Clinical and multi-omics characterisation of early neurodevelopmental disorders associated with critical congenital heart disease: the prospective cohort CATAMARAN neonatal study protocol.
Werner O, Ferchaud-Roucher V, et al. • BMJ open • 2026
CATAMARAN is a prospective, multicentre cohort study protocol designed to evaluate early neurodevelopmental status and identify intrinsic, prenatal, and postnatal determinants of developmental delay in 150 fetuses with prenatally diagnosed critical congenital heart disease across eight French tertiary centres.
Key Findings
Background
Critical congenital heart disease (CHD) requiring cardiac surgery within the first 3 months of life is associated with neurodevelopmental disorders in 30%-50% of affected children.
Neurodevelopmental disorders are recognised as 'the most common long-term morbidity' in children with critical CHD.
30%-50% of children with critical CHD have lower developmental scores.
Critical CHD is specifically defined as CHD requiring cardiac surgery within the first 3 months of life.
The study notes there is currently no scientifically evaluated care programme in France for this population.
Methods
The CATAMARAN study will enrol 150 fetuses with prenatally diagnosed critical CHD and their parents across eight French tertiary CHD centres.
The study is a prospective, multicentre cohort design.
Inclusion criteria require prenatal diagnosis of critical CHD.
Eight French tertiary CHD centres are participating.
Both fetuses and their parents are included as study participants.
Methods
The primary objective of the CATAMARAN study is to estimate the proportion of developmental delay at 6 months of age using the Bayley Scales of Infant and Toddler Development.
The Bayley Scales of Infant and Toddler Development is the chosen neurodevelopmental assessment tool.
Assessment is planned at 6 months of age.
Secondary objectives include exploring prenatal, perinatal, and perioperative determinants of developmental delay.
A case-control analysis within the cohort will explore genetic and multi-omic factors associated with developmental delay.
Methods
Data collection spans from pregnancy to 6 months of age and includes clinical assessments, maternal questionnaires, multimodal imaging, and extensive biobanking.
Biobanking includes placenta, cord and peripheral blood, and stool samples.
Maternal questionnaires assess stress and nutrition.
Multimodal imaging is included in the data collection protocol.
Clinical and biological data are collected through a secure system with anonymised samples analysed in specialised facilities under collaborative agreements.
Data confidentiality, traceability, and long-term storage are ensured through controlled access and audit trails.
Methods
The CATAMARAN study aims to explore multi-omics factors—including genetic and other biological dimensions—involved in the occurrence of developmental delay through a case-control analysis within the cohort.
The multi-omics approach is described as exploring 'potential genetic and other multi-omic factors involved in the occurrence of a developmental delay.'
The case-control analysis will be conducted within the broader prospective cohort.
Intrinsic susceptibility, as well as prenatal and postnatal factors, will be examined for functional associations with developmental delay.
Specialised facilities will handle sample analysis under collaborative agreements.
Methods
The study received ethics committee approval in November 2024 and is registered as a clinical trial.
Ethics approval was granted by a French ethics committee in November 2024 (no. 2024-A00425-42).
The study is registered under ClinicalTrials.gov identifier NCT06690151.
Study results will be published and shared with families and the public through the patient association Petit Coeur de Beurre.
What This Means
This paper describes the design of the CATAMARAN study, a French research project investigating brain development problems in babies born with serious heart defects that need surgery in the first three months of life. These heart conditions, known as critical congenital heart disease, are already known to affect brain development in a significant proportion of children — between 30% and 50% show lower developmental scores. However, there is currently no scientifically validated programme in France to identify which babies are most at risk or to support their development early on.
The CATAMARAN study plans to follow 150 babies with prenatally diagnosed critical heart disease from before birth through to 6 months of age, across eight specialised heart centres in France. Researchers will assess brain development at 6 months using a standardised test (the Bayley Scales of Infant and Toddler Development) and will collect a wide range of information including clinical data, brain scans, maternal stress and nutrition questionnaires, and biological samples such as placenta tissue, blood, and stool. This broad approach — combining clinical, genetic, and other biological (multi-omics) data — aims to identify which factors before, during, and after birth contribute to developmental problems.
This research suggests that by identifying the biological and environmental factors that put certain babies at higher risk of developmental delays, it may become possible to develop targeted early support programmes. The study could also shed light on the genetic and biological mechanisms underlying these brain development issues in children with heart defects, potentially informing future care strategies for this vulnerable population.
Werner O, Ferchaud-Roucher V, Karakachoff M, Bourgoin P, Chauvire-Drouard A, Galy J, et al.. (2026). Clinical and multi-omics characterisation of early neurodevelopmental disorders associated with critical congenital heart disease: the prospective cohort CATAMARAN neonatal study protocol.. BMJ open. https://doi.org/10.1136/bmjopen-2026-116866