Irene M. Loe

Update on Environmental Risk Factors for Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder affecting 5% to 10% of children. Although considered to be a highly familial disorder, ADHD heritability estimates of 60% to 80% highlight the considerable role that environmental factors may still play in disorder susceptibility. Proposed ADHD environmental risk factors include prenatal substance exposures, heavy metal and chemical exposures, nutritional factors, and lifestyle/psychosocial factors. This paper reviews the literature published in 2010 investigating the association between environmental risk factors and ADHD or related symptomatology. Sources of risk factor exposure and the proposed mechanism by which each exposure is linked to ADHD-related neurobehavioral changes are also reported. Methodologic limitations of the current literature are discussed, and guidelines for future study are proposed. An improved understanding of the role that environmental factors play in ADHD etiology is critical to future ADHD prevention efforts.

Behavior Problems of 9–16 Year Old Preterm Children: Biological, Sociodemographic, and Intellectual Contributions

BACKGROUND Preterm children are at risk for behavior problems. Studies examining contributions of intellectual and environmental factors to behavior outcomes in preterm children are mixed. AIMS (1) To identify the nature of maladaptive behaviors in preterm children age 9 to 16 years born across the spectrum of gestational age and birth weight (BW). (2) To examine contributions of BW as a biological factor, socioeconomic status as an environmental factor, and intelligence quotient (IQ) as indicative of intellectual ability to behavior outcomes. METHOD Using the Child Behavior Checklist, parent reports of behavior for 63 preterm children (gestational age 24 to <36 weeks) were compared to 29 full term children of similar age, gender and socioeconomic status. Multiple regression models evaluated effects of prematurity, socioeconomic status, and intellectual ability on behavioral symptom scores. RESULTS Preterm children had higher total and internalizing problem scores compared to full term children. They also had lower IQ. BW was a significant predictor of total and internalizing behavior problems. Among the syndrome scales, anxious/depressed and attention problems were elevated. Socioeconomic status did not contribute to behavior scores. IQ contributed to total, but not to internalizing or externalizing, scores. IQ contributed to attention problems, but not to anxious/depressed scores. CONCLUSION Preterm children had increased behavior problems, especially symptoms of inattention and anxiety. Lower BW predicted more behavior problems. IQ acted as a mediator between BW and attention scores, but not anxiety scores. These findings alert health care providers to assess anxiety in all preterm children regardless of intellectual ability and additional study on the influence of intellectual ability on behavioral outcomes in preterm children is needed.

White matter microstructure on diffusion tensor imaging is associated with conventional magnetic resonance imaging findings and cognitive function in adolescents born preterm

Aim  Diffusion tensor imaging (DTI) was used to evaluate white matter architecture after preterm birth. The goals were (1) to compare white matter microstructure in two cohorts of preterm‐ and term‐born children; and (2) within preterm groups, to determine if sex, gestational age, birthweight, white matter injury score from conventional magnetic resonance imaging (MRI), or IQ was associated with DTI measures.

Early Histories of School-Aged Children With Attention-Deficit/ Hyperactivity Disorder

In a prospective study of developmental outcomes in relation to early-life otitis media, behavioral, cognitive, and language measures were administered to a large, diverse sample of children at 2, 3, 4, 6, and 9-11 years of age (N = 741). At 9-11 years of age, 9% of the children were categorized as having attention-deficit/hyperactivity disorder (ADHD) based on parent report. Compared to the non-ADHD group, the ADHD group had higher (i.e., less favorable) scores on parent and teacher versions of the Child Behavior Checklist at all ages. Children in the ADHD group also had lower scores on cognitive and receptive language measures in preschool. The findings support the concept that ADHD is a cognitive as well as a behavioral disorder.

Executive function skills are associated with reading and parent-rated child function in children born prematurely.

BACKGROUND Preterm children are at risk for executive function (EF) problems, which have been linked to behavior and learning problems in full term children. In this study, we examine the relationship between EF and functional outcomes in preterm children. AIM To evaluate (1) EF skills of 9- to 16-year-old children born across the spectrum of gestational age (GA), (2) relationship of degree of prematurity to EF skills, and (3) contributions of EF skills to two functional outcomes - reading scores and parent-rated child function. METHOD Preterm children <36 weeks gestation (n=72) were compared to full term children (n=42) of similar age, gender and SES, on measures of EF, reading, and parent-ratings of child function. Multiple regression models evaluated contributions to EF skills and functional outcomes. RESULTS Compared to full term controls, preterm children had poorer EF performance on a complex planning and organization task and did not increase planning time as task difficulty increased. Their spatial memory capacity was not different. GA contributed to EF skills, but was mediated by IQ. EF contributed to the variance in reading skills but did not add to the variance in reading when IQ was considered. EF skills significantly contributed to the variance in parent-rated child function, but IQ did not. CONCLUSION EF skills contribute to measures of functional outcome in this high-risk population. The use of EF skills as an early marker for learning and functional problems and as a target for intervention in children born preterm warrants future study.

Executive function is associated with social competence in preschool-aged children born preterm or full term

BACKGROUND Executive function (EF), defined as higher-order cognitive processes used in planning and organizing actions and emotions, is often impaired in children born preterm. Few studies have assessed social competence, the processes and resources required to meet social demands and achieve social goals, in children born preterm. The relations between EF and social competence in preterm and full term preschoolers have not been well characterized. AIMS To characterize social competence and assess the relationship between EF and social competence in preschool-aged children born preterm or full term. STUDY DESIGN Cross-sectional study. SUBJECTS Study subjects had a history of preterm birth (≤34weeks of gestation) and birth weight <2500g (n=70). Controls were born full term (≥37weeks) (n=79). OUTCOME MEASURES Children completed a battery of EF tasks; a mean age-adjusted z-score for the battery was generated for each child. Parents rated child EF on one scale and child social competence on two standardized scales. RESULTS Compared to full term children, preterm children showed a lower mean EF battery z-score, poorer parent-rated EF, and poorer scores on the two social competence scales. In hierarchical multiple regression models, EF battery z-score and parent-rated EF made independent contributions to both measures of social competence. Preterm birth explained additional variance for one measure of social competence. CONCLUSIONS Standard assessment of EF skills and social competence in young preschool children, including children born preterm, may identify at-risk children for long-term social difficulties and may also provide targets for intervention.

Oculomotor Performance Identifies Underlying Cognitive Deficits in Attention-Deficit/Hyperactivity Disorder

OBJECTIVE To evaluate cognitive control in children with attention-deficit/hyperactivity disorder (ADHD) using oculomotor tests of executive function. METHOD Cross-sectional study of children aged 8 to 13 years with ADHD (n = 26) and controls (n = 33) used oculomotor tasks to assess sensorimotor function (visually guided saccades), resistance to peripheral distractors (fixation), response inhibition (antisaccades), and spatial working memory (memory-guided saccades). RESULTS All children had intact sensorimotor function and working memory. Children with ADHD showed susceptibility to peripheral distractors and deficits in response inhibition. Increased interstimulus (IS) fixation periods on the antisaccade task were associated with improved performance and decreased reaction times on correct trials for controls but not for children with ADHD. Attention-deficit/hyperactivity disorder-combined and inattentive subtypes showed different patterns of reaction time as a function of IS periods. CONCLUSIONS Response inhibition deficits in ADHD on oculomotor tasks are consistent with other studies. The failure of children with ADHD to use IS time to decrease response inhibition errors and reaction time suggests that IS time is not used to prepare a response. These findings highlight the importance of considering cognitive processing components affected by ADHD in addition to core behavioral symptoms, particularly in designing new treatment strategies.

Attention and internalizing behaviors in relation to white matter in children born preterm.

Objective: Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that provides quantitative characterization of white matter tracts in the brain. This study used DTI to examine the degree of association between parent-rated scores of attention, internalizing behaviors including anxiety symptoms, and externalizing behaviors and white matter fractional anisotropy (FA) in children born preterm. Methods: Participants were aged 9 to 16 years; 25 were born at <36 weeks of gestation (mean = 28.6 wk, birth weight = 1191 g) and 20 were full term. The authors analyzed the results using Tract-Based Spatial Statistics, a technique that generates a skeleton representing the core of white matter tracts throughout the brain. The authors examined the correlations between behavior scores and FA of (1) the whole skeleton and (2) the specific regions of interest. Results: In preterm children, scores on attention and internalizing behavior scales were each associated with whole skeleton FA and several regions of interest; unfavorable scores were consistently associated with lower FA. Externalizing behaviors were not associated with whole skeleton FA, but significant associations were found within a few regions of interest. The network of significant regions for attention and internalizing symptoms was widely distributed and overlapping. In full-term children, no associations of FA and behavior were significant. Conclusions: Attention and internalizing behaviors in preterm children were associated with FA in a widely distributed overlapping network of white matter tracts, suggesting common underlying neurobiology. DTI contributes to understanding individual differences in attention and behavior characteristics in children born preterm.

Sensory processing in preterm preschoolers and its association with executive function

BACKGROUND Symptoms of abnormal sensory processing have been related to preterm birth, but have not yet been studied specifically in preterm preschoolers. The degree of association between sensory processing and other domains is important for understanding the role of sensory processing symptoms in the development of preterm children. AIMS To test two related hypotheses: (1) preterm preschoolers have more sensory processing symptoms than full term preschoolers and (2) sensory processing is associated with both executive function and adaptive function in preterm preschoolers. STUDY DESIGN Cross-sectional study. SUBJECTS Preterm children (≤34weeks of gestation; n=54) and full term controls (≥37weeks of gestation; n=73) ages 3-5years. OUTCOME MEASURES Sensory processing was assessed with the Short Sensory Profile. Executive function was assessed with (1) parent ratings on the Behavior Rating Inventory of Executive Function - Preschool version and (2) a performance-based battery of tasks. Adaptive function was assessed with the Vineland Adaptive Behavior Scales-II. RESULTS Preterm preschoolers showed significantly more sensory symptoms than full term controls. A higher percentage of preterm than full term preschoolers had elevated numbers of sensory symptoms (37% vs. 12%). Sensory symptoms in preterm preschoolers were associated with scores on executive function measures, but were not significantly associated with adaptive function. CONCLUSIONS Preterm preschoolers exhibited more sensory symptoms than full term controls. Preterm preschoolers with elevated numbers of sensory symptoms also showed executive function impairment. Future research should further examine whether sensory processing and executive function should be considered independent or overlapping constructs.

Impact of bilirubin-induced neurologic dysfunction on neurodevelopmental outcomes

Bilirubin-induced neurologic dysfunction (BIND) is the constellation of neurologic sequelae following milder degrees of neonatal hyperbilirubinemia than are associated with kernicterus. Clinically, BIND may manifest after the neonatal period as developmental delay, cognitive impairment, disordered executive function, and behavioral and psychiatric disorders. However, there is controversy regarding the relative contribution of neonatal hyperbilirubinemia versus other risk factors to the development of later neurodevelopmental disorders in children with BIND. In this review, we focus on the empiric data from the past 25 years regarding neurodevelopmental outcomes and BIND, including specific effects on developmental delay, cognition, speech and language development, executive function, and the neurobehavioral disorders, such as attention deficit/hyperactivity disorder and autism.