Effects of Correcting for Prematurity on Executive Function Scores of Children Born Very Preterm at School Age.

OBJECTIVE: To investigate whether correction for prematurity affects executive function scores in school-aged children born very preterm. STUDY DESIGN: Executive functions were assessed with standardized neuropsychological tests in 142 children born very preterm (born at ≤32 weeks of gestational age or with a birth weight of ≤1500 g) and 391 control children, aged 7-13 years. Four-month age bands were established from the data of control children. Differences between uncorrected and corrected scores were compared against zero difference and between very preterm children born before and after 28 weeks of gestation. Regression models were used to compare the uncorrected and corrected scores of children born very preterm with control children. RESULTS: For all executive functions, significant, larger-than-zero differences between uncorrected and corrected scores were apparent in children born very preterm. Mean differences ranged from 0.04 to 0.18 SDs. Weak evidence was found that the effect of age correction is more pronounced in very preterm children born before 28 weeks of gestation than in those born after 28 weeks. Differences in executive function scores between children born very preterm and control children were attenuated if scores were corrected for prematurity. CONCLUSIONS: Test scores based on corrected rather than uncorrected age may more accurately determine the developmental stage of very preterm children's executive functions at school age. Potential consequences for clinical and research practice need to be discussed in the future.

Impact of the COVID-19 pandemic on children with and without risk for neurodevelopmental impairments.

AIM: To examine how the ongoing COVID-19 pandemic impacts child well-being and family functioning, particularly among children at risk for neurodevelopmental impairments. METHODS: Families of 73 typically developing children, 54 children born very preterm (VPT) and 73 children with congenital heart disease (CHD) from two prospective cohort studies were assessed prior to (mean age: 10.4 [SD: 1.2] years) and during (mean age: 12.8 [SD: 2.0] years) the pandemic, more specifically, in April/May 2020. Child well-being and family functioning were assessed with validated, parent-reported questionnaires and tested with linear mixed models. Group comparison of child distress and parental concerns related to medical implications of COVID-19 and homeschooling, assessed with 5-point Likert scales, was done with Mann-Whitney U tests. RESULTS: Children's psychological well-being and family functioning (both, p < 0.001) decreased significantly during the pandemic, irrespective of group. Children with CHD were reported to be more concerned about becoming infected with SARS-CoV-2 than were others. Child distress due to homeschooling and parents' concerns about children's academic achievements were significantly higher in VPT and CHD children than in typically developing peers (all p < 0.001). CONCLUSION: The COVID-19 pandemic substantially impacts the whole family and leads to additional distress in families with children at risk for neurodevelopmental impairments. These families should receive individualised counselling and assistance from healthcare providers and schools during the pandemic.

Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm.

BACKGROUND: Executive function deficits in children born very preterm (VPT) have been linked to anatomical abnormalities in white matter and subcortical brain structures. This study aimed to investigate how altered brain metabolism contributes to these deficits in VPT children at school-age. METHODS: Fifty-four VPT participants aged 8-13 years and 62 term-born peers were assessed with an executive function test battery. Brain metabolites were obtained in the frontal white matter and the basal ganglia/thalami, using proton magnetic resonance spectroscopy (MRS). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myo-Inositol (mI)/Cr were compared between groups and associations with executive functions were explored using linear regression. RESULTS: In the frontal white matter, VPT showed lower Glx/Cr (mean difference: -5.91%, 95% CI [-10.50, -1.32]), higher Cho/Cr (7.39%, 95%-CI [2.68, 12.10]), and higher mI/Cr (5.41%, 95%-CI [0.18, 10.64]) while there were no differences in the basal ganglia/thalami. Lower executive functions were associated with lower frontal Glx/Cr ratios in both groups (ß = 0.16, p = 0.05) and higher mI/Cr ratios in the VPT group only (interaction: ß = -0.17, p = 0.02). CONCLUSION: Long-term brain metabolite alterations in the frontal white matter may be related to executive function deficits in VPT children at school-age. IMPACT: Very preterm birth is associated with long-term brain metabolite alterations in the frontal white matter. Such alterations may contribute to deficits in executive function abilities. Injury processes in the brain can persist for years after the initial insult. Our findings provide new insights beyond structural and functional imaging, which help to elucidate the processes involved in abnormal brain development following preterm birth. Ultimately, this may lead to earlier identification of children at risk for developing deficits and more effective interventions.

Executive function deficits mediate the association between very preterm birth and behavioral problems at school-age.

BACKGROUND & AIMS: Children and adolescents born very preterm are at increased risk to develop executive function deficits and to suffer from social, emotional and attentional problems. This study investigated whether executive function deficits contribute to behavioral problems in children and adolescents born very preterm at school-age. STUDY DESIGN: Thirty-eight children and adolescents born very preterm and 41 age-matched term-born peers were assessed at a mean age of 12.9 (±1.8) years with a comprehensive battery of executive function tests, including working memory, planning, cognitive flexibility, and verbal fluency. A composite score was calculated to reflect overall executive function abilities. To assess behavioral problems, parents completed the Strengths and Difficulties Questionnaire (SDQ). Mediation analysis was applied to quantify the effect of preterm birth on behavioral problems with executive function abilities as a mediating variable. RESULTS: Executive function abilities were poorer in the very preterm compared to the term-born group (d = 0.62, p = .005) and the parents of very preterm children reported more behavioral problems on the SDQ Total Difficulties Score (d = 0.54, p = .01). The effect of birth status on behavioral problems was significantly mediated by executive function abilities while adjusting for age at assessment, sex, and socioeconomic status (F(2, 76) = 6.42, p = .002, R2 = 0.14). CONCLUSION: Results from this study suggest that the increase in behavioral symptoms in very preterm children at school-age compared to term-born peers may partly be explained by their executive function deficits. These findings highlight the importance of continuously monitoring the development of children born very preterm to provide optimal care as they grow up.

Inhibition is associated with whole-brain structural brain connectivity on network level in school-aged children born very preterm and at term.

Inhibition abilities are often impaired in children born very preterm. In typically-developing individuals, inhibition has been associated with structural brain connectivity (SC). As SC is frequently altered following preterm birth, this study investigated whether aberrant SC underlies inhibition deficits in school-aged children born very preterm. In a group of 67 very preterm participants aged 8-13 years and 69 term-born peers, inhibition abilities were assessed with two tasks. In a subgroup of 50 very preterm and 62 term-born participants, diffusion tensor imaging (DTI) data were collected. Using network-based statistics (NBS), mean fractional anisotropy (FAmean) was compared between groups. Associations of FAmean and inhibition abilities were explored through linear regression. The composite score of inhibition abilities was lower in the very preterm group (M â€‹= â€‹-0.4, SD â€‹= â€‹0.8) than in the term-born group (M â€‹= â€‹0.0, SD â€‹= â€‹0.8) but group differences were not significant when adjusting for age, sex and socio-economic status (ߠ​= â€‹-0.13, 95%-CI [-0.30, 0.04], p â€‹= â€‹0.13). In the very preterm group, FAmean was significantly lower in a network comprising thalamo-frontal, thalamo-temporal, frontal, cerebellar and intra-hemispheric connections than in the term-born group (t â€‹= â€‹5.21, lowest p-value â€‹= â€‹0.001). Irrespective of birth status, a network comprising parietal, cerebellar and subcortical connections was positively associated with inhibition abilities (t â€‹= â€‹4.23, lowest p-value â€‹= â€‹0.02). Very preterm birth results in long-term alterations of SC at network-level. As networks underlying inhibition abilities do not overlap with those differing between the groups, FAmean may not be adequate to explain inhibition problems in very preterm children. Future studies should combine complementary measures of brain connectivity to address neural correlates of inhibition abilities.

Long-term neuroprotective effect of erythropoietin on executive functions in very preterm children (EpoKids): protocol of a prospective follow-up study.

INTRODUCTION: Premature infants are particularly vulnerable to brain injuries with associated cognitive and behavioural deficits. The worldwide first randomised interventional multicentre trial investigating the neuroprotective effects of erythropoietin (entitled 'Does erythropoietin improve outcome in very preterm infants?' (NCT00413946)) included 450 very preterm infants in Switzerland. MRI at term equivalent age showed less white matter (WM) injury in the erythropoietin group compared with the placebo group. Despite these promising imaging findings, neurodevelopmental outcome at 2 years showed no beneficial effect of early erythropoietin. One explanation could be that the assessment of more complex cognitive functions such as executive functions (EFs) is only possible at a later age. We hypothesise that due to improved WM development and fewer WM injuries, children born preterm treated with early erythropoietin will have better EF abilities at 7-12 years than those treated with placebo. METHODS AND ANALYSIS: 365 children who were included into the primary analysis of the original trial (NCT00413946) will be eligible in this prospective follow-up study at the age of 7-12 years. 185 children born at term will be control children. Primary outcome measures are EF abilities and processing speed, while secondary outcomes are academic performance, IQ, fine motor abilities and global brain connectivity. A comprehensive test battery will be applied to assess EFs. MRI will be performed to assess global brain connectivity. Cognitive scores and MRI measures will be compared between both groups using the Wilcoxon test. Propensity score matching will be used to balance gender, age, socioeconomic status and other potentially unbalanced variables between the children born preterm and the healthy control children. ETHICS AND DISSEMINATION: The cantonal ethical committee granted ethical approval for this study (KEK 2017-00521). Written consent will be obtained from the parents. Findings from this study will be disseminated via international and national conference presentations and publications in peer-reviewed journals.

A Single-blinded, Randomized Clinical Trial of How to Implement an Evidence-based Treatment for Generalized Anxiety Disorder [IMPLEMENT]--Effects of Three Different Strategies of Implementation.

BACKGROUND: Despite long-standing calls to disseminate evidence-based treatments for generalized anxiety (GAD), modest progress has been made in the study of how such treatments should be implemented. The primary objective of this study was to test three competing strategies on how to implement a cognitive behavioral treatment (CBT) for out-patients with GAD (i.e., comparison of one compensation vs. two capitalization models). METHODS: For our three-arm, single-blinded, randomized controlled trial (implementation of CBT for GAD [IMPLEMENT]), we recruited adults with GAD using advertisements in high-circulation newspapers to participate in a 14-session cognitive behavioral treatment (Mastery of your Anxiety and Worry, MAW-packet). We randomly assigned eligible patients using a full randomization procedure (1:1:1) to three different conditions of implementation: adherence priming (compensation model), which had a systematized focus on patients' individual GAD symptoms and how to compensate for these symptoms within the MAW-packet, and resource priming and supportive resource priming (capitalization model), which had systematized focuses on patients' strengths and abilities and how these strengths can be capitalized within the same packet. In the intention-to-treat population an outcome composite of primary and secondary symptoms-related self-report questionnaires was analyzed based on a hierarchical linear growth model from intake to 6-month follow-up assessment. This trial is registered at ClinicalTrials.gov (identifier: NCT02039193) and is closed to new participants. FINDINGS: From June 2012 to Nov. 2014, from 411 participants that were screened, 57 eligible participants were recruited and randomly assigned to three conditions. Forty-nine patients (86%) provided outcome data at post-assessment (14% dropout rate). All three conditions showed a highly significant reduction of symptoms over time. However, compared with the adherence priming condition, both resource priming conditions indicated faster symptom reduction. The observer ratings of a sub-sample of recorded videos (n = 100) showed that the therapists in the resource priming conditions conducted more strength-oriented interventions in comparison with the adherence priming condition. No patients died or attempted suicide. INTERPRETATION: To our knowledge, this is the first trial that focuses on capitalization and compensation models during the implementation of one prescriptive treatment packet for GAD. We have shown that GAD related symptoms were significantly faster reduced by the resource priming conditions, although the limitations of our study included a well-educated population. If replicated, our results suggest that therapists who implement a mental health treatment for GAD might profit from a systematized focus on capitalization models. FUNDING: Swiss Science National Foundation (SNSF-Nr. PZ00P1_136937/1) awarded to CF.