Year's Top 10 Articles on Developmental Disabilities: 2003

The following ten articles dealing with Developmental Medicine, including Cerebral Palsy, and published between September 2002 and August 2003, were chosen by Dr. Gregory Liptak, University of Rochester and Dr. Gordon Worley, Duke University. They were reviewed during an Instructional Course at the Annual Meeting of the American Academy for Cerebral Palsy and Developmental Medicine in Montreal, Quebec, Canada. A summary of these articles with their abstracts is posted as a convenience for those who were unable to attend.

10. Rosenbaum PL, Walter SD, Hanna SE et al. Prognosis for gross motor function in cerebral palsy: creation of motor development curves. JAMA. 2002;288: 1357-1363.

Abstract: CONTEXT: Lack of a valid classification of severity of cerebral palsy and the absence of longitudinal data on which to base an opinion have made it difficult to consider prognostic issues accurately. OBJECTIVE: To describe patterns of gross motor development of children with cerebral palsy by severity, using longitudinal observations, as a basis for prognostic counseling with parents and for planning clinical management. DESIGN: Longitudinal cohort study of children with cerebral palsy, stratified by age and severity of motor function and observed serially for up to 4 years during the period from 1996 to 2001. SETTING: Nineteen publicly funded regional children's ambulatory rehabilitation programs in Ontario. PARTICIPANTS: A total of 657 children aged 1 to 13 years at study onset, representing the full spectrum of clinical severity of motor impairment in children with cerebral palsy. MAIN OUTCOME MEASURES: Severity of cerebral palsy, classified with the 5-level Gross Motor Function Classification System; function, formally assessed with the Gross Motor Function Measure (GMFM). RESULTS: Based on a total of 2632 GMFM assessments, 5 distinct motor development curves were created; these describe important and significant differences in the rates and limits of gross motor development among children with cerebral palsy by severity. There is substantial within-stratum variation in gross motor development. CONCLUSIONS: Evidence-based prognostication about gross motor progress in children with cerebral palsy is now possible, providing parents and clinicians with a means to plan interventions and to judge progress over time. Further work is needed to describe motor function of adolescents with cerebral palsy.

9. Liu J, Raine A, Venables PH, Dalais C, Mednick SA. Malnutrition at age 3 years and lower cognitive ability at age 11 years: independence from psychosocial adversity. Arch.Pediatr.Adolesc.Med. 2003;157: 593-600.

Abstract: BACKGROUND: Early malnutrition is linked to poor cognition, but long-term effects have not been extensively examined and psychosocial confounds have not always been controlled. OBJECTIVE: To test the hypothesis that malnutrition at age 3 years will be associated with poorer cognitive ability at age 11 years independent of psychosocial confounds. DESIGN: A prospective, longitudinal study of a birth cohort of 1559 children originally assessed at age 3 years for malnutrition (low hemoglobin level, angular stomatitis, kwashiorkor, and sparse, thin hair) and followed up to age 11 years. SETTING AND PARTICIPANTS: A community sample of 1559 children (51.4% boys and 48.6% girls) born between September 1, 1969, and August 31, 1970, in 2 towns in the island of Mauritius, with 68.7% Indians and 25.7% Creoles (African origin). MAIN OUTCOME MEASURES: Verbal and spatial ability measured at ages 3 and 11 years and reading, scholastic ability, and neuropsychologic performance measured at age 11 years. RESULTS: Malnourished children had poorer cognition at both ages. Deficits were stable across time, applied to all sex and ethnic groups, and remained after controlling for multiple measures of psychosocial adversity. Children with 3 indicators of malnutrition had a 15.3-point deficit in IQ at age 11 years. CONCLUSIONS: Malnutrition at age 3 years is associated with poor cognition at age 11 years independent of psychosocial adversity. Promoting early childhood nutrition could enhance long-term cognitive development and school performance, especially in children with multiple nutritional deficits.

8. Dammann O, Drescher J, Veelken N. Maternal fever at birth and non-verbal intelligence at age 9 years in preterm infants. Dev.Med.Child Neurol. 2003;45: 148-151.

Abstract: To test the hypothesis that characteristics of perinatal infection are associated with long-term cognitive limitations among preterm infants, we analyzed data from 294 infants (142 females, 152 males) < or = 1500 g birthweight and <37 completed weeks of gestation who were examined at age 9 years. We identified 47 children (20 females, 27 males) who had a non-verbal Kaufman Assessment Battery for Children (K-ABC) scale standard value below 70, i.e. more than 2 SDs below the age-adjusted mean. The 247 children (122 females, 125 males) with a score > or = 70 served as control participants. Maternal nationality and education, and low gestational age were significantly associated with a K-ABC non-verbal standard value <70. Both neonatal brain damage (intraventricular hemorrhage) and long-term sequelae (cerebral palsy [CP], diagnosed at age 6 years) were significantly associated with a below-normal non-verbal K-ABC score. Maternal fever at birth was present in five cases (11%) and eight controls (3%; odds ratio 3.6, 95% confidence interval 1.1 to 11.4). Clinical chorioamnionitis and preterm labor and/or premature rupture of membranes (as opposed to toxemia and other initiators of preterm delivery) were also more common among cases than control participants. When adjusting for potential confounders such as gestational age, maternal education and nationality, and CP, the risk estimate for maternal fever remained unchanged (3.8, 0.97 to 14.6). We conclude that perinatal infection might indeed contribute to an increased risk for long-term cognitive deficits in preterm infants.

7. Koenen KC, Moffitt TE, Caspi A, Taylor A, Purcell S. Domestic violence is associated with environmental suppression of IQ in young children. Dev.Psychopathol. 2003;15: 297-311.

Abstract: Research suggests that exposure to extreme stress in childhood, such as domestic violence, affects children's neurocognitive development, leading to lower intelligence. But studies have been unable to account for genetic influences that might confound the association between domestic violence and lower intelligence. This twin study tested whether domestic violence had environmentally mediated effects on young children's intelligence. Children's IQs were assessed for a population sample of 1116 monozygotic and dizygotic 5-year-old twin pairs in England. Mothers reported their experience of domestic violence in the previous 5 years. Ordinary least squares regression showed that domestic violence was uniquely associated with IQ suppression in a dose-response relationship. Children exposed to high levels of domestic violence had IQs that were, on average, 8 points lower than unexposed children. Structural equation models showed that adult domestic violence accounted for 4% of the variation, on average, in child IQ, independent of latent genetic influences. The findings are consistent with animal experiments and human correlational studies documenting the harmful effects of extreme stress on brain development Programs that successfully reduce domestic violence should also have beneficial effects on children's cognitive development.

6. Castellanos FX, Lee PP, Sharp W et al. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA. 2002;2288:1740-1748.

Abstract: CONTEXT: Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder (ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls (-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were <.05). CONCLUSIONS: Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.

5. Cowan F, Rutherford M, Groenendaal F et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet. 2003;361: 736-742.

Abstract: BACKGROUND: The role of intrapartum asphyxia in neonatal encephalopathy and seizures in term infants is not clear, and antenatal factors are being implicated in the causal pathway for these disorders. However, there is no evidence that brain damage occurs before birth. We aimed to test the hypothesis that neonatal encephalopathy, early neonatal seizures, or both result from early antenatal insults. METHODS: We used brain MRI or post-mortem examination in 351 fullterm infants with neonatal encephalopathy, early seizures, or both to distinguish between lesions acquired antenatally and those that developed in the intrapartum and early post-partum period. We excluded infants with major congenital malformations or obvious chromosomal disorders. Infants were divided into two groups: those with neonatal encephalopathy (with or without seizures), and evidence of perinatal asphyxia (group 1); and those without other evidence of encephalopathy, but who presented with seizures within 3 days of birth (group 2). FINDINGS: Brain images showed evidence of an acute insult without established injury or atrophy in 197 (80%) of infants in group 1, MRI showed evidence of established injury in only 2 infants (<1%), although tiny foci of established white matter gliosis, in addition to acute injury, were seen in three of 21 on post-mortem examination. In group 2, acute focal damage was noted in 62 (69%) of infants. Two (3%) also had evidence of antenatal injury. INTERPRETATION: Although our results cannot exclude the possibility that antenatal or genetic factors might predispose some infants to perinatal brain injury, our data strongly suggest that events in the immediate perinatal period are most important in neonatal brain injury.

4. DeLong GR, Ritch CR, Burch S. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. Dev.Med.Child Neurol. 2002;44: 652-659.

Abstract: One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Autism Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

3. Canfield RL, Henderson CR, Jr., Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N.Engl.J.Med. 2003;348: 1517-1526.

Abstract: BACKGROUND: Despite dramatic declines in children's blood lead concentrations and a lowering of the Centers for Disease Control and Prevention's level of concern to 10 microg per deciliter (0.483 micromol per liter), little is known about children's neurobehavioral functioning at lead concentrations below this level. METHODS: We measured blood lead concentrations in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age and administered the Stanford-Binet Intelligence Scale at the ages of 3 and 5 years. The relation between IQ and blood lead concentration was estimated with the use of linear and nonlinear mixed models, with adjustment for maternal IQ, quality of the home environment, and other potential confounders. RESULTS: The blood lead concentration was inversely and significantly associated with IQ. In the linear model, each increase of 10 microg per deciliter in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ (P=0.004), whereas for the subsample of 101 children whose maximal lead concentrations remained below 10 microg per deciliter, the change in IQ associated with a given change in lead concentration was greater. When estimated in a nonlinear model with the full sample, IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 microg per deciliter. CONCLUSIONS: Blood lead concentrations, even those below 10 microg per deciliter, are inversely associated with children's IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated.

2. Caspi A, Sugden K, Moffitt TE et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301: 386-389.

Abstract: In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup.

1. Chase-Lansdale PL, Moffitt RA, Lohman BJ et al. Mothers' transitions from welfare to work and the well-being of preschoolers and adolescents. Science. 2003;299: 1548-1552.

Abstract: Results from a longitudinal study of 2402 low-income families during the recent unprecedented era of welfare reform suggest that mothers' transitions off welfare and into employment are not associated with negative outcomes for preschoolers (ages 2 to 4 years) or young adolescents (ages 10 to 14 years). Indeed, no significant associations with mothers' welfare and employment transitions were found for preschoolers, and the dominant pattern was also of few statistically significant associations for adolescents. The associations that did occur provided slight evidence that mothers' entry into the labor force was related to improvements in adolescents' mental health, whereas exits from employment were linked with teenagers' increased behavior problems.