Runner-Up Articles on Developmental Disabilities

September 19, 2008
Gordon Worley, MD, Gregory Liptak, MD

Winterstein AG, Gerhard T, Shuster J, Johnson M, Zito JM, Saidi A. Cardiac safety of central nervous system stimulants in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2007 Dec;120(6):e1494-501.

OBJECTIVES: Case reports have raised concerns about the risk of cardiac events associated with central nervous system stimulants for the treatment of attention-deficit/hyperactivity disorder. PATIENTS AND METHODS: This was a retrospective cohort study that used 10 years (July 1994 to June 2004) of Florida Medicaid claims data cross-linked to Vital Statistics Death Registry data. The cohort was composed of all youth 3 to 20 years old who were newly diagnosed with attention-deficit/hyperactivity disorder. Each month of follow-up was classified according to stimulant claims (methylphenidate, amphetamines, and pemoline) as current use (active stimulant claim), former use (time after periods of current use), or nonuse (time preceding the first stimulant claim, including follow-up of youth who were never exposed to stimulants). The study's end points were (1) cardiac death, (2) first hospital admission for cardiac causes or (3) first emergency department visit for cardiac causes. Risks were compared with time-dependent Cox regression analysis adjusting for various cardiac risk factors. RESULTS: During 124,932 person-years of observation (n = 55,383), 73 youth died, 5 because of cardiac causes. No cardiac death occurred during 42,612 person-years of stimulant use. Hospital admissions for cardiac cause occurred for 27 children (8 during stimulant use, 11 during 35,671 person-years of former use, and 8 during 46,649 person-years of nonuse); and 1091 children visited the emergency department for cardiac causes (8.7 per 1000 person-years). Current stimulant use was associated with a 20% increase in the hazard for emergency department visits when compared with nonuse. No increased risk was found for periods of former use when compared with nonuse. CONCLUSIONS: Incidence rates of cardiac events requiring hospitalization were small and similar to national background rates. Stimulants were associated with an increase in cardiac emergency department visits. More evidence is needed that addresses the long-term risk/benefit of the various treatment options and the effect of other cardiac risk factors and comedications.

Ellis JM, Tan HK, Gilbert RE, Muller DP, Henley W, Moy R, Pumphrey R, Ani C, Davies S, Edwards V, Green H, Salt A, Logan S. Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial. BMJ. 2008 Mar 15;336(7644):594-7. Epub 2008 Feb 21.

OBJECTIVES: To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down's syndrome. DESIGN: Randomised controlled trial with two by two factorial design. SETTING: Children living in the Midlands, Greater London, and the south west of England. PARTICIPANTS: 156 infants aged under 7 months with trisomy 21. INTERVENTION: Daily oral supplementation with antioxidants (selenium 10 mug, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo. MAIN OUTCOME MEASURES: Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months. RESULTS: Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval -2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, -1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results. CONCLUSIONS: This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down's syndrome.

Vitiello B, Abikoff HB, Chuang SZ, Kollins SH, McCracken JT, Riddle MA, Swanson JM, Wigal T, McGough JJ, Ghuman JK, Wigal SB, Skrobala AM, Davies M, Posner K, Cunningham C, Greenhill LL. Effectiveness of methylphenidate in the 10-month continuation phase of the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol. 2007 Oct;17(5):593-604.

Ghuman JK, Riddle MA, Vitiello B, Greenhill LL, Chuang SZ, Wigal SB, Kollins SH, Abikoff HB, McCracken JT, Kastelic E, Scharko AM, McGough JJ, Murray DW, Evans L, Swanson JM, Wigal T, Posner K, Cunningham C, Davies M, Skrobala AM. Comorbidity moderates response to methylphenidate in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS). J Child Adolesc Psychopharmacol. 2007 Oct;17(5):563-80.

A special section in the November 2007 issue of the Journal of Child and Adolescent Psychopharmacology presents seven papers reporting new findings from the six-site Preschoolers with ADHD Treatment Study (PATS). The PATS was designed to assess the efficacy and safety of short-term methylphenidate (MPH) and the effectiveness and tolerability of long-term MPH in children ages 3-5 with attention deficit hyperactivity disorder (ADHD). PATS was designed with investigators' input and with input from multiple government agencies and scientific review, and the study included 8 phases. The articles included in the journal's special section address the following selected topics: clinical presentation of ADHD in preschool children, predictors of treatment response, MPH effects on functional outcomes, and parent vs. teacher ratings of ADHD symptoms in preschool children referred for the PATS study. Abstracts are available at http://www.liebertonline.com/toc/cap/17/5.

[These two articles examine the effects methylphenidate on preschool children. It works and seems to be effective with the same adverse effects found in older children.]

Wright FV, Rosenbaum PL, Goldsmith CH, Law M, Fehlings DL. How do changes in body functions and structures, activity, and participation relate in children with cerebral palsy? Dev Med Child Neurol. 2008 Apr;50(4):283-9.

Rehabilitation increasingly addresses the International Classification of Functioning, Disability and Health's (ICF) concepts of activity and participation, but little is known about associations between changes in body functions and structures, activity, and participation. We conducted a before-and-after study of 35 ambulatory children with spastic diplegia or hemiplegic cerebral palsy, mean age 5 years 6 months (SD 2 y 2 mo). Children were in Gross Motor Function Classification System (GMFCS) Levels I (n=11), II (n=12), or III (n=12). We assessed body functions and structures, activity, and participation at baseline and at 2 months and 6 months post-botulinum toxin type A (BoNT-A) injection. Repeated-measures analysis of variance evaluated change, and linear regression assessed relationships. Baseline score relationships were moderate to strong but, despite similar directions of change at 2 months, change score relationships between measures of body functions and structures (spasticity and timed walk), activity (Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory), and participation (Pediatric Outcomes Data Collection Instrument) at 2 months and 6 months were poor to fair (r < 0.40). Predictor combinations accounted for < 69% of variation in activity and participation change scores. Predictors often pertained to baseline score, GMFCS level, or age. Relationships between changes at different ICF levels are complex, and activity and participation gains post-BoNT-A are likely to be influenced by the child and environment factors.

Venkateswaran S, Shevell MI. Etiologic profile of spastic quadriplegia in children. Pediatr Neurol. 2007 Sep;37(3):203-8.

The etiologic profile and possible predictors of etiology in children with spastic quadriplegia were assessed in a consecutive cohort of children with this motor impairment. Medical records from a single pediatric neurology practice over a 14-year interval were retrospectively and systematically reviewed. Variables comprised possible demographic, prenatal, perinatal, and postnatal risk factors. Of the 99 patients included in the study, 39 were premature (< 37 weeks gestation). The overall etiologic yield was 83%. The top three diagnoses were hypoxic-ischemic perinatal asphyxia (33%), periventricular leukomalacia (15%), and central nervous system infections (11%). In premature children, the most common diagnoses were periventricular leukomalacia (33%), perinatal asphyxia (26%), and central nervous system infections (15%). In term-born children, the most frequent diagnoses were perinatal asphyxia (37%), metabolic disease (12%), and structural malformation or infection (9% each). Factors predicting the identification of an etiology included male sex (P = 0.05), low birth weight (P = 0.003), prematurity (P = 0.01), perinatal complications (P = 0.002), and neonatal encephalopathy (P = 0.006). The etiologic yield in patients with spastic quadriplegia was 83%, with differing underlying etiologies depending on gestational age. These results should help guide physicians in investigating possible underlying etiologies in patients with spastic quadriplegia.

Smithers LG, Gibson RA, McPhee A, Makrides M. Effect of long-chain polyunsaturated fatty acid supplementation of preterm infants on disease risk and neurodevelopment: a systematic review of randomized controlled trials. Am J Clin Nutr. 2008 Apr;87(4):912-20.

BACKGROUND: Supplementation of preterm formulas with long-chain polyunsaturated fatty acids (LCPUFAs) is based on their effectiveness to increase blood status and improve visual outcomes. Dispute remains over their efficacy on global development. OBJECTIVE: The objective was to compare the effects of LCPUFA-supplemented with those of control formulas on neurodevelopment and diseases associated with prematurity. DESIGN: We systematically reviewed randomized controlled trials involving preterm infants that tested LCPUFA-supplemented formulas. The weighted mean differences (WMDs) in neurodevelopmental scores and relative risk (RR) of disease were calculated to compare infants fed LCPUFA-supplemented formula with those fed control formula. RESULTS: No clear differences in Bayley Scales of Infant Development (BSID) scores were observed between groups. Mental development of LCPUFA-supplemented infants was 3.4 points higher than that of control infants with BSID version II (WMD: 3.44; 95% CI: 0.56, 6.31; P = 0.02; n = 879), although it was driven by 2 trials with large effect sizes and wide CIs. Psychomotor development was lower in supplemented infants tested with BSID version I (WMD: -7.99; 95% CI: -14.00, -1.99; P = 0.009; n = 87); however, it was limited by small sample sizes. No differences in the RR of sepsis (1.08; 95% CI: 0.79, 1.46; P = 0.63; n = 1333) or in the RR of necrotizing enterocolitis (1.13; 95% CI: 0.62, 2.04; P = 0.69; n = 1333) were found. Similarly, the risks of retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were not different between groups, but data were limited by small sample sizes and trials with an increased risk of bias. CONCLUSIONS: LCPUFA-supplemented formula does not alter the risk of NEC or sepsis. Further work is needed to determine the extent of benefit of LCPUFA-supplemented formula on the mental development of preterm infants.

Bishop DV, Whitehouse AJ, Watt HJ, Line EA. Autism and diagnostic substitution: evidence from a study of adults with a history of developmental language disorder. Dev Med Child Neurol. 2008 May;50(5):341-5.

Rates of diagnosis of autism have risen since 1980, raising the question of whether some children who previously had other diagnoses are now being diagnosed with autism. We applied contemporary diagnostic criteria for autism to adults with a history of developmental language disorder, to discover whether diagnostic substitution has taken place. A total of 38 adults (aged 15-31y; 31 males, seven females) who had participated in studies of developmental language disorder during childhood were given the Autism Diagnostic Observation Schedule--Generic. Their parents completed the Autism Diagnostic Interview--Revised, which relies largely on symptoms present at age 4 to 5 years to diagnose autism. Eight individuals met criteria for autism on both instruments, and a further four met criteria for milder forms of autistic spectrum disorder. Most individuals with autism had been identified with pragmatic impairments in childhood. Some children who would nowadays be diagnosed unambiguously with autistic disorder had been diagnosed with developmental language disorder in the past. This finding has implications for our understanding of the epidemiology of autism.

Curran LK, Newschaffer CJ, Lee LC, Crawford SO, Johnston MV, Zimmerman AW. Behaviors associated with fever in children with autism spectrum disorders. Pediatrics. 2007 Dec;120(6):e1386-92.

OBJECTIVE: Clinical case reports have suggested that the behaviors of children with autism spectrum disorders may improve with fever. The purpose of this study was to investigate the effect of illness on behaviors of children with autism spectrum disorders. Understanding the role of fever, if any, may be informative regarding causative mechanisms of and treatment opportunities for autism. METHODS: We conducted a prospective study of 30 children (aged 2-18 years) with autism spectrum disorders during and after an episode of fever. Parent responses to the Aberrant Behavior Checklist were collected during fever (body temperature > or = 38.0 degrees C/100.4 degrees F), when fever had abated and the child was asymptomatic, and when the child had been fever-free for 7 days. Data were compared with those collected from parents of 30 age-, gender-, and language skills-matched afebrile children with autism spectrum disorders during similar time intervals. RESULTS: Fewer aberrant behaviors were recorded for febrile patients on the Aberrant Behavior Checklist subscales of irritability, hyperactivity, stereotypy, and inappropriate speech compared with control subjects. Per expectation, lethargy scores were greater during fevers, and all improvements were transient. Data from patients with fever were stratified on variables related to illness severity. In the majority of these subgroup comparisons, the data suggested that effects from fever persisted in the less sick patients as well as in those with more severe illness. CONCLUSIONS: We documented behavior change among children with autism spectrum disorders during fever. The data suggest that these changes might not be solely the byproduct of general effects of sickness on behavior; however, more research is needed to prove conclusively fever-specific effects and elucidate their underlying biological mechanisms (possibly involving immunologic and neurobiological pathways, intracellular signaling, and synaptic plasticity).

Thompson WW, Price C, Goodson B, Shay DK, Benson P, Hinrichsen VL, Lewis E, Eriksen E, Ray P, Marcy SM, Dunn J, Jackson LA, Lieu TA, Black S, Stewart G, Weintraub ES, Davis RL, DeStefano F; Vaccine Safety Datalink Team. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med. 2007 Sep 27;357(13):1281-92.

BACKGROUND: It has been hypothesized that early exposure to thimerosal, a mercury-containing preservative used in vaccines and immune globulin preparations, is associated with neuropsychological deficits in children. METHODS: We enrolled 1047 children between the ages of 7 and 10 years and administered standardized tests assessing 42 neuropsychological outcomes. (We did not assess autism-spectrum disorders.) Exposure to mercury from thimerosal was determined from computerized immunization records, medical records, personal immunization records, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We assessed the association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period (birth to 28 days), and the first 7 months of life. RESULTS: Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal. The detected associations were small and almost equally divided between positive and negative effects. Higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning. Increasing levels of mercury exposure from birth to 7 months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning. Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination. CONCLUSIONS: Our study does not support a causal association between early exposure to mercury from thimerosal-containing vaccines and immune globulins and deficits in neuropsychological functioning at the age of 7 to 10 years.

Rodriguez A, Miettunen J, Henriksen TB, Olsen J, Obel C, Taanila A, Ebeling H, Linnet KM, Moilanen I, Järvelin MR. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts. Int J Obes (Lond). 2008 Mar;32(3):550-7. Epub 2007 Oct 16.

OBJECTIVES: We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring. DESIGN: Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD. METHODS: Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as 'severe' and two as 'present' (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to children's ADHD core symptoms. RESULTS: Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women. CONCLUSIONS: We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.

Palumbo DR, Sallee FR, Pelham WE Jr, Bukstein OG, Daviss WB, McDermott MP. Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. J Am Acad Child Adolesc Psychiatry. 2008 Feb;47(2):180-8.

AND

Daviss WB, Patel NC, Robb AS, McDermott MP, Bukstein OG, Pelham WE Jr, Palumbo D, Harris P, Sallee FR. Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis. J Am Acad Child Adolesc Psychiatry. 2008 Feb;47(2):189-98.

Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A, Scherer N; SPD503 Study Group. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008 Jan;121(1):e73-84.

Kramer MS, Aboud F, Mironova E, Vanilovich I, Platt RW, Matush L, Igumnov S, Fombonne E, Bogdanovich N, Ducruet T, Collet JP, Chalmers B, Hodnett E, Davidovsky S, Skugarevsky O, Trofimovich O, Kozlova L, Shapiro S; Promotion of Breastfeeding Intervention Trial (PROBIT) Study Group. Breastfeeding and child cognitive development: new evidence from a large randomized trial. Arch Gen Psychiatry. 2008 May;65(5):578-84.

CONTEXT: The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother's behavior or her interaction with the infant. OBJECTIVE: To assess whether prolonged and exclusive breastfeeding improves children's cognitive ability at age 6.5 years. DESIGN: Cluster-randomized trial, with enrollment from June 17, 1996, to December 31, 1997, and follow-up from December 21, 2002, to April 27, 2005. SETTING: Thirty-one Belarussian maternity hospitals and their affiliated polyclinics. PARTICIPANTS: A total of 17,046 healthy breastfeeding infants were enrolled, of whom 13,889 (81.5%) were followed up at age 6.5 years. INTERVENTION: Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF. MAIN OUTCOME MEASURES: Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence, and teacher evaluations of academic performance in reading, writing, mathematics, and other subjects. RESULTS: The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months (43.3% for the experimental group vs 6.4% for the control group; P < .001) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months. The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures, with cluster-adjusted mean differences (95% confidence intervals) of +7.5 (+0.8 to +14.3) for verbal IQ, +2.9 (-3.3 to +9.1) for performance IQ, and +5.9 (-1.0 to +12.8) for full-scale IQ. Teachers' academic ratings were significantly higher in the experimental group for both reading and writing. CONCLUSION: These results, based on the largest randomized trial ever conducted in the area of human lactation, provide strong evidence that prolonged and exclusive breastfeeding improves children's cognitive development. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN37687716.

Manger MS; McKenzie JE; Winichagoon P; Gray A; Chavasit V; Pongcharoen T; Gowachirapant S; Ryan B; Wasantwisut E; Gibson RS. A micronutrient-fortified seasoning powder reduces morbidity and improves short-term cognitive function, but has no effect on anthropometric measures in primary school children in northeast Thailand: a randomized controlled trial. Am J Clin Nutr. 2008; 87(6):1715-22.

BACKGROUND: Reductions in iodine and zinc deficiencies and improvements in hemoglobin were achieved from a micronutrient-fortified seasoning powder consumed in school lunches by children in northeast Thailand. OBJECTIVE: The objective was to determine whether fortification with 4 micronutrients in a school lunch results in changes in children's growth, morbidity, and cognitive function compared with no fortification. DESIGN: In a randomized controlled trial of 569 children aged 5.5-13.4 y from 10 schools, we compared the efficacy of a seasoning powder fortified with or without 5 mg Fe, 5 mg Zn, 50 mug I, and 270 mug vitamin A per serving consumed with a school lunch 5 d/wk. Here we report on results of the secondary functional outcomes. RESULTS: The groups were comparable concerning compliance and loss to follow-up. The intervention had no statistically significant effect on anthropometric measures over 31 wk, but reduced the incidence of respiratory-related illnesses [rate ratio (RR): 0.83; 95% CI: 0.73, 0.94], symptoms of runny nose (RR: 0.80; 95% CI: 0.70, 0.92), cough (RR: 0.80; 95% CI: 0.66, 0.96), and diarrhea (RR: 0.38; 95% CI: 0.16, 0.90). For the visual recall test, those in the fortified group recalled 0.5 more items (95% CI: 0.1, 0.9) than did the controls. There were no statistically significant differences between groups in the results of the digits forward and backward tests or in school grades at the conclusion of the 2 semesters. CONCLUSION: The beneficial effects on morbidity and visual recall over a short period, in addition to some biochemical improvements, highlight the potential of this micronutrient-fortified seasoning powder supplied in a school lunch.

Eikeseth S. Outcome of comprehensive psycho-educational interventions for young children with autism. Res Dev Disabil. 2008 Apr 1. [Epub ahead of print]

This paper evaluates comprehensive psycho-educational research on early intervention for children with autism. Twenty-five outcome studies were identified. Twenty studies evaluated behavioral treatment, 3 studies evaluated TEACCH and 2 studies evaluated the Colorado Health Sciences Project. Outcome studies are graded according to their scientific value, and subsequently graded according to the magnitude of results documented in the studies. Based on the available evidence, treatment recommendations are made and practice parameters are suggested.

Hutchison JS, Ward RE, Lacroix J, Hébert PC, Barnes MA, Bohn DJ, Dirks PB, Doucette S, Fergusson D, Gottesman R, Joffe AR, Kirpalani HM, Meyer PG, Morris KP, Moher D, Singh RN, Skippen PW; Hypothermia Pediatric Head Injury Trial Investigators and the Canadian Critical Care Trials Group. Hypothermia therapy after traumatic brain injury in children. N Engl J Med. 2008 Jun 5;358(23):2447-56.

BACKGROUND: Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown. METHODS: In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5 degrees C for 24 hours) initiated within 8 hours after injury or to normothermia (37.0 degrees C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months. RESULTS: A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1+/-1.2 degrees C and 36.9+/-0.5 degrees C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P < 0.001) in the hypothermia group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups. CONCLUSIONS: In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality.

Motta F, Stignani C, Antonello CE. Effect of intrathecal baclofen on dystonia in children with cerebral palsy and the use of functional scales. J Pediatr Orthop. 2008 Mar;28(2):213-7.

BACKGROUND: The literature available shows that spasticity in patients with cerebral palsy (CP) is reduced by intrathecal baclofen (ITB) treatment, and various studies suggest that this treatment can also be used in dystonic patients. The aim of the present study was to evaluate dystonia treated with ITB in children with CP. METHODS: Data of 19 patients affected by dystonia as an outcome of infant CP in patients belonging to level V of Gross Motor Function Classification System treated with ITB were collected. The mean age at implant is 8.49 years.The patients are assessed using Barry-Albright Scale and Burke-Fahn-Marsden Scale before treatment and at 3, 6, and 12 months postimplant. RESULTS: The results showed a statistically significant improvement (P < 0.001) in the total scores of the 2 scales after just 3 months of treatment, an improvement that was maintained for the 1-year period of follow-up. The results also revealed a reduction in dystonias, an improvement in posture, and an easing of the task of the caregivers in managing the patient as a result of treatment with ITB. CONCLUSIONS: In patients belonging to level V of Gross Motor Function Classification System and treated with ITB, a decrease in frequency and severity of dystonia is observed. This improvement eases caregiver in patient management. LEVEL OF EVIDENCE: Therapeutic Level IV.

Venkateswaran S, Shevell MI. Comorbidities and clinical determinants of outcome in children with spastic quadriplegic cerebral palsy. Dev Med Child Neurol. 2008 Mar;50(3):216-22.

The objective of this study was to determine the major comorbidities in patients with spastic quadriplegic (SQ) cerebral palsy (CP) and their possible clinical associations. Medical records of patients with SQ CP from a pediatric neurology practice over a 14-year period were retrospectively and systematically reviewed. Variables examined included demographics, prenatal, perinatal, and postnatal risk factors. Comorbidities documented included those involving hearing, vision, feeding status, and epilepsy. Binomial logistic regression analyses were applied to identify clinical associations of the comorbidities. Ninety-two children were included in this study of whom 39 were born preterm. Mean age of presentation was 2 months (SD 3.5) and males comprised 60% of the group. A total of 57% had a Gross Motor Function Classification Score (GMFCS) of Level IV or V. The four documented comorbidities occurred at a high frequency: 66 out of 83 children (80%) had a visual impairment with 13 (21%) having a substantial impairment; 37 out of 86 children (40%) had a hearing deficit; 43 out of 92 children (47%) had epilepsy; and 29 (33%) required assisted feeding. A GMFCS Level of IV or V and documented microcephaly was associated with the need for assisted feeding (odds ratio [OR] 8.1; 95% confidence interval [CI] 2.1-29.8, p=0.002 and OR 4.9, 95% CI 1.7-14.8, p=0.004 respectively). Epilepsy was associated with the occurrence of neonatal encephalopathy (OR 2.3, 95% CI 1.0-55; p=0.05), microcephaly (OR 4.9, 95% CI 1.6-14.8; p=0.004), periventricular leukomalacia (OR 7.4, 95% CI 1.6-35.0; p=0.012), and perinatal asphyxia (OR 3.6, 95% CI 1.5-8.9; p=0.005). There is a high frequency of comorbidity in the setting of SQ CP which can impact on quality of life and burdens of care. Few clinical associations of this burden appear, thus necessitating systematic programmatic follow-up of these children to facilitate early identification and intervention.

Yeargin-Allsopp M, Van Naarden Braun K, Doernberg NS, Benedict RE, Kirby RS, Durkin MS. Prevalence of cerebral palsy in 8-year-old children in three areas of the United States in 2002: a multisite collaboration. Pediatrics. 2008 Mar;121(3):547-54.

OBJECTIVE: The goal was to estimate the prevalence of cerebral palsy and cerebral palsy subtypes among children in 3 areas of the United States by using a population-based surveillance system. METHODS: Using methods developed by the Centers for Disease Control and Prevention Metropolitan Atlanta Developmental Disabilities Surveillance Program, investigators from the Autism and Developmental Disabilities Monitoring Network conducted surveillance of cerebral palsy among 8-year-old children living in northern Alabama, metropolitan Atlanta, and southeastern Wisconsin in 2002 (N = 114,897). Cross-sectional data were collected through retrospective record review from multiple sources. Cases were linked to birth certificate and census files to obtain additional information. Period prevalence estimates were calculated per 1000 children 8 years of age. RESULTS: The average prevalence of cerebral palsy across the 3 sites was 3.6 cases per 1000, with notably similar site-specific prevalence estimates (3.3 cases per 1000 in Wisconsin, 3.7 cases per 1000 in Alabama, and 3.8 cases per 1000 in Georgia). At all sites, prevalence was higher in boys than girls (overall boy/girl ratio: 1.4:1). Also, at all sites, the prevalence of cerebral palsy was highest in black non-Hispanic children and lowest in Hispanic children. At all sites, the prevalence among children living in low- and middle-income neighborhoods was higher than that among children living in high-income neighborhoods. Spastic cerebral palsy was the most common subtype (77% of all cases), with bilateral spastic cerebral palsy dominating the spastic group (70%). CONCLUSION: These findings contribute new knowledge to the epidemiology of cerebral palsy in the United States. The similarities in prevalence rates and patterns of cerebral palsy reported for 8-year-old children at 3 geographically distinct sites provide evidence of the reliability of the surveillance methods used by the Autism and Developmental Disabilities Monitoring Network.

Akhondzadeh S, Tajdar H, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Shabstari OL, Ghelichnia HA. A double-blind placebo controlled trial of piracetam added to risperidone in patients with autistic disorder. Child Psychiatry Hum Dev. 2008 Sep;39(3):237-45. Epub 2007 Oct 11.

It has been reported that autism is a hypoglutamatergic disorder. Therefore, it was of interest to assess the efficacy of piracetam, a positive modulator of AMPA-sensitive glutamate receptors in autistic disorder. About 40 children between the ages three and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to piracetam + risperidone (Group A) or placebo + risperidone (Group B) for a 10-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of piracetam was titrated up to 800 mg/day. Patients were assessed at baseline and after 2, 4, 6, 8 and 10 weeks of starting medication. The measure of the outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale (total score). The ABC-C Rating Scale scores improved with piracetam. The difference between the two protocols was significant as indicated by the effect of group, the between subjects factor (F = 5.85, d.f. = 1, P = 0.02). The changes at the endpoint compared with baseline were: -11.90 +/- 3.79 (mean +/- SD) and -5.15 +/- 3.04 for group A and B respectively. A significant difference was observed on the change in scores in the ABC-C Rating Scale in week 10 compared with baseline in the two groups (t = 6.017, d.f. = 38, P < 0.0001). The results suggest that a combination of atypical antipsychotic medications and a glutamate agent such as piracetam, might have increase synergistic effects in the treatment of autism.

Chalfant AM, Rapee R, Carroll L. Treating anxiety disorders in children with high functioning autism spectrum disorders: a controlled trial. J Autism Dev Disord. 2007 Nov;37(10):1842-57.

A family-based, cognitive behavioural treatment for anxiety in 47 children with comorbid anxiety disorders and High Functioning Autism Spectrum Disorder (HFA) was evaluated. Treatment involved 12 weekly group sessions and was compared with a waiting list condition. Changes between pre- and post-treatment were examined using clinical interviews as well as child-, parent- and teacher-report measures. Following treatment, 71.4% of the treated participants no longer fulfilled diagnostic criteria for an anxiety disorder. Comparisons between the two conditions indicated significant reductions in anxiety symptoms as measured by self-report, parent report and teacher report. Discussion focuses on the implications for the use of cognitive behaviour therapy with HFA children, for theory of mind research and for further research on the treatment components.

Welter ML, Mallet L, Houeto JL, Karachi C, Czernecki V, Cornu P, Navarro S, Pidoux B, Dormont D, Bardinet E, Yelnik J, Damier P, Agid Y. Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol. 2008 Jul;65(7):952-7.

BACKGROUND: Tourette syndrome (TS) is thought to result from dysfunction of the associative-limbic territories of the basal ganglia, and patients with severe symptoms of TS respond poorly to medication. High-frequency stimulation has recently been applied to patients with TS in open studies using the centromedian-parafascicular complex (CM-Pf) of the thalamus, the internal globus pallidus (GPi), or the anterior limb of the internal capsule as the principal target. OBJECTIVE: To report the effect of high-frequency stimulation of the CM-Pf and/or the GPi, 2 associative-limbic relays of the basal ganglia, in patients with TS. DESIGN: Controlled, double-blind, randomized crossover study. SETTING: Medical research. PATIENTS: Three patients with severe and medically refractory TS. INTERVENTION: Bilateral placement of stimulating electrodes in the CM-Pf (associative-limbic part of the thalamus) and the GPi (ventromedial part). MAIN OUTCOME MEASURES: Effects of thalamic, pallidal, simultaneous thalamic and pallidal, and sham stimulation on neurologic, neuropsychological, and psychiatric symptoms. RESULTS: A dramatic improvement on the Yale Global Tic Severity Scale was obtained with bilateral stimulation of the GPi (reduction in tic severity of 65%, 96%, and 74% in patients 1, 2, and 3, respectively). Bilateral stimulation of the CM-Pf produced a 64%, 30%, and 40% reduction in tic severity, respectively. The association of thalamic and pallidal stimulation showed no further reduction in tic severity (60%, 43%, and 76%), whereas motor symptoms recurred during the sham condition. No neuropsychological, psychiatric, or other long-term adverse effect was observed. CONCLUSIONS: High-frequency stimulation of the associative-limbic relay within the basal ganglia circuitry may be an effective treatment of patients with TS, thus heightening the hypothesis of a dysfunction in these structures in the pathophysiologic mechanism of the disorder.

Johnson M, Ostlund S, Fransson G, Kadesjö B, Gillberg C. Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents. J Atten Disord. 2008 Apr 30. [Epub ahead of print]

Objective: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). Method: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD Rating Scale-IV and Clinical Global Impression (CGI) scale were outcome measures. Results: A majority did not respond to omega 3/6 treatment. However, a subgroup of 26% responded with more than 25% reduction of ADHD symptoms and a drop of CGI scores to the near-normal range. After 6 months, 47% of all showed such improvement. Responders tended to have ADHD inattentive subtype and comorbid neurodevelopmental disorders. Conclusion: A subgroup of children and adolescents with ADHD, characterized by inattention and associated neurodevelopmental disorders, treated with omega 3/6 fatty acids for 6 months responded with meaningful reduction of ADHD symptoms.

Buschmann A, Jooss B, Rupp A, Dockter S, Blaschtikowitz H, Heggen I, Pietz J. Children with developmental language delay at 24 months of age: results of a diagnostic work-up. Dev Med Child Neurol. 2008 Mar;50(3):223-9.

The aim of this study was to evaluate if a diagnostic work-up should be recommended for 2-year-old children with developmental language delay (LD), or if the widely chosen 'wait and see' strategy is adequate. Children with LD were identified in paediatric practices during routine developmental check-ups using a German parent-report screening questionnaire (adapted from the MacArthur Communicative Development Inventories). A standardized German instrument and the Netherlands version of Bayley Scales of Infant Development (2nd ed.) were used to assess language ability and nonverbal cognitive development respectively in 100 children with LD (65 males, 35 females; mean age 24.7 mo [SD 0.9]) and a control group of 53 children with normal language development (33 males, 20 females; mean age 24.6 mo [SD 0.8]). Neurological and audiometric testing were also performed. Sixty-one per cent of the LD group had specific expressive LD and 17% specific receptive-expressive LD. In 22%, LD was associated with other neurodevelopmental problems, 6% showed significant deficits in nonverbal cognitive abilities, and in 12%, nonverbal cognitive abilities were borderline. Four per cent fulfilled the criteria of childhood autism. LD at 2 years proved to represent a sensitive marker for different developmental problems. Adequate early intervention requires a clear distinction between specific expressive or receptive-expressive LD and LD associated with other neurodevelopmental problems. Though catch-up development is to be expected in a substantial proportion of 'late talkers', our data demonstrate that a general 'wait and see' approach is not justified in young children with LD. A proposal for a rational diagnostic work-up is presented.