Other Studies of Note: 2006

Kahneman D, Krueger AB, Schkade D, Schwarz N, Stone AA. Would you be happier if you were richer? A focusing illusion. Science. 2006 Jun 30;312(5782):1908-10.

The belief that high income is associated with good mood is widespread but mostly illusory. People with above-average income are relatively satisfied with their lives but are barely happier than others in moment-to-moment experience, tend to be more tense, and do not spend more time in particularly enjoyable activities. Moreover, the effect of income on life satisfaction seems to be transient. We argue that people exaggerate the contribution of income to happiness because they focus, in part, on conventional achievements when evaluating their life or the lives of others.
["Nothing in life is quite as important as you think it is while you are thinking about it." This paper deals with methodology related to quality of life questionnaires. It also deals with an important philosophical issue.]

Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science. 2006 Sep 8;313(5792):1402.

We used functional magnetic resonance imaging to demonstrate preserved conscious awareness in a patient fulfilling the criteria for a diagnosis of vegetative state. When asked to imagine playing tennis or moving around her home, the patient activated predicted cortical areas in a manner indistinguishable from that of healthy volunteers.
Comment: Naccache L. Psychology. Is she conscious? Science. 2006 Sep 8;313(5792):1395-6.
[The authors used fMRI to evaluate brain functioning in this person diagnosed to be in a vegetative state. Her brain activity changed in response to commands such as, 'Imagine visiting all of the rooms of your house.' The study and commentary raise important issues about the diagnosis of vegetative state.]

Shattuck PT. The contribution of diagnostic substitution to the growing administrative prevalence of autism in US special education. Pediatrics. 2006 Apr;117(4):1028-37.

OBJECTIVE: Growing administrative prevalence of autism has stirred public controversy and concern. The extent to which increases in the administrative prevalence of autism have been associated with corresponding decreases in the use of other diagnostic categories is unknown. The main objective of this study was to examine the relationship between the rising administrative prevalence of autism in US special education and changes in the use of other classification categories. METHODS: The main outcome measure was the administrative prevalence of autism among children ages 6 to 11 in US special education. Analysis involved estimating multilevel regression models of time-series data on the prevalence of disabilities among children in US special education from 1984 to 2003. RESULTS: The average administrative prevalence of autism among children increased from 0.6 to 3.1 per 1000 from 1994 to 2003. By 2003, only 17 states had a special education prevalence of autism that was within the range of recent epidemiological estimates. During the same period, the prevalence of mental retardation and learning disabilities declined by 2.8 and 8.3 per 1000, respectively. Higher autism prevalence was significantly associated with corresponding declines in the prevalence of mental retardation and learning disabilities. The declining prevalence of mental retardation and learning disabilities from 1994 to 2003 represented a significant downward deflection in their preexisting trajectories of prevalence from 1984 to 1993. California was one of a handful of states that did not clearly follow this pattern. CONCLUSIONS: Prevalence findings from special education data do not support the claim of an autism epidemic because the administrative prevalence figures for most states are well below epidemiological estimates. The growing administrative prevalence of autism from 1994 to 2003 was associated with corresponding declines in the usage of other diagnostic categories.
[Considerable controversy surrounds the documented dramatic increase in children diagnosed with autism spectrum disorders. This study indicates that much of the increase is due to a decrease in other diagnoses.]

Sofronoff K, Attwood T, Hinton S. A randomised controlled trial of a CBT intervention for anxiety in children with Asperger syndrome. J Child Psychol Psychiatry. 2005 Nov;46(11):1152-60.

BACKGROUND: The aim of the study was to evaluate the effectiveness of a brief CBT intervention for anxiety with children diagnosed with Asperger syndrome (AS). A second interest was to evaluate whether more intensive parent involvement would increase the child's ability to manage anxiety outside of the clinic setting. METHODS: Seventy-one children aged ten to twelve years were recruited to participate in the anxiety programme. All children were diagnosed with AS and the presence of anxiety symptoms was accepted on parent report via brief interview. Children were randomly assigned to one of three conditions: intervention for child only, intervention for child and parent, wait-list control. RESULTS: The two intervention groups demonstrated significant decreases in parent-reported anxiety symptoms at follow-up and a significant increase in the child's ability to generate positive strategies in an anxiety-provoking situation. There were a number of significant differences between the two interventions to suggest parent involvement as beneficial. CONCLUSIONS: The sample of children with AS in this study presented with a profile of anxiety similar to a sample of clinically diagnosed anxious children. The intervention was endorsed by parents as a useful programme for children diagnosed with Asperger syndrome and exhibiting anxiety symptoms, and active parent involvement enhanced the usefulness of the programme. Limitations of the study and future research are discussed.
[Cognitive Behavior Therapy and Family-based CBT have been used successfully in children with anxiety disorders who do not have other conditions. This study is encouraging in providing another method to treat anxiety in children with Asperger syndrome.]

Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, Vaugeois JM, Nomikos GG, Greengard P. Alterations in 5-HT1B receptor function by p11 in depression-like states. Science. 2006 Jan 6;311(5757):77-80.

The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT1B receptor agonists and reduced behavioral reactions to an antidepressant.
[This article provides insight on the mechanisms of depression and why it may take several weeks before SSRIs become effective.]

Saigal S, Stoskopf B, Streiner D, Boyle M, Pinelli J, Paneth N, Goddeeris J. Transition of extremely low-birth-weight infants from adolescence to young adulthood: comparison with normal birth-weight controls. JAMA. 2006 Feb 8;295(6):667-75.

CONTEXT: Traditionally, educational attainment, getting a job, living independently, getting married, and parenthood have been considered as markers of successful transition to adulthood. OBJECTIVE: To describe and compare the achievement and the age at attainment of the above markers between extremely low-birth-weight (ELBW) and normal birth-weight (NBW) young adults. DESIGN, SETTING, AND PARTICIPANTS: A prospective, longitudinal, population-based study in central-west Ontario, Canada, of 166 ELBW participants who weighed 501 to 1000 g at birth (1977-1982) and 145 sociodemographically comparable NBW participants assessed at young adulthood (22-25 years). Interviewers masked to participant status administered validated questionnaires via face-to-face interviews between January 1, 2002, and April 30, 2004. MAIN OUTCOME MEASURES: Markers of successful transition to adulthood, including educational attainment, student and/or worker role, independent living, getting married, and parenthood. RESULTS: At young adulthood, 149 (90%) of 166 ELBW participants and 133 (92%) of 145 NBW participants completed the assessments at mean (SD) age of 23.3 (1.2) years and 23.6 (1.1) years, respectively. We included participants with neurosensory impairments (ELBW vs NBW: 40 [27%] vs 3 [2%]) and 7 proxy respondents. The proportion who graduated from high school was similar (82% vs 87%, P = .21). Overall, no statistically significant differences were observed in the education achieved to date. A substantial proportion of both groups were still pursuing postsecondary education (47 [32%] vs 44 [33%]). No significant differences were observed in employment/school status; 71 (48%) ELBW vs 76 (57%) NBW young adults were permanently employed (P = .09). In a subanalysis, a higher proportion of ELBW young adults were neither employed nor in school (39 [26%] vs 20 [15%], P = .02 by Holm's correction); these differences did not persist when participants with disabilities were excluded. No significant differences were found in the proportion living independently (63 [42%] vs 70 [53%], P = .19), married/cohabitating (34 [23%] vs 33 [25%], P = .69), or who were parents (16 [11%] vs 19 [14%], P = .36). The age at attainment of the above markers was similar for both cohorts. CONCLUSION: Our study results indicate that a significant majority of former ELBW infants have overcome their earlier difficulties to become functional young adults.
[This reassuring article documents that the longer term outcomes of many children who were ELBW is quite good.]

de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics. 2006 Jan-Feb;47(1):75-85.

Pharmacogenetics has arrived in clinical psychiatric practice with the FDA approval of the AmpliChip CYP450 Test that genotypes for two cytochrome P450 2D6 (CYP2D6) and 2C19 (CYP2C19) genes. Other pharmacogenetic tests, including those focused on pharmacodynamic genes, are far from ready for clinical application. CYP2D6 is important for the metabolism of many antidepressants and antipsychotics, and CY2C19 is important for some antidepressant metabolism. Poor metabolizers (PMs), lacking the enzyme, account for up to 7% of Caucasians for CYP2D6 and up to 25% of East Asians for CYP2C19. Patients having three or more active CYP2D6 alleles (up to 29% in North Africa and the Middle East), are called CYP2D6 ultra-rapid metabolizers (UMs). CYP2D6 phenotypes (particularly PMs) are probably important in patients taking tricyclic antidepressants (TCAs), venlafaxine, typical antipsychotics, and risperidone. The CYP2C19 PM phenotype is probably important in patients taking TCAs and perhaps citalopram, escitalopram, and sertraline. On the basis of the literature and the authors' clinical experience, the authors provide provisional recommendations for identifying and treating CYP2D6 PMs, CYP2C19 PMs, and CYP2D6 UMs. The next few years will determine whether CYP2D6 genotyping is beneficial for patients taking the new drugs aripiprazole, duloxetine, and atomoxetine. Practical recommendations for dealing with laboratories offering CYP2D6 and CYP2C29 genotyping are provided.
[If children do not respond typically to medications like atypical neuroleptics, getting information about cytochrome systems (e.g., by using the AmpliChip) may be helpful.]

Williams DL, Goldstein G, Minshew NJ. Neuropsychologic functioning in children with autism: further evidence for disordered complex information-processing. Child Neuropsychol. 2006 Aug;12(4):279-98.

A wide range of abilities was assessed in 56 high-functioning children with autism and 56 age- and IQ-matched controls. Stepwise discriminant analyses produced good group discrimination for sensory-perceptual, motor, complex language, and complex memory domains but lower agreement for the reasoning domain than previously obtained for adults. Group discrimination did not occur for attention, simple language, simple memory, and visuospatial domains. Findings provide additional support for a complex information-processing model for autism, previously based on adult data, demonstrating a pattern across domains of selective impairments on measures with high demands for integration of information and sparing when demands were low. Children as compared to adults with autism exhibited more prominent sensory-perceptual symptoms and less pronounced reasoning deficits reflecting brain maturation.
[This study provides insight into the neuropsychological functioning of children who have autism.]

Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rasin MR, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS 4th, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Sestan N, State MW. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005 Oct 14;310(5746):317-20.

Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS.
[A gene linked with Tourette syndrome.]

Polam S, Koons A, Anwar M, Shen-Schwarz S, Hegyi T. Effect of chorioamnionitis on neurodevelopmental outcome in preterm infants. Arch Pediatr Adolesc Med. 2005;159:1032-1035.

OBJECTIVE: To assess the association of neurodevelopmental outcome with the placental diagnosis of chorioamnionitis in very low-birth-weight infants. METHODS: One hundred seventy-seven surviving very low-birth-weight infants, 22 to 29 weeks' gestational age, born after varying severity of chorioamnionitis, were evaluated at a mean +/- SD age of 19 +/- 6 months' corrected age with Bayley Scales of Infant Development II and neurologic examination. Select maternal and infant variables were abstracted from the medical records. Neonatal morbidities, Mental Developmental Index (MDI) score, Psychomotor Developmental Index (PDI) score, probability of normal MDI and PDI scores (>84), and cerebral palsy between the chorioamnionitis and the control groups were assessed, controlling for gestational age, sex, and the maternal use of steroids and antibiotics. RESULTS: The chorioamnionitis group of 102 infants was compared with 75 control infants (mean +/- SD birth weight, 947 +/- 236 g and 966 +/- 219 g, respectively; mean +/- SD gestational age, 26.1 +/- 2.8 weeks and 27.1 +/- 1.5 weeks, respectively). Infants with chorioamnionitis, compared with controls, had a significantly higher incidence of intraventricular hemorrhage (30% vs 13%) and retinopathy of prematurity (68% vs 42%). Cerebral palsy was diagnosed in 8.6% of the infants with chorioamnionitis and 6.6% of the controls. The MDI and PDI scores were similar between the chorioamnionitis and control groups (mean +/- SD MDI score, 96 +/- 16 vs 97 +/- 18 and mean +/- SD PDI score, 94 +/- 19 vs 92 +/- 19, respectively). CONCLUSIONS: In very low-birth-weight infants we found a higher incidence of intraventricular hemorrhage and retinopathy of prematurity but similar MDI and PDI scores and risk of cerebral palsy associated with chorioamnionitis.
[Prenatal infections continue to be linked with an increased occurrence of cerebral palsy.]

Cody JD, Semrud-Clikeman M, Hardies LJ, Lancaster J, Ghidoni PD, Schaub RL, Thompson NM, Wells L, Cornell JE, Love TM, Fox PT, Leach RJ, Kaye CI, Hale DE. Growth hormone benefits children with 18q deletions. Am J Med Genet A. 2005 Aug 15;137(1):9-15.

Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals.
[In these children growth hormone improved height and non-verbal cognitive function, possibly through its effect on myelinization.]

van den Bergh BR, Mennes M, Stevens V, van der Meere J, Borger N, Stiers P, Marcoen A, Lagae L. ADHD deficit as measured in adolescent boys with a continuous performance task is related to antenatal maternal anxiety. Pediatr Res. 2006 Jan;59(1):78-82.

Antenatal maternal anxiety has been shown to be related to infant temperament, childhood disorders, and impulsivity in adolescence. This study prospectively investigated whether antenatal maternal anxiety is associated with performance on a continuous performance task. Sixty-four adolescents (mean age, 15 y; 34 boys, 30 girls) were examined with a computerized continuous performance task (CPT) measuring sustained attention. Results showed that the CPT performance of boys of mothers with high levels of state anxiety during the 12th to 22nd postmenstrual week of pregnancy declined as the task progressed: their processing speed became slower and the variability in their reaction times increased. The study controlled for the possible confounding influences of postnatal maternal anxiety, the parents' educational level, and intelligence. Establishing a link between antenatal maternal anxiety and an objective measure of sustained attention/self-regulation, our results extend the growing evidence for an association between antenatal maternal anxiety and the neurobehavioral development of the offspring up into adolescence.
[Older studies have shown that calamities (like hurricanes or war) that occur during pregnancy can adversely affect the development of the offspring. This study continues in that tradition showing that maternal anxiety may be linked with ADHD in the child.]

Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van Engeland H, Scahill L, Minderaa RB, Hoekstra PJ. Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study. J Am Acad Child Adolesc Psychiatry. 2005 Nov;44(11):1137-44.

OBJECTIVE: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. METHOD: Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe tantrums, aggression, or self-injurious behavior, started 8-week open-label treatment with risperidone. Responders (n = 26) continued treatment for another 16 weeks, followed by a double-blind discontinuation (n = 24; two patients discontinued treatment because of weight gain) consisting of either 3 weeks of taper and 5 weeks of placebo only or continuing use of risperidone. Relapse was defined as a significant deterioration of symptoms based on clinical judgment and a parent questionnaire. RESULTS: Risperidone was superior to placebo in preventing relapse: this occurred in 3 of 12 patients continuing on risperidone versus 8 of 12 who switched to placebo (p = .049). Weight gain, increased appetite, anxiety, and fatigue were the most frequently reported side effects. CONCLUSIONS: This study indicates the effectiveness of risperidone during a period of several months, reducing disruptive behavior in about half of the children with autism spectrum disorders. The results provide a rationale for the continuing use of risperidone beyond 6 months, although considerable weight gain can limit the use of this agent.
[This is another of many studies showing that risperidone may be helpful in helping disruptive behavior in children who have autism.]

Dapretto M, Davies MS, Pfeifer JH, Scott AA, Sigman M, Bookheimer SY, Iacoboni M. Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nat Neurosci. 2006 Jan;9(1):28-30.

To examine mirror neuron abnormalities in autism, high-functioning children with autism and matched controls underwent fMRI while imitating and observing emotional expressions. Although both groups performed the tasks equally well, children with autism showed no mirror neuron activity in the inferior frontal gyrus (pars opercularis). Notably, activity in this area was inversely related to symptom severity in the social domain, suggesting that a dysfunctional 'mirror neuron system' may underlie the social deficits observed in autism.
[Last year we presented a study on mirror neurons. This study documents the link between poor mirror neuron functioning and autism.]

Martinez de Villarreal LE, Arredondo P, Hernandez R, Villarreal JZ. Weekly Administration of Folic Acid and Epidemiology of Neural Tube Defects. Matern Child Health J. 2006 Aug 10; [Epub ahead of print]

Objective: In 1999, a folic acid campaign for prevention of neural tube defects was started in Nuevo Leon, Mexico, with the recommendation of taking a 5000 -mcg tablet of folic acid per week. The purpose of this study was to compare the epidemiology of neural tube defects after four years of the campaign. Methods: Cases of anencephaly, spina bifida, and encephalocele (ICD Q00, Q01, Q05, 10th Ed.) from public and private hospitals were registered by immediate notification, death certificates, and fetal death registries. Comparisons of neural tube defects rates, phenotype distribution of cases, and sex ratios, registered before and after the folic acid campaign, were done using the Student's t Test and Chi square test. Results: There was a 50% reduction in the incidence of anencephaly and spina bifida cases from 93 in 1999 (1.04x1000) to 46 in the year 2003 (0.56x1000) (p < 0.001). Spina bifida cases declined up to 70% in 2002 and anencephaly cases up to 50% in 2003. In 1999, overall, the ratio (females: males) was 0.66 with female excess; the sex ratio was similar for anencephaly and spina bifida cases. In the year 2000, female cases showed a significant reduction for both spina bifida and anencephaly (75% and 56% respectively); the sex ratio was 0.57 with a greater male excess for both phenotypes. Conclusions: Weekly administration of 5000 mcg of folic acid reduces the incidence of neural tube defects 50%, primarily spina bifida, with a higher reduction of female cases.
[Apparently folic acid can decrease the occurrence of neural tube defects, especially meningomyelocele (spina bifida) even when it is given once a week, rather than every day. The current recommendation for the United States is that folic acid (0.4 mg without a family history and 4 mg with an immediate family history) be given daily before conception and for the first three months of the pregnancy.]

Taanila A, Murray GK, Jokelainen J, Isohanni M, Rantakallio P. Infant developmental milestones: a 31-year follow-up. Dev Med Child Neurol. 2005 Sep;47(9):581-6.

This study examined the association between infant developmental milestones and educational level at 31 years of age in the Northern Finland 1966 Birth Cohort (n = 12 058). Developmental data (age at standing, walking, speaking, and measures of bowel and bladder control) were gathered from children's welfare centres. Information on type of schooling at 14 years of age was reported by children and parents. School achievement at 16 years of age and educational level at 31 years were obtained from national registers. Those who reached infant developmental milestones sooner in their first year of life had significantly better (p < 0.05) mean scores in teacher ratings at 16 years, and at 31 years they were more likely to have achieved a better educational level than slower developers. The adjusted odds ratios for individuals who developed more slowly to remain at a basic educational level (7 to 16y) ranged significantly from 1.1 to 1.3. The possibility of advancing from secondary to tertiary level was 1.4 times greater in faster developers than in slow developers. In conclusion, those who develop faster during their first year of life tend to attain higher levels of education in adolescence and adulthood.
[This study in which children were followed for 31 years! showed that children who did better in the first year of life, attained higher levels of education. However, the odds ratio was only 1.4-significant, but not dramatic.]

Stoll C, Alembik Y, Dott B. Are the recommendations on the prevention of neural tube defects working? Eur J Med Genet. 2006 Jul 27; [Epub ahead of print]

Many studies showed that reduction by an estimated 80% or more of neural tube defects (NTD) by consumption of folic acid from before conception is achievable. The objectives of this study were to evaluate the effectiveness of recommendations on folic acid aimed at reducing the occurrence of NTD in our region. Cases of NTD were ascertained among liveborn infants, stillbirths, and terminations of pregnancy. Incidences and trends in rates of NTD before and after 1992 (the year of the first recommendations) and before and after 1995 (the year of local recommendations) were obtained. The results showed that the issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of NTD. The rates of NTD per 10,000 were before 1992 9.07, from 1993 to 1995 8.14, and after 1995 10.62, respectively. The incidence rate ratios (IRRs) were not different from 1.00. In conclusion new cases preventable by folic acid continue to accumulate. Recommendations alone did not influence trends in NTD in our country up to 11 years after the confirmation of the effectiveness of folic acid in clinical trials. New strategies are needed.
[This sobering study from France shows that simply recommending the use of folic acid is not sufficient by itself to decrease the birth rate of neural tube defects. Women who will become pregnant have to actually take the folic acid for it to work! Many studies have shown that giving recommendations alone often has little effect on changing behaviors.]

Dik P, Klijn AJ, van Gool JD, de Jong-de Vos van Steenwijk CC, de Jong TP. Early start to therapy preserves kidney function in spina bifida patients. Eur Urol. 2006 May;49(5):908-13.

OBJECTIVE: Renal scarring and renal failure remain life-threatening for children born with spinal dysraphism. We reviewed our data of spina bifida patients to evaluate whether optimal treatment of the neurogenic bladder from birth onwards can preserve kidney function. METHODS: We reviewed data on all newborns with spinal dysraphism who were referred to our hospital between January 1988 and June 2001. We looked at their situations at referral and at follow-up: the type of treatment, antimuscarinic agents, clean intermittent catheterisation (CIC), antibiotic prophylaxis, and operations (sling procedures, bladder augmentations, antireflux procedures). Renal function (ultrasound, DMSA scan, serum creatinin, creatinin clearance) and bladder function (urodynamic studies) were evaluated over time. RESULTS: Data of 144 children of 176 could be evaluated by the end of the study: 5 patients had pre-existing renal abnormalities, 69 had an overactive sphincter, 27 had reflux, and six had renal scarring. None are currently developing end-stage renal disease. All patients with spina bifida aperta started CIC and antimuscarinic therapy shortly after birth. Five of the six patients with renal scarring were started on therapy with intermittent catheterisation and antimuscarinic therapy several months after birth. Sixty-three of 82 children with spina bifida were dry at school age (age six), although 37 of these had not had an operation. CONCLUSION: We show that an early start to therapy helps to safeguard renal function for children born with spina bifida. Our data support other recent reports that children born with spina bifida can probably use their own kidneys for a lifetime, if they are given adequate urological treatment. To protect the upper urinary tract, we need to ensure low intravesical pressure by starting children early on CIC (the preferred treatment); antimuscarinic agents to counteract detrusor instability are indispensable in most cases. Proactive treatment of risks for upper tract deterioration results in a negligible loss of renal function, even when early urinary continence is included in the treatment protocol.
[This descriptive study reviews the experience of a center in The Netherlands in the urological management of children born with spina bifida from 1988 to 2001. Their management included routine monitoring using renal ultrasound and cystometrogram, clean intermittent catheterization, antibiotics, medications like oxybutinin (Ditropan), and occasional surgery. They found that most children preserved good kidney function and concluded, "Our data support other recent reports that children born with spina bifida can probably use their own kidneys for a lifetime, if they are given adequate urological treatment." The oldest person in this study is only 18-years-old, so no conclusions can be made regarding the fate of adults.]

Altaweel W, Jednack R, Bilodeau C, Corcos J. Repeated intradetrusor botulinum toxin type A in children with neurogenic bladder due to myelomeningocele. J Urol. 2006 Mar;175(3 Pt 1):1102-5.

PURPOSE: We evaluated the effect of repeated intradetrusor injections of BTA in pediatric myelomeningocele not responding to medical management. MATERIALS AND METHODS: After baseline history, physical examination and urodynamic assessment BTA was injected (5 IU/kg body weight, maximum 300 IU) at 10 to 30 sites. Clinical and urodynamic assessment was performed at 3 months after each injection. Re-treatment was offered when clinical symptoms returned. RESULTS: A total of 20 patients (average age 13 years) received BTA injections. Of the patients 13 became continent. MBC increased from 215.6 +/- 58.8 cc to 338.3 +/- 98.4 cc (p < 0.01), MDP decreased from 43 +/- 13.7 cm H2O to 21.6 +/- 10.5 cm H2O (p < 0.01) and compliance increased from 5.2 +/- 2.6 ml/cm H2O to 13 +/- 6.9 ml/cm H2O (p < 0.01). At an average of 8.1 months after the first injection all 13 patients received a second injection, which led to similar improvement, ie MBC increased from 200.5 +/- 41.6 cc to 404.2 +/- 57.8 cc (p < 0.001), MDP decreased from 48.18 +/- 6.1 cm H2O to 27.8 +/- 3.7 cm H2O (p < 0.01) and compliance increased from 6.0 +/- 3.1 ml/cm H2O to 15.1 +/- 5.2 ml/cm H2O (p < 0.01). Among the responders 3 received 3 injections and 1 received 4 injections, all of whom exhibited improvement similar to that seen initially. Among our initial cohort of 20 patients 7 failed to improve initially and 6 failed to improve after a second injection. CONCLUSIONS: BTA seems to be a simple and safe way to postpone or avoid invasive procedures in two thirds of children with myelomeningocele not responding to usual medical treatment. [Botulinum toxin type A (Botox) has been used to treat spasticity, drooling, dystonia and wrinkles. It works by temporarily weakening muscles. In this study, urologists injected botulinum toxin into the detrusor muscle of children and adults who had spina bifida. These were individuals in whom conservative management with anticholinergics (e.g., oxybutinin or tolterodine) and clean intermittent catheterization (CIC) had failed. In 13 out of 20, the botulinum toxin worked for an average of 8 months. All 13 patients who responded were able to stop anticholinergic medication completely and became continent until the medication wore off. Botulinum toxin may be useful to temporarily delay surgery for bladder augmentation and may be useful as a diagnostic test.]

Newman CJ, O'Regan M, Hensey O. Sleep disorders in children with cerebral palsy. Dev Med Child Neurol. 2006 Jul;48(7):564-8.

To determine the frequency and predictors of sleep disorders in children with cerebral palsy (CP) we analyzed the responses of 173 parents who had completed the Sleep Disturbance Scale for Children. The study population included 100 males (57.8%) and 73 females (42.2%; mean age 8y 10mo [SD 1y 11mo]; range 6y-11y 11mo). Eighty-three children (48.0%) had spastic diplegia, 59 (34.1%) congenital hemiplegia, 18 (10.4%) spastic quadriplegia, and 13 (7.5%) dystonic/dyskinetic CP. Seventy-three children (42.2%) were in Gross Motor Function Classification System Level I, 33 (19.1%) in Level II, 30 (17.3%) in Level III, 23 (13.3%) in Level IV, and 14 (8.1%) in Level V. Thirty children (17.3%) had epilepsy. A total sleep problem score and six factors indicative of the most common areas of sleep disorder in childhood were obtained. Of the children in our study, 23% had a pathological total sleep score, in comparison with 5% of children in the general population. Difficulty in initiating and maintaining sleep, sleep-wake transition, and sleep breathing disorders were the most frequently identified problems. Active epilepsy was associated with the presence of a sleep disorder (odds ratio [OR]=17.1, 95% confidence interval [CI] 2.5-115.3), as was being the child of a single-parent family (OR=3.9, 95% CI 1.3-11.6). Disorders of initiation and maintenance of sleep were more frequent in children with spastic quadriplegia (OR=12.9, 95% CI 1.9-88.0), those with dyskinetic CP (OR=20.6, 95% CI 3.1-135.0), and those with severe visual impairment (OR=12.5, 95% CI 2.5-63.1). Both medical and environmental factors seem to contribute to the increased frequency of chronic sleep disorders in children with CP.

Heckman JJ. Skill formation and the economics of investing in disadvantaged children. Science. 2006 Jun 30;312(5782):1900-2.

This paper summarizes evidence on the effects of early environments on child, adolescent, and adult achievement. Life cycle skill formation is a dynamic process in which early inputs strongly affect the productivity of later inputs.
[This review article emphasizes the importance of early intervention for children at risk for developmental disabilities.]