Discussion
This project’s primary goal is to demonstrate the necessity of early visuospatial memory assessment within the vulnerable population of VP children, as well as to prove the feasibility and efficacy of computerized CT using online software programs.
Neurodevelopmental problems are common in VP children. Recent publications have reported many disorders in their specific cognitive functions, one of which is WM. Although neuro-development of VP children remains a public health priority because of their increased birth and survival rates, the interventions to improve this are few. There are currently no truly effective interventions to deal with academic achievement in preschool-age VP infants and their neuropsychological problems; thus, currently no specific management care is recommended for these children.
Cogmed is based on interactive software and parental support. The program takes into account the child’s environment, a factor of great relevance since it is closely linked to the child’s future development. The expected benefits of CT (Cogmed) for those children in this study are enhanced WM, possibly leading to better EF by taking advantage of cerebral plasticity.
A better global neuropsychological development improvement (language and visuospatial processing) can be expected with an improvement in learning and decreased behavioral problems. For parents their guidance in Cogmed helps reduce their anxiety by fully embracing their role as primary agents in their child’s development. This is consistent with recommendations for family-centered healthcare and can significantly improve the quality of life for both the children and their parents. In the long term, these improvements might also reduce those global costs linked to the consequences of extreme prematurity.
Finally, if proved effective for this vulnerable population, this treatment can be a possible option or an alternative for other preschool populations complaining of early academic difficulties related to WM deficits. Furthermore, the study design based in a randomized, placebo-controlled, is considered as an appropriate design to demonstrate the efficacy of a new experimental intervention in accordance with the Levels of Evidence classification of the Evidence-Based Medicine Working Group [
63]. Our findings could be used in the future to update the national and international recommendations concerning very preterm children and training of executive functions.
Acknowledgements
The authors would like to thank all collaborators of EPIREMED-Study Group who participate in the study.
EPIREMED-Study Group:
Meriem ZAHED, Patricia GARCIA, Tristan DESILES, Ludovic ZAHED, Mélodie PACHE, Gwenaëlle MENARD, (AP-HM, France),
Nathalie BEDNAREK WEIRAUCH, Karine VOIRIN, Virginie VERRIERE (University Hospital of Reims, France),
Gilles CAMBONIE, Claire LERAT, Maythé POUJOL (University Hospital of Montpellier, France),
Olivier CLARIS, Sophie RUBIO GURUNG, Eliane BASSON, Melanie RODRIGUEZ, Anne RANNAUD, Johanna BOULANT (University Hospital of Lyon, France),
Thierry DEBILLON, Isabelle PIN, Karine GUICHARDET, Caroline TOURNEGROS (University Hospital of Grenoble, France),
Laurence FOIX L’HELIAS, Delphine MITANCHEZ, Jennifer SOMMER, Hélène RUYS MASSON (AP- HP - Armand Trousseau Hospital, France),
Michele GRANIER, Marylène RIOU, Dalia MIGNOT (Sud Francilien Hospital, France),
Bernard GUILLOIS, Valérie DORRIERE DATIN, Mireille DENAVEAUT BOULAY, Delphine ROTS (University Hospital of Caen Normandie, France),
Jean-Michel HASCOT, Hélène DEFORGE, Sabine GUIGNON (Regional University Hospital of Nancy, France),
Pierre KUHN, Anne DE SAINT MARTIN, Claire ZORES KOENIG, Hélène MUSMEAUX, Lucille SCHNEIDER, Carole RAMOUSSET, Coralie MANGIN (Regional University Hospital of Strasbourg, France),
Bénédicte LECOMTE, Angélique PANNETIER, Emmanuelle ROCHETTE, Nelly GOUDON-DUBOIS (University Hospital of Clermont-Ferrand, France),
Julie OERTEL, Sandrine LA PLANETA (University Hospital of Nice, France),
Stéphane MARRET, Marie LEMARCHAND, Nathalie MESTRE (University Hospital of Rouen, France),
Hugues PATURAL, Sophie FLORI (University Hospital of Saint-Etienne, France),
Jean-Christophe ROZE, Charlotte COUDRONNIERE, Hamida MARTIN, Alix LAURENT (University Hospital of Nantes, France),
Elie SALIBA, Patrick ZANDER, Eva AOUSTIN (University Hospital of Tour, France),
Catherine ARNAUD, Emeline DUBOIS, Stephanie IANNUZZI, Carine DUFFAUT (University Hospital of Toulouse, France),
Isabelle SOUKSI MEDIONI, Magali REBATTEL, Elodie FALQUE, Nathalie RUMEAU (University Hospital of Nîmes, France),
Valérie BENHAMMOU, Laetitia MARCHAND-MARTIN, Samira MEDJAHED (University of Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, F-75004 Paris, France)
Declarations
Ethics approval and consent to participate
The expected sponsor is represented by the Assistance Publique - Hôpitaux de Marseille and must have approvals from the French authorities prior to the study’s initiation. The sponsor and the investigators conduct the study in accordance with Good Clinical Practices and the French applicable regulatory requirements (Public Health Act No. 2004–806 of August 9, 2004 on public health policy and its implementing decrees of August 27, 2006 [Code de la Santé Publique, article L.1121–1]), as the applicable privacy requirements and ethical principles outlined in the Declaration of Helsinki. This study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud Méditerranée V) on April 12, 2016 and by the French National Agency for Medicines and Health Products Safety (Agence Nationale de Sécurité du Médicament et des Produits de Santé) on April 18, 2016 (reference number ID-RCB:2016-A00122–49 – Protocol version 2 of 29 Mars 2016). All amendments will be submitted to these two French organizations and communicated to investigators associated by sponsor. The study was registered in ClinicalTrials.gov (NCT02757794).
In accordance with applicable regulations including Good Clinical Practices, and Sponsor’s procedures, a Sponsor’s monitor will visit the investigator before, during and after the study. Sponsor’s monitors will contact the site prior to the start of the study to review with the site staff the protocol, study requirements, and their responsibilities to satisfy regulatory, ethical, and Sponsor’s requirements. When reviewing data collection procedures, the discussion will also include identification, agreement and documentation of data items for which the case report form will serve as the source document. The type and frequency of monitoring are determined using the definition of the level of monitoring based on patient risk and depend on the number of patients included, the rate of inclusions and difficulties encountered during the conduct of the study (procedures approved by the group quality promotion which determines the level of monitoring to be carried out based on risk to the subject-OECD recommendation on the Governance of Clinical Trials, December 2012). In this study, the level of monitoring is rated “minimal” with a risk for the patient level A. The Sponsor’s monitor will verify the signed informed consents. If one / multiple consents are not compliant, files will be monitored randomly. All adverse events occurring during clinical trial have to be collected, verified, registered and reported from Day 0 (inclusion day for the participant) until the last day of the study, or as soon as the investigator becomes aware of the AE that he considers linked to the protocol and this up to its resolution.
Any publication must state that Assistance Publique - Hôpitaux de Marseille is the promoter and the study’s databases will be co-owned by the promoter Assistance Publique - Hôpitaux de Marseille and by the INSERM U1153, EPOPÉ team. The results, as well as all research-related data, must under no circumstances be transmitted to third parties without compensation negotiated beforehand by the Medical Research Branch of the Assistance Publique - Hôpitaux de Marseille and/or INSERM U 1153.
All data, results, inventions and discoveries resulting from the study will automatically become the exclusive property of the sponsor which may use this information in the manner deemed suitable with the agreement of the investigator.
The EPIREMED study is part of EPIPAGE 2 and allows us to benefit from the collaboration of those involved in the EPIPAGE 2 cohort’s steering committee. The different investigators are involved in the monitoring and care of very premature babies. Their diverse training and responsibilities meet all aspects of our project. These investigators are either pediatrician-neonatologists or pediatric neurologists working in type III neonatal units, in neuro-pediatric services for very premature infants’s assessment or in a referral center for learning disabilities.
A written informed consent will be obtained from two parents or legal representative to children participating in the study. Protection of the rights will be guaranteed, and anonymity maintained. In accordance with French laws and regulations respectively, all patient records identities will remain confidential. The study’s results will be disseminated to patients via a written report in a clear and accessible language.
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