Clinical trial NCT06690151: Characterization and Support of Neurodevelopmental Disorders Associated with Congenital Cardiac MalfoRmations - Neonatal
Official title: CATAMARAN - Neonatal Cohort : Characterization and Support of Neurodevelopmental Disorders Associated with Congenital Cardiac MalfoRmations - Neonatal
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Heart Disease Congenital
Neurodevelopmental Disorder
Keywords: Congenital heart defects (CHD)
neurodevelopmental disorders (NDD)
genetics
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Pays de la Loire Laboratory of Psychology (LPPL)
name: Physiopathology of Nutritional Adaptations Joint Research Unit (UMR PhAN)
name: Institut du thorax, INSERM UMR1087
First posted: 2024-11-15
Enrollment: 450
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will focus on the inclusion of 150 fetuses with a prenatally diagnosed critical congenital heart defect (CHD), at high risk of developing developmental delays, and their two parents.

Brief summary: Congenital heart defects (CHD), as the leading cause of birth defects, affect 12 million people globally and approximately 41,000 newborns each year in Europe. CHD presents a significant public health concern due to its association with high morbidity and mortality rates across the lifespan. Over 50% of infants born with critical CHD will develop neurodevelopmental disorders (NDD), requiring specialized care and impacting their quality of life. NDDs, involving early and persistent disruptions in cognitive, emotional, and behavioral development due to abnormal brain development, are highly variable. They may impact language, learning, motor skills, intellectual efficiency, social cognition, attention, memory, and executive functions, often accompanied by psychosocial difficulties. These hidden disabilities constitute the primary long-term sequelae of CHD, surpassing even cardiovascular complications in impact, and affect children who often undergo multiple cardiac surgeries during early childhood. NDDs are associated not only with complex CHDs but also with simpler CHDs that are repaired in early childhood and considered 'cured.'

The origin of CHD-associated NDDs remains largely unknown. While few genetic or environmental causes have been identified, recent research suggests a possible common origin linking heart malformations and neurodevelopmental abnormalities. The CATAMARAN neonatal cohort project aims to detect developmental delays associated with CHD as early as six months of age and to identify both individual susceptibility factors and acquired vulnerabilities contributing to the development of NDDs in infants with CHD.


Eligibility criteria: The inclusion criteria are as follows:

* Fetus with a congenital heart defect (CHD) detected prenatally (prenatal diagnosis of the heart defect)
* Fetus with a critical CHD defined as requiring cardiac surgery during the first three months of the infant's life
* Parents affiliated with or beneficiaries of a social security or equivalent system
* Parents' good understanding of the French language
* Voluntary, informed, and written consent from both parents for themselves and the unborn child

Criteria for parents\*:

- Biological parents \*The inclusion of the father in the project does not limit the participation of the child (patient) in the study.

\*The father will be encouraged to participate in the project by providing a blood sample to create a trio (mother/father/infant) for future genetic analyses.

However, if the father is unavailable or does not consent to the collection and storage of samples for analysis (as part of the CATAMARAN study or future research projects related to biobanking), the child can still be included in the study.

Exclusion Criteria:

* Medical termination of pregnancy considered
* Genetic anomaly or malformative syndrome identified prior to inclusion

Primary outcomes:
measure: Evaluate the prevalence of developmental delays in infants with a critical congenital heart defect (CHD) at 6 months of age.
timeFrame: 6 months
Secondary outcomes:
measure: Evaluate the prevalence of developmental delay in infants with congenital heart defects (CHD) based on the type of heart defect.
timeFrame: 6 months
measure: Assess the presence of developmental delay in infants with CHD based on the complexity of cardiac surgery.
timeFrame: 6 months
measure: Evaluate and describe affected developmental domains.
timeFrame: 6 months
measure: Identify rare genetic variants associated with developmental delays in CHD patients through genome-wide analysis.
timeFrame: 6 months
measure: Identify common genetic variants associated with developmental delays in CHD patients through genome-wide analysis.
timeFrame: 6 months
measure: Characterize placental anatomopathological anomalies in CHD and their correlation with developmental delay at 6 months.
timeFrame: 6 months
measure: Determine maternal dietary habits during the third trimester, their correlation with placental anomalies, and developmental delay at 6 months.
timeFrame: 6 months
measure: Characterize maternal behavioral exposures (e.g., tobacco, alcohol, drugs) and obstetric complications (e.g., hypertension, preeclampsia, gestational diabetes) during pregnancy, and their correlation with placental anomalies and developmental delay
timeFrame: 6 months
measure: Characterize antenatal determinants of developmental delay through multi-omics analysis (metabolomics, lipidomics, transcriptomics, and epigenetics) of maternal blood, placental function, and fetal blood, and their correlation with developmental delay
timeFrame: 6 months
measure: Characterize neonatal microbiota and its association with developmental delay at 6 months.
timeFrame: 6 months
measure: Identify perioperative determinants of developmental delay in CHD.
timeFrame: 6 months
measure: Identify optimal perfusion pressure targets during and after neonatal cardiac surgery under cardiopulmonary bypass in three participating centers using continuous analysis of invasive blood pressure and cerebral oxygen saturation
timeFrame: up to 3 months
measure: For CHU Nantes patients only: identify fetal neuronal biomarkers at birth, track their evolution before and after cardiac surgery in CHD infants, and establish associations with developmental delay at 6 months.
timeFrame: 6 months
measure: Evaluate parental post-traumatic stress at 1) antenatal inclusion, 2) perioperative period, and 3) 6 months post-surgery, and its correlation with developmental delay at 6 months.
timeFrame: 6 months
Other outcomes:
Locations:
city: Nantes
country: France
facility: Nantes University Hospital
state: Loire Atlantique
Study officials:
References: