Characterization and Support of Neurodevelopmental Disorders Associated With Congenital Cardiac malfoRmations - Neonatal (CATAMARAN - NN)

CATAMARAN - Neonatal Cohort : 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.

Study Overview

• Status: Recruiting
• Conditions: Neurodevelopmental Disorder; Heart Disease Congenital
• Intervention / Treatment: Behavioral: Neurodevelopmental assessment (Bayley-IV); 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); Other: Biological sampling

• Study Type: Observational
• Enrollment (Estimated): 450

Contacts and Locations

• Study Contact: Name: Alban Baruteau; Phone Number: +33 2 40 08 77 42; Email: albanelouen.baruteau@chu-nantes.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU de Bordeaux
    • Principal Investigator: Loic SENTILHES
    • Contact: Marion AUDIE; Phone Number: +33 556795679; Email: marion.audie@chu-bordeaux.fr
    • Principal Investigator: Marion AUDIE
    • Sub-Investigator: Caroline Thambo-Rooryck
    • Sub-Investigator: Julie THOMAS-CHABANEIX
  • Clamart, France, 92140
    • Recruiting
    • APHP - Antoine Béclère
    • Contact: Alexandre VIVANTI; Phone Number: +33 145374366; Email: alexandre.vivanti@aphp.fr
    • Principal Investigator: Alexandre VIVANTI
  • Le Plessis-Robinson, France, 92350
    • Recruiting
    • Hopital Marie Lannelongue
    • Contact: Sébastien HASCOËT; Phone Number: +33 140942429; Email: s.hascoet@ghpsj.fr
    • Principal Investigator: Sébastien HASCOUËT
  • Marseille, France
    • Recruiting
    • AP-HM
    • Principal Investigator: Florence BRETELLE
    • Principal Investigator: Caroline OVAERT
    • Contact: Caroline OVAERT; Phone Number: +334 91386496; Email: caroline.ovaert@ap-hm.fr
    • Sub-Investigator: Béatrice DESNOUS
  • Paris, France
    • Not yet recruiting
    • AP-HP Necker
    • Principal Investigator: Damien BONNET
    • Contact: Damien BONNET; Phone Number: +33 144494344; Email: Damien.bonnet@aphp.fr
  • Toulouse, France, 31000
    • Not yet recruiting
    • CHU de Toulouse
    • Principal Investigator: Clément KARSENTY
    • Contact: Clément KARSENTY; Phone Number: +33 534558734; Email: karsenty.cl@chu-toulouse.fr
    • Sub-Investigator: Yves DULAC
    • Sub-Investigator: Paul GUERBY
  • Tours, France
    • Recruiting
    • CHRU Tours
    • Principal Investigator: Bruno Lefort
    • Principal Investigator: Franck PERROTIN
    • Contact: Bruno LEFORT; Phone Number: +33 247474755; Email: b.lefort@univ-tours.fr
  • Loire Atlantique
    • Nantes, Loire Atlantique, France, 44093
      • Recruiting
      • Nantes University Hospital
      • Principal Investigator: Alban Baruteau
      • Sub-Investigator: Norbert WINER
      • Contact: Alban BARUTEAU; Phone Number: +33 253482835; Email: albanelouen.baruteau@chu-nantes.fr
      • Sub-Investigator: Oscar WERNER
      • Sub-Investigator: Bénédicte ROMEFORT
      • Sub-Investigator: Nadir BENBRIK

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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); Assessment of developmental delays through administration of the Bayley-4 test by a neuropsychologist; Behavioral: ELFE dietary questionnaire; Questionnaire on diet and lifestyle during pregnancy (only for the mother); Behavioral: Post-Traumatic Stress Questionnaire IES-R (Impact of Event Scale - Revised); The IES-R is a 22-item self-report measure (for DSM-IV) that assesses subjective distress caused by traumatic events.; Other: Data collection for the study (Cardiovascular, developemental, fetal, pregnancy, MRI); 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).; Other: Biological sampling; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Characterize placental anatomopathological anomalies in CHD and their correlation with developmental delay at 6 months.	6 months
Determine maternal dietary habits during the third trimester, their correlation with placental anomalies, and developmental delay at 6 months.	6 months
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	6 months
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	6 months
Characterize neonatal microbiota and its association with developmental delay at 6 months.	6 months
Identify perioperative determinants of developmental delay in CHD.	6 months
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	up to 3 months
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.	6 months
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.	6 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Estimated): August 28, 2027
• Study Completion (Estimated): August 28, 2027

Study Registration Dates

• First Submitted: November 13, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: genetics; Congenital heart defects (CHD); neurodevelopmental disorders (NDD)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Mental Disorders; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Heart Defects, Congenital; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Therapeutics; Circulatory and Respiratory Physiological Phenomena; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Patient Care; Health Services; Health Care Facilities Workforce and Services; Community Health Services; Chemistry Techniques, Analytical; Spectrum Analysis; Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Cardiovascular Physiological Phenomena; Maternal Health Services; Magnetic Resonance Spectroscopy; Data Collection; Blood Circulation; Prenatal Care; Pregnancy
• Other Study ID Numbers: RC23_0547; IDRCB (ANSm) : 2024-A00425-42 (Other Identifier: Agence nationale de sécurité du médicament et des produits de santé (ANSM))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No