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NCT Number: NCT06690151

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

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.

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Key information

Conditions

Heart Disease Congenital Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Heart Defects, Congenital Heart Diseases Mental Disorders Neurodevelopmental Disorder Neurodevelopmental Disorders

Sex eligibility

All sexes

Study type

Observational

Primary location

Nantes University Hospital, Nantes, Loire Atlantique, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Neurodevelopmental assessment (Bayley-IV)

Behavioral

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

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.

ELFE dietary questionnaire

Behavioral

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

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.

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).

Primary outcomes

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

    Time frame: 6 months

Secondary outcomes

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

    Time frame: 6 months

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

    Time frame: 6 months

  3. Evaluate and describe affected developmental domains.

    Time frame: 6 months

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

    Time frame: 6 months

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

    Time frame: 6 months

  6. Characterize placental anatomopathological anomalies in CHD and their correlation with developmental delay at 6 months.

    Time frame: 6 months

  7. Determine maternal dietary habits during the third trimester, their correlation with placental anomalies, and developmental delay at 6 months.

    Time frame: 6 months

  8. 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

    Time frame: 6 months

  9. 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

    Time frame: 6 months

  10. Characterize neonatal microbiota and its association with developmental delay at 6 months.

    Time frame: 6 months

  11. Identify perioperative determinants of developmental delay in CHD.

    Time frame: 6 months

  12. 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

    Time frame: up to 3 months

  13. 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.

    Time frame: 6 months

  14. 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.

    Time frame: 6 months

Study contacts

Contact information is provided by the study sponsor or research team.

Alban Baruteau

CONTACT

[email protected]

+33 2 40 08 77 42

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Collaborators

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

Registry information

Official study title

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

Acronym: CATAMARAN - NN

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Nov 15, 2024
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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