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.
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
Medical termination of pregnancy considered
Genetic anomaly or malformative syndrome identified prior to inclusion
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.
Cohort
Prospective
Neurodevelopmental assessment (Bayley-IV)
BehavioralAssessment of developmental delays through administration of the Bayley-4 test by a neuropsychologist
Biological sampling
Other interventionThe 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
BehavioralQuestionnaire on diet and lifestyle during pregnancy (only for the mother)
Post-Traumatic Stress Questionnaire IES-R (Impact of Event Scale - Revised)
BehavioralThe 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 intervention* 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).
Evaluate the prevalence of developmental delays in infants with a critical congenital heart defect (CHD) at 6 months of age.
Evaluate the prevalence of developmental delay in infants with congenital heart defects (CHD) based on the type of heart defect.
Assess the presence of developmental delay in infants with CHD based on the complexity of cardiac surgery.
Evaluate and describe affected developmental domains.
Identify rare genetic variants associated with developmental delays in CHD patients through genome-wide analysis.
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Nantes University Hospital
Lead sponsor
Pays de la Loire Laboratory of Psychology (LPPL)
Collaborator
Physiopathology of Nutritional Adaptations Joint Research Unit (UMR PhAN)
Collaborator
Institut du thorax, INSERM UMR1087
Collaborator
