Developmental Neuropsychological Assessment Research Articles

A - 37 ADHD-Related Hyperactivity and Impulsivity: Distinct or Overlapping Dimensions?

Abstract Objective It is debated whether hyperactivity and impulsivity should remain combined within the (DSM) hyperactivity/impulsivity domain or be separated. To address this dispute, we sought to determine whether hyperactivity and impulsivity are differentially related to executive functioning (EF), a common deficit area in ADHD. Method Participants included 120 children (ages 8–11; 89.9% White; 51.6% girls) from a community sample tested in a laboratory setting. To be included, they must have ADHD (59.4%) or be typically developing (40.6%). Hyperactivity and impulsivity scales were created from symptoms from a parent-report Behavior Assessment System for Children and DSM-IV questionnaire, ADHD section. The Behavior Rating Inventory of Executive Functioning (BRIEF) Working Memory scale (WMsc) and the Children’s Memory Scale Picture Locations (visuospatial sketchpad), Numbers Forward (phonological loop), and Sequences (central executive) subtests were used to assess working memory (WM). Inhibition was assessed with the BRIEF Inhibition scale (Isc) and A Developmental Neuropsychological Assessment (NEPSY) Tower Rule Violations (RV). Emotional control (EC) was measured with the BRIEF’s EC scale. Results Confirmatory linear regressions (SPSS Enter method) with all EF measures as IVs revealed Isc and WMsc were significant predictors of impulsivity [F(7,120) = 24.85, p < 0.001]. For hyperactivity [F(7,120) = 21.40, p < 0.001], WMsc, Isc, and RV were significant predictors. Exploratory analyses revealed WMsc was related to hyperactivity in controls but impulsivity in ADHD. Conclusions Similarities and differences were found between hyperactivity and impulsivity in relation to EF. Whereas inhibition was similarly related to hyperactivity and impulsivity, WM’s relationships were dissociable between groups. Hence, further research is needed, including areas affected in ADHD besides EF.

QOL-07. EFFICIENT NEUROPSYCHOLOGICAL ASSESSMENT IN PATIENTS WITH BRAIN TUMORS AND ACUTE LYMPHOBLASTIC LEUKEMIA

Abstract BACKGROUND Children treated for cancer may experience a decline in performance for a variety of reasons, one of which is the impact of treatment. Children treated for leukemias and brain tumours are at the highest risk of developing neurocognitive sequale (Daly and Brown, 2015). METHODS In our study we used Bayesian regression to identify assessment tools that would best predict the sequale of brain tumors (BT) and acute lymphoblastic leukemia (ALL) in children and adolescents. Using data from 15 patients with BT, 15 patients with (ALL) and 9 siblings controls we compared the predictive validity of the Wechsler Intelligence Scales for Children (WISC-V), Delis-Kaplan Executive Function System (D-KEFS), Continuous Performance Test (CPT-3), the Developmental Neuropsychological Assessment (NEPSY-II) and the parent and teacher report forms of the Achenbach Assessment System (ASEBA). RESULTS We found that the best predictors of ALL were d’ scores on the CPT (BF = 20.69, pd =.05) and CPT ommission scores (BF = 17.50, pd =.05), while the best predictor a BT was the WISC-IV Coding subtest (BF = 21.17, pd =.05) in addition to CPT omission scores (BF = 12.00, pd =.08) and HRT SD scores (BF = 11.91, pd =.08). CPT d’s scores were also predictive of Methotrexate treatment (MTX) (BF = 32.61, pd = 0.03), as were WISC-V Symbol Search scores (BF = 32.61, pd = 0.03) and the NEPSY-II Auditory Attention subtest (BF = 26.06, pd = 0.04). We also noted differential sensitivity of the ASEBA teacher report form for detecting deficits identified during the neuropsychological assessment. CONCLUSIONS We feel our findings will, together with previous meta-analyses, contribute to more efficient neuropsychological assessment in patients with BT and ALL. Neuropsychological asseessment is vital for identifying potential sequale of disease and treament in pediatric oncology.

What does the Developmental Neuropsychological Assessment–II (NEPSY-II) measure in children ages 7 to 12? A structural and psychometric analysis

ABSTRACT The Developmental Neuropsychological Assessment – II (NEPSY-II) is a widely used assessment battery in pediatric settings, but its internal structure has not been adequately examined. This study employed a rational, empirical approach to examine the construct validity of 23 NEPSY-II subtest scores from children ages 7–12 (M = 9.99, SD = 2.76) in the NEPSY-II norming sample (N = 600; 50% girls). Competing higher-order models based on prior research, hypothesized NEPSY-II domains, and conceptual subtest classifications were evaluated via confirmatory factor analysis and a sequential approach to model comparisons. The results supported the multidimensionality of NEPSY-II subtests and the organization of subtests by hypothesized neuropsychological domains. The best fitting model included a general factor and four first-order factors. Factor loadings from the general factor to first-order factors were very strong. However, general factor loadings for most subtests were less than .50 (range = .21–.69, M = .44), and domain-specific effects for all subtests, independent of the general factor, were even lower (range = .00–.45, M = .44). Interestingly, all subtests demonstrated strong subtest-specific effects, but it is not clear what construct(s) the subtest-specific effects represent. Findings support NEPSY-II authors’ emphasis on subtest-level interpretations rather than composite-level interpretations and highlight that NEPSY-II subtest scores should be interpreted carefully and with caution.

Efficacy and safety of transcranial direct current stimulation over the left dorsolateral prefrontal cortex in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, triple-blinded, sham-controlled, crossover trial.

Although pharmacological treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) has demonstrated efficacy, several individuals persist in experiencing social and academic impairment. Additionally, the occurrence of significant side effects may render the use of psychotropic medications untenable. However, Transcranial Direct Current Stimulation (tDCS), a non-invasive brain stimulation technique, shows promising results in treating ADHD. To investigate the efficacy and safety of tDCS on the performance of children and adolescents with ADHD in neuropsychological tests involving visual attention, visual and verbal working memory, and inhibitory control. This study was a triple-blind, randomized, sham-controlled, crossover clinical trial. The intervention consisted of a daily session of tDCS (2 mA) or sham targeting the left dorsolateral prefrontal cortex (L-DLPFC), for 30 min, on five consecutive days. The primary outcome was change in the Visual Attention Test, Fourth Edition (TAVIS-4) before and after each intervention. Subjects were also evaluated pre and post-tDCS using the Digit Span subtest of the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V), the Developmental Neuropsychological Assessment, Second Edition (NEPSY-II) Inhibiting Response (IR) subtest, and the Corsi Block-Tapping Task. Fifteen individuals were included, and no statistically significant difference was observed when comparing the results of the TAVIS-4, the IR of NEPSY-II, and the intragroup Digit Span subtest of WISC-V undertaken before and after the procedure. Adverse events were mainly self-limiting and transient. The participants did not perceive any benefit from tDCS when measured on the Patient Global Impression of Improvement (PGI-I) Scale. This study did not meet its primary endpoint and found no performance enhancement in any investigated neuropsychological outcomes relating to the intervention group.

B - 02 The Impact of Cardiovascular Surgeries on Attention and Executive Functioning Outcomes in Children with Congenital Heart Defects with and without Attention-Deficit/Hyperactivity Disorder (ADHD) Diagnoses.

Children with congenital heart defects (CHDs) exhibit attention and executive functioning (EF) difficulties resulting in increased risk for attention-deficit/hyperactivity disorder (ADHD). Anesthesia events are also associated with worsened cognitive outcomes. This study aims to elucidate how ADHD and cardiovascular surgeries (CVS) in children with CHDs impact attention and EF performance. Attention and EF measures (Continuous Performance Test, 3rd edition [CPT-3], Delis Kaplan Executive Function System [DKEFS], Test of Everyday Attention in Children [TEA-Ch], A Developmental Neuropsychological Assessment, 2nd edition [NEPSY-II]) were used in 58 children ages 8-17years (mean = 11.44years; 48.3% male; 70.7% Caucasian) with CHDs. MANOVAs were utilized to assess if children with ADHD diagnoses demonstrated poorer cognitive outcomes. Correlations were performed within subgroups to assess the relationship between number of CVS and measures. ADHD subgroups did not statistically differ on attention and EF outcomes. Number of CVS approached significance with DKEFS Verbal Fluency Category Accuracy for children without ADHD diagnoses but was significantly negatively correlated with NEPSY Auditory Attention (r = -0.628, p < 0.05) and Response Set (r = -0.601, p < 0.05) for those with ADHD. Results suggest clinical ADHD diagnoses are not related to worse attention and EF outcomes in a pediatric CHD population. The number of cardiovascular surgeries impacted performance on different measures irrespective of diagnosis. Discrepancies may reflect use of multiple data points in deciding on a diagnosis, the behavioral nature of ADHD, poor construct validity of measures, patient medical comorbidities, and/or differences in clinical judgment. Future studies should explore weightage of objective measures in clinical decision-making in medically complex populations.

Developmental coordination disorder subtypes in children: An unsupervised clustering.

To identify subtypes of developmental coordination disorder (DCD) in children. Children with DCD diagnosed through comprehensive evaluation at Robert-Debré Children's University Hospital (Paris, France) were consecutively enrolled from February 2017 to March 2020. We performed an unsupervised hierarchical clustering based on principal component analysis using a large set of variables encompassing cognitive, motor, and visuospatial scores (Wechsler Intelligence Scale for Children, Fifth Edition; Developmental Neuropsychological Assessment, Second Edition; Movement Assessment Battery for Children, Second Edition). One hundred and sixty-four children with DCD were enrolled (median age 10 years 3 months; male:female ratio 5.56:1). We identified distinct subgroups with mixed visuospatial and gestural disorders, or with pure gestural disorders that predominantly impaired either speed or precision. Associated neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder, did not influence the results of the clustering. Importantly, we identified a subgroup of children with marked visuospatial impairment with the lowest scores in almost all of the evaluated domains, and the poorest school performance. The classification of DCD into distinct subgroups could be indicative of prognosis and provide critical information to guide patient management, taking into account the child's neuropsychological profile. Beyond this clinical interest, our findings also provide a relevant framework with homogeneous subgroups of patients for research on the pathogenesis of DCD. Unsupervised hierarchical clustering identified four subgroups of children with developmental coordination disorder. Two subgroups had combined visuospatial/gestural difficulties, and two had pure gestural disorders. Severe visuospatial impairment was associated with poor performance in most domains including school. Difficulties in the gestural-only clusters were predominantly either gestural precision or speed.

Extremely preterm children and relationships of minor neurodevelopmental impairments at 6 years.

This study investigated minor impairments in neurological, sensorimotor, and neuropsychological functioning in extremely preterm-born (EPT) children compared to term-born children. The aim was to explore the most affected domains and to visualize their co-occurrences in relationship maps. A prospective cohort of 56 EPT children (35 boys) and 37 term-born controls (19 boys) were assessed at a median age of 6 years 7 months with Touwen Neurological Examination, Movement Assessment Battery for Children, 2nd edition (MABC-2), Sensory Integration and Praxis Test (SIPT), and a Developmental Neuropsychological Assessment, 2nd edition (NEPSY-II). Altogether 20 test domains were used to illustrate the frequency of impaired test performances with a bar chart profile and to construct relationship maps of co-occurring impairments. The EPT children were more likely to perform inferiorly compared to the term-born controls across all assessments, with a wider variance and more co-occurring impairments. When aggregating all impaired test domains, 45% of the EPT children had more impaired domains than any term-born child (more than five domains, p < 0.001). Relationship maps showed that minor neurological dysfunction (MND), NEPSY-II design copying, and SIPT finger identification constituted the most prominent relationship of co-occurring impairments in both groups. However, it was ten times more likely in the EPT group. Another relationship of co-occurring MND, impairment in NEPSY-II design copying, and NEPSY-II imitation of hand positions was present in the EPT group only. Multiple minor impairments accumulate among EPT children at six years, suggesting that EPT children and their families may need support and timely multi-professional interventions throughout infancy and childhood.

Cognitive and Socioemotional Development at 5 and 9 Years of Age of Children Born with Very Low Birth Weight and Extremely Low Birth Weight in the Czech Republic.

BackgroundThere is a high prevalence of cognitive and socioemotional dysfunction in very low birth weight (VLBW <1500 g) and extremely low birth weight (ELBW <1000 g) children. This study from the Czech Republic aimed to compare the cognitive and socioemotional development at 5 and 9 years of age of children born with VLBW/ELBW with children born with normal birth weight (NBW ≥2500 g).Material/MethodsThe clinical group consisted of 118 VLBW/ELBW children and the control group consisted of 101 children with NBW at ages 5 to 9 years. The research battery included selected subscales from the Intelligence and Development Scales (IDS), A Developmental Neuropsychological Assessment – second edition (NEPSY-II), and the Behavior Rating Inventory of Executive Function (BRIEF). Data were analyzed using STATA IC v. 15 software and G*Power (descriptive statistic, analysis of variance (ANOVA), correlations, multivariate analysis of variance – MANOVA, post hoc power analysis).ResultsWe found a statistically significant difference in cognitive and socioemotional development between children with VLBW/ELBW and those with NBW. The average intelligence quotient (IQ) of VLBW/ELBW children was 96.38, while that of NBW children was 12.98 points higher (P<0.001). NBW children achieved better results on all subtests of the IDS (P<0.001) as well as in affect recognition (P<0.001). All results for both groups were within normal range. Parents of VLBW/ELBW children did not recognize impaired executive functioning (P=0.494).ConclusionsThis study has shown significant cognitive and socioemotional deficit in children born with VLBW and ELBW when evaluated at 5 and 9 years of age.

Characterizing Emotion Recognition and Theory of Mind Performance Profiles in Unaffected Siblings of Autistic Children.

Emotion recognition skills and the ability to understand the mental states of others are crucial for normal social functioning. Conversely, delays and impairments in these processes can have a profound impact on capability to engage in, maintain, and effectively regulate social interactions. Therefore, this study aimed to compare the performance of 42 autistic children (Mage = 8.25 years, SD = 2.22), 45 unaffected siblings (Mage = 8.65 years, SD = 2.40), and 41 typically developing (TD) controls (Mage = 8.56 years, SD = 2.35) on the Affect Recognition (AR) and Theory of Mind (TOM) subtests of the Developmental Neuropsychological Assessment Battery. There were no significant differences between siblings and TD controls. Autistic children showed significantly poorer performance on AR when compared to TD controls and on TOM when compared to both TD controls and unaffected siblings. An additional comparison of ASD, unaffected sibling and TD control subsamples, matched on full-scale IQ, revealed no group differences for either AR or TOM. AR and TOM processes have received less research attention in siblings of autistic children and remain less well characterized. Therefore, despite limitations, findings reported here contribute to our growing understanding of AR and TOM abilities in siblings of autistic children and highlight important future research directions.

Characteristics of Children Likely to Have Spontaneous Resolution of Obstructive Sleep Apnea: Results from the Childhood Adenotonsillectomy Trial (CHAT).

Objective: To evaluate if cardiopulmonary coupling (CPC) calculated sleep quality (SQI) may have a role in identifying children that may benefit from other intervention than early adenotonsillectomy (eAT) in management of obstructive sleep apnea (OSA). Methods: A secondary analysis of electrocardiogram-signals (ECG) and oxygen saturation-data (SpO2) collected during polysomnography-studies in the prospective multicenter Childhood Adenotonsillectomy Trial (CHAT) to calculate CPC-SQI and apnea hypopnea index (AHI) was executed. In the CHAT, children 5–9 years with OSA without prolonged oxyhemoglobin desaturations were randomly assigned to adenotonsillectomy (eAT) or watchful waiting with supportive care (WWSC). The primary outcomes were to document change in attention and executive function evaluated with the Developmental Neuropsychological Assessment (NEPSY). In our analysis, children in the WWSC-group with spontaneous resolution of OSA (AHIObstructive < 1.0) and high-sleep quality (SQI ≥ 75) after 7-months were compared with children that showed residual OSA. Results: Of the 227 children randomized to WWSC, 203 children had available data at both baseline and 7-month follow-up. The group that showed resolution of OSA at month 7 (n = 43, 21%) were significantly more likely to have high baseline SQI 79.96 [CI95% 75.05, 84.86] vs. 72.44 [CI95% 69.50, 75.39], p = 0.005, mild OSA AHIObstructive 4.01 [CI95% 2.34, 5.68] vs. 6.52 [CI95% 5.47, 7.57], p= 0.005, higher NEPSY-attention-executive function score 106.22 [CI95% 101.67, 110.77] vs. 101.14 [CI95% 98.58, 103.72], p = 0.038 and better quality of life according to parents 83.74 [CI95% 78.95, 88.54] vs. 77.51 [74.49, 80.53], p = 0.015. The groups did not differ when clinically evaluated by Mallampati score, Friedman palate position or sleep related questionnaires. Conclusions: Children that showed resolution of OSA were more likely to have high-SQI and mild OSA, be healthy-weight and have better attention and executive function and quality of life at baseline. As this simple method to evaluate sleep quality and OSA is based on analyzing signals that are simple to collect, the method is practical for sleep-testing, over multiple nights and on multiple occasions. This method may assist physicians and parents to determine the most appropriate therapy for their child as some children may benefit from WWSC rather than interventions. If the parameters can be used to plan care a priori, this would provide a fundamental shift in how childhood OSA is diagnosed and managed.

Baseline apnea-hypopnea index threshold and adenotonsillectomy consideration in children with OSA

ObjectivesAdenotonsillectomy (AT) is the first line of treatment for pediatric obstructive sleep apnea (OSA). In some treatment guidelines, children with moderate to severe OSA, defined as apnea-hypopnea index (AHI) ≥ 5, may be recommended AT regardless of symptoms. The differences in outcomes between children randomized to watchful waiting with supportive care (WWSC) or AT were compared based on baseline OSA severity threshold of AHI≥ 5. MethodsA secondary analysis of the Childhood Adenotonsillectomy Trial, a randomized controlled trial of children with OSA aged 5–9 years who underwent AT or WWSC, was performed. The primary outcome was the change in neurocognition measured by Developmental Neuropsychological Assessment (NEPSY). Secondary outcomes included changes in behavior, symptoms of OSA, and quality of life. Outcomes were measured at baseline and the seven-month follow-up after grouping children based on whether their AHI was greater than or equal to 5. Comparisons were performed using two-way analysis of covariance (ANCOVA) while controlling for age, sex and race. Differences in treatment effect were measured using Cohen's d. ResultsOf the 397 children included, 203 received WWSC and 194 underwent AT. The treatment effects on post-randomization changes in neurocognition, measured by NEPSY in children with AHI ≥5 (Cohen's d = 0.1 [95% CI, −0.1 to 0.4]) was not significantly different from children with AHI <5 (Cohen's d = 0.1 [95% CI, −0.1 to 0.4]). Furthermore, among children in the AT group alone, the effects of AT on post-treatment changes in NEPSY did not differ based on AHI threshold (Cohen's d = −0.06 [95% CI, −0.3 to 0.2]). Additionally, the treatment effects on post-randomization changes in behavior, symptoms, and quality of life did not vary based on AHI threshold. ConclusionThe outcomes of neurocognition, behavior, symptoms, and quality of life did not differ between children with OSA randomized to WWSC or AT based on OSA severity threshold alone. Additionally, the effects of AT on post-treatment outcomes did not differ based on AHI threshold.

An iPad-based intervention to improve visual-motor, visual-attention, and visual-perceptual skills in children with surgically treated hydrocephalus: A pilot study.

Develop and pilot an iPad-based intervention for improving visual-motor coordination, visual-spatial processing/reasoning, and visual attention in children with surgically treated hydrocephalus (HCP). We developed an intervention protocol targeting visual-motor coordination, visual-spatial processing/reasoning, and visual attention. Fourteen participants with HCP completed 30h of training over 6weeks. The primary outcome measure was the Perceptual Reasoning Index from the Wechsler Abbreviated Scale of Intelligence, Second Edition. Secondary measures included subtests from the Wechsler Intelligence Scale for Children, Fourth Edition, Developmental NEuroPSYchological Assessment, Second Edition (NEPSY-II), and Purdue Pegboard. Children with HCP demonstrated gains with statistical significance on the Perceptual Reasoning Index. We also observed significant improvement on a timed test of visuo-motor coordination (Wechsler Intelligence Scale for Children, Fourth Edition, Coding). Our iPad-application-based intervention may promote visual-motor coordination, visual-spatial processing/reasoning, and visual attention skills in children with HCP, offering an engaging and economical supplement to more conventional therapies.

Association of High Screen-Time Use With School-age Cognitive, Executive Function, and Behavior Outcomes in Extremely Preterm Children

Both preterm birth and increased screen time are known to be associated with an increase in risk of developmental and behavioral sequelae. The association between high screen time or a television or computer in the bedroom in early school age and adverse cognitive, executive function, language, and behavior outcomes of extremely preterm children (EPT) is not well understood. To assess the association of high screen time with cognition, language, executive function, and behavior of EPT children aged 6 to 7 years; a second objective was to examine the association between high screen time and rates of structured physical activity and weight. This cohort study was a secondary analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial Neuroimaging and Neurodevelopmental Outcomes school-aged cohort and includes 414 EPT children born between February 1, 2005, and February 28, 2009, and evaluated in between 2012 and 2016 at ages 6 years 4 months to 7 years 2 months. The study was conducted from July 7, 2012, and August 15, 2016, and data were analyzed between December 10, 2018, and April 1, 2021. Cohorts included children exposed to low (≤2 hours per day) vs high (>2 hours per day) amounts of screen time and by the presence (no vs yes) of a television/computer in the bedroom. In addition to growth parameters, assessments included the Wechsler Intelligence Scale for Children-IV, the Behavior Rating Inventory of Executive Function, the Developmental Neuropsychological Assessment, the Conners 3rd Edition-Parent Short-Form, and the Social Communication Questionnaire. Of the 414 children included in the analysis, 227 (55%) were boys; mean (SD) birth weight was 870.6 (191) g. A total of 238 children (57%) had high screen time and 266 (64%) had a television/computer in their bedroom. In multivariable linear regressions adjusted for center, male sex, gestational age, and social determinants of health, high screen time was independently associated with the following mean (SE) test score changes: lower full-scale IQ (-3.92 [1.64]; P = .02); an increase in association with deficits in executive functions, including metacognition (8.18 [3.01]; P = .007), global executive function (7.49 [2.99]; P = .01), inhibition (-0.79 [0.38]; P = .03), and Conners 3rd Edition-Parent Short-Form inattention (3.32 [1.67]; P = .047). A television/computer in the bedroom was associated with an increase in inhibition (-0.80 [0.39]; P = .04) and hyperactivity/impulsivity (3.50 [1.75]; P = .046) problems. The findings of this study suggest that high screen time contributes to adverse cognitive, executive function, and behavior outcomes at ages 6 to 7 years in children born at less than 28 weeks. These findings support the need for clinicians to have heightened awareness of the risks for EPT children and discuss both the benefits and risks of screen time with families.

Psychometric Evaluation of Social Cognition and Behavior Measures in Children and Adolescents with Down Syndrome

Individuals with Down syndrome (DS) are often described as socially engaged; however, challenges with social cognition, expressive language, and social interaction are also common in DS and are prospective outcomes of interest for clinical trials. The current study evaluates the psychometric properties of standardized measurements of social cognition and social behavior for potential use as outcome measures for children and adolescents with DS. Seventy-three youth ages 6 to 17 years old (M = 12.67, SD = 3.16) with DS were assessed on social cognition subtests of a neuropsychological assessment at two time points. Caregivers also completed a parent-report measure of social behavior. Measures were evaluated for feasibility, test-retest reliability, practice effects, convergent validity, and associations with broader developmental domains (i.e., age, cognition, and language). All social cognition and behavior measures met criteria for a portion of the psychometric indices evaluated, yet feasibility limitations were identified for the Developmental Neuropsychological Assessment, Second Edition (NEPSY-II) Affect Recognition subtest, and the NEPSY-II Theory of Mind subtest had problematic floor effects for percentile ranks. The Social Responsiveness Scale, Second Edition (SRS-2; T-scores) had high feasibility, moderate to excellent test-retest reliability, and no practice effects, suggesting this measure could be appropriate for use in clinical trials involving youth with DS.

Long-Term Neurodevelopmental Outcomes of Children with Congenital Heart Defects

To assess whether children with symptomatic congenital heart defects (CHDs) at birth (cyanosis and/or heart failure) are at greater risk of adverse neurodevelopmental outcomes at 8years of age. From a prospective population-based cohort study of newborns with CHDs (EPICARD), we included 473 children with available neurodevelopmental assessments at 8years of age. We grouped the CHD based on symptoms at birth and need for early neonatal intervention. Ventricular septal defects that closed spontaneously within the first year of life were considered the control group. Neurodevelopmental outcomes were assessed using the Kauffman Assessment Battery Test for Children, Second Edition, for IQ (mean 100±15), and the Developmental NEuroPSYchological Assessment Battery, Second Edition, for detailed assessment of specific neurocognitive domains (mean 10±3). Multivariable regression analysis was used to compare the outcomes across the CHD groups after considering potentially confounding variables. Compared with the control group, children with cyanotic CHD without heart failure had lower scores for IQ, -7.2 (95% CI -13.4 to -1.2). Children with noncyanotic CHD with heart failure had lower scores in the specific domains of language -1.5 (95% CI -2.2 to -0.7), and memory and learning -1.3 (95% CI -2.4; -0.3). Those with both cyanotic CHD and heart failure had lower scores for IQ, -7.6 (95% CI -13.5 to -1.8), as well as the specific domains of language and memory and learning, -2.0 (95% CI -2.9 to -1.0) and -1.1 (95% CI -2.3 to -0.1), respectively. Children with symptomatic CHD at birth are at greater risk of adverse neurodevelopmental outcomes at 8years of age, with the greatest risk for those who were born with both cyanosis and heart failure.

The Impact of Sex Chromosome Trisomies (XXX, XXY, XYY) on Early Social Cognition: Social Orienting, Joint Attention, and Theory of Mind.

ObjectiveAbout 1:650–1,000 children are born with an extra X or Y chromosome (XXX; XXY; XYY), which results in a sex chromosome trisomy (SCT). This study aims to cross-sectionally investigate the impact of SCT on early social cognitive skills. Basic orienting toward social cues, joint attention, and theory of mind (ToM) in young children with SCT were evaluated.MethodAbout 105 children with SCT (range: 1–7 years old) were included in this study, as well as 96 age-matched nonclinical controls. Eyetracking paradigms were used to investigate the eye gaze patterns indicative of joint attention skills and orienting to social interactions. The ToM abilities were measured using the subtest ToM of the Developmental NEuroPSYchological Assessment, second edition, neuropsychological test battery. Recruitment and assessment took place in the Netherlands and in the United States.ResultsEyetracking results revealed difficulties in children with SCT in social orienting. These difficulties were more pronounced in children aged 3 years and older, and in boys with 47,XYY. Difficulties in joint attention were found over all age groups and karyotypes. Children with SCT showed impairments in ToM (26.3% in the [well] below expected level), increasing with age. These impairments did not differ between karyotypes.ConclusionsAn impact of SCT on social cognitive abilities was found already at an early age, indicating the need for early monitoring and support of early social cognition. Future research should explore the longitudinal trajectories of social development in order to evaluate the predictive relationships between social cognition and outcome later in life in terms of social functioning and the risk for psychopathology.

One-Carbon Metabolism in Nepalese Infant–Mother Pairs and Child Cognition at 5 Years Old

One-carbon metabolism (OCM) refers to the transfer of methyl groups central to DNA methylation and histone modification. Insufficient access to methyl donors and B-vitamin cofactors affects epigenetic maintenance and stability, and when occurring in early life may impact future health and neurodevelopment. The objective of this study was to examine the relative associations between one-carbon metabolites in Nepalese mother-infant pairs and child cognition measured at 5 y of age. This is a cross-sectional study from Bhaktapur, Nepal, in a population at high risk of subclinical B-vitamin deficiencies and cumulative infection burden. Venous blood samples from 500 mother-infant pairs were collected when the infants were 2 to 12 mo old, and metabolite concentrations measured by microbiological assays and GC-tandem MS. We re-enrolled 321 of these children at 5 y and assessed cognition by the Ages and Stages Questionnaire, 3rd edition, and subtests from the Developmental Neuropsychological Assessment, 2nd edition (NEPSY-II). The associations of the independent metabolites or unobserved metabolic phenotypes (identified by latent class analysis) with the cognitive outcomes were estimated by seemingly unrelated regression. We explored direct and indirect relations between the OCM pathway and the cognitive outcomes using path analysis. Infant cystathionine concentration was inversely associated with 4 cognitive outcomes (standardized βs ranging from -0.22 to -0.11, P values from <0.001 to 0.034). Infants with a metabolic phenotype indicating impaired OCM and low vitamin B-12 status had poorer cognitive outcomes compared with infants with normal OCM activity and adequate vitamin B-12 status (standardized βs ranging from -0.80 to -0.40, P <0.001 and 0.05). In the path analysis, we found several OCM biomarkers were associated with affect recognition through infant plasma cystathionine. Elevated plasma cystathionine during infancy reflects a metabolic phenotype of impaired OCM and low vitamin B-12 status and is associated with poorer cognitive function when the children are 5 y old.

Prenatal phthalate exposures and executive function in preschool children

BackgroundPrenatal phthalate exposure has been linked with altered neurodevelopment, including externalizing behaviors and attention-deficit hyperactivity disorder (ADHD). However, the implicated metabolite, neurobehavioral endpoint, and child sex have not always been consistent across studies, possibly due to heterogeneity in neurodevelopmental instruments. The complex set of findings may be synthesized using executive function (EF), a construct of complex cognitive processes that facilitate ongoing goal-directed behaviors. Impaired EF can be presented with various phenotypes of poor neurodevelopment, differently across structured conditions, home/community, or preschool/school. We evaluated the relationship between prenatal phthalate exposure and comprehensive assessment of preschool EF. MethodsOur study comprised 262 children with clinically significant/subthreshold ADHD symptoms and 78 typically developing children who were born between 2003 and 2008 and participated in the Preschool ADHD Substudy, which is nested within a population-based prospective cohort study, the Norwegian Mother, Father, and Child Cohort (MoBa). Twelve phthalate metabolites were measured from urine samples that their mothers had provided during pregnancy, at 17 weeks’ gestation. All children, at approximately 3.5-years, took part in a detailed clinical assessment that included parent-and teacher-rated inventories and administered tests. We used instruments that measured constructs related to EF, which include a parent-and teacher-reported Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and three performance-based tests: A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet intelligence test V (SB5), and the cookie delay task (CDT). The standard deviation change in test score per interquartile range (IQR) increase in phthalate metabolite was estimated with multivariable linear regression. We applied weighting in all models to account for the oversampling of children with clinically significant or subthreshold symptoms of ADHD. Additionally, we assessed modification by child sex and potential co-pollutant confounding. ResultsElevated exposure to mono-benzyl phthalate (MBzP) during pregnancy was associated with poorer EF, across all domains and instruments, in both sex. For example, an IQR increase in MBzP was associated with poorer working memory rated by parent (1.23 [95% CI: 0.20, 2.26]) and teacher (1.13 [0.14, 2.13]) using BRIEF-P, and administered tests such as SB5 (no-verbal: 0.19 [0.09, 0.28]; verbal: 0.13 [0.01, 0.25]). Adverse associations were also observed for mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), although results varied by instruments. EF domains reported by parents using BRIEF-P were most apparently implicated, with stronger associations among boys (e.g., MnBP and inhibition: 2.74 [1.77, 3.72]; MiBP and inhibition: 1.88 [0.84, 2.92]) than among girls (e.g., MnBP and inhibition: −0.63 [−2.08, 0.83], interaction p-value: 0.04; MiBP and inhibition: −0.15 [−1.04, 0.74], interaction p-value: 0.3). Differences by sex, however, were not found for the teacher-rated BRIEF-P or administered tests including NEPSY, SB5, and CDT. Conclusion and relevanceElevated mid-pregnancy MBzP, MiBP, and MnBP were associated with more adverse profiles of EF among preschool-aged children across a range of instruments and raters, with some associations found only among boys. Given our findings and accumulating evidence of the prenatal period as a critical window for phthalate exposure, there is a timely need to expand the current phthalate regulations focused on baby products to include pregnancy exposures.

Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9\xa0years of age

BackgroundVery preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later.ObjectiveThe aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning.Materials and methodsThe prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning.ResultsVery preterm children had significantly higher fractional anisotropy and axial diffusivity values (P<0.05, corrected for multiple comparison) in dorsolateral prefrontal caudate and ventrolateral prefrontal caudate tracts as compared to term-born children. We found negative correlations between the diffusion tensor imaging metrics of frontostriatal tracts and inhibition functions (P<0.05, corrected for multiple comparison) in very preterm children.ConclusionPrematurity has a long-term effect on frontostriatal white matter microstructure that might contribute to difficulties in executive functioning.

Difficulties in developmental follow-up of preterm neonates in a randomised-controlled trial of Bifidobacterium breve M16-V — Experience from Western Australia

BackgroundProbiotics may be neuroprotective for preterm neonates due to their anti-inflammatory effects and ability to facilitate nutrition. AimTo assess long-term effects of early probiotic supplementation on neuropsychological development in preterm infants. Study designFollow up study. SubjectsChildren at age 3 to 5 years who had participated as preterm infants (<33 week) in the randomised controlled trial. OutcomesPrimary: Continuous early learning composite measure derived from the Mullen's Scale of Early Learning (MSEL). Other outcomes were assessed by the Developmental, Dimensional and Diagnostic Interview, Developmental NEuroPSYchological assessment–2nd Edition, Parental questionnaires using children's communication checklist–2nd edition, social responsiveness scale, and Vineland Adaptive Behavioural Scales–2nd edition. MeasuresContinuous scores derived from all the measures. Results67 children of the 159 participants (42%) (Probiotic: 36/79, Placebo: 31/80) were followed-up for at least one neuropsychological assessment. All six assessments were completed in 18/31 (58.1%) of the control vs. 11/36 (30.6%) probiotic group children. Multivariable analysis of MSEL composite score showed no evidence of probiotic effect univariately, or after adjustment for gestation, intrauterine growth restriction, Apgar <7 at 5 min and age at assessment (adjusted mean effect in probiotic group: −2.7, 95% CI −8.5–3.0, p = 0.349). ConclusionThere was no significant effect on neurodevelopment of children assessed at the age of 3 to 5 years who participated as preterm neonates in the RCT of B. breve M-16V. The validity of these results is limited by the reduced sample size due to high rate of loss to follow up.