Differential Diagnosis of Autism Spectrum Disorder Versus Language Disorder in Children Ages 2 to 5 Years: Contributions of Parent-Reported Development and Behavior.

Early diagnosis of autism spectrum disorder (ASD) has focused on differentiating children with ASD from neurotypical children. However, many children presenting with concern for ASD are ultimately diagnosed with language disorder (LD). This study aimed to identify differences in parent-rated development and behavior among children ages 2 to 5 years presenting with concern for ASD who were diagnosed with either ASD or LD. Children with ASD were rated as more socially withdrawn and more delayed in social development and self-help skills than those with LD. Parent-rated developmental delays were positively correlated with scores on an autism screening measure and with social withdrawal and pervasive developmental problems among children with ASD. Among those with LD, parent-rated social and self-help development were positively correlated with social withdrawal and attention problems. Thus, parent ratings of social withdrawal and development of social and self-help skills may facilitate differential diagnosis of ASD and LD in children ages 2 to 5 years.

Brief Report: Neuropsychological Testing and Informant-Ratings of Children with Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, or Comorbid Diagnosis.

This study aimed to examine the neuropsychological correlates of child patients diagnosed with ADHD, autism spectrum disorder (ASD), or comorbid ASD + ADHD through a multidisciplinary ASD evaluation clinic. Patients completed standardized tests of intellectual, attention, social-affective/cognitive, and executive functioning; and a semi-structured assessment commonly used for autism diagnosis. The majority of patients were medicated for ADHD concerns during testing. Parents and teachers also completed inventories of day-to-day social and attentional functioning. Group effects were found across objective social measures but not across related respondent-ratings. In contrast, group differences were observed in parent-ratings of attention difficulties, but not on standardized tests of attention or executive functioning. Findings underscore importance of integrating objective and functional measures when assessing ASD and/or ADHD.

Development and validation of PediaTrac™: A web-based tool to track developing infants.

OBJECTIVE: PediaTrac™, a 363-item web-based tool to track infant development, administered in modules of ∼40-items per sampling period, newborn (NB), 2--, 4--, 6--, 9-- and 12--months was validated. Caregivers answered demographic, medical, and environmental questions, and questions covering the sensorimotor, feeding/eating, sleep, speech/language, cognition, social-emotional, and attachment domains. METHODS: Expert Panel Reviews and Cognitive Interviews (CI) were conducted to validate the item bank. Classical Test Theory (CTT) and Item Response Theory (IRT) methods were employed to examine the dimensionality and psychometric properties of PediaTrac with pooled longitudinal and cross-sectional cohorts (N = 132). RESULTS: Intraclass correlation coefficients (ICC) for the Expert Panel Review revealed moderate agreement at 6 -months and good reliability at other sampling periods. ICC estimates for CI revealed moderate reliability regarding clarity of the items at NB and 4 months, good reliability at 2--, 9-- and 12--months and excellent reliability at 6 -months. CTT revealed good coefficient alpha estimates (α ≥ 0.77 for five of the six ages) for the Social-Emotional/Communication, Attachment (α ≥ 0.89 for all ages), and Sensorimotor (α ≥ 0.75 at 6-months) domains, revealing the need for better targeting of sensorimotor items. IRT modeling revealed good reliability (r = 0.85-0.95) for three distinct domains (Feeding/Eating, Social-Emotional/Communication and Attachment) and four subdomains (Feeding Breast/Formula, Feeding Solid Food, Social-Emotional Information Processing, Communication/Cognition). Convergent and discriminant construct validity were demonstrated between our IRT-modeled domains and constructs derived from existing developmental, behavioral and caregiver measures. Our Attachment domain was significantly correlated with existing measures at the NB and 2-month periods, while the Social-Emotional/Communication domain was highly correlated with similar constructs at the 6-, 9- and 12-month periods. CONCLUSION: PediaTrac has potential for producing novel and effective estimates of infant development via the Sensorimotor, Feeding/Eating, Social-Emotional/Communication and Attachment domains.

Visual Attention and Math Performance in Survivors of Childhood Acute Lymphoblastic Leukemia.

OBJECTIVE: Attentional and academic difficulties, particularly in math, are common in survivors of childhood acute lymphoblastic leukemia (ALL). Of cognitive deficits experienced by survivors of childhood ALL, attention deficits may be particularly responsive to intervention. However, it is unknown whether deficits in particular aspects of attention are associated with deficits in math skills. The current study investigated relationships between math calculation skills, performance on an objective measure of sustained attention, and parent- and teacher-reported attention difficulties. METHOD: Twenty-four survivors of childhood ALL (Mage = 13.5 years, SD = 2.8 years) completed a computerized measure of sustained attention and response control and a written measure of math calculation skills in the context of a comprehensive clinical neuropsychological evaluation. Parent and teacher ratings of inattention and impulsivity were obtained. RESULTS: Visual response control and visual attention accounted for 26.4% of the variance observed among math performance scores after controlling for IQ (p < .05). Teacher-rated, but not parent-rated, inattention was significantly negatively correlated with math calculation scores. CONCLUSIONS: Consistency of responses to visual stimuli on a computerized measure of attention is a unique predictor of variance in math performance among survivors of childhood ALL. Objective testing of visual response control, rather than parent-rated attentional problems, may have clinical utility in identifying ALL survivors at risk for math difficulties.

Improved behavior after adenotonsillectomy in children with higher and lower IQ.

OBJECTIVES: To examine whether high intellectual ability, in comparison to average or lower performance, reflects the consequences of sleep-disordered breathing and limits behavioral benefit observed 6 months after adenotonsillectomy. METHODS: Children aged 3-12 years (n=147) recruited from otolaryngology practices at two hospitals and assessed with Conners' Parent Rating Scales and an age range-appropriate intellectual measure, the Stanford-Binet Intelligence Scale at baseline and 6 months after clinically-indicated adenotonsillectomy. Subjects were classified as having high (IQ≥110), average (90≤IQ<110), or low (IQ<90) cognitive ability. RESULTS: After adenotonsillectomy, improvements in Conners' internalizing, externalizing, hyperactivity, and cognitive domains were observed across IQ groups (main effects for time, all p<0.01 or better), with no evidence for differential improvements among the groups (no significant time by IQ group interactions). The magnitude of behavioral improvement among children with high IQ resembled that observed among the other two groups. Changes in the Conners' domains were not significantly correlated with baseline IQ, age, socioeconomic status, body mass index z-score, or respiratory disturbance index. CONCLUSION: Behavioral function can improve after adenotonsillectomy even among children with relatively high intellectual ability at baseline. Diagnosis and treatment with expectation of neurobehavioral benefit should be considered among high-performing children as readily as it is more traditionally among their lower-performing peers.

Prognosis for Spontaneous Resolution of OSA in Children.

BACKGROUND: Adenotonsillectomy (AT) is commonly performed for childhood OSA syndrome (OSAS), but little is known about prognosis without treatment. METHODS: The Childhood Adenotonsillectomy Trial (CHAT) randomized 50% of eligible children with OSAS to a control arm (watchful waiting), with 7-month follow-up symptom inventories, physical examinations, and polysomnography. Polysomnographic and symptomatic resolution were defined respectively by an apnea/hypopnea index (AHI) <2 and obstructive apnea index (OAI) <1 and by an OSAS symptom score (Pediatric Sleep Questionnaire [PSQ]) < 0.33 with ≥ 25% improvement from baseline. RESULTS: After 194 children aged 5 to 9 years underwent 7 months of watchful waiting, 82 (42%) no longer met polysomnographic criteria for OSAS. Baseline predictors of resolution included lower AHI, better oxygen saturation, smaller waist circumference or percentile, higher-positioned soft palate, smaller neck circumference, and non-black race (each P < .05). Among these, the independent predictors were lower AHI and waist circumference percentile < 90%. Among 167 children with baseline PSQ scores ≥ 0.33, only 25 (15%) experienced symptomatic resolution. Baseline predictors were low PSQ and PSQ snoring subscale scores; absence of habitual snoring, loud snoring, observed apneas, or a household smoker; higher quality of life; fewer attention-deficit/hyperactivity disorder symptoms; and female sex. Only lower PSQ and snoring scores were independent predictors. CONCLUSIONS: Many candidates for AT no longer have OSAS on polysomnography after 7 months of watchful waiting, whereas meaningful improvement in symptoms is not common. In practice, a baseline low AHI and normal waist circumference, or low PSQ and snoring score, may help identify an opportunity to avoid AT. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00560859; URL: www.clinicaltrials.gov.

Periodic leg movements during sleep in children scheduled for adenotonsillectomy: frequency, persistence, and impact.

OBJECTIVE: The aim of this study was to assess the frequency and potential clinical impact of periodic leg movements during sleep (PLMS), with or without arousals, as recorded incidentally from children before and after adenotonsillectomy (AT). METHODS: Children scheduled for AT for any clinical indications who participated in the Washtenaw County Adenotonsillectomy Cohort II were studied at enrollment and again 6 months thereafter. Assessments included laboratory-based polysomnography, a Multiple Sleep Latency Test (MSLT), parent-completed behavioral rating scales, neuropsychological testing, and psychiatric evaluation. RESULTS: Participants included 144 children (81 boys) aged 3-12 years. Children generally showed mild to moderate obstructive sleep apnea (median respiratory disturbance index 4.5 (Q1 = 2.0, Q3 = 9.5)) at baseline, and 15 subjects (10%) had at least five periodic leg movements per hour of sleep (PLMI ≥ 5). After surgery, 21 (15%) of n = 137 subjects who had follow-up studies showed PLMI ≥ 5 (p = 0.0067). Improvements were noted after surgery in the respiratory disturbance index; insomnia symptoms; sleepiness symptoms; mean sleep latencies; hyperactive behavior; memory, learning, attention, and executive functioning on NEPSY assessments; and frequency of attention-deficit/hyperactivity disorder (DSM-IV criteria). However, PLMI ≥ 5 failed to show associations with worse morbidity in these domains at baseline or follow-up. New appearance of PLMI ≥ 5 after surgery failed to predict worsening of these morbidities (all p > 0.05), with only one exception (NEPSY) where the magnitude of association was nonetheless negligible. Similar findings emerged for periodic leg movements with arousals (PLMAI ≥ 1). CONCLUSION: PLMS, with and without arousals, become more common after AT in children. However, results in this setting did not suggest substantial clinical impact.

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT00233194.

Esophageal pressures, polysomnography, and neurobehavioral outcomes of adenotonsillectomy in children.

BACKGROUND: Esophageal pressure monitoring during polysomnography in children offers a gold-standard, "preferred" assessment for work of breathing, but is not commonly used in part because prospective data on incremental clinical utility are scarce. We compared a standard pediatric apnea/hypopnea index to quantitative esophageal pressures as predictors of apnea-related neurobehavioral morbidity and treatment response. METHODS: Eighty-one children aged 7.8 ± 2.8 (SD) years, including 44 boys, had traditional laboratory-based pediatric polysomnography, esophageal pressure monitoring, multiple sleep latency tests, psychiatric evaluations, parental behavior rating scales, and cognitive testing, all just before clinically indicated adenotonsillectomy, and again 7.2 ± 0.8 months later. Esophageal pressures were used, along with nasal pressure monitoring and oronasal thermocouples, not only to identify respiratory events but also more quantitatively to determine the most negative esophageal pressure recorded and the percentage of sleep time spent with pressures lower than -10 cm H(2)O. RESULTS: Both sleep-disordered breathing and neurobehavioral measures improved after surgery. At baseline, one or both quantitative esophageal pressure measures predicted a disruptive behavior disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined attention-deficit/hyperactivity disorder, conduct disorder, or oppositional defiant disorder) and more sleepiness and their future improvement after adenotonsillectomy (each P < .05). The pediatric apnea/hypopnea index did not predict these morbidities or treatment outcomes (each P > .10). The addition of respiratory effort-related arousals to the apnea/hypopnea index did not improve its predictive value. Neither the preoperative apnea/hypopnea index nor esophageal pressures predicted baseline hyperactive behavior, cognitive performance, or their improvement after surgery. CONCLUSIONS: Quantitative esophageal pressure monitoring may add predictive value for some, if not all, neurobehavioral outcomes of sleep-disordered breathing.

Changes in neuropsychological and behavioral functioning in children with and without obstructive sleep apnea following Tonsillectomy.

The most common treatment for sleep disordered breathing (SDB) is adenotonsillectomy (AT). Following AT, SDB resolves in most cases, and gains in cognitive and behavior scores are consistently reported, although persistent neuropsychological deficits or further declines also have been noted. This study presents results of the comprehensive 1-year follow-up neuropsychological examinations for children in the Washtenaw County Adenotonsillectomy Cohort I (95% return rate). After adjusting for normal developmental and practice-effect related changes in control children, significant improvements 1 year following AT were noted in polysomnography and sleepiness, as well as parental reports of behavior, although cognitive outcomes were mixed. Children undergoing AT with and without polysomnography-confirmed obstructive sleep apnea improved across a range of academic achievement measures, a measure of delayed visual recall, short-term attention/working memory, and executive functioning, along with parental ratings of behavior. On the other hand, measures of verbal abstraction ability, arithmetic calculations, visual and verbal learning, verbal delayed recall, sustained attention, and another measure of visual delayed recall demonstrated declines in ability, while other measures did not improve over time. These findings call into question the expectation that AT resolves most or all behavioral and cognitive difficulties in children with clinical, office-based diagnoses of SDB.

Neuropsychological and behavioral functioning in children with and without obstructive sleep apnea referred for tonsillectomy.

Adenotonsillectomy (AT) is among the most common pediatric surgical procedures and is performed as often for obstructive sleep apnea (OSA) as for recurrent tonsillitis. This study compared behavioral, cognitive, and sleep measures in 27 healthy control children recruited from a university hospital-based pediatric general surgery clinic with 40 children who had OSA (AT/OSA+) and 27 children who did not have OSA (AT/OSA-) scheduled for AT. Parental ratings of behavior, sleep problems, and snoring, along with specific cognitive measures (i.e., short-term attention, visuospatial problem solving, memory, arithmetic) reflected greater difficulties for AT children compared with controls. Differences between the AT/OSA- and control groups were larger and more consistent across test measures than were those between the AT/OSA+ and control groups. The fact that worse outcomes were not clearly demonstrated for the AT/OSA+ group compared with the other groups was not expected based on existing literature. This counterintuitive finding may reflect a combination of factors, including age, daytime sleepiness, features of sleep-disordered breathing too subtle to show on standard polysomnography, and academic or environmental factors not collected in this study. These results underscore the importance of applying more sophisticated methodologies to better understand the salient pathophysiology of childhood sleep-disordered breathing.

DSM-IV diagnoses and obstructive sleep apnea in children before and 1 year after adenotonsillectomy.

OBJECTIVE: Obstructive sleep apnea, a common indication for adenotonsillectomy in children, has been linked to behavioral morbidity. We assessed psychiatric diagnoses in children before and after adenotonsillectomy and examined whether baseline sleep apnea predicted improvement after surgery. METHOD: Subjects of this prospective cohort study were children ages 5.0 to 12.9 years old who had been scheduled for adenotonsillectomy (n = 79) or care for unrelated surgical conditions (n = 27, among whom 13 had surgery after baseline assessment). Before intervention and 1 year later, subjects underwent structured diagnostic interviews and polysomnography. The main outcome measure was frequency of DSM-IV attention and disruptive behavior disorder diagnoses at baseline and follow-up. RESULTS: At baseline, attention and disruptive behavior disorders were diagnosed in 36.7% of adenotonsillectomy subjects and 11.1% of controls (p < .05); attention-deficit/hyperactivity disorder was found in 27.8% and 7.4%, respectively (p < .05). One year later, group differences were nonsignificant; attention and disruptive behavior disorders were diagnosed in only 23.1% (p < .01), and 50% of subjects with baseline attention-deficit/hyperactivity disorder no longer met diagnostic criteria. Obstructive sleep apnea on polysomnography at baseline did not predict concurrent psychiatric morbidity or later improvement. CONCLUSIONS: Attention and disruptive behavior disorders, diagnosed by DSM-IV criteria, were more common before clinically indicated adenotonsillectomy than 1 year later. Surgery may be associated with reduced morbidity, even among subjects lacking polysomnographic evidence of obstructive sleep apnea.

Pediatric sleep questionnaire: prediction of sleep apnea and outcomes.

OBJECTIVES: To further validate a questionnaire about symptoms of childhood obstructive sleep apnea (OSA) and to compare the questionnaire with polysomnography in their ability to predict outcomes of adenotonsillectomy. DESIGN: Retrospective analysis of data from a longitudinal study. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: The Washtenaw County Adenotonsillectomy Cohort, comprising 105 children aged 5.0 to 12.9 years at entry. Intervention Parents completed the 22-item Sleep-Related Breathing Disorder (SRBD) scale of the Pediatric Sleep Questionnaire, and children underwent polysomnography before and 1 year after clinically indicated adenotonsillectomy (n = 78, usually for suspected OSA) or unrelated surgical care (n = 27). MAIN OUTCOME MEASURES: Findings from commonly used hyperactivity ratings, attention tests, and sleepiness tests. RESULTS: At baseline, a high SRBD scale score (1 SD above the mean) predicted an approximately 3-fold increased risk of OSA on polysomnography (odds ratio, 2.80; 95% confidence interval, 1.68-4.68). One year later, OSA and symptoms had largely resolved, but a high SRBD score still predicted an approximately 2-fold increased risk of residual OSA on polysomnography (odds ratio, 1.89; 95% confidence interval, 1.13-3.18). Compared with several standard polysomnographic measures of OSA, the baseline SRBD scale better predicted initial hyperactivity ratings and 1-year improvement, similarly predicted sleepiness and its improvement, and similarly failed to predict attention deficit or its improvement. CONCLUSIONS: The SRBD scale predicts polysomnographic results to an extent useful for research but not reliable enough for most individual patients. However, the SRBD scale may predict OSA-related neurobehavioral morbidity and its response to adenotonsillectomy as well or better than does polysomnography.

Sleep-disordered breathing, behavior, and cognition in children before and after adenotonsillectomy.

OBJECTIVES: Most children with sleep-disordered breathing (SDB) have mild-to-moderate forms, for which neurobehavioral complications are believed to be the most important adverse outcomes. To improve understanding of this morbidity, its long-term response to adenotonsillectomy, and its relationship to polysomnographic measures, we studied a series of children before and after clinically indicated adenotonsillectomy or unrelated surgical care. METHODS: We recorded sleep and assessed behavioral, cognitive, and psychiatric morbidity in 105 children 5.0 to 12.9 years old: 78 were scheduled for clinically indicated adenotonsillectomy, usually for suspected SDB, and 27 for unrelated surgical care. One year later, we repeated all assessments in 100 of these children. RESULTS: Subjects who had an adenotonsillectomy, in comparison to controls, were more hyperactive on well-validated parent rating scales, inattentive on cognitive testing, sleepy on the Multiple Sleep Latency Test, and likely to have attention-deficit/hyperactivity disorder (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) as judged by a child psychiatrist. In contrast, 1 year later, the 2 groups showed no significant differences in the same measures. Subjects who had an adenotonsillectomy had improved substantially in all measures, and control subjects improved in none. However, polysomnographic assessment of baseline SDB and its subsequent amelioration did not clearly predict either baseline neurobehavioral morbidity or improvement in any area other than sleepiness. CONCLUSIONS: Children scheduled for adenotonsillectomy often have mild-to-moderate SDB and significant neurobehavioral morbidity, including hyperactivity, inattention, attention-deficit/hyperactivity disorder, and excessive daytime sleepiness, all of which tend to improve by 1 year after surgery. However, the lack of better correspondence between SDB measures and neurobehavioral outcomes suggests the need for better measures or improved understanding of underlying causal mechanisms.