G. Liptak G. Worley Other Studies of Note, 2004-2005 Cederlund M, Gillberg C. One hundred males with Asperger syndrome: a clinical study of background and associated factors. Dev.Med.Child Neurol. 2004 Oct;46(10):652-60. Abstract: The objective of this study was to investigate the background and associated factors in a representative group of young males with Asperger syndrome (AS) presenting at a specialized autism clinic. One hundred males aged 5 years 6 months to 24 years 6 months, with a mean age of 11 years 4 months (SD 3y 10mo), who had a clinical diagnosis of AS were included in the study. An in-depth review of their medical records and neuropsychological test data was performed. There was a high rate (51%) of non-verbal learning disability (defined as Verbal IQ more than 15 points higher than Performance IQ), but otherwise there was little or no support for the notion of right-hemisphere brain dysfunction being at the core of the syndrome. There was a very high rate of close relatives with autism spectrum problems, but also high rates of prenatal and perinatal problems, including prematurity and postmaturity. In comparison with general population data, those with AS very often had a combination of genetic and prenatal and perinatal risk factors. Non-verbal learning disability test results applied in about half the group. There was a subgroup of individuals with AS who had macrocephalus. However, there was no support for an association of AS with low body mass index. Chakrabarti S, Fombonne E. Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am.J.Psychiatry 2005 Jun;162(6):1133-41. Abstract: OBJECTIVE: The rate of reported pervasive developmental disorders has increased, and the authors found a rate of 62.6 per 10,000 in a previous study of preschoolers in Stafford, U.K. They conducted another survey in 2002 to estimate the prevalence in children in a later birth cohort and to compare it to previous findings from the same area. METHOD: Screening for developmental problems included 10,903 children ages 4.0 to 6.0 years who were living in a Midlands town on the survey date. Children with symptoms suggestive of pervasive developmental disorders were intensively assessed by a multidisciplinary team using standardized diagnostic interviews, psychometric tests, and medical workups. RESULTS: Sixty-four children (85.9% boys) were diagnosed with pervasive developmental disorders. The prevalence was 58.7 per 10,000, with a 95% confidence interval (CI) of 45.2-74.9, for all pervasive developmental disorders, 22.0 per 10,000 (95% CI=14.1-32.7) for autistic disorder, and 36.7 per 10,000 (95% CI=26.2-49.9) for other variants. These rates were not significantly different from the previous rates. The mean age at diagnosis was 37.8 months, and 53.1% of the children were originally referred by health visitors. Of the 64 children with pervasive developmental disorders, 29.8% had mental retardation, but this rate varied by disorder subtype. Few children had associated medical conditions. CONCLUSIONS: The rate of pervasive developmental disorders is higher than reported 15 years ago. The rate in this study is comparable to that in previous birth cohorts from the same area and surveyed with the same methods, suggesting a stable incidence. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc.Natl.Acad.Sci.U.S.A 2004 Dec 7;101(49):17312-5. Abstract: Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets "under the skin" remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress--both perceived stress and chronicity of stress--is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases. Gibson PA, Newton RW, Selby K, Price DA, Leyland K, Addison GM. Longitudinal study of thyroid function in Down's syndrome in the first two decades. Arch.Dis.Child 2005 Jun;90(6):574-8. Abstract: AIMS AND METHODS: Thyroid function tests were initially carried out on 122 children with Down's syndrome aged 6-14 years and then repeated four to six years later in 103 adolescents (85% of the group of 122) when they were aged 10-20 years (median 14.4 years). At the second test two were hypothyroid and two with isolated raised thyroid stimulating hormone (IR-TSH) were receiving thyroxine. RESULTS: At the first test there were 98 (80%) euthyroid children: 83 were retested and four (5%) had IR-TSH. At the first test 24 had IR-TSH: 20 were retested and 14 (70%) had become normal. Seventeen with IR-TSH on initial testing had a thyrotrophin releasing hormone test within three months; TSH had become normal in eight (47%) of these children. There was no association between reported clinical symptoms and IR-TSH, but there were clear symptoms in one of the two with definite hypothyroidism. CONCLUSIONS: The likelihood ratio for a positive result on second testing when raised TSH and positive antibody status on first testing are combined is 20. This suggests initial testing results could be used as a basis to select a subgroup for further testing at say five yearly intervals unless new symptoms emerge in the interim. It also suggests that yearly screening (as recommended by the American Academy of Pediatrics, 2001) is probably not justified in the first 20 years of life. Hack M, Taylor HG, Drotar D, Schluchter M, Cartar L, Andreias L, Wilson-Costello D, Klein N. Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s. JAMA 2005 Jul 20;294(3):318-25. Abstract: CONTEXT: Information on the school-age functioning and special health care needs of extremely low- birth-weight (ELBW, <1000 g) children is necessary to plan for medical and educational services. OBJECTIVE: To examine neurosensory, developmental, and medical conditions together with the associated functional limitations and special health care needs of ELBW children compared with normal-birth-weight (NBW) term-born children (controls). DESIGN, SETTING, AND PARTICIPANTS: A follow-up study at age 8 years of a cohort of 219 ELBW children born 1992 to 1995 (92% of survivors) and 176 NBW controls of similar sociodemographic status conducted in Cleveland, Ohio. MAIN OUTCOME MEASURES: Parent Questionnaire for Identifying Children with Chronic Conditions of 12 months or more and categorization of specific medical diagnoses and developmental disabilities based on examination of the children. RESULTS: In logistic regression analyses adjusting for sociodemographic status and sex, ELBW children had significantly more chronic conditions than NBW controls, including functional limitations (64% vs 20%, respectively; odds ratio [OR], 8.1; 95% confidence interval [CI], 5.0-13.1; P<.001), compensatory dependency needs (48% vs 23%, respectively; OR, 3.0; 95% CI, 1.9-4.7; P<.001), and services above those routinely required by children (65% vs 27%, respectively; OR, 5.4; 95% CI, 3.4-8.5; P<.001). These differences remained significant when the 36 ELBW children with neurosensory impairments were excluded. Specific diagnoses and disabilities for ELBW vs NBW children included cerebral palsy (14% vs 0%, respectively; P<.001), asthma (21% vs 9%; OR, 3.0; 95% CI, 1.6-5.6; P = .001), vision of less than 20/200 (10% vs 3%; OR, 3.1; 95% CI, 1.2-7.8; P = .02), low IQ of less than 85 (38% vs 14%; OR, 4.5; 95% CI, 2.7-7.7; P<.001), limited academic skills (37% vs 15%; OR, 4.2; 95% CI, 2.5-7.3; P<.001), poor motor skills (47% vs 10%; OR, 7.8; 95% CI, 4.5-13.6; P<.001), and poor adaptive functioning (69% vs 34%; OR, 6.5; 95% CI, 4.0-10.6; P<.001). CONCLUSION: The ELBW survivors in school at age 8 years who were born in the 1990s have considerable long- term health and educational needs. Hagglund G, Andersson S, Duppe H, Pedertsen HL, Nordmark E, Westbom L. Prevention of severe contractures might replace multilevel surgery in cerebral palsy: results of a population- based health care programme and new techniques to reduce spasticity. J.Pediatr.Orthop.B 2005 Jul;14(4):269-73. Abstract: During the 1990s three new techniques to reduce spasticity and dystonia in children with cerebral palsy (CP) were introduced in southern Sweden: selective dorsal rhizotomy, continuous intrathecal baclofen infusion and botulinum toxin treatment. In 1994 a CP register and a health care programme, aimed to prevent hip dislocation and severe contractures, were initiated in the area. The total population of children with CP born 1990-1991, 1992-1993 and 1994-1995 was evaluated and compared at 8 years of age. In non-ambulant children the passive range of motion in hip, knee and ankle improved significantly from the first to the later age groups. Ambulant children had similar range of motion in the three age groups, with almost no severe contractures. The proportion of children treated with orthopaedic surgery for contracture or skeletal torsion deformity decreased from 40 to 15% (P = 0.0019). One-fifth of the children with spastic diplegia had been treated with selective dorsal rhizotomy. One-third of the children born 1994-1995 had been treated with botulinum toxin before 8 years of age. With early treatment of spasticity, early non-operative treatment of contracture and prevention of hip dislocation, the need for orthopaedic surgery for contracture or torsion deformity is reduced, and the need for multilevel procedures seems to be eliminated. Hancox RJ, Milne BJ, Poulton R. Association of television viewing during childhood with poor educational achievement. Arch.Pediatr.Adolesc.Med. 2005 Jul;159(7):614-8. Abstract: BACKGROUND: Excessive television viewing in childhood has been associated with adverse effects on health and behavior. A common concern is that watching too much television may also have a negative impact on education. However, no long-term studies have measured childhood viewing and educational achievement. OBJECTIVE: To explore these associations in a birth cohort followed up to adulthood. DESIGN: Prospective birth cohort study. SETTING: Dunedin, New Zealand. PARTICIPANTS: Approximately 1000 unselected individuals born between April 1, 1972, and March 31, 1973. Ninety-six percent of the living cohort participated at 26 years of age. MAIN OUTCOME MEASURES: Educational achievement by 26 years of age. RESULTS: The mean time spent watching television during childhood and adolescence was significantly associated with leaving school without qualifications and negatively associated with attaining a university degree. Risk ratios for each hour of television viewing per weeknight, adjusted for IQ and sex, were 1.43 (95% confidence interval [CI], 1.24-1.65) and 0.75 (95% CI, 0.67-0.85), respectively (both, P<.001). The findings were similar in men and women and persisted after further adjustment for socioeconomic status and early childhood behavioral problems. Television viewing during childhood (ages 5-11 years) and adolescence (ages 13 and 15 years) had adverse associations with later educational achievement. However, adolescent viewing was a stronger predictor of leaving school without qualifications, whereas childhood viewing was a stronger predictor of nonattainment of a university degree. CONCLUSIONS: Television viewing in childhood and adolescence is associated with poor educational achievement by 26 years of age. Excessive television viewing in childhood may have long-lasting adverse consequences for educational achievement and subsequent socioeconomic status and well-being. Khemka I, Hickson L, Reynolds G. Evaluation of a decision-making curriculum designed to empower women with mental retardation to resist abuse. Am.J.Ment.Retard. 2005 May;110(3):193-204. Abstract: The effectiveness of an abuse-prevention curriculum, designed to empower women with mental retardation to become effective decision-makers able to protect themselves against abuse was examined. Thirty-six women with mental retardation were randomly assigned to either an intervention or a control group. Results indicate that the performance of the women in the intervention group was superior to that of the women in the control group on measures of knowledge, decision-making, and empowerment but not on a measure of stress management. The findings suggest that women with mental retardation can acquire effective decision-making strategies and apply them to situations of abuse in their lives. Kim HS, Steinbok P, Wickenheiser D. Predictors of poor outcome after selective dorsal rhizotomy in treatment of spastic cerebral palsy. Childs Nerv.Syst. 2005 May 19. Abstract: OBJECTIVES: The purpose of the study was to determine if there are preoperative clinical characteristics that might be predictive of a poor outcome after selective dorsal rhizotomy (SDR) surgery in children with spastic cerebral palsy (CP). METHODS: A retrospective analysis was performed on 174 children who had undergone SDR from 1983 to 2001. Patients were divided into two groups according to their outcome at approximately 1 year after surgery: "acceptable" or "poor" outcome. As predictors of outcome, the factors compared were age at operation, types of CP (diplegia, quadriplegia), history of prematurity, prior lower limb orthopedic surgeries, history of seizures, dystonic limbs, opisthotonic posturing, lumbar hyperlordosis, truncal hypotonia, preoperative ambulatory function, preoperative Gross Motor Function Classification System (GMFCS) scores, and presence of intellectual delay and speech delay. RESULTS: Eleven children (6.3%) had a "poor" outcome. The type of CP (P<0.001) and intellectual delay (P=0.015) were significant predictors of outcome in the univariate regression analysis, but only the type of CP retained significant predictive power in the multivariate analysis. CONCLUSION: These data suggest that preoperative diagnosis is the strongest predictor of outcome after SDR. Intellectual delay demonstrated predictive power only in the univariate model, suggesting that it might have some prognostic value but less than the diagnosis. O'Shea TM, Shankaran S, Bhaskar B. Adverse neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: prevalence and antecedents. Pediatrics 2005 Mar;115(3):673-80. Abstract: OBJECTIVE: Severe abnormalities of the head ultrasound (HUS) are important predictors of cerebral palsy (CP) and mental retardation, and a normal HUS usually ensures the absence of major impairments. With the increasing survival of extremely low birth weight (ELBW) infants (birth weight <1000 g), the prognostic significance of a normal HUS may differ. This study examined the prevalence of and risk factors for CP and impaired mental development among ELBW infants with a normal HUS. METHODS: Study infants were ELBW infants who were cared for in Neonatal Research Network centers in the years 1995-1999, had a normal early and late HUS, survived to discharge, and returned for follow-up assessments at 18 to 22 months' corrected age. The outcomes of interest were a score <70 on the Bayley Scales of Infant Development-II Mental Developmental Index (MDI) and CP. Risk factors included maternal demographics; infant characteristics; and interventions or morbidities related to the lung, infection, and nutrition. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A time-oriented approach was used to select variables for inclusion in logistic models. RESULTS: Of 1749 infants with a normal early and late HUS (performed at a mean age of 6 and 47 days, respectively), 1473 (84%) returned for follow-up assessment. Infants had a birth weight of 792 +/- 134 g (mean +/- SD) and gestational age of 26 +/- 2 weeks. Rates of CP and MDI <70 were 9.4% and 25.3%, respectively, and 29.2% of infants had either CP or MDI <70. In multivariate analyses, factors associated with CP were male gender (OR: 1.8; 95% CI: 1.2-2.6), multiple birth, (OR: 1.6; 95% CI: 1.1-2.5), decreasing birth weight (OR: 1.3 for each 100-g decrease; 95% CI: 1.1-1.5), pneumothorax (OR: 2.3; 95% CI: 1.2-4.4), and days of conventional ventilation (OR: 1.2 for each additional 10 days; 95% CI: 1.1-1.3). With the exception of pneumothorax, these same factors were associated with MDI <70, in addition to less maternal education (OR: 1.4; 95% CI: 1.0-1.9) and Medicaid or lack of coverage for maternal insurance (OR: 1.7; 95% CI: 1.2-2.4). CONCLUSIONS: Nearly 30% of ELBW infants with a normal HUS had either CP or a low MDI. Risk factors that are associated with this high rate of adverse outcomes include pneumothorax, prolonged exposure to mechanical ventilation, and educational and economic disadvantage. Improvements in pulmonary care to reduce duration of ventilation and avoid air leaks might improve neurodevelopmental outcome for ELBW infants. Lee J, Croen LA, Backstrand KH, Yoshida CK, Henning LH, Lindan C, Ferriero DM, Fullerton HJ, Barkovich AJ, Wu YW. Maternal and infant characteristics associated with perinatal arterial stroke in the infant. JAMA 2005 Feb 9;293(6):723-9. Abstract: CONTEXT: Perinatal arterial ischemic stroke (PAS) is a common cause of hemiplegic cerebral palsy. Risk factors for this condition have not been clearly defined. OBJECTIVE: To determine maternal and infant characteristics associated with PAS. DESIGN, SETTING, AND PATIENTS: Case-control study nested within the cohort of all 199,176 infants born from 1997 through 2002 in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were confirmed by review of brain imaging and medical records (n = 40). Three controls per case were randomly selected from the study population. MAIN OUTCOME MEASURE: Association of maternal and infant complications with risk of PAS. RESULTS: The population prevalence of PAS was 20 per 100,000 live births. The majority (85%) of infants with PAS were delivered at term. The following prepartum and intrapartum factors were more common among case than control infants: primiparity (73% vs 44%, P = .002), fetal heart rate abnormality (46% vs 14%, P<.001), emergency cesarean delivery (35% vs 13%, P = .002), chorioamnionitis (27% vs 11%, P = .03), prolonged rupture of membranes (26% vs 7%, P = .002), prolonged second stage of labor (25% vs 4%, P<.001), vacuum extraction (24% vs 11%, P = .04), cord abnormality (22% vs 6%, P = .01), preeclampsia (19% vs 5%, P = .01), and oligohydramnios (14% vs 3%, P = .01). Risk factors independently associated with PAS on multivariate analysis were history of infertility (odds ratio [OR], 7.5; 95% confidence interval [CI], 1.3-45.0), preeclampsia (OR, 5.3; 95% CI, 1.3-22.0), prolonged rupture of membranes (OR, 3.8; 95% CI, 1.1-12.8), and chorioamnionitis (OR, 3.4; 95% CI, 1.1-10.5). The rate of PAS increased dramatically when multiple risk factors were present. CONCLUSIONS: Perinatal arterial ischemic stroke in infants is associated with several independent maternal risk factors. How these complications, along with their potential effects on the placenta and fetus, may play a role in causing perinatal stroke deserves further study. Lenhard W, Breitenbach E, Ebert H, Schindelhauer-Deutscher HJ, Henn W. Psychological benefit of diagnostic certainty for mothers of children with disabilities: lessons from Down syndrome. Am.J.Med.Genet.A 2005 Mar 1;133(2):170-5. Abstract: Diagnostic and prognostic uncertainty is one of the major psychological stressors for patients in acute and chronic illness, as well as for parents of children with disabilities or chronic disease. Whereas the parents' feeling of uncertainty is undoubtedly very strong shortly after the birth of a child with disabilities, the long-term effects on the parents of having or not having a precise genetic diagnosis, in terms of emotional stress, remain unclear. In this study, mothers of non-disabled children are compared to mothers of children with Down syndrome, and to mothers of children with a diagnostically unassigned mental retardation with regard to the level of anxiety, feelings of guilt, and emotional burden. While the mothers of children with Down syndrome score comparably to the mothers of non- disabled children, the results show broad psychoemotional disadvantages for mothers of children with a mental retardation of unknown etiology. Consequently, the value of genetic diagnosis of infantile disabilities encompasses, beyond clinical considerations like therapy planning and assignment of the recurrence risk for siblings, significant and long-lasting emotional relief for the parents. Linnet KM, Wisborg K, Obel C, Secher NJ, Thomsen PH, Agerbo E, Henriksen TB. Smoking during pregnancy and the risk for hyperkinetic disorder in offspring. Pediatrics 2005 Aug;116(2):462-7. Abstract: OBJECTIVE: Maternal smoking during pregnancy may increase the risk for behavioral disorders. The aim of this study was to investigate the association between smoking during pregnancy and hyperkinetic and attention- deficit/hyperactivity disorder in the offspring in a large population-based study. METHODS: This study was designed as a nested case-control study. Data were obtained from Danish longitudinal registers and included 170 children with hyperkinetic disorder and 3765 population-based control subjects, who were matched by age, gender, and date of birth. Potential confounders, including newborn characteristics, socioeconomic status, and family history of psychiatric illnesses, were evaluated by conditional logistic regression analyses. RESULTS: Women who smoked during pregnancy had a 3-fold increased risk for having offspring with hyperkinetic disorder compared with nonsmokers. Socioeconomic factors and history of mental disorder in the parents or siblings seemed to confound the result to some extent (adjusted relative risk: 1.9; 95% confidence interval: 1.3-2.8). Adjustment for parental age or exclusion of children with low birth weight (<2500 g), preterm delivery (<37 weeks completed gestation), and Apgar scores <7 at 5 minutes revealed no changes in the results. Also, excluding children with conduct disorders or comorbid disorders revealed no change in the results. CONCLUSIONS: Our results showed an increased risk for hyperkinetic disorder in children of mothers who smoked during pregnancy. This could not be explained by newborn characteristics, parental socioeconomic status, family history of psychiatric hospitalizations or contact as outpatients, conduct disorders, or comorbidity. Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch.Dis.Child Fetal Neonatal Ed 2005 Sep;90(5):F380-F387. Abstract: BACKGROUND: Adverse cognitive and educational outcomes are often ascribed to perinatal hypoxia without good evidence. OBJECTIVE: To investigate neurocognitive and behavioural outcomes after neonatal encephalopathy. METHODS: Sixty five children with neonatal encephalopathy, identified using the Trent Neonatal Survey database for 1992-1994, were followed up at the age of 7 years. They were examined at school, with a classmate for those in mainstream school, by a paediatrician and a psychologist. Neonatal encephalopathy was graded as moderate or severe using published definitions.Findings: Fifteen children had major disability, all with cerebral palsy; eight were in special school with severe cognitive impairment (IQ<55). Disability was present in 6% of the moderate and 42% of the severe encephalopathy group. Of the 50 children without motor disability, cognitive scores were lowest in the severe group (mean IQ difference from peers -11.3 points (95% confidence interval (CI) - 19.0 to -3.6) and with similar scores for the moderate group compared with classmates (mean difference -1.7 points (95% CI -7.3 to +3.9). Neuropsychological testing showed similar findings in all domains. In particular, memory and attention/executive functions were impaired in the severe group. Despite relatively small differences in performance of the moderate group, special educational needs were identified more often in both encephalopathy groups, associated with lower achievement on national curriculum attainment targets. INTERPRETATION: After neonatal encephalopathy, subtle cognitive impairments are found in the absence of neuromotor impairment. Subtle impairments are found more commonly after a more severe clinical course. Studies of brain protection strategies require long term follow up to study effects on cognitive outcome. Marlow N, Wolke D, Bracewell MA, Samara M. Neurologic and developmental disability at six years of age after extremely preterm birth. N.Engl.J.Med. 2005 Jan 6;352(1):9-19. Abstract: BACKGROUND: Birth before 26 weeks of gestation is associated with a high prevalence of neurologic and developmental disabilities in the infant during the first two years of life. METHODS: We studied at the time of early school age children who had been born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland in 1995. Each child had been evaluated at 30 months of age. The children underwent standardized cognitive and neurologic assessments at six years of age. Disability was defined as severe (indicating dependence on caregivers), moderate, or mild according to predetermined criteria. RESULTS: Of 308 surviving children, 241 (78 percent) were assessed at a median age of six years and four months; 160 classmates delivered at full term served as a comparison group. Although the use of test reference norms showed that cognitive impairment (defined as results more than 2 SD below the mean) was present in 21 percent of the children born extremely preterm (as compared with 1 percent in the standardized data), this value rose to 41 percent when the results were compared with those for their classmates. The rates of severe, moderate, and mild disability were 22 percent, 24 percent, and 34 percent, respectively; disabling cerebral palsy was present in 30 children (12 percent). Among children with severe disability at 30 months of age, 86 percent still had moderate-to-severe disability at 6 years of age. In contrast, other disabilities at the age of 30 months were poorly predictive of developmental problems at 6 years of age. CONCLUSIONS: Among extremely preterm children, cognitive and neurologic impairment is common at school age. A comparison with their classroom peers indicates a level of impairment that is greater than is recognized with the use of standardized norms. McDougle CJ, Scahill L, Aman MG, McCracken JT, Tierney E, Davies M, Arnold LE, Posey DJ, Martin A, Ghuman JK, et al. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Am.J.Psychiatry 2005 Jun;162(6):1142-8. Abstract: OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self- injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. CONCLUSIONS: Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism. Natowicz M. Newborn screening--setting evidence-based policy for protection. N.Engl.J.Med. 2005 Sep 1;353(9):867-70. This article provides a table of conditions for which neonates should be screened; it is based on the consensus of geneticists from around the country. Nelson KB, Dambrosia JM, Iovannisci DM, Cheng S, Grether JK, Lammer E. Genetic polymorphisms and cerebral palsy in very preterm infants. Pediatr.Res. 2005 Apr;57(4):494-9. Abstract: In the present study, we examine whether selected genetic polymorphisms contribute to the development of cerebral palsy (CP) in very preterm infants. Subjects were 96 singleton infants with later-diagnosed CP and 119 control children, white non-Hispanic (n for CP=74, controls=88) or white Hispanic (CP=22, controls=31), born <32 wk gestation. Presence of CP was identified through state service agencies, with review of medical records. DNA extracted from archived neonatal blood was genotyped using multi-locus polymerase chain reaction amplification and immobilized sequence-specific oligonucleotide probes. Single nucleotide polymorphisms (SNPs) showing evidence of association with development of CP were endothelial nitric oxide synthase (eNOS) A(-922)G, factor 7 (F7) arg353gln and del(-323)10bp-ins, and lymphotoxin A (LTA) thr26asn. In white non-Hispanic children, beta-2 adrenergic receptor gln27glu was associated with CP risk; in Hispanic children, plasminogen activator inhibitor-1 (PAI-1) 4G(-675)5G and G11053T were associated with risk of CP. In a logistic regression considering these SNPs simultaneously in non-Hispanics, an association with CP was observed for heterozygotes of eNOS -922 (OR 3.0, CI 1.4-6.4), F7 (OR 2.7, CI 1.1-6.5), LTA (OR 2.1, CI 1.0-4.6), and PAI-1 (OR 3.2, CI 1.2-8.7). Factor 5, Factor 2, methylene tetrahydrofolate reductase, tumor necrosis factor-alpha, and other SNPs tested were not significantly associated with CP risk. We conclude that further study of genetic factors that may influence susceptibility to CP in very preterm infants is warranted. Neufeld MD, Frigon C, Graham AS, Mueller BA. Maternal infection and risk of cerebral palsy in term and preterm infants. J.Perinatol. 2005 Feb;25(2):108-13. Abstract: OBJECTIVE: We tested the hypothesis that term and preterm infants exposed to maternal infection at the time of delivery are at increased risk of developing cerebral palsy (CP). STUDY DESIGN: A population-based case- control study was conducted using Washington State birth certificate data linked to hospital discharge data. Cases (688) were children <or=6 years old, singleton births, hospitalized during 1987 to 1999 with an ICD-9 diagnosis code for CP. Controls were 3,068 singleton birth infants randomly selected from birth records for the same years without CP-related hospitalizations. Infection information was available only for the birth hospitalization. RESULTS: Infants of women who had any infection during their hospitalization for delivery were at increased risk of CP (odds ratio (OR) 3.1, 95% confidence interval (CI) 2.3 to 4.2). This was observed for term deliveries (OR 1.8, 95% CI 1.1 to 2.8) and preterm deliveries (OR 2.3, 95% CI 1.3 to 4.2). CONCLUSIONS: Our results suggest that maternal infection is a risk factor for CP in both term and preterm infants. Onishi KH, Baillargeon R. Do 15-month-old infants understand false beliefs? Science 2005 Apr 8;308(5719):255-8. Abstract: For more than two decades, researchers have argued that young children do not understand mental states such as beliefs. Part of the evidence for this claim comes from preschoolers' failure at verbal tasks that require the understanding that others may hold false beliefs. Here, we used a novel nonverbal task to examine 15-month-old infants' ability to predict an actor's behavior on the basis of her true or false belief about a toy's hiding place. Results were positive, supporting the view that, from a young age, children appeal to mental states--goals, perceptions, and beliefs--to explain the behavior of others. Paradise JL, Campbell TF, Dollaghan CA, Feldman HM, Bernard BS, Colborn DK, Rockette HE, Janosky JE, Pitcairn DL, Kurs-Lasky M, et al. Developmental outcomes after early or delayed insertion of tympanostomy tubes. N.Engl.J.Med. 2005 Aug 11;353(6):576-86. Abstract: BACKGROUND: To prevent later developmental impairments, myringotomy with the insertion of tympanostomy tubes has often been undertaken in young children who have persistent otitis media with effusion. We previously reported that prompt as compared with delayed insertion of tympanostomy tubes in children with persistent effusion who were younger than three years of age did not result in improved developmental outcomes at three or four years of age. However, the effect on the outcomes of school-age children is unknown. METHODS: We enrolled 6350 healthy infants younger than 62 days of age and evaluated them regularly for middle-ear effusion. Before three years of age, 429 children with persistent middle-ear effusion were randomly assigned to have tympanostomy tubes inserted either promptly or up to nine months later if effusion persisted. We assessed developmental outcomes in 395 of these children at six years of age. RESULTS: At six years of age, 85 percent of children in the early-treatment group and 41 percent in the delayed-treatment group had received tympanostomy tubes. There were no significant differences in mean (+/-SD) scores favoring early versus delayed treatment on any of 30 measures, including the Wechsler Full-Scale Intelligence Quotient (98+/-13 vs. 98+/-14); Number of Different Words test, a measure of word diversity (183+/-36 vs. 175+/-36); Percentage of Consonants Correct-Revised test, a measure of speech-sound production (96+/-2 vs. 96+/-3); the SCAN test, a measure of central auditory processing (95+/-15 vs. 96+/-14); and several measures of behavior and emotion. CONCLUSIONS: In otherwise healthy children younger than three years of age who have persistent middle-ear effusion within the duration of effusion that we studied, prompt insertion of tympanostomy tubes does not improve developmental outcomes at six years of age. Ramaekers VT, Rothenberg SP, Sequeira JM, Opladen T, Blau N, Quadros EV, Selhub J. Autoantibodies to folate receptors in the cerebral folate deficiency syndrome. N.Engl.J.Med. 2005 May 12;352(19):1985-91. Abstract: In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum specimens from 28 children with cerebral folate deficiency, 5 of their mothers, 28 age-matched control subjects, and 41 patients with an unrelated neurologic disorder. Serum from 25 of the 28 patients and 0 of 28 control subjects contained high-affinity blocking autoantibodies against membrane-bound folate receptors that are present on the choroid plexus. Oral folinic acid normalized 5MTHF levels in the cerebrospinal fluid and led to clinical improvement. Cerebral folate deficiency is a disorder in which autoantibodies can prevent the transfer of folate from the plasma to the cerebrospinal fluid. Rao MR, Brenner RA, Schisterman EF, Vik T, Mills JL. Long term cognitive development in children with prolonged crying. Arch.Dis.Child 2004 Nov;89(11):989-92. Abstract: BACKGROUND: Long term studies of cognitive development and colic have not differentiated between typical colic and prolonged crying. OBJECTIVE: To evaluate whether colic and excessive crying that persists beyond 3 months is associated with adverse cognitive development. DESIGN: Prospective cohort study. A sample of 561 women was enrolled in the second trimester of pregnancy. Colic and prolonged crying were based on crying behaviour assessed at 6 and 13 weeks. Children's intelligence, motor abilities, and behaviour were measured at 5 years (n = 327). Known risk factors for cognitive impairment were ascertained prenatally, after birth, at 6 and 13 weeks, at 6, 9, and 13 months, and at 5 years of age. RESULTS: Children with prolonged crying (but not those with colic only) had an adjusted mean IQ that was 9 points lower than the control group. Their performance and verbal IQ scores were 9.2 and 6.7 points lower than the control group, respectively. The prolonged crying group also had significantly poorer fine motor abilities compared with the control group. Colic had no effect on cognitive development. CONCLUSIONS: Excessive, uncontrolled crying that persists beyond 3 months of age in infants without other signs of neurological damage may be a marker for cognitive deficits during childhood. Such infants need to be examined and followed up more intensively. Sanz EJ, De-las-Cuevas C, Kiuru A, Bate A, Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 2005 Feb 5;365(9458):482-7. Abstract: BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with withdrawal symptoms. We investigated whether use of these drugs in pregnant women might cause neonatal withdrawal syndrome. METHODS: An association between paroxetine and neonatal convulsions was identified in December, 2001, by the data mining method routinely used to screen the WHO database of adverse drug reactions. An information component (IC) measure was used to screen for unexpected adverse reactions relative to the information in the database. We then assessed cases of neonatal convulsions and neonatal withdrawal syndrome associated with drugs included in the anatomical therapeutic chemical groups N06AB and N06AX. FINDINGS: By November, 2003, a total of 93 suspected cases of SSRI-induced neonatal withdrawal syndrome had been reported, and were regarded as enough information to confirm a possible causal relation. 64 of the cases were associated with paroxetine, 14 with fluoxetine, nine with sertraline, and seven with citalopram. The IC-2 SD for the group became greater than 0 in the first quarter of 1991, and the IC increased to 2.68 (IC-2 SD 0.32) by the second quarter of 2003. For each individual compound, the IC-2 SD was greater than 0. INTERPRETATION: SSRIs, especially paroxetine, should be cautiously managed in the treatment of pregnant women with a psychiatric disorder. Schlumberger E, Narbona J, Manrique M. Non-verbal development of children with deafness with and without cochlear implants. Dev.Med.Child Neurol. 2004 Sep;46(9):599-606. Abstract: Deprivation of sensory input affects neurological development. Our objective was to explore clinically the role of hearing in development of sensorimotor integration and non-verbal cognition. The study involved 54 children (15 males, 839 females; 5 to 9 years old) with severe or profound bilateral prelocutive deafness but without neurological or cognitive impairment. Of these, 25 had received an early cochlear implant (CIm). Patients were compared with 40 children with normal hearing. All were given a battery of non-verbal neuropsychological tests and a balance test, and were timed for simple and complex movement of limbs. Deafness, whether treated by CIm or not, resulted in a delay in development of complex motor sequences and balance. Lack of auditory input was also associated with lower, but non-pathological, scores in visual gnoso-praxic tasks and sustained attention. Such differences were not observed in children with CIm. Hearing contributes to clinical development of spatial integration, motor control, and attention. An early CIm enables good verbal development and might also improve non-verbal capacities. Skotko BG. Prenatally diagnosed Down syndrome: mothers who continued their pregnancies evaluate their health care providers. Am.J.Obstet.Gynecol. 2005 Mar;192(3):670-7. Abstract: OBJECTIVE: This study was undertaken to ask mothers who had children with Down syndrome after receiving a prenatal diagnosis: How was the process and what, if anything, could be improved? STUDY DESIGN: An 11-page survey was mailed to 2945 persons on the membership lists of 5 Down syndrome parent organizations. The survey gathered both quantitative and qualitative data from yes/no questions, open-ended questions, and a series of statements asking the mothers to rate their level of agreement on a 1-to-7 Likert scale. Qualitative data were analyzed using the Constant Comparative Method of Qualitative Analysis, and quantitative data were summarized using linear regressions, mixed stepwise multiple regressions, and grouped means, 1-way analysis of variance analyses. RESULTS: Of 1126 surveys received, 141 (12.5%) were from mothers who had received a prenatal diagnosis. Though satisfied with the care that they had received, the majority of respondents expressed frustration with the process. The most common suggestions were that the diagnosis be conveyed in person, that up-to-date printed materials on Down syndrome (DS) be provided, and that mothers be referred to local DS support groups. CONCLUSION: Receiving a prenatal diagnosis of DS need not be a negative experience. By implementing suggestions proposed herein by the mothers, health care providers can even make the situation a positive one. van Schie PE, Vermeulen RJ, van Ouwerkerk WJ, Kwakkel G, Becher JG. Selective dorsal rhizotomy in cerebral palsy to improve functional abilities: evaluation of criteria for selection. Childs Nerv.Syst. 2005 Jun;21(6):451-7. Abstract: OBJECTIVES: The aim of this study is to evaluate the effect of selective dorsal rhizotomy (SDR) on functional abilities in a well-defined group of ambulatory children with spastic diplegia. METHODS: Nine children were selected for SDR (mean age 65 months, range 43-82 months). Gross motor function was measured with the Gross Motor Function Measure (GMFM-88). Self-care was assessed with the Pediatric Evaluation of Disability Inventory (PEDI) and gait pattern was measured with the Edinburgh Visual Gait Score (EGS). There were nine single-case research designs with a 12-month follow-up after surgery. RESULTS: After 12 months the mean improvement in the total GMFM-88 scores was 8.8%. On an individual level, all patients improved significantly in comparison with baseline. Functional skills and care-giver assistance measured with the PEDI showed significant improvement. Improvement in gait was also found; in particular, better initial contact and heel-lift resulted in an increased EGS. CONCLUSION: In this well-defined group of ambulatory children SDR had a small but significant positive effect on gross motor function, self-care and gait pattern. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann.Neurol. 2005 Jan;57(1):67-81. Abstract: Brain tissues from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.
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