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BACKGROUND AND PURPOSE: Microstructural white matter abnormalities on DTI using Tract-Based Spatial Statistics at term-equivalent age are associated with cognitive and motor outcomes at 2 years of age or younger. However, neurodevelopmental tests administered at such early time points are insufficiently predictive of mild-moderate motor and cognitive impairment at school age. Our objective was to evaluate the microstructural antecedents of cognitive and motor outcomes at 3 years' corrected age in a cohort of very preterm infants. MATERIALS AND METHODS: We prospectively recruited 101 very preterm infants (

Objective Computer-assisted interventions (CAIs) are popular for educating children with autism, but their effectiveness is not well established. This study evaluated the effectiveness of 1 CAI designed to improve children’s language, cognitive, and academic skills, TeachTown: Basics, in a large urban school district. Method Teachers (n = 59) in autism support classrooms and their consented students in kindergarten through second grade (n = 154) were randomized to TeachTown: Basics or waitlist control. Child outcome was measured at baseline and after 1 academic year using the Bracken Basic Concepts Scale–Receptive and Expressive versions and the Differential Ability Scales, Second Edition (DAS-II). Random effects regression models that included clustering of time within students and students within classrooms were used to test whether the change over time in each outcome differed between groups. Results There were no statistically significant differences in outcomes for children who received TeachTown: Basics or treatment as usual. Increased time spent using TeachTown: Basics was associated with worse receptive language outcomes for children in the experimental group after 1 academic year. However, there was no association between minutes spent using TeachTown and changes in expressive language or DAS-II score. Conclusion Despite growing enthusiasm for CAIs in autism treatment, the present findings indicate that CAI might not be effective at improving language and cognitive outcomes for children with autism spectrum disorder. The decision to implement CAIs in schools should be carefully balanced against the evidence for effectiveness of these programs. Schools might be better served by investing in treatment strategies with established evidence. Clinical trial registration information RCT of TeachTown in Autism Support Classrooms: Innovation and Exnovation; https://clinicaltrials.gov/ ; NCT02695693

Effects of prenatal alcohol exposure (PAE) are rarely measured in preschool children due to relative insensitivity of assessment methods at this age. To examine the potential of a nonverbal battery in early identification of cognitive problems in alcohol-exposed children, 291 prospectively identified Ukrainian children were evaluated using a test battery focusing on early executive functioning (EF) and visuospatial skills, areas of cognitive development particularly sensitive to PAE in older children. Tests included the Differential Ability Scales, 2(nd) Edition (DAS-2) and several NEPSY/NEPSY-II subtests, standardized in the United States. Others were adapted from commonly used non-standardized neuropsychological measures of EF (Preschool Spatial Span, Imitation Hand Game, A not B, Delayed Attention, Subject Ordered Pointing). Children in two sites in Ukraine, Rivne and Khmelnitsky, were tested at 3 ½−4 ½ years to identify effects of PAE. Although most children performed within the average range, Alcohol-Exposed preschoolers had lower scores on DAS-II Summary Scores as well as on specific subtests. To evaluate the effects of alcohol dose during the pre-pregnancy recognition period and during midgestation of pregnancy, generalized linear regression models were used controlling for demographic and individual variables. In addition to DAS-II variables, measures reflecting sustained attention, working memory and ability to shift cognitive set were impacted by alcohol dose. Early executive function appears to subsume these performance differences. In conclusion, findings indicate that the effects of PAE can be identified in the preschool period and reliably measured using tests assessing nonverbal and spatial skills supported by executive functioning.

Objective Social skills difficulties are commonly reported by parents and teachers of school age (SA) children with neurofibromatosis type 1 (NF1). Investigations of social skills of young children with NF1 are scarce. This study aimed to characterize the emergence of social skills challenges beginning in early childhood, examine social skills longitudinally into SA, and explore interrelations with attention-deficit hyperactivity disorder (ADHD) symptomatology and cognitive functioning among children with NF1 cross-sectionally and longitudinally. Method Three samples of children with NF1 and their parents participated: (1) early childhood (n = 50; ages 3-6; mean [M] = 3.96, SD = 1.05), (2) SA (n = 40; ages 9-13; [M] = 10.90, SD = 1.59), and (3) both early childhood and SA (n = 25). Parent-reported social skills (Social Skills Rating System and Social Skills Improvement System), ADHD symptomatology (Conners Parent Rating Scales - Revised and Conners - Third Edition), and parent-reported cognitive abilities (Differential Ability Scales - Second Edition) were evaluated. Results Parental ratings of social skills were relatively stable throughout childhood. Ratings of social skills at the end of early childhood significantly predicted school-age social skills. Parental ratings of ADHD symptomatology showed significant negative relations with social skills. Early childhood inattentive symptoms predicted school-age social skills ratings. Cognitive functioning was not significantly related to social skills. Conclusion Parent-reported social skills difficulties are evident during early childhood. This work adds to the literature by describing the frequency and stability of social skills challenges in early childhood and in the school-age period in NF1. Research about interventions to support social skills when difficulties are present is needed.

Objective Positional plagiocephaly/brachycephaly (PPB) is associated with lower cognitive scores in school-aged children. This study tested the hypothesis that infant motor skills mediate this association. Methods Children with a history of PPB (cases, n = 187) and without PPB (controls, n = 149) were followed from infancy through approximately 9 years of age. Infant motor skills were assessed using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3), and cognition was assessed using the Differential Ability Scales, 2nd edition (DAS-2). The Bayley-3 motor composite was examined as a mediator of the association between PPB and DAS-2 general cognitive ability (GCA) scores. In secondary analyses, mediation models were examined for the DAS-2 verbal ability, nonverbal ability, and working memory scores; models using the Bayley-3 fine versus gross motor scores also were examined. Results Cases scored lower than controls on the DAS-GCA (β = −4.6; 95% CI = −7.2 to −2.0), with an indirect (mediated) effect of β = −1.5 (95% CI = −2.6 to −0.4) and direct effect of β = −3.1 (95% CI = −5.7 to −0.5). Infant motor skills accounted for approximately 33% of the case–control difference in DAS-2 GCA scores. Results were similar for other DAS-2 outcomes. Evidence of mediation was greater for Bayley-3 gross motor versus fine motor scores. Conclusion Infant motor skills partially mediate the association between PPB and cognition in school-aged children. Monitoring motor development and providing intervention as needed may help offset associated developmental concerns for children with PPB. Impact To our knowledge, this study is the first longitudinal investigation of the development of children with and without PPB from infancy through the early school years and the first to examine motor skills as a mediator of cognitive outcomes in this population. The findings highlight the importance of early motor skills for other developmental outcomes. Lay Summary Infants’ motor skills are related to the development of PPB and its association with later cognition. If your child has PPB, physical therapists may have an important role in assessing and providing treatment to promote motor development.

IMPORTANCE: Universal developmental screening is widely recommended, yet studies of the accuracy of commonly used questionnaires reveal mixed results, and previous comparisons of these questionnaires are hampered by important methodological differences across studies. OBJECTIVE: To compare the accuracy of 3 developmental screening instruments as standardized tests of developmental status. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional diagnostic accuracy study recruited consecutive parents in waiting rooms at 10 pediatric primary care offices in eastern Massachusetts between October 1, 2013, and January 31, 2017. Parents were included if they were sufficiently literate in the English or Spanish language to complete a packet of screening questionnaires and if their child was of eligible age. Parents completed all questionnaires in counterbalanced order. Participants who screened positive on any questionnaire plus 10% of those who screened negative on all questionnaires (chosen at random) were invited to complete developmental testing. Analyses were weighted for sampling and nonresponse and were conducted from October 1, 2013, to January 31, 2017. EXPOSURES: The 3 screening instruments used were the Ages & Stages Questionnaire, Third Edition (ASQ-3); Parents’ Evaluation of Developmental Status (PEDS); and Survey of Well-being of Young Children (SWYC): Milestones. MAIN OUTCOMES AND MEASURES: Reference tests administered were Bayley Scales of Infant and Toddler Development, Third Edition, for children aged 0 to 42 months, and Differential Ability Scales, Second Edition, for older children. Age-standardized scores were used as indicators of mild (80-89), moderate (70-79), or severe (

Hunter syndrome, or mucopolysaccharidosis (MPS) II, is a rare lysosomal disorder characterized by progressive, multi-system disease. As most symptoms cannot be reversed once established, early detection and treatment prior to the onset of clinical symptoms are critical. However, it is difficult to identify affected individuals early in disease, and therefore the long-term outcomes of initiating treatment during this optimal time period are incompletely described. We report long-term clinical outcomes of treatment when initiated prior to obvious clinical signs by comparing the courses of two siblings with neuronopathic Hunter syndrome (c.1504T>G[p.W502G]), one who was diagnosed due to clinical disease (Sibling-O, age 3.7 years) and the other who was diagnosed before disease was evident (Sibling-Y, age 12 months), due to his older sibling’s findings. The brothers began enzyme replacement therapy within a month of diagnosis. Around the age of 5 years, Sibling-O had a cognitive measurement score in the impaired range of

There is a paucity of literature examining the relationship between executive and social functioning in children with autism spectrum disorder (ASD). Twenty-three school-aged children with ASD participated. Executive functioning was measured using the Developmental Neuropsychological Assessment, Second Edition and Differential Ability Scales, Second Edition, and the teacher-rated Behavior Rating of Inventory of Executive Function. Independent assessors observed children’s social functioning on the playground while children with ASD and their peers completed a survey to measure peer friendships and rejections. Overall, poorer executive functioning was associated with increased playground isolation and less engagement with peers. This suggests that metacognitive skills such as initiation, working memory, and planning and organization are associated with children’s social functioning.

BACKGROUND: Studies have revealed an association between positional plagiocephaly and/or brachycephaly (PPB) and development, although little is known about long-term outcomes. We examined cognition and academic achievement in children with and without PPB, testing the hypothesis that children who had PPB as infants would score lower than controls. METHODS: We enrolled 187 school-aged children with a history of PPB and 149 controls. Exposures were the presence or absence and severity of infancy PPB (mild, moderate to severe). Cognitive and academic outcomes were assessed by using the Differential Ability Scales, Second Edition and Wechsler Individual Achievement Test, Third Edition, respectively. RESULTS: Children with PPB scored lower than controls on most scales of the Differential Ability Scales, Second Edition (standardized effect sizes [ESs] = −0.38 to −0.20) and the Wechsler Individual Achievement Test, Third Edition (ESs = −0.22 to −0.17). Analyses by PPB severity revealed meaningful differences among children with moderate to severe PPB (ESs = −0.47 to −0.23 for 8 of 9 outcomes), but few differences in children with mild PPB (ESs = −0.28 to 0.14). CONCLUSIONS: School-aged children with moderate to severe PPB scored lower than controls on cognitive and academic measures; associations were negligible among children with mild PPB. The findings do not necessarily imply that these associations are causal; rather, PPB may serve as a marker of developmental risk. Our findings suggest a role for assessing PPB severity in clinical practice: providing developmental assessment and intervention for infants with more severe deformation and reassurance and anticipatory guidance for patients with mild deformation.

Aim To assess the predictive validity at 4 years of the Movement Assessment Battery for Children - Second Edition (MABC-2) for motor impairment at 8 years in children born preterm. We also aimed to determine if sex, cognition, medical, or social risks were associated with motor impairment at 8 years or with a change in MABC-2 score between 4 years and 8 years. Method Ninety-six children born at less than 30 weeks’ gestation were assessed with the MABC-2 at 4 years and 8 years of age. Motor impairment was defined as less than or equal to the 5th centile. The Differential Ability Scales - Second Edition (DAS-II) was used to measure General Conceptual Ability (GCA) at 4 years, with a score

Aim To evaluate the relationship between corticotropin-releasing hormone (CRH) expression in the placenta and the risk of school-related dysfunctions at the age of 10 years among children born extremely preterm (EP). Methods Corticotropin-releasing hormone expression was measured in the placenta of 761 EP children, who had the following assessments at the age of 10 years: Differential Ability Scales, Oral and Written Language Scales, the Wechsler Individual Achievement Test-III, NEPSY-II and the Child Symptom Inventory-4. We evaluated whether lowest and highest quartiles of CRH mRNA were associated with undesirable scores on these assessments. With 272 evaluations, we would expect 14 to be significant at p Results Only 16 associations were statistically significant. On the other hand, seven of these were social limitations among girls whose placenta CRH mRNA was in the top quartile. Adjusting for delivery indication or restricting the sample to one delivery indication group resulted in few differences. Conclusion Overall, placenta CRH mRNA concentrations in the top or bottom quartiles were not associated with increased risks of dysfunctions 10 years later. Girls whose placenta CRH expression was in the top quartile, however, were at increased risk of seven indicators/correlates of social limitations.

OBJECTIVES:To compare neurocognitive, language, executive function, academic achievement, neurologic and behavioral outcomes, and quality of life at age 10 years in children born extremely preterm who developed bronchopulmonary dysplasia (BPD) to children who did not develop BPD.METHODS:The Extremely Low Gestational Age Newborns study population included 863 children born extremely preterm whose BPD status before discharge was known had an IQ (Differential Ability Scales II [DAS II]) assessment at 10 years. We evaluated the association of BPD with any cognitive (DAS II), executive function (NEuroPSYchological Assessment II), academic achievement (Wechsler Individual Achievement Test-III and Oral and Written Language Scales [OWLS]) as well as social dysfunctions (Social Responsiveness Scale). We used logistic regression models, adjusting for potential confounding factors, to assess the strength of association between the severity of BPD and each outcomes.RESULTS:Three hundred and seventy-two (43%) children were oxygen-dependent at 36 weeks postconception age, whereas an additional 78 (9%) were also oxygen- and ventilator-dependent. IQ scores 2 or more SDs below the expected mean (ie, z scores ≤−2) occurred twice as commonly among children who had BPD as among those who did not. Children with severe BPD consistently had the lowest scores on DAS II, OWLS, Wechsler Individual Achievement Test-III, NEuroPSYchological Assessment II, and Social Responsiveness Scale assessments.CONCLUSIONS:Among 10-year-old children born extremely preterm, those who had BPD were at increased risk of cognitive, language, and executive dysfunctions; academic achievement limitations; social skill deficits; and low scores on assessments of health-related quality of life.

Estimates of intelligence in young children with neurodevelopmental disorders are critical for making diagnoses, in characterizing symptoms of disorders, and in predicting future outcomes. The limitations of standardized testing for children with developmental delay or cognitive impairment are well known: Tests do not exist that provide developmentally appropriate material along with norms that extend to the lower reaches of ability. Two commonly used and interchanged instruments are the Mullen Scales of Early Learning (MSEL), a test of developmental level, and the Differential Ability Scales, second edition (DAS-II), a more traditional cognitive test. We evaluated the correspondence of contemporaneous MSEL and the DAS-II scores in a mixed sample of children aged 2-10 years with autism spectrum disorder (ASD), non-ASD developmental delays, and typically developing children across the full spectrum of cognitive ability. Consistent with published data on the original DAS and the MSEL, scores on the DAS-II and MSEL were highly correlated. However, curve estimation revealed large mean differences that varied as a function of the child's cognitive ability level. We conclude that interchanging MSEL and DAS-II scores without regard to the discrepancy in scores may produce misleading results in both cross-sectional and longitudinal studies of children with and without ASD, and, thus, this practice should be implemented with caution.

Lower cognitive performance is associated with poorer health and functioning throughout the lifespan and disproportionately affects children from lower socioeconomic status (SES) populations. Previous studies reporting positive associations between child home enrichment and cognitive performance generally had a limited distribution of SES. We evaluated the associations of SES and child enrichment with cognitive performance in a population with a wide range of SES, particularly whether enrichment attenuates associations with SES. Children were sampled from a case–control study of small-for-gestational-age (SGA) conducted in a public hospital serving a low SES population (final n = 198) and a private hospital serving a middle-to-high SES population (final n = 253). SES (maternal education and income) and perinatal factors (SGA, maternal smoking and drinking) were obtained from maternal birth interview. Five child home enrichment factors (e.g. books in home) and preschool attendance were obtained from follow-up interview at age 4.5 years. Cognitive performance was assessed with the Differential Ability Scales (DAS), a standardized psychometric test administered at follow-up. SES and enrichment scores were created by combining individual factors. Analyses were adjusted for perinatal factors. Children from the public birth hospital had a significantly lower mean DAS general cognitive ability (GCA) score than children born at the private birth hospital (adjusted mean difference −21.4, 95% CI: −24.0, −18.7); this was substantially attenuated by adjustment for individual SES, child enrichment factors, and preschool attendance (adjusted mean difference −5.1, 95% CI: −9.5, −0.7). Individual-level SES score was associated with DAS score, beyond the general SES effect associated with hospital of birth. Adjustment for preschool attendance and home enrichment score attenuated the association between individual SES score and adjusted mean DAS-GCA among children born at both of the hospitals. The effect of being in the lower compared to the middle tertile of SES score was reduced by approximately a quarter; the effect of being in the upper compared to the middle tertile of SES score was reduced by nearly half, but this comparison was possible only for children born at the private hospital. A child's individual SES was associated with cognitive performance within advantaged and disadvantaged populations. Child enrichment was associated with better cognitive performance and attenuated the SES influence. Health care providers should reinforce guidelines for home enrichment and refer children with delays to early intervention and education, particularly children from disadvantaged populations.

This randomized field trial comparing Strategies for Teaching based on Autism Research and Structured Teaching enrolled educators in 33 kindergarten-through-second-grade autism support classrooms and 119 students, aged 5–8 years in the School District of Philadelphia. Students were assessed at the beginning and end of the academic year using the Differential Ability Scales. Program fidelity was measured through video coding and use of a checklist. Outcomes were assessed using linear regression with random effects for classroom and student. Average fidelity was 57% in Strategies for Teaching based on Autism Research classrooms and 48% in Structured Teaching classrooms. There was a 9.2-point (standard deviation = 9.6) increase in Differential Ability Scales score over the 8-month study period, but no main effect of program. There was a significant interaction between fidelity and group. In classrooms with either low or high program fidelity, students in Strategies for Teaching based on Autism Research experienced a greater gain in Differential Ability Scales score than students in Structured Teaching (11.2 vs 5.5 points and 11.3 vs 8.9 points, respectively). In classrooms with moderate fidelity, students in Structured Teaching experienced a greater gain than students in Strategies for Teaching based on Autism Research (10.1 vs 4.4 points). The results suggest significant variability in implementation of evidence-based practices, even with supports, and also suggest the need to address challenging issues related to implementation measurement in community settings.

Objectives The aims for this study were to determine the prevalence of sleep-bruxism among young children, explore child behavior problems that may be associated with sleep-bruxism, and identify relations among sleep-bruxism, health problems, and neurocognitive performance. Methods The current study was a retrospective analysis of parent report surveys, and behavioral and neurocognitive assessments. Parents of 1953 preschool and 2888 first grade children indicated their child's frequency of bruxism during sleep. A subsample of preschool children ( n =249) had additional behavioral, as well as neurocognitive assessments. Among the subsample, parents also reported on their child's health, and completed the Child Behavioral Checklist; children were administered the Differential Ability Scales, and Pre-Reading Abilities subtests of the Developmental Neuropsychological Assessment. Results 36.8% of preschoolers and 49.6% of first graders were reported to brux ⩾1time per week. Among the preschool subsample, bruxing was independently associated with increased internalizing behaviors ( β =.17). Bruxism was also associated with increased health problems ( β =.19), and increased health problems were associated with decreased neurocognitive performance ( β =.22). Conclusions The prevalence of sleep-bruxism was high. A dynamic and potentially clinically relevant relation exists among sleep-bruxism, internalizing behaviors, health, and neurocognition. Pediatric sleep-bruxism may serve as a sentinel marker for possible adverse health conditions, and signal a need for early intervention. These results support the need for an interdisciplinary approach to pediatric sleep medicine, dentistry, and psychology.

Considerable animal research and available human studies suggest that psychological distress experienced by mothers during gestation is associated with later neurodevelopmental deficits in offspring; however, little research has examined potential protective factors that might mitigate this risk. The current study examined the impact of maternal prenatal psychological distress during pregnancy on cognitive outcomes in preschoolers (ages 2.5-5 years) and positive parenting as a potential protective factor. Mother-child dyads (N = 162, mean child age = 44 months, 49 % female) were recruited from a longitudinal cohort of women who had previously participated in a study of maternal mood disorders during pregnancy. Maternal prenatal distress was assessed with multiple measures collected throughout pregnancy. During a follow-up visit, mothers were interviewed about their psychological symptoms since the birth of the child, parenting behaviors were recorded during a parent-child interaction, and children's cognitive abilities were measured using the Differential Ability Scales, 2nd Edition. Maternal prenatal distress significantly predicted lower general cognitive abilities; however, this relationship was strongest for children whose mothers exhibited low levels of positive engagement and not significant when mothers exhibited high levels of positive engagement. Results suggest that positive parental engagement can protect against the detrimental effects of maternal prenatal distress on preschoolers' cognitive abilities.

Sleep-disordered breathing (SDB) in children is associated with cognitive challenges. However, potential associations between SDB severity and neurocognitive function, as well as the presence of an SDB cutoff, have not been fully explored.To determine whether SDB-associated adverse changes in neurocognitive functioning are severity dependent.A total of 1,010 snoring and nonsnoring children ages 5-7 years were prospectively recruited from public schools and underwent polysomnography and neurocognitive assessments of intellectual, attention, memory, language, and executive function development. The children were subdivided into four severity groups on the basis of apnea-hypopnea index (AHI), followed by comparisons of cognitive function, with a particular focus on standardized subtests of intellectual, language, attention, memory, and executive function.Differential Ability Scales Verbal (P 0.001) and Nonverbal (P = 0.002) performance, as well as global conceptual ability (IQ) (P 0.001) scores, differed significantly across the groups, with individuals with higher AHI showing worse performance. Additionally, specific NEPSY (a Developmental Neuropsychological Assessment) subscores focused on attention and executive skills differed across the groups, indicating differences in levels of engagement and problem solving. Children with higher AHI (5 per hour of total sleep time) were significantly more impaired than all three lower AHI groups, indicating a dose-response impact of SDB.This large community-based sample of children highlights the significant deleterious impact of SDB, particularly in children with moderate to severe obstructive sleep apnea, and also that even snoring alone affects neurocognitive function. By affecting developing capabilities, as illustrated by cognitive measures in a severity-graded manner, SDB could adversely impact children's capacity to attain academic and adaptive goals, ultimately hampering their ability to reach independence. Our findings support the need for increased awareness of SDB, with particular emphasis on children with more severe obstructive sleep apnea.

Some researchers have argued that discrepant broad index scores invalidate IQs, but others have questioned the fundamental logic of that argument. To resolve this debate, the present study used a nationally representative sample of children (N 1,200) who were matched individually for IQ. Children with significantly uneven broad index score profiles and those with even broad index score profiles had equivalent reading and math skills. Discrepant broad index scores found in only 15%, 10%, 5%, and 1% of the population, respectively, also failed to differentially predict academic achievement. In addition, significantly higher Verbal broad index scores were not differentially predictive of reading achievement, nor were significantly higher Nonverbal/Spatial broad index scores differentially predictive of math achievement. It was concluded that the global ability score is the most parsimonious predictor of academic achievement, despite the presence of significant and rare variability among broad index scores.

IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapymay be harmful.We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES Differential Ability Scales IQwas the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS In total, 42.9%of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P

Previous research has found associations but not established mechanisms of developmental linkage between language ability and inattentive–hyperactive (I-H) behavior problems. The present study examined whether self-regulation mediates the effect of language ability on later I-H behavior problems among young children (N = 120) assessed at 30, 36, and 42 months of age. Cross-lagged panel models tested the direction of effect between language ability and self-regulation and longitudinal effects of language ability on later I-H problems mediated by self-regulation. Language ability was measured by children's scores on the receptive and expressive language subtests of the Differential Ability Scales. Self-regulation was measured by three behavioral tasks requiring inhibitory control. I-H problems were reported by parents and secondary caregivers. Language ability predicted later self-regulation as measured by all three tasks. There was no association, however, between self-regulation and later language ability, suggesting that the direction of effect was stronger from language ability to later self-regulation. Moreover, the effect of language ability on later I-H behavior problems was mediated by children's self-regulation in one of the tasks (for secondary caregivers' but not parents' ratings). Findings suggest that language deficits may explain later I-H behavior problems via their prediction of poorer self-regulatory skills.

OBJECTIVE To test the hypothesis that prenatal exposure to serotonin reuptake inhibitors (SRIs) is associated with language and behavioral outcomes in preschool-aged children, while accounting for confounds such as concomitant exposures and maternal mental illness. METHOD An observational, prospective, longitudinal study of mental illness in pregnancy was conducted at a university-based women's mental health clinic (April 2010-November 2012). A sample of 178 mother-child dyads participated in a laboratory visit at preschool age (2.5-5.5 years). The majority of women (87%) received psychotropic medication during pregnancy. Psychiatric status (based on DSM-IV), other medication use, and substance use were serially assessed and tested as confounds. Primary outcome measures included standardized measures of expressive language and cognitive function and mother and alternate caregiver ratings of child behavior problems, including the Pervasive Developmental Disorders (PDD) subscale of the Child Behavior Checklist. RESULTS Linear regression analyses revealed that, after controlling for relevant covariates, expressive language scores from the Test of Early Language Development, 3rd edition, were negatively associated with prenatal SRI exposure (β = -0.15, t = -2.41), while the PDD behavioral problems subscales completed by alternate caregivers and mothers were positively associated with prenatal SRI exposure (β = 0.17, t = 2.01; β = 0.16, t = 2.00, respectively). Cognitive function, measured using the Differential Ability Scales, 2nd edition, was not associated with any medication exposures. CONCLUSIONS The current data suggest a small but significant association between prenatal SRI exposure and preschool outcomes, including expressive language and behavior problems. These data corroborate data from recent, population-based studies, although overall, published findings are mixed. Replication and identification of moderating risk factors are needed to understand potential clinical implications.

Despite widespread use of the Mullen Scales of Early Learning (MSEL; E. M. Mullen, 1995) as a cognitive test for children with autism spectrum disorders and other developmental disabilities, the instrument has not been independently validated for use in these populations. Convergent validity of the MSEL and the Differential Ability Scales (DAS; C. D. Elliott, 1990, 2007) was examined in 53 children with autism spectrum disorder and 19 children with nonspectrum diagnoses. Results showed good convergent validity with respect to nonverbal IQ (NVIQ), verbal IQ (VIQ), and NVIQ–VIQ profiles. These findings provide preliminary support for the practice of using MSEL age-equivalents to generate NVIQ and VIQ scores. Establishing convergent validity of cognitive tests is needed before IQs derived from different tests can be conceptualized as a uniform construct.

We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and understand the underlying mechanisms.

BACKGROUND: This study assessed the co-occurrence of cognitive problems and difficult temperament characteristics in children aged 3 to 5 years exhibiting aggressive behavior. METHODS: Thirty-one children with high ratings on the Aggressive Behavior subscale of the Achenbach Child Behavior Checklist or Teacher Report Form were recruited from a school district-based clinic. Cognitive ability and temperament were assessed with the Differential Ability Scales and the Carey Temperament Scales Behavioral Styles Questionnaire, respectively. Cluster analysis was applied to these variables. RESULTS: Three prominent groups of children sharing cognitive and temperament characteristics emerged. The first, comprising 41.9% of the sample, demonstrated low adaptability, low persistence, high activity, negative mood, and low rhythmicity, along with borderline-deficient cognitive scores. The second (38.7%) demonstrated low adaptability, low persistence, high activity, and negative mood, along with average cognitive scores. The third (19.4%) demonstrated essentially midrange temperament characteristics and average cognitive scores. All 3 groups shared temperamental tendencies toward a higher threshold of response. Most children in the sample also had significant sleep disturbances (54.5%), other health problems (63.6%), and/or suspected developmental problems (54.5%). CONCLUSIONS: The widespread presence of sleep, health, cognitive, temperament, and developmental problems in this sample supports the involvement of medical and developmental health experts in teams evaluating young children who present with high levels of aggressive behavior. The diverse nature of cognitive-temperament profiles in this sample also suggests a need to assess cognitive ability and temperament in young, aggressive children to provide individualized interventions. Language: en

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.

Background— Changes in neurocognitive function after cardiopulmonary bypass (CPB) are difficult to assess in children with congenital cardiovascular malformations in part because identification of a suitable control group of children is difficult. Methods and Results— We evaluated neurocognitive function in subjects aged 3 to 17 years both before and after surgical repair of an atrial septal defect (ASD). Eighteen subjects underwent testing within a median of 3 days (range, 1 to 27) before surgery and 5.8 months (range, 5.5 to 9) after surgery. The Differential Ability Scales was administered to subjects in a single testing session. All subjects were considered to be healthy, and they had no activity limitations. The mean General Conceptual Ability (GCA) scores (analogous to IQ) for the group were in the normal range before and after ASD repair. No significant difference was detected between the GCA scores before and after surgery. The GCA score was 90.8±18.6 before surgery and 93.1±16.3 after surgery. Conclusions— Use of CPB was not associated with changes in cognitive function in our subjects who underwent repair of an ASD.

The relevance of IQ to the etiology and symptomatic expression of autism remains unclear. Although approximately three-quarters of individuals with autism have below-average IQ (< 70), autism can occur with equal severity in individuals of average and above-average IQ. While the finding that IQ can vary widely between identical twins with autism (Le Couteur et al., 1996) would also suggest that it is not a useful marker of genetic subgroup differences in autism, there is nonetheless evidence from large-scale behavioral genetic studies (Bolton et al., 1994; Fein et al., 1999; Szatmari et al., 2000) that IQ broadly defined (e.g., high versus low Verbal or Full Scale IQ) may index etiological heterogeneity and provide a basis for subtyping in autism. In addition to ongoing attempts to elucidate the complex relationship of general intelligence, and particularly of mental retardation, to autism (Bailey, Phillips, & Rutter, 1996), there has also been longstanding interest in the uneven intellectual abilities of individuals with autism. One question has been whether routinely administered IQ tests reveal any consistent pattern of cognitive strengths and weaknesses in autism. A Wechsler (1991, 1997) IQ profile with Verbal IQ (VIQ) depressed relative to Performance IQ (PIQ) and peak subtest score on Block Design (Happe, 1994; Lincoln, Allen, & Kilman, 1995) has traditionally been associated with autism and has even been suggested as a possible diagnostic aid (Lincoln, Courshesne, Kilman, Elmasian, & Allen, 1988). Although a recent meta-analytic review of 23 published studies (Lincoln, Courchesne, Allen, Hanson, & Ene, 1998) confirmed that VIQ is generally lower than PIQ in autism, a VIQ < PIQ profile has not been found consistently across studies (see review by Siegel, Minshew, & Goldstein, 1996). Some authors (Rumsey, 1992; Siegel et al., 1996) have attempted to explain these inconsistent findings by proposing that the difference between Verbal and Performance IQ in autism depends on the severity of impairment and diminishes as intellectual ability approaches the normal range. Yet, a VIQ < PIQ profile has been reported in several studies of high-functioning individuals with autism (see reviews by Lincoln et al., 1998; Siegel et al., 1996). It has also been suggested that the difference between Verbal and Performance IQ lessens with age and associated improvements in language functioning, at least among higher-functioning individuals with autism (Lincoln et al., 1998). This hypothesis has been difficult to evaluate because most studies have included individuals spanning a wide range of ages, and very few studies have provided the opportunity to compare developmental differences between younger and older children. VIQ–PIQ discrepancies have also played a prominent role in efforts to define Asperger syndrome as distinct from autism. Klin, Volkmar, Sparrow, Cicchetti, and Rourke (1995) demonstrated a VIQ > PIQ discrepancy among a sample of individuals diagnosed with Asperger syndrome, opposite to the pattern typically found in autism. However, subsequent studies (Manjiova & Prior, 2000; Ozonoff, South, & Miller, 2000) have failed to differentiate Asperger syndrome from autism on the basis of Wechsler IQ profiles. These inconsistent findings may reflect differences in the way Asperger syndrome was diagnosed. The Klin et al. study used the most stringent criteria, requiring a circumscribed interest and motor clumsiness for inclusion in their Asperger group. It is possible that these specific criteria selected for individuals with a VIQ > PIQ profile, as the development of circumscribed interests is likely to be mediated by verbal skills, and motor problems might be expected to be associated with deficits in PIQ. The problem of circularity in attempts to provide external validation for the distinction between autism and Asperger syndrome has been well recognized (e.g., Klin & Volkmar, 1997; Volkmar & Klin, 2001). Questions of their broader nosological value aside, analyses of cognitive profiles within autism have suffered from two major limitations. First, emphasis on identifying a prototypical cognitive profile has been at the expense of considering the possibility of more than one cognitive profile in autism. At a conceptual level, recent advances in genetics and the understanding of autism as a complex disorder allow for the possibility of genetically meaningful variation in the cognitive phenotype of autism, which could potentially account for variation in the behavioral expression of autism. Yet, little attention has been paid to individual differences in cognitive profiles in autism. Particularly in the case of VIQ–PIQ differences, the report of group means for autistic samples could have the effect of ‘averaging out’ significant individual discrepancies that actually occur in both directions. The second limitation concerns the usefulness of Wechsler subscale discrepancies for characterizing cognitive profiles in autism. Individuals with autism have frequently been reported to exhibit a characteristic pattern of unevenness in the subtest scores from which Wechsler Verbal and Performance IQs are derived (Happe, 1994; Siegel et al., 1996). For example, Block Design, a measure of visuospatial constructional ability, reliably yields the highest Wechsler subtest score in autism. In contrast, Picture Arrangement, another Performance subtest, but one which requires social-inductive reasoning, yields one of the lowest subtest scores on the Wechsler scales. Factor analysis has shown that Picture Arrangement and Block Design are weakly correlated and measure distinct abilities in individuals with autism (Lincoln et al., 1988). Characteristic patterns of scatter are also found on the Wechsler Verbal scale. For example, Digit Span is regularly reported to be a relative strength on the Wechsler scales. Findings such as these raise questions about the interpretability of VIQ and PIQ scores in autism, and of any discrepancy that is (or is not) found between these scores. In the present study, we addressed two main issues. The first was whether children with autism exhibit characteristic patterns of unevenness in their cognitive abilities and, if so, whether such patterns or profiles differ as a function of age or overall ability. To answer these questions, we assessed the cognitive abilities of a large sample of children with autism using the Differential Ability Scales (DAS; Elliott, 1991), a revised version of the British Ability Scales (Elliott, Murray, & Pearson, 1979). The DAS is comprised of a Preschool and a School-Age battery. Each battery consists of only six core subtests, selected for their high loadings on psychometric g, but with sufficient specific variance to support separate cluster scores. The DAS factor structure and corresponding cluster scores are in accord with current models of human intelligence (Carroll, 1993; Mackintosh, 1998). They include Verbal and Nonverbal ability, the latter of which is further differentiated into Nonverbal Reasoning and Spatial ability in the School-Age battery. The DAS thus distinguishes between nonverbal subtests that primarily measure visual-spatial organization from nonverbal subtests that primarily measure inductive reasoning abilities.1 This is in contrast to the Wechsler system, which subsumes similarly divergent nonverbal subtests under its Performance subscale (Elliot, 1990). The second issue was whether different cognitive profiles in autism are associated with differences in core symptomatology. To address this issue, we assessed children’s social and communicative functioning using the Autism Diagnostic Observation Schedule (ADOS; Lord, Rutter, DiLavore, & Risi, 1999). The ADOS is a semi-structured, interactive observation scale that provides quantitative ratings of communicative and social behaviors corresponding to DSM-IV (APA, 1994) and ICD-10 (WHO, 1993) criteria for autism. The summary ratings from the ADOS allowed us to relate children’s neurocognitive profiles to quantitative measures of symptom severity in both the communication and social domains. This approach provided a way of potentially accounting for empirically defined phenotypic variance in autism while avoiding the methodological pitfalls involved in using a priori definitions, such as in recent attempts to differentiate Asperger syndrome from autism.

This paper introduces the School-Years Screening Test for Evaluation of Mental Status (SYSTEMS). It was designed to be used by neurologists, pediatricians, and other health professionals assessing children with suspected cognitive problems or changes. SYSTEMS was initially based on the adult Mini-Mental State Examination developed by Folstein, Folstein, and McHugh in 1975. SYSTEMS is a 7- to 12-minute, one-on-one interview test containing 46 items for use in children between 5 and 12 years of age. Although a full diagnosis cannot be made, the results do provide an indication of whether to send a child for further detailed cognitive assessment. The development of SYSTEMS comprised seven studies with a total of 1207 children involved from Sydney primary schools and neurology clinics of the New Children's Hospital, Westmead, New South Wales, Australia. All children were administered the SYSTEMS. Some of the children also were administered the Stanford-Binet Intelligence Test, 4th edition, or the Differential Ability Scales. Results showed that the SYSTEMS was internally consistent, unbiased by sex, socioeconomic indicators, or language groups; discriminated well by age; and strongly correlated (r = 0.88) with mental age. No significant differences in results obtained by two trained administrators were evident and no indication of apparent practice effect was found. The SYSTEMS was found to have desirable levels of sensitivity (83% and 92%), specificity (76% and 95%), and likelihood ratio for cognitive impairment (3.63 and 17.5) when compared with neurologic judgments and the Differential Ability Scales, respectively. (J Child Neurol 1999; 14:772-780).