ObjectiveThe huntingtin gene is critical for the formation and differentiation of the CNS, which raises questions about the neurodevelopmental effect of CAG expansion mutations within this gene (mHTT) that cause Huntington disease (HD). We sought to test the hypothesis that child and adolescent carriers of mHTT exhibit different brain growth compared to peers without the mutation by conducting structural MRI in youth who are at risk for HD. We also explored whether the length of CAG expansion affects brain development.MethodsChildren and adolescents (age 6–18) with a parent or grandparent diagnosed with HD underwent MRI and blinded genetic testing to confirm the presence or absence of mHTT. Seventy-five individuals were gene-expanded (GE) and 97 individuals were gene-nonexpanded (GNE). The GE group was estimated to be on average 35 years from clinical onset. Following an accelerated longitudinal design, age-related changes in brain regions were estimated.ResultsAge-related striatal volume changes differed significantly between the GE and GNE groups, with initial hypertrophy and more rapid volume decline in GE. This pattern was exaggerated with CAG expansion length for CAG > 50. A similar age-dependent group difference was observed for the globus pallidus, but not in other major regions.ConclusionOur results suggest that pathogenesis of HD begins with abnormal brain development. An understanding of potential neurodevelopmental features associated with mHTT may be needed for optimized implementation of preventative gene silencing therapies, such that normal aspects of neurodevelopment are preserved as neurodegeneration is forestalled.

This article reviews behavioral, neuropsychological, and academic outcomes of individuals with cleft across three age levels: 1) infancy/early development, 2) school age, and 3) adolescence/young adulthood. The review points out that attachment, neurocognitive functioning, academic performance/learning, and adjustment outcomes are the result of a complex interaction between biological and environmental factors and vary with developmental level, sex, and craniofacial anomaly diagnosis. The degree to which associated genetic or neurodevelopmental conditions may explain inconsistent findings is unknown and suggests the need for caution in generalizing from group data on cleft.

Objective To assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Research Design and Methods Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10yrs across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data and T1D glycemic history since diagnosis were collected. Results The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5yrs and average onset age was 4yrs. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < 0.001). Learning and memory (p = 0.46) and processing speed (p = 0.25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Conclusions Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time.

OBJECTIVE By using behavioral outcome measures of children who were born preterm, we evaluated differences between children who were born at term and children who were born at extremely low (ELBW; <1000 g) and very low birth weights (VLBW; 1000 –1499 g) and assessed the relationship of birth weight, socioeconomic status, and cognitive ability to behavioral outcome. METHODS We studied a total of 104 children (aged 7–16 years). Of these, 49 had a preterm birth (31 of ELBW and 18 of VLBW). The remaining 55 were healthy control subjects. Children were administered tests of cognitive ability. Parents and teachers completed behavioral assessments. Multivariate analyses of covariance assessed differences between children who were born at term and those who were born of ELBW and of VLBW on behavioral measures. Hierarchical linear regressions were used to assess relationships among biological (birth weight), environmental (socioeconomic status), intellectual, and behavioral variables. RESULTS Children who were born at term had fewer parent reports of hyperactivity/inattention and depression/anxiety symptoms than children of ELBW and VLBW. Teacher ratings were not significant between groups. Birth weight was consistently the strongest predictor of parent ratings of behavioral outcome, and intelligence level did not seem to mediate this relationship. CONCLUSIONS Negative behavioral sequelae of preterm birth remain significant in middle childhood and adolescence, although the contribution of multiple factors to neurobehavioral outcome is complex. Research to assess these relationships, integrated with anatomic and functional neuroimaging, is needed to advance knowledge and improve outcomes for children who are born preterm.

Objective Evaluate neuropsychological functioning in children with non-syndromic cleft of the lip and/or palate (NSCL/P) through profile variance within type of cleft and comparisons to controls. Methods Children ages 7 to 17 years participated; 66 had a diagnosis of NSCL/P and 87 were healthy controls. Neuropsychological tests of language, visual-perceptual, executive functioning, and memory skills were administered. Between- and within-group differences were assessed. Results Within cleft types, children with NSCLP had an even profile with equal Verbal and Performance IQ (VIQ and PIQ, respectively). Children with non-syndromic cleft palate only (NSCP) had significantly lower VIQ than PIQ, while children with non-syndromic cleft lip only (NSCL) showed a nonsignificant trend for higher VIQ than PIQ. Overall, subjects with NSCL/P performed lower on measures of expressive language and verbal memory than controls. Conclusions While deficits in verbal and memory skills for children with NSCL/P remain apparent, there is still uncertainty around the possible influence of cleft type on the pattern of deficits.

Objective Evaluate speech, hearing, and neuropsychological correlates to reading among children, adolescents and young adults with non-syndromic cleft of the lip and/or palate (NSCL/P). Method All testing was completed in one visit at a Midwestern university hospital. Subjects in both the NSCL/P (n = 80) and control group (n = 62) ranged in age from 7 to 26 years (average age = 17.60 and 17.66, respectively). Subjects completed a battery of standardized tests evaluating intelligence, neuropsychological skills, and word reading. Subjects with NSCL/P also underwent speech assessment and past audiology records were evaluated. Results After controlling for age and SES, subjects with cleft performed significantly worse on a test of word reading. For subjects with cleft, word reading deficits were not associated with measures of speech or hearing, but were correlated with impairments in auditory memory. Conclusions These findings show poorer reading among subjects with NCL/P compared to those without. Further work needs to focus on correlates of reading among subjects with cleft to allow early identification and appropriate intervention/accommodation for those at risk.

Objective-Preterm infants are frequently transfused with red blood cells based on standardized guidelines or clinical concern that anemia taxes infants' physiological compensatory mechanisms and thereby threatens their health and well-being. The impact of various transfusion guidelines on long-term neurocognitive outcome is not known. The purpose of this study is to evaluate longterm neurocognitive outcome on children born prematurely and treated at birth with different transfusion guidelines.Methods-Neurocognitive outcomes were examined at school age for 56 preterm infants randomly assigned to a liberal (n = 33) or restrictive (n = 23) transfusion strategy. Tests of intelligence, achievement, language, visual-spatial/motor, and memory skills were administered. Between-group differences were assessed.Results-Those in the liberal transfusion group performed more poorly than those in the restrictive group on measures of associative verbal fluency, visual memory, and reading.Conclusions-Findings highlight possible long-term neurodevelopmental consequences of maintaining higher hematocrit levels. KeywordsPreterm; Neuropsychology; Red Blood Cell Transfusion; Hematocrit; LongitudinalThe high incidence of anemia in preterm, very low birth weight (VLBW; <1500 grams) infants mandates frequent red blood cell (RBC) transfusions during the first few weeks after birth. Though all infants experience decreased hemoglobin (i.e., physiologic anemia) during the first months after birth, anemia of prematurity is common in infants weighing less than 1 kg (< 32 weeks gestation), and is essentially low endogenous erythropoietin (EPO; a hormone that stimulates RBC production in response to low oxygen saturation) production and exaggeration of physiologic anemia in which hemoglobin levels fall 7-10 g/dl more than in term infants and remain lower for longer periods of time (Bain & Blackburn, 2004). Concern regarding the preterm infant's capacity to tolerate anemia as well as the potential consequences (e.g., increased risk of death), have resulted in routine RBC transfusions among preterm infants (Hebert et al., 1999; Straus, 1995). Views on the risks of anemia and the effectiveness of RBC transfusion in addressing these risks, however, are varied, while the clinical signs of anemia are nonspecific and require significant physician interpretation (Maier et al., 2000;Strauss, 1995). Information has begun to emerge about the impact of transfusion strategy on the outcome of anemic preterm infants, but the outcomes analyzed to date have been limited to the neonatal period and later infancy (i.e., up to 18 to 21 months of (Whyte et al., 2009). Evaluating long-term neurodevelopmental outcomes associated with different transfusion thresholds is critical for assessing the safety of current transfusion practice especially in terms of potential cognitive and behavioral morbidity. The Impact of Preterm Birth on Neurocognitive OutcomesThe survival rate of preterm infants has improved in recent decades as a result of advances in neonatal in...

The purpose of this study is to evaluate quantitative structural measures of the ventromedial prefrontal cortex (vmPFC) in boys with isolated clefts of the lip and/or palate (ICLP) relative to a comparison group and to associate measures of brain structure with quantitative measures of hyperactivity, impulsivity, and inattentiveness. A total of 50 boys with ICLP were compared to 60 healthy boys without clefts. Magnetic resonance imaging brain scans were used to evaluate vmPFC structure. Parents and teachers provided quantitative measures of hyperactivity, impulsivity, and inattentiveness using the Pediatric Behavior Scale. Boys with ICLP had significantly higher ratings of hyperactivity/impulsivity/inattention (HII) and significantly increased volume of the right vmPFC relative to the comparison group. There was a direct relationship between HII score and vmPFC volume in both the ICLP group and control group, but the relationship was in the opposite direction: in ICLP, the higher the vmPFC volume, the higher the HII score; for the comparison group, the lower the vmPFC volume, the greater the HII score. The vmPFC is a region of the brain that governs behaviors of hyperactivity, impulsivity and inattention (HII). In boys with ICLP, there are higher levels of HII compared to the controls and this is directly related to a significantly enlarged volume of the right vmPFC. Enlargement of this region of the brain is therefore considered to be pathological in the ICLP group and supports the notion that abnormal brain structure (from abnormal brain development) is the underlying etiology for the abnormal behaviors seen in this population.