Characterization and Support of Neurodevelopmental Disorders Associated With Congenital Cardiac malfoRmations - Neonatal

NCT06690151 | Recruiting

• 2 other identifiers: RC23_0547IDRCB (ANSm) : 2024-A00425-42
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 8

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.

Conditions

Heart Disease Congenital; Neurodevelopmental Disorder

Keywords

Congenital heart defects (CHD); neurodevelopmental disorders (NDD); genetics

Outcome Measures

Primary Outcomes (1)

• Evaluate the prevalence of developmental delays in infants with a critical congenital heart defect (CHD) at 6 months of age.

  6 months

Secondary Outcomes (14)

• Evaluate the prevalence of developmental delay in infants with congenital heart defects (CHD) based on the type of heart defect.

  6 months

• Assess the presence of developmental delay in infants with CHD based on the complexity of cardiac surgery.

  6 months

• Evaluate and describe affected developmental domains.

  6 months

• Identify rare genetic variants associated with developmental delays in CHD patients through genome-wide analysis.

  6 months

• Identify common genetic variants associated with developmental delays in CHD patients through genome-wide analysis.

  6 months

Study Arms (1)

Study population (Newborns with congenital heart defects and their two parents)

The study population will consist of 150 fetuses with a prenatally diagnosed critical congenital heart defect (CHD), at high risk of developing developmental delays, and their two parents.

Behavioral: Neurodevelopmental assessment (Bayley-IV); Other: Biological sampling; Behavioral: ELFE dietary questionnaire; Behavioral: Post-Traumatic Stress Questionnaire IES-R (Impact of Event Scale - Revised); Other: Data collection for the study (Cardiovascular, developemental, fetal, pregnancy, MRI)

Interventions

Post-Traumatic Stress Questionnaire IES-R (Impact of Event Scale - Revised) BEHAVIORAL

The IES-R is a 22-item self-report measure (for DSM-IV) that assesses subjective distress caused by traumatic events.

Study population (Newborns with congenital heart defects and their two parents)

Neurodevelopmental assessment (Bayley-IV) BEHAVIORAL

Assessment of developmental delays through administration of the Bayley-4 test by a neuropsychologist

Study population (Newborns with congenital heart defects and their two parents)

Biological sampling OTHER

The samples to be collected at delivery will include: * A 4 ml maternal blood sample in an EDTA tube for lipidomic and metabolomic analyses at delivery * A 6 ml maternal blood sample in an EDTA tube (2 tubes of 3 ml) for genetic analysis * A 4 ml venous cord blood sample in an EDTA tube for transcriptomic and epigenetic analysis; and a 2 ml EDTA tube for metabolomic/lipidomic analysis * Samples from fresh placenta for transcriptomic, epigenetic, metabolomic, and lipidomic analyses * A meconium sample collected as soon as possible after birth in a dry tube for microbiome analysis During hospitalization for the cardiac surgery: * Genome analysis samples will be collected from the father and the infant. These samples will be taken in two EDTA tubes of 3 ml each. * Perioperative neurobiomarker samples will be collected (one EDTA tube of 500 μL preoperatively and postoperatively on Day 1 and 2). At 1 month, a stool sample will be collected from the infants for microbiome analysis.

Study population (Newborns with congenital heart defects and their two parents)

ELFE dietary questionnaire BEHAVIORAL

Questionnaire on diet and lifestyle during pregnancy (only for the mother)

Study population (Newborns with congenital heart defects and their two parents)

Data collection for the study (Cardiovascular, developemental, fetal, pregnancy, MRI) OTHER

* Cardiovascular follow-up data collection * Developmental follow-up data collection * Collection of postoperative brain MRI data, scheduled between Day 5 post-surgery and the end of the hospital stay * Collection of data on pregnancy exposure, obstetric events, and delivery data. * Collection of fetal ultrasound data (T2 and T3). * Collection of fetal echocardiography data (T2 and T3).

Study population (Newborns with congenital heart defects and their two parents)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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\*:
• \*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.

You may not qualify if:

• Medical termination of pregnancy considered

Sponsors & Collaborators

• Nantes University Hospital: lead
• Physiopathology of Nutritional Adaptations Joint Research Unit (UMR PhAN): collaborator
• Institut du thorax, INSERM UMR1087: collaborator
• Pays de la Loire Laboratory of Psychology (LPPL): collaborator

Study Sites (8)

Nantes University Hospital

Nantes, Loire Atlantique, 44093, France

RECRUITING

CHU de Bordeaux

Bordeaux, France

RECRUITING

APHP - Antoine Béclère

Clamart, 92140, France

RECRUITING

Hôpital Marie Lannelongue

Le Plessis-Robinson, 92350, France

RECRUITING

AP-HM

Marseille, France

RECRUITING

AP-HP Necker

Paris, France

NOT YET RECRUITING

CHU de Toulouse

Toulouse, 31000, France

NOT YET RECRUITING

CHRU Tours

Tours, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* Infant blood sample * Infant stool collection * Paternal blood sample * Maternal blood sample * Umbilical cord venous blood sample * Meconium

MeSH Terms

Conditions

Heart Defects, Congenital; Neurodevelopmental Disorders

Interventions

Data Collection; Blood Circulation; Prenatal Care; Pregnancy; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mental Disorders

Intervention Hierarchy (Ancestors)

Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Patient Care; Therapeutics; Maternal Health Services; Community Health Services; Health Services; Health Care Facilities Workforce and Services; Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Spectrum Analysis; Chemistry Techniques, Analytical

Central Study Contacts

Alban Baruteau

CONTACT

+33 2 40 08 77 42; albanelouen.baruteau@chu-nantes.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2024
• First Posted: November 15, 2024
• Study Start: February 28, 2025
• Primary Completion (Estimated): August 28, 2027
• Study Completion (Estimated): August 28, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

FR (8)