Mean Full-scale Intelligence Quotient Research Articles

Giftedness and Twice-Exceptionality in Children Suspected of ADHD or Specific Learning Disorders: A Retrospective Study

The expression “twice-exceptionality” has been used to describe conditions in which giftedness and specific disorders coexist. Our study offers a retrospective analysis of clinical reports of gifted children evaluated for suspected specific learning disorders (SLD) or attention-deficit/hyperactivity disorder (ADHD). The initial sample included 456 school-aged children referred to our clinic for suspected SLD and/or ADHD over a two-year interval. The inclusion criteria were: a General Ability Index score above 120 in the cognitive assessment; age 6–18 years; and not satisfying diagnostic criteria for autism spectrum disorder. Forty children were selected for the study. We grouped patients according to the final diagnosis: neurodevelopmental disorder (SLD and/or ADHD) (n = 15), psychopathological disorder (n = 8), mixed neurodevelopmental and psychopathological (n = 13), no emerging disorder (n = 4). The study included 36 (90%) males. Mean age was 9.3 years (SD 1.62). Mean Full-Scale Intelligence Quotient was 121.7 (SD 7.77), mean General Ability Index was 130.2 (SD 6.79). Furthermore, the cognitive assessment of the different groups highlighted a non-homogeneous profile in all groups, with lower scores on working memory and processing speed indexes. Our results support the hypothesis that difficulties in gifted children’s adaptation to scholastic and social settings could be misinterpreted as a manifestation of a clear disease.

Hydroxyurea Improves Intelligence Quotient Scores in Children with Sickle Cell Anemia and Elevated Transcranial Doppler Velocity

Introduction: Structural brain abnormalities resulting from sickle cell disease because of strokes, silent cerebral infarcts (SCI) and other biophysical characteristics of parenchymal damage from repeated sickling affect cognitive functioning. Hydroxyurea therapy reduces transcranial Doppler (TCD) velocities and improves SCI and other neurological outcomes in children with sickle cell anaemia. Hence the objectives of EXpanding Treatment for Existing Neurological Disease (EXTEND, NCT02556099), a phase 2 clinical trial, was to determine whether hydroxyurea titrated to maximum tolerated dose was effective in lowering transcranial Doppler (TCD) velocities and improving cognitive function in Jamaican children with sickle cell anemia (SCA) with increased stroke risk. Methods: Full-Scale Intelligence Quotient (FSIQ), verbal and nonverbal IQ were measured with the Wechsler Abbreviated Scale of Intelligence (WASI-II) at baseline and after 18 months of hydroxyurea treatment in 30 of the 43 enrolled children. Verbal Comprehension Index (VCI) was assessed using the Vocabulary and Similarities subtests. Perceptual Reasoning Index (PRI) was scored with the Block Design and Matrix Reasoning subtests. Members of the team conducting the tests were trained and test results were verified by an experienced member of the Epidemiology Research Unit, Caribbean Institute for Health Research. Participants were enrolled in the EXTEND trial based on a pre-treatment conditional or abnormal TCD velocity. They were assigned to one of three risk categories according to treatment status and stroke history at study enrollment: Group 1 (low stroke risk: no previous stroke, on hydroxyurea treatment n= 12), Group 2 (medium stroke risk: no previous stroke, no hydroxyurea, n=10) and Group 3 (High stroke risk: previous stroke, no hydroxyurea n=8). Anthropometric variables, including height and weight, were recorded as well as oxygen saturation and hematological variables. Differences in post treatment outcome were modelled using mixed linear regression. A p-value of <0.05 was considered statistically significant. Results: There was no difference in mean anthropometric values or gender distribution at baseline by stroke risk category groups (Table 1). The mean(sd) age in years of participants in Group 1 was 8.2(1.7), while for Group 2 the average age was 7.7(2.1) and for Group 3 it was 10.5(2.8). The mean age of Group 3 was significantly greater than Group 1. After 18 months of hydroxyurea treatment, participants were taking an average dose of 25 mg/kg/d, range 13.7 to 34.9 mg/kg/d. On treatment TCD velocities decreased by mean(sd) of 29.5 cm/sec (31.5). Hemoglobin (Hb) concentration was lowest in Group 3 but all groups showed increases during treatment with the rate of increase in Groups 2 and 3 being greater than Group 1 (p<0.001). Absolute neutrophil counts and absolute reticulocyte counts were not different by group, and both decreased significantly post treatment (p<0.001) (Table 1). At both time points, the VCI, PRI and FSIQ mean scores in Group 3 were low [Overall means(sd); 71(11.7), 71(12.6),69(11.6), respectively] and were significantly lower compared with Group 1 (p<0.001) (Table 1). While there was no significant effect of treatment on VCI and PRI scores, the mean FSIQ score increased on average by 2.9 units (95%CI 0.3, 5.4) post treatment among participants. Adjusting for age at enrollment had no effect on the improvement on FSIQ, however adjusting for changes in hemoglobin resulted in an increase in FSIQ by 3.3 units (95%CI -0.4, 7.0) which approached statistical significance (p=0.079). Conclusion: Participants treated with hydroxyurea at maximum tolerated dose for 18 months with or without a previous stroke had significant improvement in hematological variables and neuropsychological scores. Children with sickle cell anemia with high risk of stroke may benefit from routine neuropsychological testing, hydroxyurea treatment in addition to educational interventions.

Neurocognitive outcomes in pediatric brain tumor survivors treated with proton radiotherapy: a study from the Pediatric Proton/Photon Consortium Registry (PPCR)

<h3>Objectives</h3> Radiation (RT), while an essential component of curative treatment, is associated with negative long-term cognitive sequelae. We examined cognitive functioning at follow-up in patients <22 years treated with proton RT for a primary brain tumor. <h3>Methods</h3> Patients enrolled on the PPCR between 9/2012-11/2020 were assessed at baseline and follow-up using age-appropriate Weschler measures for intellectual ability [full scale intelligence quotient (FSIQ)] from cognitive functioning index scores. We used univariate linear regression to analyze the relationship over time between cognitive outcomes and patient characteristics of gender, age at RT, tumor location, RT target (CSI vs. focal), dose, and chemotherapy. <h3>Results</h3> Of 298 patients assessed at baseline, 58 had granular data entered at both baseline and follow-up. Median age at RT was 8.9 years (2.3-21.5). Patients received RT for tumors present in posterior fossa (43%), supratentorial (38%), and midline (19%) locations. Median time from RT to follow-up neurocognitive assessment was 2.9 years (1.2-9.9). Overall, mean FSIQ declined from 104.0 to 99.1 (p=0.02) and mean processing speed declined from 96.4 to 91.1 (p=0.04). Change in other index scores were not significant. Patients that received CSI had a significant 6.4pts decline in FSIQ (p=0.01) while those who received focal RT maintained similar scores at both timepoints (105.5 vs 102.9, p=0.2). Patient characteristics of age <6 years at RT, posterior fossa or midline tumor location, CSI dose >36GyE, and total dose >54GyE all correlated to statistically significant FSIQ decline relative to their counterparts. Notably, those who received a CSI dose of >36GyE lost 10.2pts relative to those with <36GyE (p=0.03). <h3>Conclusion</h3> At 2.9-years after RT, mean cognitive scores remained in the average range. Declines in scores were found among patients that are younger at RT, received CSI, or have a non-supratentorial tumor. Additional school and IEP data will be presented at the meeting.

Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years

BackgroundDocosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks’ gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood.MethodsWe assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks’ gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI.ResultsA total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available — 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P=0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups.ConclusionsIn infants born before 29 weeks’ gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.)

Portable HEPA Filter Air Cleaner Use during Pregnancy and Children's Cognitive Performance at Four Years of Age: The UGAAR Randomized Controlled Trial.

Background:Developmental exposure to air pollution is associated with diminished cognitive abilities in observational studies, but no randomized controlled trial has examined the effect of reducing air pollution on cognition in children.Objectives:We sought to quantify the impact of reducing exposure to particulate matter (PM) during pregnancy on children’s cognitive performance at 4 y of age.Methods:In this single-blind, parallel-group, randomized controlled trial in Ulaanbaatar, Mongolia, we randomly assigned 540 nonsmoking pregnant women (268 intervention and 272 control) to receive 1–2 portable high-efficiency particulate air (HEPA) filter air cleaners or no air cleaners. The air cleaners were used from a median of 11 wk gestation until the end of pregnancy. The primary outcome was full-scale intelligence quotient (FSIQ) assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) when children were a median of 48 months old. We imputed missing outcome data using multiple imputation with chained equations, and our primary analysis was by intention to treat.Results:After excluding known miscarriages, stillbirths, neonatal deaths, and medical conditions that impeded cognitive testing and imputation, 475 (233 control and 242 intervention) children were included in our analyses. In an unadjusted analysis, the mean FSIQ of children who were randomly assigned to the intervention group was 2.5 points [95% confidence interval (CI): , 5.4 points] higher than that of children in the control group. After adjustment to account for an imbalance in preterm birth between groups, the effect estimate increased to 2.8 points (95% CI: , 5.7).Conclusions:Reducing PM air pollution during pregnancy may improve cognitive performance in childhood. https://doi.org/10.1289/EHP10302

Neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia: Experience from a tertiary care center in India.

Data of neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL) is scarce from low middle-income countries (LMICs), and is influenced by biological and cultural variations. The objective of this study was to assess the prevalence and spectrum of neurocognitive deficits in a cohort of survivors from India. Seventy survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IVINDIA ). The prevalence of neurocognitive deficits was calculated based on the full-scale intelligence quotient (FSIQ), and scores in discrete domains like verbal comprehension, perceptual reasoning, working memory, and processing speed were calculated and compared to demographics, treatment, and sociocultural factors. The mean (SD) current age and time since diagnosis was 10.5 (±3.2) years and 5 (±2.8) years, respectively. The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit (FSIQ <90) being prevalent in 50% (95% CI: 38%-62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory, and processing speed were 49%, 50%, 47%, and 44%, respectively. The odds of having neurocognitive deficits were higher when a child belonged to lower socioeconomic strata (OR 5.7, p=.004), parents with lower education attainment (OR 4.3, p=.041), and whose birth order was higher (OR 20.1, p=.005). Age at diagnosis/assessment, chemotherapy received, or dose of radiotherapy did not have a direct impact on neurocognition. Rates of neurocognitive deficits are higher in survivors in LMICs, with socioeconomic variables contributing more than the direct neurotoxic effects of treatment.

Cognitive and academic outcomes in children with chronic kidney disease

BackgroundFew data exist on the cognitive and academic functioning of children with chronic kidney disease (CKD) over the trajectory of their illness. We aimed to determine the association between CKD stages and cognitive and academic performance in children over time.MethodsWe included 53 participants (aged 6–18 years) with CKD stages 1–5 (n = 37), on dialysis (n = 3), or with functioning kidney transplant (n = 22) from three units in Australia from 2015 to 2019. Participants undertook a series of psychometric tests and were invited for repeated assessments annually. We used linear regression and linear mixed models to investigate the effect of CKD stage, adjusted for socioeconomic status.ResultsAt baseline, full-scale intelligence quotient (FSIQ) (95%CI) of children on kidney replacement therapy (KRT) was in the low average range (87: 78, 96) and average (101: 95, 108) for children with CKD 1–5. Mean (95%CI) FSIQ, word reading, numerical operations, and spelling scores for children on KRT were 14.3 (− 25.3, − 3.3), 11 (− 18.5, − 3.6), 8.5 (− 17.6, 0.76), and 10 (− 18.6, − 1.3) points lower than children with CKD Stages 1–5. Spelling and numerical operations scores declined by 0.7 (− 1.4, − 0.1) and 1.0 (− 2.0, 0.2) units per year increase in age, regardless of CKD stage.ConclusionsChildren treated with KRT have low average cognitive abilities and lower academic performance for numeracy and literacy compared to both children with CKD 1–5 and to the general population. However, the rate of decline in academic performance over time is similar for children across the full spectrum of CKD.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

Prenatal and early childhood predictors of intelligence quotient (IQ) in 7-year-old Danish children from the Odense Child Cohort.

Cognitive development measured as intelligence quotient can predict socioeconomic markers in adulthood. It is therefore of interest to determine predictors of childhood intelligence quotient. To assess intelligence quotient scores based on standardised Danish age-appropriate scores and to evaluate potential predictors of intelligence quotient. At 7 years of age children in the Odense Child Cohort completed an abbreviated version of the Wechsler intelligence scale for children 5th edition consisting of four subtests (vocabulary, similarities, block design and matrix reasoning) from which the full scale intelligence quotient and verbal comprehension index were estimated. Potential predictors from pregnancy through childhood were collected from questionnaires, birth records and clinical examinations. Intelligence quotient scores were investigated through descriptive statistics and linear regression models. The mean full scale intelligence quotient among 1375 children was 99.1 (95% confidence interval 98.5; 99.8) points. Higher full scale intelligence quotient scores were observed in girls 100.8 (95% confidence interval 100.0; 101.8) compared to boys 97.6 (96.7; 98.4), and in children of mothers with high and intermediate education 101.7 (100.4; 103.1) and 99.6 (98.7; 100.5), respectively, compared to low education 96.1 (94.9; 97.3). In linear regression analyses, longer maternal education and child sex (girls) remained strong predictors of intelligence quotient at age 7 years. In addition, paternal education, child head circumference and longer duration of breastfeeding were associated with higher intelligence quotient, whereas maternal overweight and obesity before pregnancy was associated with lower intelligence quotient. Mean intelligence quotient scores were comparable to the standardised mean intelligence quotient of 100 point of Danish peers. It is important to follow up these children to determine which predictors persist into adulthood.

Intellectual development of patients with biliary atresia who underwent living donor liver transplantation in infancy.

The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. The Wechsler Intelligence Scale for Children-fourth edition test was administered to 20 patients who survived [Formula: see text] 5years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.

Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver.

ABSTRACTObjective:To evaluate neurodevelopmental status among children with inherited cholestatic liver diseases with native liver and variables predictive of impairment.Methods:Participants with Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha 1 antitrypsin deficiency (A1AT) enrolled in a longitudinal, multicenter study and completed the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV. Full Scale Intelligence Quotient (FSIQ) was analyzed continuously and categorically (>100, 85–99, 70–84, <70). Univariate linear regression was performed to study association between FSIQ and risk factors, stratified by disease.Results:Two hundred and fifteen completed testing (ALGS n = 70, PFIC n = 43, A1AT n = 102); median age was 7.6 years (3.0–16.9). Mean FSIQ in ALGS was lower than A1AT (94 vs 101, P = 0.01). Frequency of FSIQ < 85 (>1 standard deviation [SD] below average) was highest in ALGS (29%) versus 18.6% in PFIC and 12.8% in A1AT, and was greater than expected in ALGS based on normal distribution (29% vs 15.9%, P = 0.003). ALGS scored significantly lower than test norms in almost all Wechsler composites; A1AT scored lower on Working Memory and Processing Speed; PFIC was not different from test norms. Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were significantly associated with FSIQ.Conclusions:Patients with ALGS are at increased risk of lower FSIQ, whereas our data suggest A1AT and PFIC are not. A1AT and ALGS appear vulnerable to working memory and processing speed deficits suggestive of attention/executive function impairment. Malnutrition, liver disease severity, and sociodemographic factors appear related to FSIQ deficits, potentially identifying targets for early interventions.

Assessment of chemotherapy-induced cognitive impairment: a prospective study of the cognitive effects of platinum/taxane-based chemotherapy in gynecologic cancer patients

<h3>Background:</h3> Chemotherapy-induced cognitive impairment (CICI), ‘chemo-brain,' involves concentration and executive functioning difficulty and slowed processing speed and memory. Although cognitive changes in CICI can be subtle and difficult to quantify, CICI affects up to 75% of cancer survivors and impacts quality of life. <h3>Objectives:</h3> The objective of our study was to add to the definition of CICI by quantifying changes in specific cognitive domains before and after administration of platinum/taxane-based chemotherapy in gynecologic cancer patients using a tailored battery of neurocognitive tests. <h3>Methods:</h3> Following institutional review board approval, chemotherapy-naïve gynecologic cancer patients scheduled to receive six cycles of intravenous platinum/taxane-based chemotherapy were identified. Baseline demographic, social, and clinical characteristics were obtained. Eleven neurocognitive assessments measured cognitive domains of interest (Table 1), including a brief cognitive screen, evaluation of fine motor skills, verbal fluency, working memory, information processing speed, visuospatial learning and memory, attention, mental flexibility, and abstract problem-solving skills. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and Psychiatric Diagnostic Screening Questionnaire assessed emotional functioning. The Functional Assessment of Cancer Therapy - Cognitive Function assessed self-perceived cognitive functioning. Testing was performed prior to the first and three to four weeks after the last cycle of chemotherapy. Descriptive statistics identified trends in individual indices of cognitive dysfunction and quality of life. <h3>Results:</h3> Fourteen patients enrolled and nine were eligible for complete analyses. The mean age was 60.6 years. The mean full scale intelligence quotient prior to therapy was 103.5. Most patients were White (8/9, 89%), had obtained at least a Bachelor's degree (5/9, 55.6%), and were diagnosed with high grade (6/9, 66.7%) stage III or IV disease (5/9, 55.6%). The majority of patients declined on cognitive screening performance (5/9, 55.6%) as well as worse scores on indices of attention (7/9, 77.8%), mental flexibility (5/8, 62.5%) verbal learning (5/9, 55.6%), and fine motor skills (5/9, 55.6%) after completion of chemotherapy. Most patients improved on indices of verbal memory (7/9, 77.8%), visuospatial learning (6/8, 75%), and verbal fluency (5/9, 55.6%). Despite changes in indices of cognitive function, most patients' perceived quality of life improved (5/9, 55.6%) after chemotherapy. <h3>Conclusions:</h3> Although gynecologic cancer patients complain of CICI, there is discrepancy regarding its incidence and affected cognitive domains. This pilot study highlights attention and mental flexibility as indices of cognitive dysfunction that may be at risk following receipt of chemotherapy in gynecologic cancer patients. Future research may focus on targeted assessment strategies.

Intellectual functioning among case-matched cohorts of children treated with proton or photon radiation for standard-risk medulloblastoma.

Proton therapy may reduce cognitive deficits after radiotherapy among brain tumor survivors, although current data are limited to retrospective comparisons between historical cohorts. The authors compared intelligence quotient scores within a case-matched cohort of children with medulloblastoma treated with proton radiation (PRT) or photon radiation (XRT) over the same time period. Among 88 consecutive patients with standard-risk medulloblastoma treated with PRT or XRT at 2 institutions from 2000 to 2009, 50 were matched 1:1 (25 with PRT and 25 with XRT) according to age, gender, date of diagnosis, histology, radiation boost, and craniospinal irradiation dose. One-way analyses of variance were performed to compare the Full-Scale Intelligence Quotient (FSIQ) and associated index scores between the 2 cohorts. Neurocognitive data were available for 37 survivors (17 with PRT and 20 with XRT) from the matched cohort. The mean age was 8.5 years (SD, 4.14 years). The median follow-up was 5.3 years (range, 1.0-11.4 years) and 4.6 years (range, 1.1-11.2 years) for the PRT and XRT cohorts, respectively (P = .193). Patients treated with PRT had significantly higher mean FSIQ (99.6 vs 86.2; P = .021), verbal (105.2 vs 88.6; P = .010), and nonverbal scores (103.1 vs 88.9; P = .011) than the XRT-treated cohort. Differences in processing speed (82.9 vs 77.2; P = .331) and working memory (97.0 vs 92.7; P = .388) were not statistically significant. Radiotherapy-associated cognitive effects appear to be more attenuated after proton therapy. Comprehensive prospective studies are needed to appropriately evaluate the neurocognitive advantages of proton therapy.

Abstract 3032: A pilot study of epigenetic age acceleration and neurocognitive outcomes among survivors of pediatric medulloblastoma

Abstract Background: Medulloblastoma is the most common malignant brain tumor diagnosed in children. Treatments for medulloblastoma are associated with neurocognitive impairment; however, there is little known about the biological factors which influence variability in neurocognitive outcomes. There is emerging evidence that epigenetic age acceleration (EAA) – the difference between DNA methylation-based predicted age and chronological age – is associated with chronic health conditions among pediatric cancer survivors. Therefore, we sought to evaluate the association between EAA and neurocognitive outcomes in pediatric medulloblastoma survivors. Methods: Neurocognitive tests were obtained between 2003 and 2012 from &amp;gt;1-year survivors of pediatric medulloblastoma (n=49). Assessments included the following: Full Scale Intelligence Quotient (FSIQ), Working Memory Index (WMI), and Processing Speed Index (PSI). Whole blood samples were obtained, and DNA was extracted for genome-wide DNA methylation using the Illumina HumanMethylation450K chip. DNA methylation age was calculated using the Horvath DNA Methylation Age Calculator. Associations were assessed using linear regression models with statistical significance defined at p&amp;lt;0.05. Results: Patients were predominantly male (n=36, 73.5%), non-Hispanic White (n=34, 69%) and diagnosed at a mean age of 7.5 years. Patients received intensity-modulated radiation (n=39, 80%) or proton beam radiation (n=10, 20%). The mean FSIQ was 82.2 (95% CI: 76.9-87.6), WMI was 82.2 (95% CI: 76.2-88.2), and PSI was 79.5 (95% CI: 73.5-85.6) a median of 3.03 years (range: 1.0 – 15.2 years) post-radiotherapy. On average, the DNA methylation age of participants was significantly higher than their chronologic age at the time of sample collection (mean difference = 2.4 years; 95% CI: 1.2-3.5; p &amp;lt;0.01). Time from diagnosis to sample collection was significantly (p &amp;lt;0.01) associated with a larger deviation between DNA methylation and chronologic age. While not significantly associated with poorer neurocognitive performance on FSIQ or PSI in unadjusted models, EAA was associated with poorer WMI (beta coefficient = -1.99, p = 0.03), which was slightly attenuated after accounting for age at radiation therapy, radiation modality, dose, and time post-radiation (beta coefficient = -1.24, p = 0.15). Conclusions: In this pilot study of pediatric medulloblastoma survivors, we report that the biologic age assessed by DNA methylation profiles often exceeds the chronologic age of survivors. We also identified suggestive associations between EAA and the degree of neurocognitive impairment in survivors of medulloblastoma. These findings highlight the potential utility of evaluating measures of biological aging to better understand variability in neurocognitive performance in larger, longitudinal cohorts of patients with pediatric medulloblastoma. Citation Format: Kevin O. Wilhelm, Philip J. Lupo, Kimberly P. Raghubar, Lisa S. Kahalley, Murali Chintagumpala, Mehmet F. Ocku, Michael E. Scheurer, Austin L. Brown. A pilot study of epigenetic age acceleration and neurocognitive outcomes among survivors of pediatric medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3032.

A neuropsychological study of chromatin disorders

AimsAnalyse neuropsychological assessment data collected from a chromatin disorder clinic to determine the neuropsychological profile associated with chromatin disorders. Assess for differences in neuropsychological profile by diagnostic group and gender. Hypothesis: A systematic neuropsychological review of chromatin disorders will reveal previously unknown patterns.BackgroundChromatin disorders (CD) are a group of genetic conditions that result in developmental delay and intellectual disability. Thus far the neuropsychological profile of CDs has been poorly studied.MethodCognitive functioning, adaptive behaviour, psychosocial difficulties and perceived impact on the family were systematically assessed in a cohort of 42 patients with CDs from November 2016 to February 2019. Cognitive functioning was assessed via Full-Scale Intelligence Quotient (FSIQ), adaptive behaviour was assessed via Vineland's Adaptive Behaviour Scores (VABS), anxiety and depression was assessed via the Revised Children's Anxiety and Depression Scale (RCADS) and communication skills were assessed via the Social Responsiveness Scale-2 (SRS-2). Family Impact Scale was used to assess for the perceived impact on the family. Mean scores for each neuropsychological domain were calculated firstly sorting patients by diagnosis, and then by gender. Unpaired t-tests were run to asses for statistically significant differences in mean scores by diagnosis and gender. Spearman's correlation was used to determine and potential correlations between FSIQ, VABS, RCADS and SRS-2 scores and Family Impact Score.ResultPatients with CDs were found generally to have mild intellectual disability (mean FSIQ = 64.57) and markedly deficient adaptive behaviour functioning (mean VABS = 50.19). Patients had a mean SRS-2 score of 70, indicative of high rates of autism spectrum disorder associated symptoms. RCADS and SRS-2 scores were negatively correlated with Family Impact Score with statistical significance (–0.562 and –0.429 Correlation coefficient for RCADS and SRS-2 respectively). Females had statistically significant average higher RCADS scores than males. CHARGE Syndrome was frequently an outlier having a mean higher FSIQ score, lower adaptive functioning and lower psychosocial impairment; however, these differences were not statistically significant.ConclusionAdaptive behaviour functioning of patients with CDs is lower than expected for their FSIQ. Females with chromatin disorders have higher levels of anxiety and depression than males however the reasons for this are unknown. The psychosocial challenges and family's impact should be considered in the clinical management of CDs. Further research with a larger data set is needed to identify the neuropsychological profiles of different CDs and to confirm whether the observed differences in CHARGE Syndrome are significant.

Cognitive and Behavioral Outcomes of School-aged Children Born Extremely Preterm: a Korean Single-center Study with Long-term Follow-up

BackgroundSchool-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population.MethodsA total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used. Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed.ResultsThe mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001). In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort.ConclusionThis is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems were not different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD.

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: NCT02165878

Comparison of Neurocognitive Outcomes in Postoperative Adolescents with Unilateral Coronal Synostosis

Unilateral coronal nonsyndromic craniosynostosis is associated with asymmetric skull growth, which may influence cerebral long-term function. Twenty affected adolescents who underwent cranial vault remodeling at a mean age of 8.2 months (12 from the Yale Craniofacial Clinic and eight from the Children's Hospital of Philadelphia) all completed a double-blinded neurodevelopmental assessment at an average age of 12.1 years. The study cohort included 55 percent female and 50 percent right-sided craniosynostosis. Mean verbal intelligence quotient was highest at 117.3, and mean performance intelligence quotient was 106.4, for a mean full-scale intelligence quotient of 112.5. Patients performed above the national average on all academic achievements except for numerical operations, which was significantly lower than word reading (p = 0.022). Patients performed below average on all Beery-Buktenica visual motor tests; motor-coordination was poorer than both visual motor integration and visual perception (p = 0.027 and p = 0.005). Significant positive correlations existed between paternal education/visual perception (r = 0.450; p = 0.046) and household income/verbal intelligence quotient (r = 0.628; p = 0.004). Patients with right unilateral coronal nonsyndromic craniosynostosis had improved spelling compared with left-sided patients on multivariate regression (p = 0.033). Female patients had higher motor coordination (p = 0.024). Breast-fed patients had better performance intelligence quotient (p = 0.024), visual motor integration (p = 0.014), and visual perception (p = 0.031). Adolescents who underwent cranial vault remodeling at two institutions had above average intelligence quotient scores, but worse mathematical and visual motor achievement compared with control subjects. Left-side craniosynostosis patients performed worse in spelling than right-side patients. Breast-feeding was an independent predictor for improved performance intelligence quotient, visual motor achievement, and visual perception performance. Study findings are limited by the cohort size. A larger population study is required, which could validate or modify the study conclusions.

Clinical characterization of children and adolescents with NF1 microdeletions

PurposeAn estimated 5–11% of patients with neurofibromatosis type 1 (NF1) harbour NF1 microdeletions encompassing the NF1 gene and its flanking regions. The purpose of this study was to evaluate the clinical phenotype in children and adolescents with NF1 microdeletions.MethodsWe retrospectively analysed 30 children and adolescents with NF1 microdeletions pertaining to externally visible neurofibromas. The internal tumour load was determined by volumetry of whole-body magnetic resonance imaging (MRI) in 20 children and adolescents with NF1 microdeletions. Furthermore, the prevalence of global developmental delay, autism spectrum disorder and attention deficit hyperactivity disorder (ADHD) were evaluated.ResultsChildren and adolescents with NF1 microdeletions had significantly more often cutaneous, subcutaneous and externally visible plexiform neurofibromas than age-matched patients with intragenic NF1 mutations. Internal neurofibromas were detected in all 20 children and adolescents with NF1 microdeletions analysed by whole-body MRI. By contrast, only 17 (61%) of 28 age-matched NF1 patients without microdeletions had internal tumours. The total internal tumour load was significantly higher in NF1 microdeletion patients than in NF1 patients without microdeletions. Global developmental delay was observed in 28 (93%) of 30 children with NF1 microdeletions investigated. The mean full-scale intelligence quotient in our patient group was 77.7 which is significantly lower than that of patients with intragenic NF1 mutations. ADHD was diagnosed in 15 (88%) of 17 children and adolescents with NF1 microdeletion. Furthermore, 17 (71%) of the 24 patients investigated had T-scores ≥ 60 up to 75, indicative of mild to moderate autistic symptoms, which are consequently significantly more frequent in patients with NF1 microdeletions than in the general NF1 population. Also, the mean total T-score was significantly higher in patients with NF1 microdeletions than in the general NF1 population.ConclusionOur findings indicate that already at a very young age, NF1 microdeletions patients frequently exhibit a severe disease manifestation which requires specialized long-term clinical care.

Comparison of Intelligence Quotient in Early Treated Neonates with Congenital Hypothyroidism Compared to Healthy Children

Background: Congenital hypothyroidism (CH) is one of the preventable causes of intellectual disability. The aim of this study was to compare intelligence quotient (IQ) in early treated children with CH and healthy children. Materials and Methods: This cohort study was conducted on 78 early treated children with CH (patient group) identified in screening program in Qazvin, Iran, started in 2006 and 90 age and sex matched healthy children (control group). The Persian version of Wechsler scale was performed to assess IQ (full scale, verbal, performance). Full-scale score among 70 and 80 were defined as borderline IQ and score among 50 and 69 were defined as mild mental retardation. Data were analyzed using SPSS software version 16.0. Results: Mean age was 6.57±1.92 in patients group and 6.94±1.57 in control group (P>0.05). 46/78 of the patient group and 51/90 of the control group were male (P>0.05). Mean full scale (87.01±13.47 vs. 107.45±10.49; P< 0.001), verbal (85.73±13.54 vs. 106.86±10.18; P< 0.001), and performance (89.44±13.66 vs. 110.62±9.82; P< 0.001) IQ in the patients group were significantly lower than the control group. 73.1% of the patients group had average and above IQ. Borderline IQ (14.1% vs. 0) and mild mental retardation (12.8% vs. 1.1%, P<0.001) in the patients group were significantly higher than the control group (P<0.001). Conclusion: Based on the results, although mean IQ in treated children with congenital hypothyroidism was lower than the control group, 73.1% of them had normal IQ. Early diagnosis and treatment of congenital hypothyroidism with high doses of thyroid hormone as well as patients' compliance can prevent mental retardation.

Effects of prenatal bacterial infection on cognitive performance in early childhood.

Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up. We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection. We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n=11984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models. ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters. We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring.