The Top Ten Articles in Developmental Pediatrics, 2007

Presented at the annual meeting of the AACPDM, Vancouver, October 12, 2007

10. Badawi N, Dixon G, Felix JF, Keogh JM, Petterson B, Stanley FJ, Kurinczuk JJ. Autism following a history of newborn encephalopathy: more than a coincidence? Dev Med Child Neurol. 2006 Feb;48(2):85-9.

Between June 1993 and December 1996, 276 term newborn infants with encephalopathy and 564 randomly selected term controls were enrolled in a population-based study of moderate and severe term newborn encephalopathy (NE) in Western Australia. During comprehensive neurobehavioural and cognitive follow-up of all patients and controls at 3 years and again at 5 years of age we found an unexpected but strong association between NE and autism spectrum disorders (ASDs). A diagnosis of ASD by age 5 years was reached using criteria according of the Diagnostic Statistical Manual, 4th edition. Linking records to the Western Australian Disability Services Commission Register ensured that no child in the study with ASD was missed. By age 5 years, 37 (13.4%) infants with NE and one (0.2%) control had died. Among the 239 survivors of NE, 12 (5%) were diagnosed with an ASD. Of these, 10 (4.2%) met the full criteria for autism, one had pervasive developmental disorder-not otherwise specified, and one had Asperger syndrome. Among the 563 surviving controls, five (0.8%) were diagnosed with an ASD: three with autism, one with autism/possible Asperger syndrome, and one with Asperger syndrome. Compared with the controls, the children who had experienced NE were 5.9 times (95% confidence interval 2.0-16.9) more likely to have been diagnosed with an ASD.

9. Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet. 2006 Apr 15;367(9518):1241-6.

BACKGROUND: Patients with end-stage bladder disease can be treated with cystoplasty using gastrointestinal segments. The presence of such segments in the urinary tract has been associated with many complications. We explored an alternative approach using autologous engineered bladder tissues for reconstruction. METHODS: Seven patients with myelomeningocele, aged 4-19 years, with high-pressure or poorly compliant bladders, were identified as candidates for cystoplasty. A bladder biopsy was obtained from each patient. Urothelial and muscle cells were grown in culture, and seeded on a biodegradable bladder-shaped scaffold made of collagen, or a composite of collagen and polyglycolic acid. About 7 weeks after the biopsy, the autologous engineered bladder constructs were used for reconstruction and implanted either with or without an omental wrap. Serial urodynamics, cystograms, ultrasounds, bladder biopsies, and serum analyses were done. RESULTS: Follow-up range was 22-61 months (mean 46 months). Post-operatively, the mean bladder leak point pressure decrease at capacity, and the volume and compliance increase was greatest in the composite engineered bladders with an omental wrap (56%, 1.58-fold, and 2.79-fold, respectively). Bowel function returned promptly after surgery. No metabolic consequences were noted, urinary calculi did not form, mucus production was normal, and renal function was preserved. The engineered bladder biopsies showed an adequate structural architecture and phenotype. CONCLUSIONS: Engineered bladder tissues, created with autologous cells seeded on collagen-polyglycolic acid scaffolds, and wrapped in omentum after implantation, can be used in patients who need cystoplasty.

8. Sullivan PB, Morrice JS, Vernon-Roberts A, Grant H, Eltumi M, Thomas AG. Does gastrostomy tube feeding in children with cerebral palsy increase the risk of respiratory morbidity? Arch Dis Child. 2006 Jun;91(6):478-82.

BACKGROUND: Children with severe neurological impairment may have significant oral motor dysfunction and are at increased risk of nutritional deficiencies, poor growth, and aspiration pneumonia. Gastrostomy tube feeding is increasingly being used for nutritional support in these children. AIM: To examine the occurrence of respiratory morbidity before and after gastrostomy feeding tube insertion in children with severe neurological disabilities. METHODS: This study was nested in a longitudinal, prospective, uncontrolled, multicentre cohort study designed to investigate the outcomes of gastrostomy tube feeding in 57 children with severe neurological disabilities. Parents completed a questionnaire prior to (visit 1) and 6 and 12 months (visits 2 and 3) following the gastrostomy, detailing number of chest infections requiring antibiotics and/or hospital admission. RESULTS: Mean number of chest infections requiring antibiotics was 1.8 on visit 1 and 0.9 on visit 3. Hospital admissions for chest infections fell significantly from 0.5 to 0.09. CONCLUSION: This study provides no evidence for an increase in respiratory morbidity following insertion of a feeding gastrostomy in children with cerebral palsy.

7. Srour M, Mazer B, Shevell MI. Analysis of clinical features predicting etiologic yield in the assessment of global developmental delay. Pediatrics. 2006 Jul;118(1):139-45.

OBJECTIVE: Global developmental delay is a common reason for presentation for neurologic evaluation. This study examined the role of clinical features in predicting the identification of an underlying cause for a child's global developmental delay. METHODS: Over a 10-year inclusive interval, the case records of all consecutive children <5 years of age referred to a single ambulatory practice setting for global developmental delay were systematically reviewed. The use of clinical features in predicting the identification of a specific underlying cause for a child's delay was tested using chi2 analysis. RESULTS: A total of 261 patients eventually met criteria for study inclusion. Mean age at initial evaluation was 33.6 months. An underlying cause was found in 98 children. Commonest etiologic groupings were genetic syndrome/chromosomal abnormality, intrapartum asphyxia, cerebral dysgenesis, psychosocial deprivation, and toxin exposure. Factors associated with the ability to eventually identify an underlying cause included female gender (40 of 68 vs 58 of 193), abnormal prenatal/perinatal history (52 of 85 vs 46 of 176), absence of autistic features (85 of 159 vs 13 of 102), presence of microcephaly (26 of 40 vs 72 of 221), abnormal neurologic examination (52 of 71 vs 46 of 190), and dysmorphic features (44 of 84 vs 54 of 177). In 113 children without any abnormal features identified on history or physical examination, routine screening investigations (karyotype, fragile X molecular genotyping, and neuroimaging) revealed an underlying etiology in 18. CONCLUSIONS: Etiologic yield in an unselected series of young children with global developmental delay is close to 40% overall and 55% in the absence of any coexisting autistic features. Clinical features are readily apparent that may enhance an expectation of a successful etiologic search. Screening investigations may yield an underlying cause.

6. 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.

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.

5. Weissman MM, Pilowsky DJ, Wickramaratne PJ, Talati A, Wisniewski SR, Fava M, Hughes CW, Garber J, Malloy E, King CA, Cerda G, Sood AB, Alpert JE, Trivedi MH, Rush AJ; STAR*D-Child Team. Remissions in maternal depression and child psychopathology: a STAR*D-child report. JAMA. 2006 Mar 22;295(12):1389-98.

CONTEXT: Children of depressed parents have high rates of anxiety, disruptive, and depressive disorders that begin early, often continue into adulthood, and are impairing. OBJECTIVE: To determine whether effective treatment with medication of women with major depression is associated with reduction of symptoms and diagnoses in their children. DESIGN: Assessments of children whose depressed mothers were being treated with medication as part of the multicenter Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial conducted (between December 16, 2001 and April 24, 2004) in broadly representative primary and psychiatric outpatient practices. Children were assessed by a team of evaluators not involved in maternal treatment and unaware of maternal outcomes. Study is ongoing with cases followed at 3-month intervals. SETTING AND PATIENTS: One hundred fifty-one mother-child pairs in 8 primary care and 11 psychiatric outpatient clinics across 7 regional centers in the United States. Children were aged 7 to 17 years. MAIN OUTCOME MEASURES: Child diagnoses based on the Kiddie Schedule for Affective Disorders and Schizophrenia; child symptoms based on the Child Behavior Checklist; child functioning based on the Child Global Assessment Scale in mothers whose depression with treatment remitted with a score of 7 or lower or whose depression did not remit with a score higher than 7 on the Hamilton Rating Scale for Depression. RESULTS: Remission of maternal depression after 3 months of medication treatment was significantly associated with reductions in the children's diagnoses and symptoms. There was an overall 11% decrease in rates of diagnoses in children of mothers whose depression remitted compared with an approximate 8% increase in rates of diagnoses in children of mothers whose depression did not. This rate difference remained statistically significant after controlling for the child's age and sex, and possible confounding factors (P = .01). Of the children with a diagnosis at baseline, remission was reported in 33% of those whose mothers' depression remitted compared with only a 12% remission rate among children of mothers whose depression did not remit. All children of mothers whose depression remitted after treatment and who themselves had no baseline diagnosis for depression remained free of psychiatric diagnoses at 3 months, whereas 17% of the children whose mothers remained depressed acquired a diagnosis. Findings were similar using child symptoms as an outcome. Greater level of maternal response was associated with fewer current diagnoses and symptoms in the children, and a maternal response of at least 50% was required to detect an improvement in the child. CONCLUSIONS: Remission of maternal depression has a positive effect on both mothers and their children, whereas mothers who remain depressed may increase the rates of their children's disorders. These findings support the importance of vigorous treatment for depressed mothers in primary care or psychiatric clinics and suggest the utility of evaluating the children, especially children whose mothers continue to be depressed.

4. Schneider H, Eisenberg D. Who receives a diagnosis of attention-deficit/ hyperactivity disorder in the United States elementary school population? Pediatrics. 2006 Apr;117(4):e601-9.

OBJECTIVE: To investigate factors that are associated with the probability of attention-deficit/hyperactivity disorder (ADHD) diagnosis among U.S. elementary school children, including child, family, school, and policy factors. METHODS: Logistic regression was used to estimate relative risks associated with independent variables using a nationally representative sample of 9278 children in the 2002 follow-up of the Early Childhood Longitudinal Survey-Kindergarten Cohort. Most children in the sample were in third grade at this point. Previous ADHD diagnoses by professionals were reported by parent respondents. RESULTS: A total of 5.44% of children were reported to have received an ADHD diagnosis. Girls, black children, and Hispanic children were less likely to have the diagnosis even after controlling for other characteristics. Living with one's biological father was negatively associated with ADHD diagnosis. We also found regional variation in diagnosis with the western region of the United States having significantly lower instances of ADHD cases. Higher diagnosis rates were associated with having an older teacher, and lower rates were associated with having a white teacher, relative to a nonwhite teacher. In schools that were subject to stricter state-level performance accountability laws, we found higher odds of ADHD diagnoses, but we found no differences associated with larger class sizes or the presence of state laws that restrict school personnel from discussing ADHD treatment options with parents. CONCLUSIONS: ADHD diagnosis is likely to be influenced by a child's social and school environment as well as exogenous child characteristics. Concerns that increased pressures for school performance are associated with increased ADHD diagnoses may be justified.

3. Anderson V, Catroppa C, Morse S, Haritou F, Rosenfeld J. Functional plasticity or vulnerability after early brain injury? Pediatrics. 2005 Dec;116(6):1374-82.

CONTEXT: Traumatic brain injury (TBI) is a common, acquired, childhood disability that may be used as a model to understand more completely the impact of early brain injury on both brain structure and day-to-day function. Contrary to previously held views of the "plasticity" of the young brain, recent research suggests that such early insults may have a profound impact on development. To date, these suggestions remain largely untested. OBJECTIVES: To plot changes in cognitive abilities after childhood TBI over the 30 months after injury and to examine the impact of age at injury on cognitive outcomes. DESIGN: Prospective longitudinal study. SETTING: Royal Children's Hospital, Victoria, Australia. MAIN OUTCOME MEASURES: Global intellectual ability, verbal and nonverbal skills, attention, and processing speed. PARTICIPANTS: A total of 122 children admitted to the hospital with a diagnosis of TBI were divided according to injury age, ie, young (age: 3-7 years) or old (age: 8-12 years), and injury severity (mild, moderate, or severe) and were evaluated acutely and at 12 and 30 months after injury. An additional sample of children injured before 3 years of age (n = 27) was compared with these groups with respect to global intellectual ability only. RESULTS: A clear relationship was documented between injury severity and cognitive performance. For children who sustained severe injury, younger age at injury was associated with minimal, if any, recovery after injury, but better outcomes were observed after severe TBI among older children. Age at injury was not predictive of outcomes for children with mild or moderate TBI, although infants (age: 0-2.11 years) with moderate TBI showed poorer outcomes than did older children with injury of similar severity. CONCLUSIONS: Findings support a "double-hazard" model for severe and early brain insults and add to the ongoing debate regarding cerebral plasticity, suggesting that, contrary to traditional views, young children who sustain severe TBI in early childhood or moderate or severe TBI in infancy may be particularly vulnerable to significant residual cognitive impairment. From a clinical perspective, results indicate that long-term follow-up monitoring and management should be targeted to this high-risk group.

2. Fetissov SO, Harro J, Jaanisk M, Jarv A, Podar I, Allik J, Nilsson I, Sakthivel P, Lefvert AK, Hokfelt T. Autoantibodies against neuropeptides are associated with psychological traits in eating disorders. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14865-70. Epub 2005 Sep 29.

Previously, we identified that a majority of patients with anorexia nervosa (AN) and bulimia nervosa (BN) as well as some control subjects display autoantibodies (autoAbs) reacting with alpha-melanocyte-stimulating hormone (alpha-MSH) or adrenocorticotropic hormone, melanocortin peptides involved in appetite control and the stress response. In this work, we studied the relevance of such autoAbs to AN and BN. In addition to previously identified neuropeptide autoAbs, the current study revealed the presence of autoAbs reacting with oxytocin (OT) or vasopressin (VP) in both patients and controls. Analysis of serum levels of identified autoAbs showed an increase of IgM autoAbs against alpha-MSH, OT, and VP as well as of IgG autoAbs against VP in AN patients when compared with BN patients and controls. Further, we investigated whether levels of these autoAbs correlated with psychological traits characteristic for eating disorders. We found significantly altered correlations between alpha-MSH autoAb levels and the total Eating Disorder Inventory-2 score, as well as most of its subscale dimensions in AN and BN patients vs. controls. Remarkably, these correlations were opposite in AN vs. BN patients. In contrast, levels of autoAbs reacting with adrenocorticotropic hormone, OT, or VP had only few altered correlations with the Eating Disorder Inventory-2 subscale dimensions in AN and BN patients. Thus, our data reveal that core psychobehavioral abnormalities characteristic for eating disorders correlate with the levels of autoAbs against alpha-MSH, suggesting that AN and BN may be associated with autoAb-mediated dysfunctions of primarily the melanocortin system.

1. Cohen GL, Garcia J, Apfel N, Master A. Reducing the racial achievement gap: a social-psychological intervention. Science. 2006 Sep 1;313(5791):1307-10.

Two randomized field experiments tested a social-psychological intervention designed to improve minority student performance and increase our understanding of how psychological threat mediates performance in chronically evaluative real-world environments. We expected that the risk of confirming a negative stereotype aimed at one's group could undermine academic performance in minority students by elevating their level of psychological threat. We tested whether such psychological threat could be lessened by having students reaffirm their sense of personal adequacy or "self-integrity." The intervention, a brief in-class writing assignment, significantly improved the grades of African American students and reduced the racial achievement gap by 40%. These results suggest that the racial achievement gap, a major social concern in the United States, could be ameliorated by the use of timely and targeted social-psychological interventions.