Assessing Neurodevelopment in Congenital Heart Disease.

Congenital Heart Disease Clinical Trial

— NEUROHEART  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02996630
• Other study ID #: PR(AMI)317/2012
• Status: Recruiting
• Phase: N/A
• First received: October 31, 2016
• Last updated: December 14, 2016
• Start date: May 2013
• Est. completion date: May 2018

Study information

• Verified date: October 2016
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: Irene Ribera, MD
• Phone: 934893000
• Email: irene.ribera[@]vhir.org
• Is FDA regulated: No
• Health authority: Spain: Ministerio de Sanidad, Servicios Sociales e Igualdad
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: May 2018
• Est. primary completion date: May 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases

Intervention

Procedure:
• Sonography
Fetal Ultrasound exploration

Device:
• Magnetic Resonance Imaging
Fetal MRI for brain study

Other:
• Bailey Test
Neurodevelopment paediatric assessment test performed at 2 years of age.

Procedure:
• Surgical intervention
Congenital Heart Disease repair
• Brain monitoring
EEG and continuous brain oximetry before surgery.
• cord blood sample
Cord blood samples will be taken after birth in both groups.

Locations

Country	Name	City	State
Spain	Hospital Universitari Vall d'Hebrón	Barcelona

Sponsors (6)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute	Hospital General Universitario Gregorio Marañon, Hospital Sant Joan de Deu, Hospital Universitario 12 de Octubre, Hospital Universitario La Paz, Institut Universitari Dexeus

Country where clinical trial is conducted

Spain, 

References & Publications (5)

Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, Barnes PD, Holmes GL, Hickey PR, Strand RD, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary by — View Citation

Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900. Review. — View Citation

Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurodevelopmental status of newborns and infants with congenital heart defects before and after open heart surgery. J Pediatr. 2000 Nov;137(5):638-45. — View Citation

Masoller N, Martínez JM, Gómez O, Bennasar M, Crispi F, Sanz-Cortés M, Egaña-Ugrinovic G, Bartrons J, Puerto B, Gratacós E. Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease. Ultrasound Obst — View Citation

Ruiz A, Cruz-Lemini M, Masoller N, Sanz-Cortés M, Ferrer Q, Ribera I, Martínez JM, Crispi F, Arévalo S, Gómez O, Pérez-Hoyos S, Carreras E, Gratacós E, Llurba E. Longitudinal changes in fetal biometries and cerebroplacental haemodynamics in fetuses with c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bailey-III test punctuation	Results in pediatric Bailey-III test scale	45 minutes	No
Secondary	Biparietal diameter (mm)	Biparietal diameter (mm) measured with MRI	one day	No
Secondary	Lateral sulcus depth	Lateral sulcus depth (mm) measured with MRI	one day	No
Secondary	Cerebral insula	Insula (mm) measured with MRI	one day	No
Secondary	Brain biometries	Calcarine sulcus depth (mm)	one day	No
Secondary	Cerebral cingulata sulcus	Cingulata sulcus depth (mm) measured with MRI	one day	No
Secondary	Corpus callosum	Corpus callosum (mm) measured with MRI	one day	No
Secondary	Cerebellum	Cerebellum vermis (mm) measured with MRI	one day	No
Secondary	Umbilical doppler	Umbilical artery pulsatility index	one day	No
Secondary	Middle cerebral artery doppler	Middle cerebral artery pulsatility index	one day	No
Secondary	Angiogenic PLGF (placental growth factor)	Placental growth factor in maternal serum	Two days	No
Secondary	Angiogenic s-FLt (soluble fms-like tyrosine kinase)	Soluble fms-like tyrosine kinase factor in maternal serum	Two days	No