AACPDMrunnersup2005 by I91J4s


									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
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
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
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
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

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
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
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
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
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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