Neurocognitive outcomes at age 5 years after prophylactic hydrocortisone in infants born extremely preterm.

AIM: To assess the 5-year neurocognitive outcomes of children born extremely preterm exposed to prophylactic hydrocortisone to improve survival without bronchopulmonary dysplasia. METHOD: This was a prespecified secondary analysis of the PREMILOC clinical trial (trial registration: EudraCT no. 2007-002041-20, NCT00623740). The primary outcome was full-scale IQ based on the Wechsler Preschool and Primary Scale of Intelligence. RESULTS: Among 109 surviving children recruited at the Robert Debré Children's Hospital, Paris, outcome data were available for 42 out of 56 infants (75%) in the group treated with hydrocortisone and 41 out of 53 (77%) in the placebo group. Mean scores were not significantly different between the two groups on full-scale IQ (hydrocortisone: 91.9 [SD = 13.9], placebo: 86.3 [SD = 15.4]; mean difference = 5.7, 95% confidence interval [CI] = -1.0 to 12.3, p = 0.10); however, working memory and retention ability were significantly better in the group treated with hydrocortisone. In a multivariate logistic regression including potential confounding variables, hydrocortisone treatment was significantly associated with a greater chance to survive at 5 years of age with a full-scale IQ equal to or greater than 90 compared to placebo (adjusted odds ratio = 4.26, 95% CI = 1.47-12.36, p = 0.008). INTERPRETATION: This exploratory analysis provides reassuring data regarding the long-term neurodevelopmental safety of prophylactic hydrocortisone in infants born extremely preterm.

Temporosylvian arachnoid cysts in children. Part 2: Postoperative neuropsychological and clinical improvement.

OBJECTIVE: The authors' objective was to study clinical, imaging, and neuropsychological changes in children who underwent surgery for a temporal arachnoid cyst (TAC). METHODS: Thirty-four children were prospectively assessed similarly at diagnosis and postoperatively (mean 14 months) with clinic visits, images, cognitive tests, and parental questionnaires on mood/behavior and executive functions. The scores were compared pre- and postoperatively for the entire cohort and individually. The scores of 25 children were also compared with a control group of 23 healthy age-matched children. Parents were administered an outcome questionnaire on average 4 years postoperatively. RESULTS: The 34 children selected for surgery had signs of raised intracranial pressure (74%) and/or selective neuropsychological disorders presumably linked to cyst location (learning difficulties in 65%, cognitive difficulties in 56%, and mood/behavior difficulties in 47%). The majority of patients had a convex cyst (85%) and underwent microsurgical fenestration (85%). The TAC volume decreased ≥ 50% for 59% of children. On the Wechsler Intelligence Scale, the entire cohort significantly improved on Full Scale IQ and verbal and perceptual nonverbal indexes. Individually, nearly half of the children (47%) highly increased their scores (≥ 15 points) on at least one IQ index and 26% on at least two indexes. Language, working memory, episodic memory, and executive functions were also significantly improved. Improvements were more pronounced in patients with a preoperative heterogeneous profile with isolated lower scores and a left-sided cyst. Parental questionnaires showed reduction in anxiety, aggressiveness, social problems, and daily life executive disorders. Preschool-aged children improved significantly in language and verbal IQ, as did middle/high school-aged children in many domains. Individual analyses revealed improvement in 76% of cases. Cognitive scores were lower for patients preoperatively than for controls and were no longer significantly different postoperatively in verbal fluency, visual memory, and working memory. Four years later, 97% of parents described an improvement in their child, correlated with cognitive improvements. CONCLUSIONS: Among children with a TAC, some have no clinical signs or neuropsychological difficulties, and others may show signs of raised intracranial pressure and/or specific neuropsychological disorders that impact daily life and require significant and long-lasting rehabilitation. In these cases, consideration may be given to surgical decompression. It is interesting to note that 76% of this surgically treated cohort improved regardless of the child's age, particularly in patients with selective disorders and an impact on daily life. However, a larger number of children will need to be investigated before the true benefit of such treatment can be known.

Temporosylvian arachnoid cysts in children. Part 1: Cognitive profile of children with a temporal cyst and impact of the cyst in daily life. A prospective study in 100 consecutive children.

OBJECTIVE: The aim of this study was to determine the cognitive profile of children with a temporal arachnoid cyst (TAC) and its impact on daily life. METHODS: The authors prospectively analyzed the cognitive and psychological profiles of 100 consecutive children relative to age and cyst characteristics (side, cyst size, and cyst shape: convex or nonconvex) and their outcome 4 years later. RESULTS: Mean IQs were normal but with high heterogeneity on Full Scale IQ (FSIQ; range 59-150); 29% of children had at least one Wechsler index below the norm, in particular, Processing Speed and Working Memory Indexes. Impairments were observed in language for 31% of children, as well as in verbal memory (28%), visual memory (23%), executive function (21%), and visual attention (24%). Half of the children (50%) needed rehabilitation for learning difficulties, and 26% had academic difficulties. The parental questionnaire BRIEF (Behavior Rating Inventory of Executive Function) revealed significant executive dysfunctions in daily life for 22% of the children. One-third of the patients (34%) required psychotherapy for anxiety or social disorders, with higher rates in patients with a right-sided cyst and older children. Cyst size had very little neuropsychological impact. Convex cysts were significantly associated with worse performance than nonconvex cysts on all Wechsler indexes and FSIQ, and in language, verbal memory, attention, and visuospatial skills. Children with a convex cyst had significantly more executive and behavior difficulties in daily life and more psychotherapy than other children. The effect of cyst shape was independent of Galassi type and cyst side. Children with a ruptured cyst or an incidentally discovered cyst usually had a good cognitive level. Four years later, children without initial disorders remained stable, whereas those with difficulties who did not undergo surgery needed more rehabilitation and school adaptations. CONCLUSIONS: This large cohort study revealed a varied profile of children with a TAC: at initial assessment, 50% had neuropsychological difficulties and needed rehabilitation and/or psychotherapy for learning or behavior difficulties, and 50% had no difficulties, which may explain the debate about this pathology. Patients with neuropsychological difficulties had a heterogeneous profile with normal intelligence but selective cognitive and/or behavior disorders that may have a long-term impact on their quality of life, particularly those with a right-sided cyst. A neuropsychological evaluation is not always necessary for a cyst discovered incidentally, but early evaluation is essential in patients with academic, learning, or psychological disorders. When assessment shows selective disorders presumably linked to cyst location, surgery may be considered, particularly for convex cysts, as this study revealed more effects in association with cyst shape than with cyst size and significantly poorer performance with a convex cyst.

Immaturity of Oculomotor Capabilities During a Reading Task in Children Born Prematurely: An Eye Tracker Study.

To our knowledge, there are no studies recording the reading eye movements of children born prematurely. We examined the oculomotor patterns during reading of 23 children born prematurely (M age = 7.8, SD = 0.2 years) to compare them with those from two groups of children born at full-term who were matched for chronological age or reading age, respectively. We found the oculomotor reading pattern in children who were preterm to be similar to that of children who were full-term and matched for reading age; this shared pattern was characterized by longer duration of fixations, frequent prosaccades of smaller amplitude and several backward saccades. In contrast, when these two groups were compared to full-term children matched for chronological age, the latter group showed significantly shorter duration of fixations, less frequent saccades and larger amplitude prosaccades. Thus, the oculomotor pattern we observed in 7-year-old children who were either preterm or reading-delayed, relative to their age-matched peers, reflected delayed development of brain areas involved in reading-related eye movements.

Immature brain structures were associated with poorer eye movement performance at 8 years of age in preterm born children.

AIM: Eye movements have rarely been explored in preterm born children. The aim of this study was to compare horizontal eye movements in children born preterm and full term when they reached 8 years of age. METHODS: Eye movements were recorded in 24 preterm born children (18 boys) and 26 matched controls (19 boys), recruited by a French hospital, using an eye tracker. This identified different types of visually guided saccades, namely step, gap, overlap and antisaccades and pursuit eye movements. The saccades task measured the latency and the percentage of anticipatory and express saccades and errors. The pursuit task measured the gain and percentage of intrusive saccades. RESULTS: This study confirmed that children born at 24-28 weeks of gestation demonstrated a global deficit in inhibitory processes compared to children born full term. The saccades were less precise in the preterm group, anticipatory and express saccades were elevated and there was a high occurrence of intrusive saccades during pursuit movements. CONCLUSION: These findings suggest that preterm born children have immature brain structures, particularly the parietal and frontal cortexes that are responsible for both saccade and pursuit performance. These could have been the cause of the abnormal inhibitory control measured in this study.

Two-year neurodevelopmental outcomes of extremely preterm infants treated with early hydrocortisone: treatment effect according to gestational age at birth.

OBJECTIVE: To determine whether early hydrocortisone treatment in extremely preterm infants affects neurodevelopmental outcomes at 2 years of age according to gestational age at birth. PATIENTS AND METHODS: This is an exploratory analysis of neurodevelopmental outcomes by gestational age strata from the PREMILOC trial, in which patients were randomly assigned to receive either placebo or low-dose hydrocortisone and randomisation was stratified by gestational age groups (24-25 and 26-27 weeks of gestation). Neurodevelopmental impairment (NDI) was assessed using a standardised neurological examination and the revised Brunet-Lézine scale at 22 months of corrected age. RESULTS: A total of 379 of 406 survivors were evaluated, 96/98 in the gestational age group of 24-25 weeks and 283/308 in the gestational age group of 26-27 weeks. Among surviving infants born at 24-25 weeks, significant improvement in global neurological assessment was observed in the hydrocortisone group compared with the placebo group (P=0.02) with a risk of moderate-to-severe NDI of 2% and 18%, respectively (risk difference 16 (95% CI -28% to -5%)). In contrast, no statistically significant difference between treatment groups was observed in infants born at 26-27 weeks (P=0.95) with a similar risk of moderate-to-severe NDI of 9% in both groups. The incidence of cerebral palsy or other major neurological impairments were found similar between treatment groups in each gestational group. CONCLUSIONS: In an exploratory analysis of neurodevelopmental outcomes from the PREMILOC trial, early low-dose hydrocortisone was associated with a statistically significant improvement in neurodevelopmental outcomes in infants born at 24 and 25 weeks of gestation.

Spatial and temporal postural analysis in children born prematurely.

The aim of this study was to compare postural stability in a group of preterm-born children aged 4-6 years old and in a group of age-matched full-term control children by exploring both spatial and temporal analysis of the Center of Pressure (CoP). Twenty-nine children born prematurely (mean age: 5.38±0.17) and twenty-nine age-matched full-term control children participated in this study. Postural control was tested on both a stable and an unstable platform (from Framiral®) in three different visual conditions: eyes open fixating a target, eyes closed, and with vision perturbed by optokinetic stimulation. We observed a significant increase of both surface area and mean velocity of the CoP in pre-term children compared to full-term control children, particularly in an unstable postural condition. The spectral power indices increased significantly in pre-term children with respect to full-term control children, while the cancelling time was not different between the two groups of children tested. We suggested that poor postural stability observed in preterm children could be due to immaturity of the cortical processes (the occipital parietal prefrontal cortex) involved in motor control. Preterm children could have an inappropriate compensation of sensory inputs when they are tested in difficult postural and/or visual conditions.

Association Between Early Low-Dose Hydrocortisone Therapy in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years of Age.

Importance: Dexamethasone to prevent bronchopulmonary dysplasia in very preterm neonates was associated with adverse neurodevelopmental events. Early low-dose hydrocortisone treatment has been reported to improve survival without bronchopulmonary dysplasia but its safety with regard to neurodevelopment remains to be assessed. Objective: To assess whether early hydrocortisone therapy in extremely preterm infants is associated with neurodevelopmental impairment at 2 years of age. Design, Setting, and Participants: An exploratory secondary analysis of the PREMILOC (Early Low-Dose Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia in Extremely Preterm Infants) randomized clinical trial conducted between 2008 and 2014 in 21 French neonatal intensive care units. Randomization was stratified by gestational age groups. Neurodevelopmental assessments were completed from 2010 to 2016. Interventions: After birth, patients were randomly assigned to receive placebo or hydrocortisone (0.5 mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days). Main Outcomes and Measures: The prespecified exploratory secondary outcome of neurodevelopmental impairment was based on a standardized neurological examination and the revised Brunet-Lézine scale (global developmental quotient score and subscores; mean norm, 100 [SD, 15]). The minimal clinically important difference on the global developmental quotient was 5 points. Results: Of 1072 neonates screened, 523 were assigned to hydrocortisone (n = 256) or placebo (n = 267) and 406 survived to 2 years of age. A total of 379 patients (93%; 46% female) were evaluated (194 in the hydrocortisone group and 185 in the placebo group) at a median corrected age of 22 months (interquartile range, 21-23 months). The distribution of patients without neurodevelopmental impairment (73% in the hydrocortisone group vs 70% in the placebo group), with mild neurodevelopmental impairment (20% in the hydrocortisone group vs 18% in the placebo group), or with moderate to severe neurodevelopmental impairment (7% in the hydrocortisone group vs 11% in the placebo group) was not statistically significantly different between groups (P = .33). The mean global developmental quotient score was not statistically significantly different between groups (91.7 in the hydrocortisone group vs 91.4 in the placebo group; between-group difference, 0.3 [95% CI, -2.7 to 3.4]; P = .83). The incidence of cerebral palsy or other major neurological impairments was not significantly different between groups. Conclusions and Relevance: In this exploratory analysis of secondary outcomes of a randomized clinical trial of extremely preterm infants, early low-dose hydrocortisone was not associated with a statistically significant difference in neurodevelopment at 2 years of age. Further randomized studies are needed to provide definitive assessment of the neurodevelopmental safety of hydrocortisone in extremely preterm infants. Trial Registration: clinicaltrials.gov Identifier: NCT00623740.

Subjective visual vertical and postural capability in children born prematurely.

PURPOSE: We compared postural stability and subjective visual vertical performance in a group of very preterm-born children aged 3-4 years and in a group of age-matched full-term children. MATERIALS AND METHODS: A platform (from TechnoConcept) was used to measure postural control in children. Perception of subjective visual vertical was also recorded with posture while the child had to adjust the vertical in the dark or with visual perturbation. Two other conditions (control conditions) were also recorded while the child was on the platform: for a fixation of the vertical bar, and in eyes closed condition. RESULTS: Postural performance was poor in preterm-born children compared to that of age-matched full-term children: the surface area, the length in medio-lateral direction and the mean speed of the center of pressure (CoP) were significantly larger in the preterm-born children group (p < 0.04, p < 0.01, and p < 0.04, respectively). Dual task in both groups of children significantly affected postural control. The subjective visual vertical (SVV) values were more variable and less precise in preterm-born children. DISCUSSION-CONCLUSIONS: We suggest that poor postural control as well as perception of verticality observed in preterm-born children could be due to immaturity of the cortical processes involved in the motor control and in the treatment of perception and orientation of verticality.