ImportanceCompared 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.ObjectiveTo 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 ParticipantsThis 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.InterventionChildren 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 MeasuresThe 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).ResultsThere 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 RelevanceThis 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 RegistrationClinicalTrials.gov Identifier: NCT02757794

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 51/2 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 51/2 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 51/2 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.

BACKGROUND:Regionalisation programmes aim to ensure that very preterm infants are born in level III units (inborn) through antenatal referral or transfer. Despite widespread knowledge about better survival without disability for inborn babies, 10%-30% of women deliver outside these units (outborn).OBJECTIVE:To investigate risk factors associated with outborn deliveries and to estimate the proportion that were probably or possibly avoidable.METHODS:We used a national French population-based cohort including 2205 women who delivered between 24 and 30+6  weeks in 2011. We examined risk factors for outborn delivery related to medical complications, antenatal care, sociodemographic characteristics and living far from a level III unit using multivariable binomial regression. Avoidable outborn deliveries were defined by pregnancy risk (obstetric history, antenatal hospitalisation) and time available for transfer.RESULTS:25.0% of women were initially booked in level III, 9.1% were referred, 49.8% were transferred, and 16.1% had outborn delivery. Risk factors for outborn delivery were gestational age <26 weeks (adjusted relative risk (aRR) 1.37, 95% confidence interval (CI) 1.13, 1.66), inadequate antenatal care (aRR 1.39, 95% CI 1.10, 1.81), placental abruption (aRR 1.66, 95% CI 1.27, 2.17), and increased distance to the closest level III unit ((aRR 2.79, 95% CI 2.00, 3.92) in the 4th versus 1st distance quartile). Among outborn deliveries, 16.7% were probably avoidable, and 25.6% possibly avoidable, which could increase the proportion of inborn deliveries between 85.9% and 92.9%. Avoidable outborn deliveries were mainly associated with gestational age, intrauterine growth restriction, preterm premature rupture of membranes, and haemorrhage, but not distance.CONCLUSIONS:Our study identified some modifiable risk factors for outborn delivery; however, when regionalised care relies heavily on antenatal transfer, as it does in France, only some outborn deliveries may be prevented. Earlier referral of high-risk women will be needed to achieve full access to tertiary care.

Objectives To investigate the relation between neonatal intensive care unit (NICU) volume and survival, and neuromotor and sensory disabilities at 2 years in very preterm infants. Study design The EPIPAGE-2 (Etude Epidemiologique sur les Petits Ages Gestationnels-2) national prospective population-based cohort study was used to include 2447 babies born alive in 66 level III hospitals between 24 and 30 completed weeks of gestation in 2011. The outcome was survival without disabilities (levels 2-5 of the Gross Motor Function Classification System for cerebral palsy with or without unilateral or bilateral blindness or deafness). Units were grouped in quartiles according to volume, defined as the annual admissions of very preterm babies. Multivariate logistic regression analyses with population average models were used. Results Survival at discharge was lower in hospitals with lower volumes of neonatal activity (aOR 0.55, 95% CI 0.33-0.91). Survival without neuromotor and sensory disabilities at 2 years increased with hospital volume, from 75% to 80.7% in the highest volume units. After adjustment for gestational age, small for gestational age, sex, maternal age, infertility treatment, multiple pregnancy, principal cause of prematurity, parental socioeconomic status, and mother's country of birth, survival without neuromotor or sensory disabilities was significantly lower in hospitals with a lower volume of neonatal activity (aOR 0.60, 95% CI 0.38-0.95) than in the highest quartile hospitals. Conclusions These results suggest that lower neonatal intensive care unit volume is associated with lower survival without an increase in disabilities at 2 years. These results could be useful to generate improvements of perinatal regionalization.

We report a case of lethal toxoplasma meningo-encephalitis diagnosed postnataly despite antenatal follow up and treatment of the mother and normal clinical and laboratory findings of the infant at birth.