A randomized EPIREMED protocol study on the long-term visuo spatial effects of very preterm children with a working memory deficit
Authors: Gire Catherine , Beltran Anzola Any , Kaminski Monique , Baumstarck Karine , Ancel Pierre-Yves , Berbis Julie ,   for EPIREMED-Study Group, Zahed Meriem , Garcia Patricia , Desiles Tristan , Zahed Ludovic , Pache Mélodie , Menard Gwenaëlle , Bednarek Weirauch Nathalie , Voirin Karine , Verriere Virginie , Cambonie Gilles , Lerat Claire , Poujol Maythé , Claris Olivier , Rubio Gurung Sophie , Basson Eliane , Rodriguez Melanie , Rannaud Anne , Boulant Johanna , Debillon Thierry , Pin Isabelle , Guichardet Karine , Tournegros Caroline , Foix L’Helias Laurence , Mitanchez Delphine , Sommer Jennifer , Ruys Masson Hélène , Granier Michele , Riou Marylène , Mignot Dalia , Guillois Bernard , Dorriere Datin Valérie , Denaveaut Boulay Mireille , Rots Delphine , Hascot Jean-Michel , Deforge Hélène , Guignon Sabine , Kuhn Pierre , de Saint Martin Anne , Zores Koenig Claire , Musmeaux Hélène , Schneider Lucille , Ramousset Carole , Mangin Coralie , Lecomte Bénédicte , Pannetier Angélique , Rochette Emmanuelle , Goudon-Dubois Nelly , Oertel Julie , La Planeta Sandrine , Marret Stéphane , Lemarchand Marie , Mestre Nathalie , Patural Hugues , Flori Sophie , Roze Jean-Christophe , Coudronniere Charlotte , Martin Hamida , Laurent Alix , Saliba Elie , Zander Patrick , Aoustin Eva , Arnaud Catherine , Dubois Emeline , Iannuzzi Stephanie , Duffaut Carine , Souksi Medioni Isabelle , Rebattel Magali , Falque Elodie , Rumeau Nathalie , Benhammou Valérie , Marchand-Martin Laetitia , Medjahed Samira 
Published: September 2021

Abstract
Background
Very preterm children generally perform poorly in executive functions and particularly in working memory. Adaptive training tasks encouraging these children to work continuously on their personal working memory capacity can be very useful. Above all in preschool-age children, several cognitive training programs focused on improving working memory capacity. Cogmed is a computerized visuospatial cognitive training program that improves working memory in children and adolescents with attention-deficit/hyperactivity disorder. The main objective is to assess the long-term effects (18 months) of cognitive training (Cogmed) on visuospatial processing in preschool-age very preterm children with working memory impairment.

Methods
The EPIREMED study is a prospective, randomized, controlled, multicentric trial nested in a population based epidemiological survey. An intervention group (Cogmed cognitive training) and a control group (standard care management) will compare children aged 5½ to 6 years, born between 24- and 34-weeks’ gestational age, with a global intelligence quotient > 70 and a working memory index < 85. The study will include 166 children from national study EPIPAGE-2 (Epidemiological Study on Small Gestational Ages). The intervention consists of 25 sessions administered over a 5- to 8-week period. The primary endpoint will be the visuospatial processing, assessed by the score of the visuospatial index: score of the WPPSI-IV (Wechsler Preschool and Primary Scale of Intelligence). The secondary endpoints will allow to assess the executive functions, language and abilities, infant behavior, quality of life assessment, school performance and parental anxiety.

Discussion
This project’s primary goal is to demonstrate the necessity of early visuospatial memory assessment within the vulnerable population of very preterm children, and to prove the feasibility and efficacy of computerized cognitive training using online software programs. A better global neuropsychological development improvement (visuospatial processing and other far transfer) can be expected with an improvement in learning and decreased behavioral problems. In the long term, these improvements might also reduce those global costs linked to the consequences of extreme prematurity.

Trial registration
NCT02757794 (registered on 2nd May 2016 at ClinicalTrial.gov).