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Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning.Method: Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity.Results: The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables.Conclusions: There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders. [ABSTRACT FROM AUTHOR]

We examined the effectiveness of a metacognitive intervention for written language performance, based on the Hayes model of written expression, for 73 fourth-grade (n = 38) and fifth-grade (n = 35) students. The intervention consisted of twenty 45-min writing lessons designed to improve their awareness of writing as a problem-solving process. Each of the lessons addressed some aspect of planning, translating, and reflecting on written products; their self-regulation of these processes; and actual writing practice. All instruction was conducted in intact classrooms. Prior to the intervention, all students received a battery of neurocognitive tests measuring executive functions, attention, and language. In addition, preintervention writing samples were obtained and analyzed holistically and for errors in syntax, semantics, and spelling. Following the intervention, the writing tasks were readministered and cluster analysis of the neurocognitive data was conducted. Cluster analytic procedures yielded 7 reliable clusters: 4 normal variants, 1 Problem Solving weakness, 1 Problem Solving Language weaknesses, and 1 Problem Solving strength. The response to the single treatment by these various subtypes revealed positive but modest findings. Significant group differences were noted for improvement in syntax errors and spelling, with only spelling showing differential improvement for the Problem Solving Language subtype. In addition, there was a marginally significant group effect for holistic ratings. These findings provide initial evidence that Writing Aptitude (subtype) x Single Treatment interactions exist in writing, but further research is needed with other classification schemes and interventions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to provide a reliable and valid classification scheme for written expression that captured the linguistic variability present in a typical elementary school sample. This empirically derived classification model was based on the following linguistic-based writing skills: (a) understandability of discourse, (b) grammar, (c) semantics, (d) spelling, and (e) reading comprehension. The sample included 257 fourth-grade (n = 142) and fifth-grade (n = 115) students (46.3% boys, 79.4% White, age range = 8;3-11;7 years; M = 10.10). All of the students were receiving their writing instruction in the regular education setting, with approximately one third receiving some type of educational assistance. The sample fell in the middle socioeconomic stratum. Cluster analytic techniques derived different possible solutions. Results of a series of internal validity studies provided strong evidence that the six-cluster solution was both stable and interpretable, with subtypes reflecting normal as well as writing disability variants. Further, the writing disability subtypes ranged from global impairment to more specific linguistic impediments. Based on their characteristics, the clusters were named (a) Average Writers (n = 102), (b) Low Semantics (n = 31), (c) Low Grammar (n = 18), (d) Expert Writers (n = 33), (e) Low Spelling-Reading (n = 13), and (f) Poor Text Quality (n = 60). Subtypes differed on the percentages of children in selected subtypes manifesting specific writing deficits as well as on selected aspects of measures of metacognition, self-efficacy, and self-regulation of the writing process. Results provide researchers with a foundation to further investigate the underlying neurolinguistic and neurocognitive processes that may strengthen or undermine students' ability to produce a quality written product and to design and implement intervention techniques to address the various subtype patterns inherent in a regular elementary school classroom. [ABSTRACT FROM AUTHOR]

To determine whether history of chronic lung disease (CLD) in children born at very low birthweight (VLBW) confers additional risk for impaired health, growth, and neurodevelopment, 17 VLBW children born in 1984 who had CLD (requiring supplemental oxygen more than 30 days after birth) in infancy and 28 VLBW children who did not have CLD were assessed at age 7 years. Assessments included a medical history, standard physical and neurological examinations, pulmonary-function tests, and tests of neuropsychological and psychoeducational functioning. Health status did not differ between the groups. In contrast, children with CLD did not perform as well in neuropsychological and psychoeducational assessments. Although CLD confers little added risk to health, it seems to add significantly to risks for poor school performance that are known to be associated with very low birthweight. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The purpose of this work was to determine cognitive and adaptive behavioral outcomes of children with traumatic brain injury acquired before age 2 years and to compare outcomes between inflicted versus noninflicted brain injury. PATIENTS AND METHODS: All North Carolina children hospitalized in an ICU for a traumatic brain injury before age 2 years between the years 2000 and 2001 were eligible for study entry. A total of 112 surviving children were prospectively identified, 52 (46%) of whom had complete follow-up. Thirty-one control children were recruited from preschool settings. Control subjects were chosen to be demographically similar to case subjects. Child measures of cognition and adaptive behavior at age 3 years were measured and compared between children with and without traumatic brain injury and children with inflicted and noninflicted traumatic brain injury. RESULTS: Sixty percent of injured children were > 1 SD below normal on cognitive testing. Forty percent of injured children scored > 1 SD below normal on adaptive behavior testing. Children with inflicted traumatic brain injury performed more poorly on tests of cognition and adaptive behavior. Glasgow Coma Scale > or = 13, absence of seizures, income above twice the poverty guidelines, and high social capital were associated with improved outcomes. Injured children had lower scores than uninjured control children after adjustment for socioeconomic status. CONCLUSIONS: Very young children with mild-to-severe traumatic brain injury as measured by the Glasgow Coma Scale are at risk for global cognitive deficits more than a year after the time of injury. Inflicted brain injury is associated with more severe injury and worse outcomes. This is less optimistic than findings in this same cohort 1 year after injury. Family characteristics seem to play a role in recovery after injury. [ABSTRACT FROM AUTHOR]

Turner syndrome, caused by complete or partial loss of an X-chromosome, is often accompanied by specific cognitive challenges. Magnetic resonance imaging studies of adults and children with Turner syndrome suggest these deficits reflect differences in anatomical and functional connectivity. However, no imaging studies have explored connectivity in infants with Turner syndrome. Consequently, it is unclear when in development connectivity differences emerge. To address this gap, we compared functional connectivity and white matter microstructure of 1-year-old infants with Turner syndrome to typically developing 1-year-old boys and girls. We examined functional connectivity between the right precentral gyrus and five regions that show reduced volume in 1-year old infants with Turner syndrome compared to controls and found no differences. However, exploratory analyses suggested infants with Turner syndrome have altered connectivity between right supramarginal gyrus and left insula and right putamen. To assess anatomical connectivity, we examined diffusivity indices along the superior longitudinal fasciculus and found no differences. However, an exploratory analysis of 46 additional white matter tracts revealed significant group differences in nine tracts. Results suggest that the first year of life is a window in which interventions might prevent connectivity differences observed at later ages, and by extension, some of the cognitive challenges associated with Turner syndrome., (© The Author(s) 2024. Published by Oxford University Press.)

Background: We studied whether increased systolic blood pressure (SBP), as determined by auscultatory SBP, ambulatory SBP, and the number of cardiovascular health risk indicators, are associated with neurocognition in adolescents., Methods: This cross-sectional study included 365 adolescents (mean age, 15.5 years) from 6 academic medical centers in the United States. The sample was 59.5% male, 52.6% White, with 23.9% of the caregivers having less than or equal to a high school degree. Primary exposures included the following: auscultatory SBP, ambulatory SBP, and the number of cardiovascular risk factors. Neurocognitive outcomes comprised nonverbal IQ, attention, and parent ratings of executive functions., Results: After examining the models for the effects of targeted covariates (eg, maternal education), higher auscultatory SBP was associated with lower nonverbal IQ (β=-1.39; P <0.001) and verbal attention (β=-2.39; P <0.05); higher ambulatory 24 hours. SBP (β=-21.39; P <0.05) and wake SBP (β=-21.62; P <0.05) were related to verbal attention; and all 3 ambulatory blood pressure measures were related to sustained attention accounting for small to medium amounts of variance (adjusted R 2 =0.08-0.09). Higher ambulatory blood pressure sleep SBP also was significantly associated with parent ratings of behavior regulation (β=12.61; P <0.05). These associations remained stable after a sensitivity analysis removed cases with hypertension. Number of cardiovascular risk factors performed similarly, with more risk factors being associated with lower nonverbal IQ (β=-1.35; P <0.01), verbal attention (β=-1.23; P <0.01), and all parent ratings of executive functions., Conclusions: Elevated SBP, even below the hypertension range, and general cardiovascular health are associated with neurocognitive outcomes in adolescents. How these findings might guide clinical care is worthy of additional study., Competing Interests: None.

Objective: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood., Study Design: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model., Results: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10., Conclusion: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years., Competing Interests: Declaration of Competing Interest The authors have no financial relationships or any other conflicts of interest relevant to this article to disclose. This study was supported by the National Institute of Neurological Disorders and Stroke (grants 5U01NS040069-05 and 2R01NS040069-09) and the Office of the Director of the National Institutes of Health (1UG3OD023348-01)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: ZIKV has neuroinvasive properties, and in utero exposure can cause birth defects, but little is known about the neurological and neurocognitive impacts of acquired ZIKV infection, particularly in children., Methods: We assessed neurological symptoms frequency among ZIKV-infected children within one year after ZIKV infection. Three to 5 years post-infection, these children and a matched group of uninfected children were assessed via questionnaires, neurological exams, and neuropsychological testing to evaluate the association between prior ZIKV infection and subsequent neurological symptoms, and cognitive-behavioral function., Results: Among 194 ZIKV-infected children, 3 reported asthenia, 4 reported neck pain, and 10 reported back pain within one year post-infection. At follow-up, clinician-observed cranial nerve abnormalities were significantly more common among ZIKV-infected vs. uninfected children (16 vs. 3; p < 0.01), with vestibulocochlear nerve abnormalities observed most frequently. While ZIKV-infected children scored better than uninfected on cognitive measures, this difference was not clinically meaningful., Conclusions: Neurological signs, including paresthesia and cranial nerve abnormalities, were observed among ZIKV-infected participants in our study. However, we did not observe a meaningful link between acquired ZIKV infection and subsequent neurological, cognitive, or behavioral outcomes in a representative sample. An exception may be hearing impairment and loss, which should be explored further in future studies., Impact: Neurological symptoms, though rare, were observed and reported more frequently among ZIKV-infected vs. uninfected children. These included: asthenia, neck pain, back pain, paresthesia, and cranial nerve abnormalities. Neurocognitive and behavioral test scores were similar among ZIKV-infected and uninfected children. Our study suggests that ZIKV-infected children should be monitored for neurological symptoms and cranial neuropathy to better understand the full burden of acquired ZIKV infection among children., (© 2024. The Author(s).)

For children and young adults, living with chronic kidney disease (CKD) poses physical, mental, and social challenges. The mental health functioning of children and adolescents with CKD plays an important role in the medical, educational, vocational, and quality of life outcomes, yet receives little systematic attention in the busy pediatric nephrology clinic. This article will provide an overview of the prevalence of mental illness and symptoms in children and young adults with CKD, strategies to assess for dysfunction, and the long-term outcomes associated with impaired functioning. While there is a relative dearth of literature regarding evidence-based interventions in this population to improve mental health functioning, we provide "best practice" strategies based on the available literature to address emotional and/or behavioral challenges once they are identified. More research is needed to define appropriate interventions to alleviate mental health issues and social-emotional distress, and this review of the literature will serve to provide directions for future research., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Primary hypertension in childhood tracks into adulthood and may be associated with increased cardiovascular risk. Studies conducted in children and adolescents provide an opportunity to explore the early cardiovascular target organ injury (CV-TOI) in a population free from many of the comorbid cardiovascular disease risk factors that confound studies in adults., Methods: Youths (n=132, mean age 15.8 years) were stratified by blood pressure (BP) as low, elevated, and high-BP and by left ventricular mass index (LVMI) as low- and high-LVMI. Systemic circulating RNA, miRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques., Results: VASH1 gene expression was elevated in youths with high-BP with and without high-LVMI. VASH1 expression levels positively correlated with systolic BP (r=0.3143, p=0.0034). The expression of hsa-miR-335-5p, one of the VASH1- predicted miRNAs, was downregulated in high-BP with high-LVMI youths and was inversely correlated with systolic BP (r=-0.1891, p=0.0489). GSE1 hypermethylation, circulating PROZ upregulation (log 2 FC=0.61, p=0.0049 and log 2 FC=0.62, p=0.0064), and SOD3 downregulation (log 2 FC=-0.70, p=0.0042 and log 2 FC=-0.64, p=0.010) were observed in youths with elevated BP and high-BP with high-LVMI. Comparing the transcriptomic and proteomic profiles revealed elevated HYAL1 levels in youths displaying high-BP and high-LVMI., Conclusions: The findings are compatible with a novel blood pressure-associated mechanism that may occur through impaired angiogenesis and extracellular matrix degradation through dysregulation of Vasohibin-1 and Hyaluronidase1 was identified as a possible mediator of CV-TOI in youth with high-BP and suggests strategies for ameliorating TOI in adult-onset primary hypertension., Competing Interests: Conflicts of interest Dr. Sadayappan provides consulting and collaborative research studies to the Leducq Foundation (CURE-PLAN), Red Saree Inc., Alexion, Affinia Therapeutics Inc., and Cosmogene Skincare Private Limited, but such work is unrelated to the content of this article.

Background: Atopic dermatitis (AD) may affect cognitive function, but studies are limited and inconsistent. The effect of AD severity on cognition remains underexplored and few previous studies have examined clinically validated or repeated measures of cognition throughout childhood., Objectives: To evaluate the relationship of AD activity and severity with validated measures of general cognition in a longitudinal birth cohort., Methods: We conducted cross-sectional analyses using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK cohort of 14 975 individuals followed prospectively since their birth in 1991-92. AD was assessed 11 times between the age of 6 and 166 months. Mothers were asked if their child had an 'itchy, dry skin rash in the joints and creases', and AD status was time-updated accordingly as 'never', 'maybe', 'inactive', 'active/mild' or 'active/moderate-severe'. General cognition [i.e. intelligence quotient (IQ)] was measured at 18, 49, 103 and 186 months of age using the Griffiths Mental Development Scales (GMDS), Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Wechsler Intelligence Scale for Children (WISC) and Wechsler Abbreviated Scale of Intelligence (WASI), respectively. Multivariable linear regression was used to compare IQ with respect to nearest time-updated AD status. Secondary analyses were stratified by the presence or absence of psychiatric or learning disorders. An exploratory longitudinal analysis of IQ across all four outcome assessments was conducted using generalized estimating equations., Results: No significant associations between AD status and full-scale IQ scores on the GMDS, WPPSI, WISC and WASI were observed after adjustment for sociodemographic factors, atopic comorbidities and sleep characteristics. However, at 8 years of age, WISC Performance IQ was slightly, although statistically significantly, lower among children with active/moderate-severe AD [β coefficient -2.16, 95% confidence interval (CI) -4.12 to -0.19] and Verbal IQ was slightly, but statistically significantly, higher among those with inactive AD (β coefficient 1.31, 95% CI 0.28-2.34) compared with those without AD. Analyses stratified by psychiatric or learning disorders, and exploratory longitudinal analyses of cognition revealed similar findings., Conclusions: We did not find any clinically meaningful associations between AD activity and severity and general cognitive function during early childhood and adolescence. Future studies should incorporate objective measures of AD severity and investigate outcomes beyond IQ., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD., Methods: We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1.73 m 2 ( n =569). NiCK is a single-center cross-sectional study of participants aged 8-25 years with eGFR<90 ml/min per 1.73 m 2 ( n =60) and matched healthy controls ( n =67). Untargeted metabolomic quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed: intelligence, attention regulation, working memory, and parent ratings of executive function. Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular versus nonglomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR., Results: There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, and NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared with healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide-and with intelligence: γ -glutamyl amino acids and aconitate., Conclusions: Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction, and altered energy metabolism, circulating toxins, and redox homeostasis., Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023&#95;11&#95;17&#95;CJN0000000000000318.mp3., (Copyright © 2023 by the American Society of Nephrology.)

Objective: This cohort study assessed perinatal factors known to be related to maternal and neonatal inflammation and hypothesized that several would be associated with emotional, cognitive, and behavioral dysregulation in youth., Method: The Environmental influences on Child Health Outcomes (ECHO) is a research consortium of 69 pediatric longitudinal cohorts. A subset of 18 cohorts that had both Child Behavior Checklist (CBCL) data on children (6-18 years) and information on perinatal exposures including maternal prenatal infections was used. Children were classified as having the CBCL-Dysregulation Profile (CBCL-DP) if the sum of their T scores for 3 CBCL subscales (attention, anxious/depressed, and aggression) was ≥180. Primary exposures were perinatal factors associated with maternal and/or neonatal inflammation, and associations between these and outcome were assessed., Results: Approximately 13.4% of 4,595 youth met criteria for CBCL-DP. Boys were affected more than girls (15.1% vs 11.5%). More youth with CBCL-DP (35%) were born to mothers with prenatal infections compared with 28% of youth without CBCL-DP. Adjusted odds ratios indicated the following were significantly associated with dysregulation: having a first-degree relative with a psychiatric disorder; being born to a mother with lower educational attainment, who was obese, had any prenatal infection, and/or who smoked tobacco during pregnancy., Conclusion: In this large study, a few modifiable maternal risk factors with established roles in inflammation (maternal lower education, obesity, prenatal infections, and smoking) were strongly associated with CBCL-DP and could be targets for interventions to improve behavioral outcomes of offspring., Diversity & Inclusion Statement: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Although genomic research offering next-generation sequencing (NGS) has increased the diagnoses of rare/ultra-rare disorders, populations experiencing health disparities infrequently participate in these studies. The factors underlying non-participation would most reliably be ascertained from individuals who have had the opportunity to participate, but decline. We thus enrolled parents of children and adult probands with undiagnosed disorders who had declined genomic research offering NGS with return of results with undiagnosed disorders (Decliners, n = 21) and compared their data to those who participated (Participants, n = 31). We assessed: (1) practical barriers and facilitators, (2) sociocultural factors-genomic knowledge and distrust, and (3) the value placed upon a diagnosis by those who declined participation. The primary findings were that residence in rural and medically underserved areas (MUA) and higher number of barriers were significantly associated with declining participation in the study. Exploratory analyses revealed multiple co-occurring practical barriers, greater emotional exhaustion and research hesitancy in the parents in the Decliner group compared to the Participants, with both groups identifying a similar number of facilitators. The parents in the Decliner group also had lower genomic knowledge, but distrust of clinical research was not different between the groups. Importantly, despite their non-participation, those in the Decliner group indicated an interest in obtaining a diagnosis and expressed confidence in being able to emotionally manage the ensuing results. Study findings support the concept that some families who decline participation in diagnostic genomic research may be experiencing pile-up with exhaustion of family resources - making participation in the genomic research difficult. This study highlights the complexity of the factors that underlie non-participation in clinically relevant NGS research. Thus, approaches to mitigating barriers to NGS research participation by populations experiencing health disparities need to be multi-pronged and tailored so that they can benefit from state-of -the art genomic technologies., (© 2023 National Society of Genetic Counselors.)

Background: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency., Methods: A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1 st -5 th percentile) or very low (< 1 st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates., Results: Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (- 0.75, 95% CI - 1.36, - 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (β =  - 0.98; 95% CI - 1.78, - 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (β = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (β =  - 1.33, 95% CI - 2.16, - 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (β =  - 1.09, 95% CI - 2.09, - 0.10, p = 0.03)., Conclusions: The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Elevated serum uric acid concentration is a risk factor for CKD progression. Its change over time and association with CKD etiology and concomitant changes in estimated glomerular filtration rate (eGFR) in children and adolescents are unknown., Methods: Longitudinal study of 153 children/adolescents with glomerular (G) and 540 with non-glomerular (NG) etiology from the CKD in Children (CKiD) study. Baseline serum uric acid, change in uric acid and eGFR over time, CKD etiology, and comorbidities were monitored. Adjusted linear mixed-effects regression models quantified the relationship between within-person changes in uric acid and concurrent within-person changes in eGFR., Results: Participants with stable uric acid over follow-up had CKD progression which became worse for increased baseline uric acid (average annual percentage changes in eGFR were - 1.4%, - 7.7%, and - 14.7% in those with G CKD with baseline uric acid < 5.5 mg/dL, 5.5 - 7.5 mg/dL, and > 7.5 mg/dL, respectively; these changes were - 1.4%, - 4.1%, and - 8.6% in NG CKD). Each 1 mg/dL increase in uric acid over follow-up was independently associated with significant concomitant eGFR decreases of - 5.7% (95%CI - 8.4 to - 3.0%) (G) and - 5.1% (95%CI - 6.3 to - 4.0%) (NG) for those with baseline uric acid < 5.5 mg/dL and - 4.3% (95%CI - 6.8 to - 1.6%) (G) and - 3.3% (95%CI - 4.1 to - 2.6%) (NG) with baseline uric acid between 5.5 and 7.5 mg/dL., Conclusions: Higher uric acid levels and increases in uric acid over time are risk factors for more severe progression of CKD in children and adolescents. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: The increased risk of developing attention-deficit hyperactivity disorder (ADHD) in extremely preterm infants is well-documented. Better understanding of perinatal risk factors, particularly those that are modifiable, can inform prevention efforts., Methods: We examined data from the Extremely Low Gestational Age Newborns (ELGAN) Study. Participants were screened for ADHD at age 10 with the Child Symptom Inventory-4 ( N = 734) and assessed at age 15 with a structured diagnostic interview (MINI-KID) to evaluate for the diagnosis of ADHD ( N = 575). We studied associations of pre-pregnancy maternal body mass index (BMI), pregestational and/or gestational diabetes, maternal smoking during pregnancy (MSDP), and hypertensive disorders of pregnancy (HDP) with 10-year and 15-year ADHD outcomes. Relative risks were calculated using Poisson regression models with robust error variance, adjusted for maternal age, maternal educational status, use of food stamps, public insurance status, marital status at birth, and family history of ADHD. We defined ADHD as a positive screen on the CSI-4 at age 10 and/or meeting DSM-5 criteria at age 15 on the MINI-KID. We evaluated the robustness of the associations to broadening or restricting the definition of ADHD. We limited the analysis to individuals with IQ ≥ 70 to decrease confounding by cognitive functioning. We evaluated interactions between maternal BMI and diabetes status. We assessed for mediation of risk increase by alterations in inflammatory or neurotrophic protein levels in the first week of life., Results: Elevated maternal BMI and maternal diabetes were each associated with a 55-65% increase in risk of ADHD, with evidence of both additive and multiplicative interactions between the two exposures. MSDP and HDP were not associated with the risk of ADHD outcomes. There was some evidence for association of ADHD outcomes with high levels of inflammatory proteins or moderate levels of neurotrophic proteins, but there was no evidence that these mediated the risk associated with maternal BMI or diabetes., Conclusion: Contrary to previous population-based studies, MSDP and HDP did not predict ADHD outcomes in this extremely preterm cohort, but elevated maternal pre-pregnancy BMI, maternal diabetes, and perinatal inflammatory markers were associated with increased risk of ADHD at age 10 and/or 15, with positive interaction between pre-pregnancy BMI and maternal diabetes., Competing Interests: Author JF has received grant or research support from Healix and Syneos Health, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cochran, Jensen, Frazier, Jalnapurkar, Kim, Roell, Joseph, Hooper, Santos, Kuban, Fry and O’Shea.)

Background: Hypertension-related increased arterial stiffness predicts development of target organ damage (TOD) and cardiovascular disease. We hypothesized that blood pressure (BP)-related increased arterial stiffness is present in youth with elevated BP and is associated with TOD., Methods: Participants were stratified by systolic BP into low- (systolic BP <75th percentile, n=155), mid- (systolic BP ≥80th and <90th percentile, n=88), and high-risk BP categories (≥90th percentile, n=139), based on age-, sex- and height-specific pediatric BP cut points. Clinic BP, 24-hour ambulatory BP monitoring, anthropometrics, and laboratory data were obtained. Arterial stiffness measures included carotid-femoral pulse wave velocity and aortic stiffness. Left ventricular mass index, left ventricular systolic and diastolic function, and urine albumin/creatinine were collected. ANOVA with Bonferroni correction was used to evaluate differences in cardiovascular risk factors, pulse wave velocity, and cardiac function across groups. General linear models were used to examine factors associated with arterial stiffness and to determine whether arterial stiffness is associated with TOD after accounting for BP., Results: Pulse wave velocity increased across groups. Aortic distensibility, distensibility coefficient, and compliance were greater in low than in the mid or high group. Significant determinants of arterial stiffness were sex, age, adiposity, BP, and LDL (low-density lipoprotein) cholesterol. Pulse wave velocity and aortic compliance were significantly associated with TOD (systolic and diastolic cardiac function and urine albumin/creatinine ratio) after controlling for BP., Conclusions: Higher arterial stiffness is associated with elevated BP and TOD in youth emphasizing the need for primary prevention of cardiovascular disease.

Background: Children born extremely preterm (EP) are at increased risk of cognitive deficits that persist into adulthood. Few large cohort studies have examined differential impairment of cognitive function in EP-born adolescents in relation to early life risk factors, including maternal social disadvantage, gestational age at delivery, and neonatal morbidities prevalent among EP neonates., Objectives: To assess cognitive abilities in relation to early life risk factors in an EP-born cohort at 15 years of age., Methods: 681 of 1198 surviving participants (57%) enrolled from 2002 to 2004 in the Extremely Low Gestational Age Newborn Study returned at age 15 years for an assessment of cognitive abilities with the Wechsler Abbreviated Scale of Intelligence-II and the NIH Toolbox Cognition Battery (NTCB) verbal cognition and fluid processing composites, the latter of which measured executive functions and processing speed. Three cognitive outcomes, WASI-II IQ, NTCB verbal cognition, and NTCB fluid processing, were analyzed for associations with maternal social disadvantage and gestational age. Mediation of maternal social disadvantage by gestational age and mediation of gestational age by neonatal morbidities were also examined., Results: Test scores were lower for NTCB fluid processing relative to IQ and NTCB verbal abilities. Social disadvantage and gestational age were associated with all three cognitive outcomes. Mediation analyses indicated partial mediation of gestational age associations with all three outcomes by neonatal morbidities but did not support mediation by gestational age of social risk associations with cognitive outcomes., Conclusions: Greater maternal social disadvantage and lower gestational age are associated with less favorable cognitive outcomes among EP-born adolescents at 15 years of age. Neonatal morbidities partially mediate associations between lower gestational age and cognitive outcomes. These findings highlight the need for improved medical and remedial interventions to mitigate risk of poor cognitive outcomes among EP-born adolescents.

Objectives: To describe the presence and persistence of neurological and neuropsychological sequelae among children with acquired Zika virus infection and assess whether those sequelae were more common in children infected with Zika virus compared to uninfected children., Methods: We conducted a prospective cohort study of children with and without Zika virus infection in León, Nicaragua, using a standard clinical assessment tool and questionnaire to collect data on symptoms at three visits, about 6 months apart, and a battery of standardized instruments to evaluate neurocognitive function, behavior, depression, and anxiety at the last two visits., Results: Sixty-two children were enrolled, with no significant differences in demographics by infection group. Children infected with Zika virus had a range of neurological symptoms, some of which persisted for 6 to 12 months; however, no consistent pattern of symptoms was observed. At baseline a small percentage of children infected with Zika virus had an abnormal finger-to-nose test (13%), cold touch response (13%), and vibration response (15%) versus 0% in the uninfected group. Neurocognitive deficits and behavioral problems were common in both groups, with no significant differences between the groups. Children infected with Zika virus had lower cognitive efficiency scores at the 6-month visit. Anxiety and depression were infrequent in both groups., Conclusions: Larger studies are needed to definitively investigate the relationship between Zika virus infection and neurological symptoms and neurocognitive problems, with adjustment for factors affecting cognition and behavior, including mood and sleep disorders, home learning environment, history of neuroinvasive infections, and detailed family history of neuropsychological problems.

Objective: To evaluate the prevalence, co-occurrence, sex differences, and functional correlates of DSM-5 psychiatric disorders in 15-year-old adolescents born extremely preterm., Method: The Extremely Low Gestational Age Newborns (ELGAN) Study is a longitudinal study of children born <28 weeks gestation. At age 15, 670 adolescents completed the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), the Youth Self-Report, a disability scale of participation in social roles, and cognitive testing. Parents completed a family psychiatric history questionnaire., Results: The most prevalent psychiatric disorders were anxiety, attention-deficit/hyperactivity disorder, and major depression. More girls met criteria for anxiety than boys. Though 66% of participants did not meet criteria for a psychiatric disorder, 15% met criteria for 1, 9% for 2, and 8% for ≥3 psychiatric disorders. Participants with ≥2 psychiatric disorders were more likely to have repeated a grade, to have an individualized educational program, and to have a lower nonverbal IQ than those with no psychiatric disorders. Participants with any psychiatric disorder were more likely to use psychotropic medications; to have greater cognitive and functional impairment; and to have mothers who were single, were on public health insurance, and had less than a high school education. Finally, a positive family psychiatric history was identified more frequently among adolescents with ≥3 psychiatric disorders., Conclusion: Among adolescents born extremely preterm, anxiety, major depression, and attention-deficit/hyperactivity disorder were the most prevalent psychiatric disorders at age 15. Adolescents with >1 psychiatric disorder were at increased risk for multiple functional and participatory challenges., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To compare specific attention functions for school-age children with chronic kidney disease (CKD) to those of a typically developing control group., Methods: A cross-sectional study examined attention dimensions for children and adolescents with CKD ( n = 30) in comparison to a typically developing control group ( n = 41). The CKD group consisted of those receiving maintenance dialysis ( n = 15) and those with mild/moderate CKD treated conservatively ( n = 15). Measures aligning with Mirsky's conceptual multidimensional model of attention were selected to compare groups across five dimensions of attention: Focus/Execute, Sustain, Stability, Shift, and Encode., Results: Significant group differences were revealed, with the CKD group performing worse than controls on the Focus/Execute, Sustain, and Encode dimensions. The CKD group also had a larger proportion of children with scores one standard deviation or more below the mean on the Shift and Encode domains, suggesting an at-risk level of functioning in these dimensions. Secondary analyses showed disease severity to be correlated with worse attention functions for children with CKD., Conclusion: Children with CKD may be vulnerable to subtle, specific deficits in numerous attention dimensions relative to their typically developing peers, particularly for those with more severe disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Duquette, Gipson and Hooper.)

Background: Development of cardiovascular disease in adults has been directly linked to an adverse metabolic phenotype. While there is evidence that development of these risk factors in childhood persists into adulthood and the development of cardiovascular disease, less is known about whether these risk factors are associated with target organ damage during adolescence., Methods: We collected data from 379 adolescents (mean age 15.5, 60% male) with blood pressure between the 75th and 95th percentile to determine if there is a metabolic phenotype that predicts cardiovascular changes (left ventricular mass, systolic and diastolic function, pulse wave velocity, and renal function). We determined the number of risk factors for cardiovascular disease (hypertension, dyslipidemia, obesity, and insulin resistance) present in each participant. Generalized linear models were constructed to determine if the number of cardiovascular risk factors (CVRFs) were associated with measures of target organ damage., Results: The number of CVRFs present were associated with statistically significant differences in increased left ventricular mass index, increased pulse wave velocity, decreased peak longitudinal strain, urine albumin to creatine ratio and echocardiographic parameters of diastolic dysfunction. Generalized linear models showed that dyslipidemia and insulin resistance were independently associated with markers of diastolic dysfunction (P ≤ .05) while increased blood pressure was associated with all makers of target organ damage (P ≤ .03)., Conclusions: These data suggest the of the number of CVRFs present is independently associated with early changes in markers of target organ damage during adolescence., (Copyright © 2022 by the American Academy of Pediatrics.)

Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background: Children and adolescents with mild to moderate chronic kidney disease (CKD) are at high risk for mild but persistent impairment in executive functions, which have been associated with low health-related quality of life (HRQOL) among children and adolescents with chronic health conditions. However, no similar link has been established among children and adolescents with mild to moderate CKD. Given the essential role executive functions play in the development of adequate cognitive, emotional and social skills, it is essential to gain a clearer understating of the magnitude and attributes of executive functions and its link to HRQOL in order to inform appropriate medical and educational interventions for this patient population., Objective: The aim of this study is to examine the relationship between executive functions, socio-emotional functioning and HRQOL in children and adolescents with mild to moderate CKD., Methods: A cross-sectional design was used for this secondary data analysis of 199 children and adolescents (ages 6-17) with mild to moderate CKD from the United States and Canada who receive care at hospitals associated with the Chronic Kidney Disease in Children Study (CKiD)., Results: The presence of impairment in executive functions and socio-emotional functioning (internalizing problems) significantly predicted lower HRQOL after controlling for key covariates (i.e., maternal education, anaemia and hypertension). Further, internalizing problems partially mediated the relationship between executive functions and HRQOL such that impairment in executive functions predicted lower HRQOL directly and indirectly by contributing to higher internalizing problems, which further contributed to low HRQOL., Conclusion: This study underscores the importance of executive functions and socio-emotional functioning in the manifestation of HRQOL. Given that HRQOL is potentially compromised for many children and adolescents with mild to moderate CKD, it will be important for both clinicians and researchers to examine a range of factors, including executive functions and socio-emotional functioning, in order to optimize HRQOL., (© 2021 John Wiley & Sons, Ltd.)

The Chronic Kidney Disease in Children (CKiD) prospective cohort study was designed to address the neurocognitive, growth, cardiovascular, and disease progression of children and adolescents with mild to moderate CKD. The study has had continuous funding from NIDDK for 17 years and has contributed significant advances in pediatric CKD. The goals of this educational review are threefold: (1) to provide an overview of the neurocognitive and psychosocial studies from CKiD to date; (2) to provide best practice recommendations for those working with the neurocognitive and psychosocial aspects of pediatric CKD based on CKiD findings; and (3) to help chart future goals and directives for both research and clinical practice. This collection of 22 empirical studies has produced a number of key findings for children and adolescents with mild to moderate CKD. While various studies suggest a relatively positive presentation for this population as a whole, without evidence of significant impairment or deterioration, findings do indicate the presence of neurocognitive dysfunction, emotional-behavioral difficulties, and lower quality of life for many children with CKD. These findings support the promotion of best practices that are accompanied by additional future clinical and research initiatives with this patient population., (© 2021. IPNA.)

Background: There is currently a dearth of research on the neural framework of writing tasks in children, as measured by neuroimaging techniques., Objective: This paper provides an overview of the current literature examining the neurological underpinnings of written expression in children., Design: Using a scoping review approach, with thorough searches of key databases, this paper presents the available literature comprising 13 different studies using both structural and functional neuroimaging techniques with the 0-18 English speaking population., Results: Studies largely presented small sample sizes, with most studies utilizing elementary or middle school-aged children. Emergent findings revealed a complex network of neural contributions to the writing process in children. There were associations between the left fusiform gyrus and orthographic coding (i.e., handwriting), and spelling and written composition measures were significantly correlated with activity in the left posterior cingulate, left precuneus, and right precuneus regions. Additionally, results revealed that good versus poor writers manifested differential brain activation patterns during many tasks associated with written expression, with good writers performing more efficiently than poor writers with respect to brain regions activated during a writing task across handwriting, spelling, and idea generation., Conclusions: The findings from this scoping review lay the foundation for future studies examining the interface between writing skills in children and underlying neural pathways that support the various components of the writing process. It will be important for future research to examine the neurological bases of the various components of written expression in children and adolescents.

The Genome Empowerment Scale (GEmS), developed as a research tool, assesses perspectives of parents of children with undiagnosed disorders about to undergo exome or genome sequencing related to the process of empowerment. We defined genomic healthcare empowerment as follows: perceived ability to understand and seek new information related to the genomic sequencing, manage emotions related to the diagnostic process and outcomes, and utilize genomic sequencing information to the betterment of the individual/child and family. The GEmS consists of four scales, two are primarily emotion-focused (Meaning of a Diagnosis, and Emotional Management of the Process) and two are action-oriented (Seeking Information and Support, and Implications and Planning). The purpose of this research was to provide a strategy for interpreting results from the GEmS and present illustrative cases. These illustrations should serve to facilitate use of the GEmS in the clinical and research arena, particularly with respect to guiding genetic counseling processes for parents of children with undiagnosed conditions., (© 2021 National Society of Genetic Counselors.)

Pediatric chronic kidney disease (CKD) appears to be a heterogeneous group of conditions, but this heterogeneity has not been explored with respect to its impact on neurocognitive functioning. This study investigated the neurocognitive functioning of those with glomerular (G) vs. non-glomerular (NG) diagnoses. Data from the North American CKiD Study were employed and the current study included 1,003 children and adolescents with mild to moderate CKD. The G Group included 260 participants (median age = 14.7 years) and the NG Group included 743 individuals (median age = 9.0 years). Neurocognitive measures assessed IQ, inhibitory control, attention regulation, problem solving, working memory, and overall executive functioning. Data from all visits were included in the linear mixed model analyses. After adjusting for sociodemographic and CKD-related covariates, results indicated no differences between the diagnostic groups on measures of IQ, problem solving, working memory, and attention regulation. There was a trend for the G group to receive better parent ratings on their overall executive functions ( p < 0.07), with a small effect size being present. Additionally, there was a significant G group X hypertension interaction ( p < 0.003) for inhibitory control, indicating that those with both a G diagnosis and hypertension performed more poorly than the NG group with hypertension. These findings suggest that the separation of G vs. NG CKD produced minimal, but specific group differences were observed. Ongoing examination of the heterogeneity of pediatric CKD on neurocognition, perhaps at a different time point in disease progression or using a different model, appears warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hooper, Johnson, Lande, Matheson, Shinnar, Kogon, Harshman, Spinale, Gerson, Warady and Furth.)

Background: Turner syndrome (TS) is a genetic disorder associated with complete or partial absence of an X chromosome affecting approximately 1/2000 live female births. Available evidence suggests that, in the school-age years, girls with TS often require speech and language services; however, little is known about the language development of infants and toddlers., Method: This study (N = 31) explored the language profiles of 12- and 24-month-old girls with TS, as well as the percentage of girls who might be "at risk" for language delays. We also followed a subset of 12-month-old girls with TS to 24 months of age to determine the stability of the 12-month findings., Results: Although all mean scores were within the average range at both time points, results revealed a higher prevalence of 24-month-old girls with TS "at risk" for receptive language difficulties. In addition, expressive language skills significantly exceeded receptive language skills at both time points. We found 12-month-old girls to be "at risk" for social and symbolic difficulties based on clinical assessment; only symbolic difficulties were significant based on caregiver report. At 24 months, clinical assessment indicated greater use of speech sounds and words than normative expectations. Caregivers reported greater use of speech sounds, and also, greater use of gestures. Although some changes occurred over a 1-year time span (12 to 24 months), all mean test scores remained within the average range and the changes in the percentage of girls manifesting "at risk" status on either the PLS-4 or CSBS-DP were non-significant., Conclusions: Although within normal limits, receptive language skills were found to be significantly lower than expressive language skills at both ages. Social and symbolic communication skills also were in the average range, with both showing significant improvement from 12 to 24 months based on clinical assessment. Caregiver report found that use of gestures and production of speech sounds not only improved from 12 to 24 months, but also exceeded normative expectations. Findings suggest the presence of relatively intact speech and language abilities during the first 2 years of life, with perhaps some emergent concerns for receptive language development. Ongoing developmental surveillance will be important., (© 2021. The Author(s).)

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cognitive measure as a covariate, these differences were virtually non-existent, indicating a strong correlation between cognition and brain activity at the network level. The data indicate robust and pervasive effects on functional neural network activity among FAP patients and these effects are likely involved in cognitive deficits associated with this disease., (© 2021 The Authors. Published by Elsevier Ltd on behalf of International Brain Research Organization.)

Objective: Utilize a random sample to estimate the prevalence, child traits, and maternal risk for fetal alcohol spectrum disorders (FASD) in a Southeastern United States county., Methods: From all first-grade students (n = 1073) a simple random sample was drawn, and 32 % (n = 231) were consented. All 231 children were examined for dysmorphology and growth, 84 were tested and rated on neurobehavior, and 72 mothers were interviewed for maternal risk., Results: Significant differences (α = .05) between the physical traits of children diagnosed with FASD and the entire sample were height, weight, head circumference, body mass index, and total dysmorphology scores, and all three cardinal features of fetal alcohol syndrome: palpebral fissure length, smooth philtrum, and narrow vermilion. Intellectual function and inhibition were not significantly different between FASD and typically-functioning children, but two executive function measures and one visual/spatial measure approached significance (α = .10). Three behavioral measures were significantly worse for the FASD group: parent-rated problems of communication, daily living, and socialization. Significant maternal risk factors reported were postpartum depression, frequency of drinking, and recovery from problem drinking. The prevalence of FASD was 71.4 per 1,000 or 7.1 %. This rate falls clearly within the prevalence range identified in eight larger samples of other communities in the Collaboration on FASD Prevalence (CoFASP) study in four regions of the United States., Conclusion: Careful and detailed clinical evaluation of children from small random samples can be useful for estimating the prevalence and traits of FASD in a community., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To examine the association between neonatal cranial ultrasound (CUS) abnormalities among infants born extremely preterm and neurodevelopmental outcomes at 10 years of age., Study Design: In a multicenter birth cohort of infants born at <28 weeks of gestation, 889 of 1198 survivors were evaluated for neurologic, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal CUS findings were classified as intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD., Results: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes., Conclusions: Among children born extremely preterm, CUS abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

An increasing amount of literature has indicated that chronic kidney disease (CKD) is associated with cognitive deficits that increase with worsening disease severity. Although abnormalities in brain structure have been widely documented, few studies to date have examined the functioning of brain areas associated with the specific cognitive domains affected by CKD (namely, attention and executive functions). Furthermore, few studies have examined functional connectivity among CKD youth who are relatively early in the course of the disease. The present study used functional magnetic resonance imaging to examine the resting state connectivity in 67 youth with CKD (mean age, 17 y) and 58 age-matched healthy controls. Using seed-based multiple regression, decreased connectivity was observed within the anterior cingulate portion of the default mode network. In addition, decreased connectivity within the dorsolateral prefrontal cortex, paracingulate gyrus, and frontal pole were correlated significantly with disease severity. These data indicate that connectivity deficits in circuits implementing attentional processes may represent an early marker for cognitive decline in CKD., (Copyright © 2021. Published by Elsevier Inc.)

This cross-sectional study provides preliminary findings from one of the first functional brain imaging studies in children with chronic kidney disease (CKD). The sample included 21 children with CKD (ages, 14.4 ± 3.0 y) and 11 healthy controls (ages, 14.5 ± 3.4 y). Using functional magnetic resonance imaging during a visual-spatial working memory task, findings showed that the CKD group and healthy controls invoked similar brain regions for encoding and retrieval phases of the task, but significant group differences were noted in the activation patterns for both components of the task. For the encoding phase, the CKD group showed lower activation in the posterior cingulate, anterior cingulate, precuneus, and middle occipital gyrus than the control group, but more activation in the superior temporal gyrus, middle frontal gyrus, middle temporal gyrus, and the insula. For the retrieval phase, the CKD group showed underactivation for brain systems involving the posterior cingulate, medial frontal gyrus, occipital lobe, and middle temporal gyrus, and greater activation than the healthy controls in the postcentral gyrus. Few group differences were noted with respect to disease severity. These preliminary findings support evidence showing a neurologic basis to the cognitive difficulties evident in pediatric CKD, and lay the foundation for future studies to explore the neural underpinnings for neurocognitive (dys)function in this population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (p adj  = 6.73 × 10 -6 ). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)