A Road Map for Academic Developmental-Behavioral Pediatric Practices to Increase Access.

ABSTRACT: There are currently at least 19 million children and adolescents in the United States with disorders of development (learning disorders, attention-deficit/hyperactivity disorder, intellectual disabilities, autism, motor incoordination/cerebral palsy, etc.) and only approximately 800 board-certified developmental-behavioral pediatricians (DBPs) practicing nationally. Given the astronomical mismatch between the number of children and adolescents with developmental disorders and the number of board-certified DBPs, developmental-behavioral pediatric consultations are likely the most inaccessible in all of medicine. With the goal of increasing access to these consultations, an academic developmental-behavioral practice in a large urban hospital system developed a longitudinal "Road Map," led by our team of social workers, which is designed to provide such services while continuing to focus DBP efforts on initial consultative evaluation and diagnosis of as many children as possible. The programs that this new Road Map has provided have allowed the DBP practice not only to increase access to developmental evaluations but also to provide more holistic and targeted care from the point of being added to the waiting list and then throughout the life span at vital transition periods. Especially given the extreme mismatch between the scarce number of practicing DBPs and the prodigious number of pediatric patients with disorders of development, our hope is that other centers will consider replicating this innovative care model to address the ever-growing need for specialized DBP consultation and longitudinal wraparound care for our patients and families.

Incidence of Celiac Disease in Down Syndrome: A Longitudinal, Population-Based Birth Cohort Study.

American Academy of Pediatrics (AAP) guidelines for children with Down syndrome (DS) include assessment for celiac disease (CD), although data to support this recommendation have been inconsistent. We determined the incidence of CD among children with DS in a population-based birth cohort of children born from 1976 to 2000 in Olmsted County, Minnesota. Individuals with karyotype-confirmed DS and CD (using diagnosis codes, positive serology, and duodenal biopsies) were identified. The incidence of CD in DS was compared with the published incidence of CD for Olmsted County residents (17.4 [95% confidence interval = 15.2-19.6] per 100 000 person-years). Among 45 individuals with DS from the birth cohort, 3 (6.7%) were identified with positive celiac serology and confirmatory biopsies at ages 9, 12, and 23 years, for an incidence of 325 per 100 000 person-years. Thus, individuals with DS have more than 18 times the incidence rate of CD compared with the general population, supporting the AAP guidelines.

Examining genetic counselors' implicit attitudes toward disability.

Genetic counselors have a unique role in healthcare that requires a balance between being a patient educator and patient advocate when discussing disability. This study aimed to determine genetic counselors' implicit attitudes toward disability, and identify what factors affect these implicit attitudes. Case scenarios involving disability were used to examine hypothetical estimates of time spent on different topics within a genetic counseling session. Implicit attitudes were measured using the validated Disability Attitudes Implicit Association Test (DA-IAT), and personal/professional experiences with disability were assessed. Analysis of 382 respondents of the electronic survey revealed that personal experience with individuals with disabilities was not significantly associated with implicit attitudes scores. In addition, results demonstrated that genetic counselors have a stronger bias toward ability (Dmean  = 0.62, Dstd  = ±0.45) compared to previous participants of the DA-IAT (p < .005). Practice specialty, length of time in the genetic counseling field, or whether the participant was a practicing counselor or genetic counseling student were not associated with implicit attitudes scores. The bias toward ability observed across practice specialties may be due to shared factors that influence interest in this field, but may also potentially reflect the inability of the DA-IAT to capture the complexity of genetic counselors' relationship to individuals with disability. This study emphasizes the importance of incorporating patients' individual definitions of disability into genetic counseling sessions and building an environment of patient advocacy and education around their personal perspectives and needs.

Urologic self-management through intermittent self-catheterization among individuals with spina bifida: A journey to self-efficacy and autonomy.

PURPOSE: To describe the age of independence in intermittent self-catheterization (ISC) in a diverse patient population and identify factors associated with ISC in individuals with spina bifida. METHODS: Two hundred patients with myelomeningocele or lipomyelomeningocele, who were ⩾ 3 years of age and utilized catheterization for bladder management were included. Data regarding diagnosis, functional level of lesion, race, ethnicity, presence of shunt, method of catheterization, self-management skills, fine motor skills, and cognitive abilities were collected. RESULTS: Fifty-five percent of individuals were able to perform ISC with a mean age of 9.45 years (SD = 2.97) and 22.7% used a surgically created channel. Higher level of lesion and female gender were associated with a lower rate of ISC. Intellectual disability was present in 15% of the individuals able to perform ISC and in 40% of those not able to perform ISC (p= 0.0005). Existent self-efficacy regarding activities of daily living (i.e. dressing, bathing, skin care) were associated with ISC (p< 0.0001). CONCLUSIONS: The average age of ISC emerged as a target for culturally-appropriate educational interventions to stimulate greater early independence. Future research on factors that may foster an 'independent spirit' early in childhood leading to self-management are warranted.

A chronic care model for spina bifida transition.

Providing comprehensive transition care for adolescents and young adults with spina bifida (AYASB) requires a structured approach to addressing chronic condition management, self-management, care coordination, and health care navigation that is adaptable to the various levels of cognitive ability, physical function, and family/community environments within the population. This commentary (1) highlights AYASB transition program needs identified in the literature and within a local community, (2) analyzes advantages and limitations of published AYASB transition care models in addressing these needs, (3) demonstrates how a spina bifida (SB) transition clinic used the Chronic Care Model (CCM) to develop a comprehensive AYASB transition program, and (4) examines the potential feasibility in adapting this model to other SB clinics. A SB-specific transition clinic based on the CCM model facilitates the complex chronic care management and transition planning for AYASB. Further study is needed to evaluate health care outcomes using the CCM for SB transition.

Early postnatal bladder function in fetoscopic myelomeningocele repair patients.

PURPOSE: Prenatal repair of myelomeningocele (MMC) via hysterotomy has demonstrated neurosurgical and motor benefits, when compared to postnatal repairs. Urologic benefits, however, remain to be seen. The purpose of this study was to review early postnatal bladder function in patients undergoing a novel endoscopic approach for MMC repair using an exteriorized uterus. METHODS: A prospective urologic assessment of patients undergoing fetoscopic MMC repair and receiving subsequent care at our facility, was performed. Patients were managed and urodynamic studies risk-stratified according to the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida. RESULTS: Fetoscopic MMC repair was performed in 14 patients. No patients had hydronephrosis or bladder thickening at birth. Detrusor overactivity was observed in nine (64.3%) patients. Impaired compliance was seen in eight (57.1%) patients. No patients had a detrusor leak point pressure of > 40 cm H2O or evidence of detrusor sphincter dyssynergia. Three (21.4%) patients had vesicoureteral reflux, seven (50.0%) had an open bladder neck, and none had trabeculated bladders. CONCLUSION: In this early experience with fetoscopic MMC repair, postnatal bladder function does not appear to be any worse than that of previously reported prenatal or postnatal closures.

Association of copper-zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) genes with nonsyndromic myelomeningocele.

BACKGROUND: A common and severe neural tube defect (NTD) phenotype, myelomeningocele (MM), results from the defective closure of the caudal end of the neural tube with herniation of the spinal cord and meninges through the vertebral column. The exact mechanisms for NTDs are unknown, but excessive oxidative stress, particularly in association with maternal diabetes, has been postulated as a mechanism for MM. METHODS: The SNPlex Genotyping (ABI, Foster City, CA) platform was used to investigate single nucleotide polymorphisms (SNPs) across the superoxide dismutase (SOD) 1 and 2 genes to assess their association with MM risk. The study population included 329 trio (affected child and both parents) and 281 duo (affected child and one parent) families. Only cases with documented MM were studied. Seventeen SNPs across the SOD1 and SOD2 genes met the quality-control criteria to be considered for statistical analysis. Genetic association was assessed using the family-based transmission disequilibrium test in PLINK (a genome association analysis toolset). RESULTS: Four SNPs in the SOD1 gene (rs 202446, rs202447, rs4816405, and rs2070424) and one SNP in the SOD2 gene ( rs5746105) [corrected] appeared to be associated with MM risk in our population. After adjusting for multiple testing, these SNPs remained significant. CONCLUSION: This study provides the first genetic evidence to support association of myelomeningocele with superoxide scavenging. The rare alleles of the five specific SNPs within SOD1 and SOD2 appear to confer a protective effect on the susceptibility for MM risk in the MM population tested. Further evaluation of the roles of superoxide scavenging and neural tube development is warranted.

Association of retinoic acid receptor genes with meningomyelocele.

BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM. METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our cohort consisted of 610 MM families. RESULTS: One variant in the RARA gene (rs12051734), three variants in the RARB gene (rs6799734, rs12630816, rs17016462), and a single variant in the RARG gene (rs3741434) were found to be statistically significant at p < 0.05. CONCLUSION: RAR genes were associated with risk for MM. For all associated SNPs, the rare allele conferred a protective effect for MM susceptibility.

Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier (SLC19A1) genes with meningomyelocele.

BACKGROUND: Meningomyelocele (MM) results from lack of closure of the neural tube during embryologic development. Periconceptional folic acid supplementation is a modifier of MM risk in humans, leading toan interest in the folate transport genes as potential candidates for association to MM. METHODS: This study used the SNPlex Genotyping (ABI, Foster City, CA) platform to genotype 20 single polymorphic variants across the folate receptor genes (FOLR1, FOLR2, FOLR3) and the folate carrier gene (SLC19A1) to assess their association to MM. The study population included 329 trio and 281 duo families. Only cases with MM were included. Genetic association was assessed using the transmission disequilibrium test in PLINK. RESULTS: A variant in the FOLR2 gene (rs13908), three linked variants in the FOLR3 gene (rs7925545, rs7926875, rs7926987), and two variants in the SLC19A1 gene (rs1888530 and rs3788200) were statistically significant for association to MM in our population. CONCLUSION: This study involved the analyses of selected single nucleotide polymorphisms across the folate receptor genes and the folate carrier gene in a large population sample. It provided evidence that the rare alleles of specific single nucleotide polymorphisms within these genes appear to be statistically significant for association to MM in the patient population that was tested.

Characteristics of a spina bifida population including North American Caucasian and Hispanic individuals.

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes. METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and association testing using the transmission disequilibrium test. RESULTS: A total of 509 affected child/parent trios and 309 affected child/parent duos have been enrolled to date for genetic association studies. Subsets of the patients have also been enrolled for studies assessing development, brain imaging, and neurocognitive outcomes. The study recruited two major ethnic groups, with 45.9% Hispanics of Mexican descent and 36.2% North American Caucasians of European descent. The remaining patients are African-American, South and Central American, Native American, and Asian. Studies of this group of patients have already discovered distinct corpus callosum morphology and neurocognitive deficits that associate with MM. We have identified maternal MTHFR 667T allele as a risk factor for MM. In addition, we also found that several genes for glucose transport and metabolism are potential risk factors for MM. CONCLUSIONS: The enrolled patient population provides a valuable resource for elucidating the disease characteristics and mechanisms for MM development.

Neurobehavioral outcomes in spina bifida: Processes versus outcomes.

We review neurobehavioral outcomes and interventions for children with spina bifida. Focusing on children with spina bifida myelomeningocele, we contrast historical views of outcomes based on comparisons across content domains (e.g., language versus visual perceptual skills) with a view based on overarching processes that underlie strengths and weakness within content domains. Thus, we suggest that children with SBM have strengths when the skill involves the capacity to retrieve information from semantic memory and generate material that has been associatively linked or learned (associative processing) and general difficulties on tasks that require the construction or integration of a response (assembled processing). We use a hypothetical case to illustrate the differences in content domains versus general processes and also identify interventions that may be effective in addressing some of the cognitive and behavioral difficulties experienced variably by people with SBM. We extend these general principles to a discussion of variability in outcomes and use data from a large sample of children with spina bifida to illustrate the basis for this variability.