Peter W. Forbes

The NIH MRI study of normal brain development: Performance of a population based sample of healthy children aged 6 to 18 years on a neuropsychological battery

The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development is a landmark study in which structural and metabolic brain development and behavior are followed longitudinally from birth to young adulthood in a population-based sample of healthy children. The neuropsychological assessment protocol for children aged 6 to 18 years is described and normative data are presented for participants in that age range (N = 385). For many measures, raw score performance improved steeply from 6 to 10 years, decelerating during adolescence. Sex differences were documented for Block Design (male advantage), CVLT, Pegboard and Coding (female advantage). Household income predicted IQ and achievement, as well as externalizing problems and social competence, but not the other cognitive or behavioral measures. Performance of this healthy sample was generally better than published norms. This linked imaging-clinical/behavioral database will be an invaluable public resource for researchers for many years to come.

Long-term effects from a randomized trial of two public health preventive interventions for parental depression.

This article presents long-term effects of a randomized trial evaluating 2 standardized, manual-based prevention strategies for families with parental mood disorder: informational lectures and a brief, clinician-based approach including child assessment and a family meeting. A sample of 105 families, in which at least 1 parent suffered from a mood disorder and at least 1 nondepressed child was within the 8- to 15-year age range, was recruited. Parents and children were assessed separately at baseline and every 9 to 12 months thereafter on behavioral functioning, psychopathology, and response to intervention. Both interventions produced sustained effects through the 6th assessment point, approximately 4.5 years after enrollment, with relatively small sample loss of families (<14%). Clinician-based families had significantly more gains in parental child-related behaviors and attitudes and in child-reported understanding of parental disorder. Child and parent family functioning increased for both groups and internalizing symptoms decreased for both groups, with no significant group differences. These findings demonstrate that brief, family-centered preventive interventions for parental depression may contribute to long-term, sustained improvements in family functioning.

Anemia, Blood Loss, and Blood Transfusions in North American Children in the Intensive Care Unit

RATIONALE Minimizing exposure of children to blood products is desirable. OBJECTIVES We aimed to understand anemia development, blood loss, and red blood cell (RBC) transfusions in the pediatric intensive care unit (PICU). METHODS Prospective, multicenter, 6-month observational study in 30 PICUs. Data were collected on consecutive children (<18 yr old) in the PICU for 48 hours or more. MEASUREMENTS AND MAIN RESULTS Anemia development, blood loss, and RBC transfusions were measured. A total of 977 children were enrolled. Most (74%) children were anemic in the PICU (33% on admission, 41% developed anemia). Blood draws accounted for 73% of daily blood loss; median loss was 5.0 ml/day. Forty-nine percent of children received transfusions; 74% of first transfusions were on Days 1-2. After adjusting for age and illness severity, compared with nontransfused children, children who underwent transfusion had significantly longer days of mechanical ventilation (2.1 d, P < 0.001) and PICU stay (1.8 d, P = 0.03), and had increased mortality (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.43-90.9; P = 0.02), nosocomial infections (OR, 1.9; 95% CI, 1.2-3.0; P = 0.004), and cardiorespiratory dysfunction (OR, 2.1; 95% CI, 1.5-3.0; P < 0.001). High blood loss per kilogram body weight from blood draws (OR, 1.11; 95% CI, 1.03-1.2; P = 0.01) was associated with RBC transfusion more than 48 hours after admission. The most common indication for transfusion was low hemoglobin (42%). Pretransfusion hemoglobin values varied greatly (mean, 9.7 +/- 2.7 g/dl). CONCLUSIONS Critically ill children are at significant risk for developing anemia and receiving blood transfusions. Transfusion in the PICU was associated with worse outcomes. It is imperative to minimize blood loss from blood draws and to set clear transfusion thresholds.

Stability of blood phenylalanine levels and IQ in children with phenylketonuria.

Variability of metabolic control in phenylketonuria (PKU) potentially affects cognitive outcome in early and continuously treated children with this condition. The possibility that homeostasis is more important than the absolute level of exposure to phenylalanine (phe) has not previously been examined. A meta-analysis of 40 studies showed that in children with phenylketonuria (PKU), mean lifetime blood phe levels were significantly correlated with Full Scale IQ (FSIQ) (r=-0.34). A similar correlation (r=-0.35) was found between FSIQ and mean exposure during 0-12 years of age. Most of the studies in the meta-analysis, however, included children who had discontinued the phe restricted diet. None examined the impact of fluctuations in metabolic control in continuously treated children. This is important because new therapies may increase stability in blood phe levels. The question has arisen whether these therapies are beneficial in children whose blood phe levels are generally within the recommended range of 120-360 micromol/L. In this study, we describe the relationship between FSIQ and two parameters of metabolic control: (1) mean blood phe level of all reported specimens for each subject, and (2) variability of the blood phe level as indicated by the standard deviation of blood phe levels for each subject. Analyses were performed using lifetime phe levels and levels during three periods (0-6 years, 0-10 years, and >10 years of age). The most recent FSIQ for each child was used in the correlation analyses. Data were collected from medical records on all 46 children born between 1999 and 2006 with early and continuously treated PKU followed at the Metabolism Program at Childrens Hospital Boston. The mean age of the children at the time of their most recent FSIQ test was 7.5+3.3 (2.9-15.5) and their mean FSIQ was 104+15 (68-143). The mean lifetime blood phe level in these children was 312+132 micromol/L (125-852). The standard deviation of blood phe levels was 182+72 micromol/L (96-336). The correlation between lifetime blood phe levels and most recent FSIQ was -.17 (p=0.38) and the correlation between standard deviation of blood phe levels and most recent FSIQ was -.36 (p=.058), not reaching significance, but indicating a trend. These results indicate that stability of blood phe levels may be more important to cognitive functioning than overall exposure to phe in early and continuously treated PKU. In treating PKU, attention should be given to variability in blood phe levels as well as maintenance of phe levels within the recommended range.

Executive Functions and Performance on High-Stakes Testing in Children From Urban Schools

High-stakes achievement testing is a centerpiece of education reform. Children from socially disadvantaged backgrounds typically perform more poorly than their more advantaged peers. The authors evaluated 91 fifth-grade children from low-income urban schools using clinical neuropsychological tests and behavioral questionnaires and obtained fourth-grade scores on state mandated standards-based testing. Goals were to determine whether executive functions are selectively diminished in children from poor urban environments and to evaluate to what extent integrity of executive functions is associated with test scores. Neuropsychological variables (particularly executive functions) accounted for 40% of the variance in English scores and 30% in mathematics. Efforts to improve childrens academic achievement should consider developmental factors as well as curricular content.

Processing of Rapid Auditory Stimuli in School-Age Children Referred for Evaluation of Learning Disorders

Tallal hypothesized that reading disabled children have a domain-general deficit in processing rapidly occurring auditory stimuli that degrades speech perception, thereby limiting phonologic awareness and thus reading acquisition. She predicted they would be disproportionately affected by rapidly presented auditory stimuli. In this study, one hundred 7- to 11-year-old children with learning impairment (LI) and 243 non-learning impaired (NLI) children were evaluated on a two-tone auditory discrimination paradigm. LI committed more errors, but effects of timing were comparable. The same result was obtained for a subsample of good and poor readers. Task performance predicted reading, spelling, and calculation. Neural processes underlying perception of speech and other auditory stimuli may be less effective in poor readers; however, contrary to Tallals hypothesis, rate may not be specifically affected.

Variation in the management of pediatric splenic injuries in New England.

BACKGROUND Nonoperative management of stable children with splenic injuries is the standard of care but has been variably applied in New England. The influence of surgeon training on this variation was analyzed. METHODS A region-wide administrative data set was queried for children with a splenic injury from 1990 through 1998. The influence of a range of patient- and hospital-specific variables, including surgeon pediatric training, on the risk of operation was analyzed. RESULTS The risk of operation increased with age, severity of splenic injury, and the presence of multiple injuries, but also trauma center status and the presence of a surgical training program. After allowance for these variables, the risk of operation was reduced by half when children with splenic injuries were cared for by a surgeon with pediatric specialty training. CONCLUSION The risk of operation for pediatric splenic injury in New England is dependent on several variables, including the surgeons training.

Adaptive phase I study of OROS methylphenidate treatment of attention deficit hyperactivity disorder with epilepsy

OBJECTIVE The goal of this study was to pilot a randomized controlled trial of OROS methylphenidate (OROS-MPH) to treat attention deficit hyperactivity disorder (ADHD) plus epilepsy. METHODS Thirty-three patients, 6-18years of age, taking antiepileptic drugs and with a last seizure 1-60months prior were assigned to a maximum daily dose of 18, 36, or 54mg of OROS-MPH in a double-blind placebo-controlled crossover trial. RESULTS There were no serious adverse events and no carryover effects in the crossover trial. OROS-MPH reduced ADHD symptoms more than did placebo treatment. There were too few seizures during the active (5) and placebo arms (3) to confidently assess seizure risk; however, considering exposure time, we observed an increased daily risk of seizures with increasing dose of OROS-MPH, suggesting that potential safety concerns require further study. CONCLUSION A larger study to assess the effect of OROS-MPH on seizure risk is needed. A crossover design including subjects with frequent seizures could maximize power and address high patient heterogeneity and recruitment difficulties.

Sources of poor performance on the Rey-Osterrieth Complex Figure Test among children with learning difficulties: a dynamic assessment approach.

A dynamic assessment approach was used to examine the source of poor performance on the Rey–Osterrieth Complex Figure Test (ROCF) among 202 school-age children referred for learning difficulties. The ROCF was administered in the standard format and then in a structured format that highlighted the designs organizational framework. Manipulating encoding in this way improved recall to at least age-level for the majority of children. Those children who did not benefit from the structured format had relatively poor visual organizational skills. For most children with learning problems, poor ROCF performance stems from metacognitive difficulties; for a minority, the source appears to be more perceptual. A dynamic assessment procedure can enhance the diagnostic utility of the ROCF for children.

Rapid Automatized Naming in Children Referred for Evaluation of Heterogeneous Learning Problems: How Specific Are Naming Speed Deficits to Reading Disability?

Because the Rapid Automatized Naming (RAN) test reliably predicts reading skill, it is typically viewed as a diagnostic indicator of risk for reading disability (RD). Since most of the work on naming speed has been undertaken within the framework of reading research, however, the extent to which poor RAN is specifically associated with RD or with learning impairment (LI) in general is uncertain. We tested the hypothesis that slow naming speed is specific to RD. Participants were 188 children (ages 7 to 11) referred for evaluation of learning problems. Receiver operating characteristic (ROC) analysis was used to evaluate the utility of the RAN task for classifying children in diagnostic groups. RAN was an excellent tool for detecting risk for learning problems in general, but it was much less effective at distinguishing LI children with and without RD from each other.