Cognitive Training for Visuospatial Processing in Children Aged 5½ to 6 Years Born Very Preterm With Working Memory Dysfunction: A Randomized Clinical Trial.

Importance: Compared with term-born peers, children born very preterm generally perform poorly in executive functions, particularly in working memory and inhibition. By taking advantage of neuroplasticity, computerized cognitive training of working memory in those children could improve visuospatial processing by boosting visual inhibition via working memory. Objective: To evaluate the long-term effect of cognitive working memory training on visuospatial processing in children aged 5½ to 6 years born very preterm who have working memory impairment. Design, Setting, and Participants: This multicenter (18 French university hospitals), open-label randomized clinical trial with 2 parallel groups (EPIREMED) was conducted from November 2016 to April 2018, with the last follow-up during August 2019. Eligible children from the EPIPAGE 2 cohort were aged 5½ to 6 years, were born between 24 and 34 weeks' gestation, and had a global intelligence quotient greater than 70 and a working memory index less than 85. Data were analyzed from February to December 2020. Intervention: Children were randomized 1:1 to standard care management and a working memory cognitive training program (Cogmed software) for 8 weeks (25 sessions) (intervention) or to standard management (control). Main Outcomes and Measures: The primary outcome was the visuospatial index score from the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition. Secondary outcomes were working memory, intellectual functioning, executive and attention processes, language skills, behavior, quality of life, and schooling. Neurobehavioral assessments were performed at inclusion and after finishing training at 6 months (intermeditate assessment; secondary outcomes) and at 16 months (final assessment; primary outcome). Results: There were 169 children randomized, with a mean (SD) age of 5 years 11 months (2 months); 91 (54%) were female. Of the participants, 84 were in the intervention group (57 of whom [68%] completed at least 15 cognitive training sessions) and 85 were in the control group. The posttraining visuospatial index score was not different between groups at a mean (SD) of 3.0 (1.8) months (difference, -0.6 points; 95% CI, -4.7 to 3.5 points) or 12.9 (2.6) months (difference, 0.1 points; 95% CI, -5.4 to 5.1 points). The working memory index score in the intervention group significantly improved from baseline at the intermediate time point (difference, 4.7 points; 95% CI, 1.2-8.1 points), but this improvement was not maintained at the final assessment. Conclusions and Relevance: This randomized clinical trial found no lasting effect of a cognitive training program on visuospatial processing in children aged 5½ to 6 years with working memory disorders who were born very preterm. The findings suggest that this training has limited long-term benefits for improving executive function. Transient benefits seemed to be associated with the developmental state of executive functions. Trial Registration: ClinicalTrials.gov Identifier: NCT02757794.

Neurobehavioral Phenotype and Dysexecutive Syndrome of Preterm Children: Comorbidity or Trigger? An Update.

Premature birth is a worldwide public health priority. One in ten children is born before 37 weeks of gestational age and, in developed countries, survival rates without major neonatal morbidity are increasing. Although severe sequelae associated with these births have decreased, their neurobehavioral difficulties, often associated in multiple fields, remain stable but still widespread. These neurobehavioral difficulties hamper the normal development of academic achievements and societal integration and intensify the children's needs for rehabilitation during their preschool and academic years. Severe sequelae increase when gestational age decreases. This is even truer if the socio-cultural background is impeded by low income, education and language skills as compared with defined averages. However, moderate and/or minor neurocognitive and/or behavioral difficulties are almost identical for a moderate or a late preterm birth. Obtaining a better clinical description of neurobehavioral characteristics of those pretermly born, once they reach preschool age, is essential to detect behavioral issues as well as early specific cognitive difficulties (working memory, planning, inhibition, language expression and reception, attention and fine motor skills, etc.). Such information would provide a better understanding of the executive functions' role in brain connectivity, neurodevelopment and neuroanatomical correlation with premature encephalopathy.

The Neurobehavioral Phenotype of School-Aged, Very Prematurely Born Children with No Serious Neurological Sequelae: A Quality of Life Predictor.

School-aged extremely preterm (EPT) children have multiple specific neurocognitive/behavioral disorders that are often associated with other disorders; this manifests a true neurobehavioral "phenotype" of prematurity. To determine a profile of cognitive/behavioral impairments in a population of school-aged EPT children (7-10 years-old) without major disabilities, a cross-sectional study was conducted in five medical centers. An algorithm distributed the study population according to four WISC-IV subtests, five NEPSY-2 subtests, and two variables of figure of Rey. The behavior (SDQ), anxiety (Spielberg STAI-C), and generic QoL (Kidscreen 10 and VSP-A) were also evaluated. The study included 231 school-aged EPT children. Three neurobehavioral "phenotypes" were defined according to their severity: 1 = moderately, 2 = minor, and 3 = unimpaired. In all the profiles, the working memory, perceptual reasoning, as well as mental flexibility, were close to or below average, and their emotional behavior was always troubled. Self-esteem and school-work were the most impacted QoL areas. The unimpaired neurobehavior exhibited emotional behavioral impairment and executive dysfunction. The profile analysis defined distinct outcome groups and provided an informative means of identifying factors related to developmental outcomes. The QoL deterioration is determined by the severity of the three neurobehavioral "phenotypes", which is defined as well as by dysexecutive and/or behavioral disorders.

Neurodevelopment and Health-Related Quality of Life in Infants Born with Gastroschisis: A 6-Year Retrospective French Study.

Introduction Quantify quality of life (QoL) outcomes in gastroschisis children is little assessed. The primary objective was to describe the long-term outcome of newborns with gastroschisis treated in three tertiary care hospitals of France in terms of neurodevelopment and QoL. Materials and Methods The study reported was a cross-sectional, descriptive multicentric retrospective study assessing the outcome of newborns with gastroschisis, born between January 1, 2009, and December 31, 2014, treated at two large and French level III neonatal intensive care units. Long-term outcome data were assessed by questionnaires sent to the infants' parents. Questionnaires explored global health, neurological development, and quality of life (overall assessment including socio-economic and medical), Age & Stages Questionnaire, infants' quality of life (KIDSCREEN), and quality of parents' life (General Questionnaire Short Form-36). Results In this study, 50% of the survivor's families answered the assessment form (n = 33). The average follow-up age was 40 months, ranging from 8 months to 6 years. Cases of simple gastroschisis more often had a normal score for "communication" (p = 0.033), while patients who received morphine for a longer duration had significantly lower scores for the items "communication" and "problem resolving" (p = 0.024 and p = 0.011, respectively). Children's QoL was significantly lower for patients with gestational age younger than 36 weeks (p = 0.023) and for patients born following "fetal cause delivery" (p = 0.022). Parents had a significantly higher physical composite score if their child underwent primary closure (p = 0.012). Conclusion Our analyses confirm the idea that cases of complex gastroschisis and preterm delivery may lead to poorer outcome. Such hindsight (40 months in mean) allowed for an interesting assessment of development long after the patient's initial hospitalization and to confirm these results, a standardized neuropsychological evaluation of patients should be done when at least 6 years old. An accurate assessment of the social environment and its impact on the development and QoL of children will be fundamental to avoid selection bias.

Management and outcome challenges in newborns with gastroschisis: A 6-year retrospective French study.

OBJECTIVE: To identify the gestational age (GA) at which risk of mortality and severe outcome was minimized comparing preterm delivery and expectant management. METHODS: Retrospective study performed between 2009 and 2014 of newborns with gastroschisis in three large French level III neonatal intensive care units. Each department followed two distinct strategies: elective delivery at 35 weeks' GA and a delayed approach. RESULTS: We included 69 gastroschisis cases. The lengths of stay lasting more than 60 days were significantly greater in the planned delivery group than in the expectant approach group (18/30 (60%) vs. 8/39 (20.5%), p = 0.001). Gastroschisis cases receiving antenatal corticoids during the last two weeks of gestation required significantly less surgeries during their initial stay (p = 0.003) as well as shorter parenteral feedings (p = 0.002). A multivariate logistic regression showed that a GA of less than 36 weeks' GA was is a pejorative factor for a stay above 60 days, regardless of whether it was a simple or complex gastroschisis, (OR= 3.8; p = 0.021). A complex gastroschisis was a risk factor for significantly longer parenteral feedings, regardless of the center where patient is treated (Beta = -0.3, p = 0.035). CONCLUSIONS: Future research should focus on decisions about delivery timing by incorporating risk of neonatal morbidity.