Children's Hospital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University Children's Hospital, Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient-individual cerebral developmental trajectories	Brain growth and brain development from third trimester of fetal life to 4 months after birth will be analysed	6 months
Secondary	Neurodevelopmental outcome at one year of age using the Bayley III	Bayley Scales Bayley scales of Infant Development will be used as a standardized method to assess cognitive and motor development in infants.	One year
Secondary	Risk factor analysis	Risk factor analysis of fetal, neonatal, surgery-related and intensive care associated factors determining the patient-individual course for altered cerebral growth and impaired neurodevelopmental outcome at one year of age	One year