Assessing Neurodevelopment in Congenital Heart Disease.

Study Overview
=================
Brief Summary
-----------------
Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns per year. Children with CHD are a known risk population for brain injury, with neurodevelopmental alterations shown over time in up to 50% of cases. No adequate description exists of the type of neurocognitive anomalies or risk factors associated with CHD, and consequently no prognostic markers that may allow identification of high-risk cases are available.

Detailed Description
-----------------
The main objectives of this study are: 1. to describe the neurodevelopmental outcome of patients with CHD at 24 months of age; 2. identify the subgroup with poorer outcome; and 3. evaluate the utility of fetal and postnatal diagnostic techniques for early detection of patients at risk for altered neurological outcomes. Seven Spanish referral centers for CHD included in the research network on maternal and child health currently participating in this prospective multicentric case-control coordinated study. Fetuses with CHD (transposition of great arteries, tetralogy of Fallot, hypoplastic left heart syndrome and septal defects) will be studied from 24 weeks of gestation to 2 years of age. Diagnostic tests will be repeated throughout the study in all patients, from the fetal period to 24 months of age, and will include: fetal cerebral hemodynamic Doppler assessment, functional echocardiography, brain MRI, regional cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers analysis. Neurodevelopmental assessment will be made at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. From this data, statistical analysis will select the most useful as predictors of damage; to be then combined and create algorithms for predicting brain damage and poor neurodevelopment. Once description has been made, we will proceed to identify amongst our results, children with the poorest neurological outcome and remark possible common prenatal and early life markers in them as well as the CHD severity they present. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Evidence available does not allow clinicians to assess on neurological prognosis although has opened up the possibility of finding prenatal markers of brain damage. Even though, no prospective studies have been performed until now. We present a multicentric prospective study able to recruit enough fetal CHD affected pregnancies to obtain neurological prognostic tools.

Official Title
-----------------
Abnormal Neurodevelopment Detection in Congenital Heart Disease: Predictive Methods Based on Prenatal and Postnatal Factors.

Conditions
-----------------
Congenital Heart Disease

Intervention / Treatment
-----------------
* Procedure: Sonography
* Device: Magnetic Resonance Imaging
* Other: Bailey Test
* Procedure: Surgical intervention
* Procedure: Brain monitoring
* Procedure: cord blood sample


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Single pregnancies Major Congenital Heart Disease Informed Consent Signed Exclusion Criteria: Major extra-cardiac malformations Parental Refusal to participate Maternal Chronic Disease Multiple Pregnancies
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy fetuses<br>Pregnant patients carrying a healthy fetus. Interventions in this group will be: cord blood sample, sonography, Magnetic Resonance Imaging and bailey test. | Procedure: Sonography<br>* Fetal Ultrasound exploration<br>Device: Magnetic Resonance Imaging<br>* Fetal MRI for brain study<br>Other: Bailey Test<br>* Neurodevelopment paediatric assessment test performed at 2 years of age.<br>Procedure: cord blood sample<br>* Cord blood samples will be taken after birth in both groups.<br>|
| Other: Congenital Hearth Disease<br>Pregnant patients carrying a fetus with a moderate-severe congenital heart disease Interventions in this group will be: cord blood sample, sonography, Magnetic Resonance Imaging, Surgical intervention, brain monitoring and bailey test. | Procedure: Sonography<br>* Fetal Ultrasound exploration<br>Device: Magnetic Resonance Imaging<br>* Fetal MRI for brain study<br>Other: Bailey Test<br>* Neurodevelopment paediatric assessment test performed at 2 years of age.<br>Procedure: Surgical intervention<br>* Congenital Heart Disease repair<br>Procedure: Brain monitoring<br>* EEG and continuous brain oximetry before surgery.<br>Procedure: cord blood sample<br>* Cord blood samples will be taken after birth in both groups.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bailey-III test punctuation | Results in pediatric Bailey-III test scale | 45 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biparietal diameter (mm) | Biparietal diameter (mm) measured with MRI | one day | 
| Lateral sulcus depth | Lateral sulcus depth (mm) measured with MRI | one day | 
| Cerebral insula | Insula (mm) measured with MRI | one day | 
| Brain biometries | Calcarine sulcus depth (mm) | one day | 
| Cerebral cingulata sulcus | Cingulata sulcus depth (mm) measured with MRI | one day | 
| Corpus callosum | Corpus callosum (mm) measured with MRI | one day | 
| Cerebellum | Cerebellum vermis (mm) measured with MRI | one day | 
| Umbilical doppler | Umbilical artery pulsatility index | one day | 
| Middle cerebral artery doppler | Middle cerebral artery pulsatility index | one day | 
| Angiogenic PLGF (placental growth factor) | Placental growth factor in maternal serum | Two days | 
| Angiogenic s-FLt (soluble fms-like tyrosine kinase) | Soluble fms-like tyrosine kinase factor in maternal serum | Two days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LVOTO, Fallot, Great Arteries Transposition