Year's Top 10 Articles on Developmental Disabilities: 2005

10. St. Clair D, Xu M, Wang P, Yu Y, Fang Y, Zhang F, Zheng X, Gu N, Feng G, Sham P, et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959-1961. JAMA 2005 Aug 3;294(5):557-62.

Abstract: CONTEXT: Schizophrenia is a common major mental disorder. Intrauterine nutritional deficiency may increase the risk of schizophrenia. The main evidence comes from studies of the 1944-1945 Dutch Hunger Winter when a sharp and time-limited decline in food intake occurred. The most exposed cohort conceived during the famine showed a 2-fold increased risk of schizophrenia. OBJECTIVE: To determine whether those who endured a massive 1959-1961 famine in China experienced similar results. DESIGN, SETTING, AND PARTICIPANTS: The risk of schizophrenia was examined in the Wuhu region of Anhui, one of the most affected provinces. Rates were compared among those born before, during, and after the famine years. Wuhu and its surrounding 6 counties are served by a single psychiatric hospital. All psychiatric case records for the years 1971 through 2001 were examined, and clinical and sociodemographic information on patients with schizophrenia was extracted by researchers who were blinded to the nature of exposure. Data on number of births and deaths in the famine years were available, and cumulative mortality was estimated from later demographic surveys. MAIN OUTCOME MEASURES: Evidence of famine was verified, and unadjusted and mortality-adjusted relative risks of schizophrenia were calculated. RESULTS: The birth rates (per 1000) in Anhui decreased approximately 80% during the famine years from 28.28 in 1958 and 20.97 in 1959 to 8.61 in 1960 and 11.06 in 1961. Among births that occurred during the famine years, the adjusted risk of developing schizophrenia in later life increased significantly, from 0.84% in 1959 to 2.15% in 1960 and 1.81% in 1961. The mortality-adjusted relative risk was 2.30 (95% confidence interval, 1.99-2.65) for those born in 1960 and 1.93 (95% confidence interval, 1.68-2.23) for those born in 1961. CONCLUSION: Our findings replicate the Dutch data for a separate racial group and show that prenatal exposure to famine increases risk of schizophrenia in later life.

9a. Martinussen R, Hayden J, Hogg-Johnson S, Tannock R. A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder. J.Am.Acad.Child Adolesc.Psychiatry 2005 Apr;44(4):377-84.

Abstract: OBJECTIVE: To determine the empirical evidence for deficits in working memory (WM) processes in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHOD: Exploratory meta-analytic procedures were used to investigate whether children with ADHD exhibit WM impairments. Twenty-six empirical research studies published from 1997 to December, 2003 (subsequent to a previous review) met our inclusion criteria. WM measures were categorized according to both modality (verbal, spatial) and type of processing required (storage versus storage/manipulation). RESULTS: Children with ADHD exhibited deficits in multiple components of WM that were independent of comorbidity with language learning disorders and weaknesses in general intellectual ability. Overall effect sizes for spatial storage (effect size = 0.85, CI = 0.62 - 1.08) and spatial central executive WM (effect size = 1.06, confidence interval = 0.72-1.39) were greater than those obtained for verbal storage (effect size = 0.47, confidence interval = 0.36-0.59) and verbal central executive WM (effect size = 0.43, confidence interval = 0.24-0.62). CONCLUSION: Evidence of WM impairments in children with ADHD supports recent theoretical models implicating WM processes in ADHD. Future research is needed to more clearly delineate the nature, severity, and specificity of the impairments to ADHD.

9b. Slaats-Willemse D, Swaab-Barneveld H, De SL, Buitelaar J. Familial clustering of executive functioning in affected sibling pair families with ADHD. J.Am.Acad.Child Adolesc.Psychiatry 2005 Apr;44(4):385-91.

Abstract: OBJECTIVE: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. METHOD: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the Stroop test, go/no-go task, two different fine visuomotor tracking tasks, and a sustained-, divided-, and focused attention task. RESULTS: Significant correlations (r = 0.4) were found between siblings for response inhibition and attentional control and for fine visuomotor skills that made high demands on executive functioning. CONCLUSIONS: Response inhibition, higher order controlled fine visuomotor functioning, and attentional control seem to cluster in ADHD-affected siblings. This suggests that these aspects of executive dysfunctioning may reflect an endophenotype of ADHD. Measurement of these executive functions may facilitate the identification of genes involved in ADHD by forming more homogeneous subgroups.

8. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc.Natl.Acad.Sci.U.S.A 2005 Jul 26;102(30):10604-9.

Abstract: Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.

7a. Iacoboni M, Molnar-Szakacs I, Gallese V, Buccino G, Mazziotta JC, Rizzolatti G. Grasping the intentions of others with one's own mirror neuron system. PLoS.Biol. 2005 Mar;3(3):e79.

Abstract: Understanding the intentions of others while watching their actions is a fundamental building block of social behavior. The neural and functional mechanisms underlying this ability are still poorly understood. To investigate these mechanisms we used functional magnetic resonance imaging. Twenty-three subjects watched three kinds of stimuli: grasping hand actions without a context, context only (scenes containing objects), and grasping hand actions performed in two different contexts. In the latter condition the context suggested the intention associated with the grasping action (either drinking or cleaning). Actions embedded in contexts, compared with the other two conditions, yielded a significant signal increase in the posterior part of the inferior frontal gyrus and the adjacent sector of the ventral premotor cortex where hand actions are represented. Thus, premotor mirror neuron areas-areas active during the execution and the observation of an action-previously thought to be involved only in action recognition are actually also involved in understanding the intentions of others. To ascribe an intention is to infer a forthcoming new goal, and this is an operation that the motor system does automatically.

7b. Miller G. Neuroscience. Reflecting on another's mind. Science 2005 May 13;308(5724):945-7.

6. Richardson AJ, Montgomery P. The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics 2005 May;115(5):1360-6.

Abstract: BACKGROUND: Developmental coordination disorder (DCD) affects approximately 5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood. Mounting evidence suggests that a relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. Given the current lack of effective, evidence-based treatment options for DCD, the use of fatty acid supplements merits investigation. METHODS: A randomized, controlled trial of dietary supplementation with omega-3 and omega-6 fatty acids, compared with placebo, was conducted with 117 children with DCD (5-12 years of age). Treatment for 3 months in parallel groups was followed by a 1-way crossover from placebo to active treatment for an additional 3 months. RESULTS: No effect of treatment on motor skills was apparent, but significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups. After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress. CONCLUSIONS: Fatty acid supplementation may offer a safe efficacious treatment option for educational and behavioral problems among children with DCD. Additional work is needed to investigate whether our inability to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress.

5. Konofal E, Lecendreux M, Arnulf I, Mouren MC. Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch.Pediatr.Adolesc.Med. 2004 Dec;158(12):1113-5.

Abstract: BACKGROUND: Iron deficiency causes abnormal dopaminergic neurotransmission and may contribute to the physiopathology of attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To evaluate iron deficiency in children with ADHD vs iron deficiency in an age- and sex-matched control group. DESIGN: Controlled group comparison study. SETTING: Child and Adolescent Psychopathology Department in European Pediatric Hospital, Paris, France. PATIENTS: Fifty-three children with ADHD aged 4 to 14 years (mean +/- SD, 9.2 +/- 2.2 years) and 27 controls (mean +/- SD, 9.5 +/- 2.8 years). MAIN OUTCOME MEASURES: Serum ferritin levels evaluating iron stores and Conners' Parent Rating Scale scores measuring severity of ADHD symptoms have been obtained. RESULTS: The mean serum ferritin levels were lower in the children with ADHD (mean +/- SD, 23 +/- 13 ng/mL) than in the controls (mean +/- SD, 44 +/- 22 ng/mL; P < .001). Serum ferritin levels were abnormal (<30 ng/mL) in 84% of children with ADHD and 18% of controls (P < .001). In addition, low serum ferritin levels were correlated with more severe general ADHD symptoms measured with Conners' Parent Rating Scale (Pearson correlation coefficient, r = -0.34; P < .02) and greater cognitive deficits (r = -0.38; P < .01). CONCLUSIONS: These results suggest that low iron stores contribute to ADHD and that ADHD children may benefit from iron supplementation.

4a. Badawi N, Felix JF, Kurinczuk JJ, Dixon G, Watson L, Keogh JM, Valentine J, Stanley FJ. Cerebral palsy following term newborn encephalopathy: a population-based study. Dev.Med.Child Neurol. 2005 May;47(5):293-8.

Abstract: Cerebral palsy (CP) can occur in term infants with or without preceding newborn encephalopathy. We compared the type and severity of CP and associated disability in these two groups. Participants from a population-based case-control study of term newborn encephalopathy were followed up for 6 years and linked to the Western Australian Cerebral Palsy Register. The remaining term infants with CP for the same period were also identified from the Cerebral Palsy Register. 13% of neonatal survivors of term newborn encephalopathy had CP, a rate of 116 per 1000 term live births. Overall, 24% of term infants with CP followed newborn encephalopathy. CP following newborn encephalopathy was more likely to: affect males (72% vs 56%); be severe (47% vs 25%); and be of spastic quadriplegia or dyskinetic types. Cognitive impairment was more common (75% vs 43%) and severe (41% vs 16%), as was epilepsy (53% vs 29%) in survivors of encephalopathy. These children were also more likely to: be non-verbal (47% vs 22%); have a severe composite disability score (47% vs 26%); and die between time of diagnosis of CP and age 6 years (5-year cumulative mortality 19% vs 5%). Children born at term who develop CP following newborn encephalopathy have a poorer prognosis than those with CP who were not encephalopathic in the first week of life.

4b. Miller SP, Ramaswamy V, Michelson D, Barkovich AJ, Holshouser B, Wycliffe N, Gudden DV, Deming D, Partridge C, Wu YW, et al. Patterns of Brain Injury in Term Neonatal Encephalopathy. Obstet.Gynecol.Surv. 2005 Sep;60(9):576-7.

Abstract: Neonatal encephalopathy remains a major cause of neurologic and developmental disability in term infants. Approximately one in 5 affected infants die during the neonatal period, and another one fourth have permanent motor or cognitive dysfunction. Previous studies suggest that brain injury occurs at-or near-the time of birth and so might be helped by postnatal interventions. The investigators used magnetic resonance imaging (MRI) to define patterns of injury in 173 term newborn infants having neonatal encephalopathy. MRI was done 1 to 24 days after birth, the median interval being 6 days. MRI distinguished between a watershed-predominant pattern (involving white matter, especially in the vascular watershed and possibly extending to cortical gray matter); a basal ganglia/thalamus-predominant pattern (involving the deep gray nuclei and perirolandic cortex, extending to the total cortex in severe cases); and a normal state. Neuroradiologists without knowledge of the clinical findings interpreted the MRI scans. Cognitive development was assessed by the Mental Development Index of the Bayley Scales of Infant Development II.The watershed pattern of injury was found in 45% of infants and the basal ganglia/thalamus pattern in 25%; 30% had normal MRI findings. Injury patterns could not be related to maternal substance use, gestational diabetes, premature rupture of membranes, preeclampsia, or intrauterine growth restriction. The basal ganglia/thalamus pattern of injury was associated with more severe clinical signs, more intensive resuscitation at birth, more advanced encephalopathy, and more severe seizures. This pattern also correlated with the most marked impairment of motor and cognitive outcomes at age 30 months. No newborn infant with normal MRI findings had a functional motor deficit. More than half (56%) of surviving infants with the basal ganglia/thalamus pattern had spastic quadriparesis. Additional watershed injury did not worsen neuromotor scores when the basal ganglia/thalamus-predominant pattern was observed. Neuromotor scores did not change from ages 12 to 30 months.These findings show that different patterns of brain injury in term infants with neonatal encephalopathy are associated with different neurodevelopmental outcomes. Knowledge of the pattern of injury can help to identify infants who might benefit most from measures that protect the brain after injury as well as those who may benefit from rehabilitative services.

3. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005 Feb 19;365(9460):663-70.

Abstract: BACKGROUND: Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia. We did a multicentre randomised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy. METHODS: 234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography (aEEG) were randomly assigned to either head cooling for 72 h, within 6 h of birth, with rectal temperature maintained at 34-35 degrees C (n=116), or conventional care (n=118). Primary outcome was death or severe disability at 18 months. Analysis was by intention to treat. We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before randomisation--ie, severe loss of background amplitude, and seizures--and those with less severe changes. FINDINGS: In 16 babies, follow-up data were not available. Thus in 218 infants (93%), 73/110 (66%) allocated conventional care and 59/108 (55%) assigned head cooling died or had severe disability at 18 months (odds ratio 0.61; 95% CI 0.34-1.09, p=0.1). After adjustment for the severity of aEEG changes with a logistic regression model, the odds ratio for hypothermia treatment was 0.57 (0.32-1.01, p=0.05). No difference was noted in the frequency of clinically important complications. Predefined subgroup analysis suggested that head cooling had no effect in infants with the most severe aEEG changes (n=46, 1.8; 0.49-6.4, p=0.51), but was beneficial in infants with less severe aEEG changes (n=172, 0.42; 0.22-0.80, p=0.009). INTERPRETATION: These data suggest that although induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy, it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes.

2a. Sullivan PB, Juszczak E, Bachlet AM, Thomas AG, Lambert B, Vernon-Roberts A, Grant HW, Eltumi M, Alder N, Jenkinson C. Impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy. Dev.Med.Child Neurol. 2004 Dec;46(12):796-800.

Abstract: The aim of this prospective cohort study was to evaluate the impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy (CP). Short-Form 36 version II was used to measure quality of life in carers of 57 Caucasian children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) six and 12 months after insertion of a gastrostomy tube. Responses were calibrated against a normative dataset (Oxford Healthy Life Survey III). Six months after gastrostomy feeding was started, a substantial rise in mean domain scores for mental health, role limitations due to emotional problems, physical functioning, social functioning, and energy/vitality were observed. At 12 months after gastrostomy placement, carers reported significant improvements in social functioning, mental health, energy/vitality (mean increase >9.8 points;p<0.03), and in general health perception (mean increase 6.35 points;p=0.045) compared with results at baseline. Moreover, the values obtained for these domains at 12 months were not significantly different from the normal reference standard. Carers reported a significant reduction in feeding times, increased ease of drug administration, and reduced concern about their child's nutritional status. This study has demonstrated a significant, measurable improvement in the quality of life of carers after insertion of a gastrostomy feeding tube.

2b. Sullivan PB, Juszczak E, Bachlet AM, Lambert B, Vernon-Roberts A, Grant HW, Eltumi M, McLean L, Alder N, Thomas AG. Gastrostomy tube feeding in children with cerebral palsy: a prospective, longitudinal study. Dev.Med.Child Neurol. 2005 Feb;47(2):77-85.

Abstract: We report a longitudinal, prospective, multicentre cohort study designed to measure the outcomes of gastrostomy tube feeding in children with cerebral palsy (CP). Fifty-seven children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) were assessed before gastrostomy placement, and at 6 and 12 months afterwards. Three-quarters of the children enrolled (43 of 57) had spastic quadriplegia; other diagnoses included mixed CP (6 of 57), hemiplegia (3 of 57), undiagnosed severe neurological impairment (3 of 57), ataxia (1 of 57), and extrapyramidal disorder (1 of 57). Only 7 of 57 (12%) could sit independently, and only 3 of 57 (5%) could walk unaided. Outcome measures included growth/anthropometry, nutritional intake, general health, and complications of gastrostomy feeding. At baseline, half of the children were more than 38D below the average weight for their age and sex when compared with the standards for typically-developing children. Weight increased substantially over the study period; the median weight z score increased from -3 before gastrostomy placement to -2.2 at 6 months and -1.6 at 12 months. Almost all parents reported a significant improvement in their child's health after this intervention and a significant reduction in time spent feeding. Statistically significant and clinically important increases in weight gain and subcutaneous fat deposition were noted. Serious complications were rare, with no evidence of an increase in respiratory complications.

2c. Stevenson R. Beyond growth: gastrostomy feeding in children with cerebral palsy. Dev.Med.Child Neurol. 2005 Feb;47(2):76.

1. Olds DL, Robinson J, Pettitt L, Luckey DW, Holmberg J, Ng RK, Isacks K, Sheff K, Henderson CR, Jr. Effects of home visits by paraprofessionals and by nurses: age 4 follow-up results of a randomized trial. Pediatrics 2004 Dec;114(6):1560-8.

Abstract: OBJECTIVE: To examine the effects of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through age 4 years. METHODS: We conducted, in public and private care settings in Denver, Colorado, a randomized, controlled trial with 3 arms, ie, control, paraprofessional visits, and nurse visits. Home visits were provided from pregnancy through child age 2 years. We invited 1178 consecutive, low-income, pregnant women with no previous live births to participate, and we randomized 735; 85% were unmarried, 47% Mexican American, 35% white non-Mexican American, 15% black, and 3% American Indian/Asian. Outcomes consisted of maternal reports of subsequent pregnancies, participation in education and work, use of welfare, marriage, cohabitation, experience of domestic violence, mental health, substance use, and sense of mastery; observations of mother-child interaction and the home environment; tests of children's language and executive functioning; and mothers' reports of children's externalizing behavior problems. RESULTS: Two years after the program ended, women who were visited by paraprofessionals, compared with control subjects, were less likely to be married (32.2% vs 44.0%) and to live with the biological father of the child (32.7% vs 43.1%) but worked more (15.13 months vs 13.38 months) and reported a greater sense of mastery and better mental health (standardized scores [mean = 100, SD = 10] of 101.25 vs 99.31 and 101.21 vs 99.16, respectively). Paraprofessional-visited women had fewer subsequent miscarriages (6.6% vs 12.3%) and low birth weight newborns (2.8% vs 7.7%). Mothers and children who were visited by paraprofessionals, compared with control subjects, displayed greater sensitivity and responsiveness toward one another (standardized score [mean = 100, SD = 10] of 100.92 vs 98.66) and, in cases in which the mothers had low levels of psychologic resources at registration, had home environments that were more supportive of children's early learning (score of 24.63 vs 23.35). Nurse-visited women reported greater intervals between the births of their first and second children (24.51 months vs 20.39 months) and less domestic violence (6.9% vs 13.6%) and enrolled their children less frequently in preschool, Head Start, or licensed day care than did control subjects. Nurse-visited children whose mothers had low levels of psychologic resources at registration, compared with control group counterparts, demonstrated home environments that were more supportive of children's early learning (score of 24.61 vs 23.35), more advanced language (score of 91.39 vs 86.73), superior executive functioning (score of 100.16 vs 95.48), and better behavioral adaptation during testing (score of 100.41 vs 96.66). There were no statistically significant effects of either nurse or paraprofessional visits on the number of subsequent pregnancies, women's educational achievement, use of substances, use of welfare, or children's externalizing behavior problems. CONCLUSIONS: Paraprofessional-visited mothers began to experience benefits from the program 2 years after the program ended at child age 2 years, but their first-born children were not statistically distinguishable from their control group counterparts. Nurse-visited mothers and children continued to benefit from the program 2 years after it ended. The impact of the nurse-delivered program on children was concentrated on children born to mothers with low levels of psychologic resources.