Impact of Surgical Timing on the Neurodevelopmental Prognosis of Newborns With Complex Congenital Heart Disease (CINC)

We propose a prospective observational study whose main objective will be to determine whether there is an association between age at surgery (days of life) and neurodevelopmental outcome in patients with CCHD. Secondly, we will study the relationship between age at surgery and (i) the incidence of WMI observed on pre- and post-operative cerebral MRI (ii) post-operative morbidity as defined by the occurrence of post-operative complications (haemodynamic, infectious, neurological, surgical) and (iii) the length of hospital stay.

Study Overview

• Status: Recruiting
• Conditions: Complex Congenital Heart Disease
• Intervention / Treatment: Procedure: Peri-operative neurological monitoring

Detailed Description

Congenital heart disease is the most frequent congenital malformation and concerns 9 newborns per 1000 live births, i.e. nearly 1% of births. Half of these children present a complex form of congenital heart disease requiring surgery during the first months of life. More than one child in two will present a neurodevelopmental disorder resulting from brain damage beginning in utero and continuing in the post-natal period. In the newborn with complex congenital heart disease (CCHD), cerebral immaturity is synonymous with vulnerability, leading in half of the cases to the perioperative occurrence of hypoxic-ischemic cerebral lesions, most of which affect the white matter. These white matter injuries (WMI) are a prognostic factor for motor, cognitive, language and behavioural disorders that induce psycho-social difficulties in adulthood, altering the quality of life of patients. In newborns with CCHD (Transposition of Great Arteries or Left Ventricular Hypoplasia) operated on later in the neonatal period, both the incidence of perioperative BSL and post-operative morbidity are increased.

Earlier surgery may therefore be a neuroprotective strategy leading to a reduction in perioperative WMI, postoperative morbidity and a better neurodevelopmental prognosis in infants with CCHD.

The investigators propose a prospective observational study whose main objective will be to determine whether there is an association between age at surgery (days of life) and neurodevelopmental outcome in patients with CCHD. Secondly, the investigators planned to study the relationship between age at surgery and (i) the incidence of WMI observed on pre- and post-operative cerebral MRI (ii) post-operative morbidity as defined by the occurrence of post-operative complications (haemodynamic, infectious, neurological, surgical) and (iii) the length of hospital stay.

Recruitment will be performed in a prospective cohort (n=50) of neonates with CCHD requiring surgery during the first 2 months of life and benefiting from pre- and post-operative cerebral MRI, standardized neurological examinations at 4, 12, 24 months and neuropsychological evaluation with a Bayley III test at 24 months.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emilie GARRIDO-PRADALIE, Reasearch Director; Phone Number: +33 0491382747; Email: drci@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique des Hôpitaux de Marseille
    • Contact: Emilie GARRIDO-PRADALIE; Phone Number: +33 (0)4 91 38 27 47; Email: drci@ap-hm.fr
    • Contact: Béatrice DESNOUS; Email: beatrice.desnous@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Patients aged 2 months or less with complex congenital heart disease (CCHD) requiring surgery with cardiac circulation during their first 2 months of life
• Eligible heart diseases: Transposition of the Large Vessels (TGV), hypoplasia of the left ventricle, right ventricle with double outlet type Fallot or TGV, obstruction of the aortic arch, truncus arteriosus, atrioventricular duct, pulmonary atresia with or without communication inter ventricular.
• Informed consent signed by both parents
• Patient affiliated to health social security

Non-inclusion criteria:

• patients with a birth weight less than 2 kilograms and / or a gestational age less than 37 weeks
• patients with a CCHD not requiring cardiac surgery with extra-corporeal circulation in the first 2 months of life
• patients with a chromosomal abnormality or genetic syndrome proven associated with CCHD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peri-operative neurological monitoring	Procedure: Peri-operative neurological monitoring; Pre- and post-operative cerebral MRI, standardized neurological examinations at 4, 12, 24 months and neuropsychological evaluation with a Bayley III test (Bayley Scale of Infant and Toddler Development, Third Edition) at 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the association between age at surgery (days of life) and scores (mean = 100, standard deviation = 15) obtained on the Bayley II test	Measurement of the association between age at surgery (days of life) and scores (mean = 100, standard deviation = 15) obtained on the Bayley II test for each subtest: motor, cognitive and language. This association will be evaluated by a correlation coefficient	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: Béatrice DESNOUS, MD, Assistance Publique-Hôpitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2021
• Primary Completion (Estimated): December 24, 2025
• Study Completion (Estimated): December 24, 2025

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: 2019-44; 2020-A00369-30 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No