Age-Specific Probability of 4 Major Health Outcomes in Children with Spina Bifida.

OBJECTIVE: This study aimed to estimate the age-specific probability of 4 health outcomes in a large registry of individuals with spina bifida (SB). METHODS: The association between age and 4 health outcomes was examined in individuals with myelomeningocele (MMC, n = 5627) and non-myelomeningocele (NMMC, n = 1442) from the National Spina Bifida Patient Registry. Sixteen age categories were created, 1 for each year between the ages of 5 and 19 years and 1 for those aged 20 years or older. Generalized linear models were used to calculate the adjusted probability and 95% prediction intervals of each outcome for each age category, adjusting for sex and race/ethnicity. RESULTS: For the MMC and NMMC groups, the adjusted coefficients for the correlation between age and the probability of each outcome were -0.933 and -0.657 for bladder incontinence, -0.922 and -0.773 for bowel incontinence, 0.942 and 0.382 for skin breakdown, and 0.809 and 0.619 for lack of ambulation, respectively. CONCLUSION: In individuals with SB, age is inversely associated with the probability of bladder and bowel incontinence and directly associated with the probability of skin breakdown and lack of ambulation. The estimated age-specific probabilities of each outcome can help SB clinicians estimate the expected proportion of patients with the outcome at specific ages and explain the probability of the occurrence of these outcomes to patients and their families.

Factors Associated With Ambulation and Transfer Ability: A Study From the National Spina Bifida Patient Registry.

OBJECTIVES: This study used a spina bifida electronic medical record and the National Spina Bifida Patient Registry to explore the relationship between neurosurgical/orthopedic surgeries and other variables on ambulation and transfer ability over time in individuals with spina bifida. DESIGN: This study was an analysis of longitudinal data collected within the National Spina Bifida Patient Registry and spina bifida electronic medical record. Logistic regression models were used to determine which variables were associated with ambulation/transfer ability in the myelomeningocele (MMC) and non-MMC populations. RESULTS: Longitudinal data from 806 individuals were collected. In the MMC group, decreased ambulation ability was associated with higher motor levels, tethered cord releases, spine/scoliosis surgeries, hip orthopedic surgeries, and having supplemental insurance. Increased ambulatory ability was associated with lower motor levels, tibial torsion/related surgeries, ankle/foot surgeries, being female, and being non-Hispanic/Latinx. Decreased transfer ability was associated with being Hispanic/Latinx and having higher motor levels. Lower motor level and ankle/foot surgeries were associated with increased transfer ability. No significant associations were found in the non-MMC group. CONCLUSIONS: Motor level is an important predictor of ambulation and transfer ability in MMC. Surgeries distal to the knee were associated with higher levels of function; surgeries proximal to the knee were associated with lower functional levels.

Survey of U.S. adults with spina bifida.

BACKGROUND: Spina Bifida (SB) is one of the most common birth defects and causes of permanent disability in the United States (US), with approximately 3.5 cases per 10,000 live births. OBJECTIVE: To identify complications associated with SB related to skin breakdown, pain, and urinary tract infections (UTIs), and to examine socio-demographic differences related to these complications. METHODS: Exploratory cross-sectional study via online of a national US convenience sample of adults with SB. RESULTS: We collected 1485 survey responses, of which 852 had complete, useable data. Skin breakdown in one or more locations during the past year was reported by 43.1%. After controlling for socio-demographic characteristics, only mobility variables remained significant predictors of skin breakdown (assistive device use OR = 3.119, 95% CI: 1.749, 5.564; using a wheelchair OR = 6.336, 95% CI: 3.442, 11.662). Pain in past seven days was reported by 46.9%. Single respondents (OR = 0.621; 95% CI: 0.419, 0.921) and those with at least a Bachelor's degree (vs high school degree or less, OR = 0.468; 95% CI: 0.283, 0.774) were less likely, and those using assistive devices were significantly more likely (OR = 1.960; 95% CI: 1.163, 3.303), to report pain. About one-third (32.7%) reported having a UTI within the past 12 months. Notably, almost half (49.6%) of respondents did not answer this question. The presence of UTIs was not significantly related to any socio-demographic characteristics assessed. CONCLUSIONS: Adults with SB in the US live with a wide range of complications which are potentially under-monitored, with predictors of complications that require further research.

Differences in continence rates in individuals with spina bifida based on ethnicity.

BACKGROUND: Ethnic disparities in continence rates in spina bifida (SB) have been studied regionally but not nationally. National SB Patient Registry (NSBPR) data were analyzed to explore differences in prevalence of bowel and bladder continence and interventions between Hispanics/Latinos and others. METHODS: Participants 5 to 21 years were categorized into Hispanic/Latino and non-Hispanic/non-Latino. Bladder/bowel continence was defined as dry/no involuntary stool leakage during the day or none/⩽ monthly incontinence. Chi-square test, Wilcoxon Two Sample Test, and generalized estimating equation (GEE) were used for statistical analysis. RESULTS: Twenty-five percent of the 4,364 patients were Hispanic/Latino. At their most recent clinic visit, Hispanics/Latinos demonstrated lower rates of urinary continence (38.6% vs. 44.9%; p= 0.0003), bowel continence (43.9% vs. 55.8%, p< 0.0001), private insurance (p< 0.0001), bowel (p< 0.0001) or bladder surgeries (p= 0.0054), and more vesicostomies (p= 0.0427) compared to others. In multiple GEE models, Hispanic/Latino participants demonstrated lower odds of bowel continence as compared to non-Hispanic/non-Latino participants (estimated odds ratio, 0.82, 95% CI, 0.72-0.94, p= 0.0032). CONCLUSIONS: After controlling for covariates, Hispanics/Latinos with SB are less likely to report bowel continence. Clinicians are encouraged to consider the risk of negative health disparities for Hispanic patients with SB and work to mitigate this risk.

Genetic epidemiology of neural tube defects.

It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes associated with non-syndromic NTDs in humans is especially notable as the "genomic revolution" has led to new tools (e.g., genome-wide genotyping arrays, next-generation sequencing) that are helping to elucidate the full spectrum of genetic variation (from common to rare) contributing to complex traits, including structural birth defects. However, the application of modern genomic approaches to the study of NTDs has lagged behind that of some other common structural birth defects. This may be due to the difficulty of assembling large study cohorts for anencephaly or spina bifida. The purpose of this review is to outline the evolution of genetic studies of NTDs, from studies of familial aggregation to candidate gene and genome-wide association studies, through whole-exome and whole-genome sequencing. Strategies for addressing gaps in NTD genetic research are also explored.

Factors associated with pressure ulcers in individuals with spina bifida.

OBJECTIVE: To describe factors associated with pressure ulcers in individuals with spina bifida (SB) enrolled in the National Spina Bifida Patient Registry (NSBPR). DESIGN: Unbalanced longitudinal multicenter cohort study. SETTING: Nineteen SB clinics. PARTICIPANTS: Individuals with SB (N=3153) enrolled in 19 clinic sites that participate in the NSBPR. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pressure ulcer status (yes/no) at the annual visit between 2009 and 2012. RESULTS: Of 3153 total participants, 19% (n=603) reported ulcers at their most recent annual clinic visit. Seven factors-level of lesion, wheelchair use, urinary incontinence, shunt presence, above the knee orthopedic surgery, recent surgery, and male sex-were significantly associated with the presence of pressure ulcers. Of these factors, level of lesion, urinary incontinence, recent surgery, and male sex were included in the final logistic regression model. The 3 adjusting variables-SB type, SB clinic, and age group-were significant in all analyses (all P<.001). CONCLUSIONS: By adjusting for SB type, SB clinic, and age group, we found that 7 factors-level of lesion, wheelchair use, urinary incontinence, shunt presence, above the knee orthopedic surgery, recent surgery, and male sex-were associated with pressure ulcers. Identifying key factors associated with the onset of pressure ulcers can be incorporated into clinical practice in ways that prevent and enhance treatment of pressure ulcers in the population with SB.

The role of ethnicity and culture on functional status in children with spina bifida.

PURPOSE: Spina bifida is a common cause of pediatric disability and more prevalent in the Hispanic population. Significant health disparities exist in minority populations. Culturally adapted health interventions have been attempted in conditions such as pediatric asthma with improvement. This study aims to explore the influence of ethnicity and culture with regards to functional status and care satisfaction. METHODS: Study participants were recruited from the Children's Hospital Colorado Spinal Defects Clinic. Demographics and past medical and surgical history were obtained via chart review. A questionnaire assessed ethnicity, acculturation, self-care, mobility, bowel and bladder function, and care satisfaction. RESULTS: A total of 70 subjects with spina bifida were included in the statistical analysis. There was no difference in PEDI self-care and mobility scores between ethnicities. The Hispanic group had higher urinary incontinence rates, higher percentage with bladder accidents, and lower satisfaction with bladder management. Regarding bowel function, the Hispanic group had lower satisfaction rates and a trend towards lower bowel continence. CONCLUSIONS: Further work is needed to understand the social and cultural differences between Hispanic and Non-Hispanic children and their families that impact bowel and bladder continence and care satisfaction. Once identified, culturally sensitive interventions may be implemented that can alleviate these apparent health disparities.

Sports and disability.

Participation in recreational and competitive sports at an early age has long been touted as a positive influence on growth and development, and for fostering lifelong healthy lifestyles. The benefits of an active lifestyle include not only fitness, but the promotion of a sense of inclusion and improved self-esteem. These benefits are well documented in all populations, and their importance has been summarized in the recent Healthy People 2010 guidelines. The American Academy of Pediatrics has recently produced a summary statement on the benefits of activity for disabled children. They note that children with disabilities tend to have an overall lower level of fitness and an increased level of obesity. For this population, developing a lifelong desire to be active can be a simple means for limiting illness and much of the morbidity associated with sedentary lifestyles often associated with disability. For disabled youth, participation in disabled sports programs available nationally and internationally can be an effective means to promote such precepts. The goal of this focused review is to improve the learner's knowledge of the positive impact that active lifestyles can have on overall health in the disabled youth population and, as a result, modify their practice by incorporating recreational and competitive sport activities as part of improving overall patient care.

Pediatric spinal cord tumors and masses.

BACKGROUND/OBJECTIVE: Spinal cord tumors are a relatively rare diagnosis, accounting for 1% to 10% of all pediatric central nervous system tumors. Understanding the etiology and clinical outcomes of these tumors is therefore very important. This study presents detailed information regarding clinical presentation, histological findings, outcomes, functional assessment, and management of a series of patients with this diagnosis. METHOD: Retrospective, descriptive study. SUBJECTS: Thirty-five children with a final diagnosis of spinal cord tumor or mass, excluding dysraphism. RESULTS: Neurodevelopmental tumors (dermoid tumors, epidermoid tumors, and teratomas) were the most common tumor type (31%), followed by astrocytomas (29%) and neuroblastomas (14%). Other types included schwannomas, meningiomas, giant cell tumors, extradural cystic masses, leukemic-related masses, and masses related to neurofibromatosis. Mean age at diagnosis was 6.6 years (SD = 5.5 y) and did not vary significantly by tumor type except for children with neuroblastoma (mean = 0.4 y, SD = 0.5 y). More boys (57%) were identified in the series than girls (43%); however, there was no association between tumor type and sex. Presenting complaints of pain were noted in 57% and were localized to the back, neck, or extremities. Extremity weakness was reported as an initial presenting symptom in 46%. Three children had scoliosis as a presenting issue and 14 had gait abnormalities. Regardless of treatment modality, mobility was retained in 83% of children with or without gait aids. Neurogenic bowel and/or bladder were present in 23% of the population. CONCLUSIONS: This study corroborates other studies indicating that intramedullary tumors are the predominant form of pediatric spinal cord tumor. This population, however, presented with an unusually large number of developmental tumors, contrary to several published studies. The disparity may be the result of this institution acting as a regional referral center, thus increasing the number of this type of patient. The population is too small to make any other conjecture. The predominance of astrocytomas and neuroblastomas among those patients with poor outcomes and the prevalence of developmental tumors suggest the need for broader investigation. Although, in general, spinal cord tumors are relatively rare, this preliminary study supports the need to further evaluate associations between tumor type, presenting symptoms, treatment, and functional outcome in children with spinal cord tumors.

Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: long-term effect.

OBJECTIVE: To determine and compare the long-term effects of prednisone and deflazacort on the functional status of children with Duchenne muscular dystrophy. DESIGN: A total of 49 boys with Duchenne muscular dystrophy, between the age of 12 and 15 yrs, who were observed over a 7-yr period were reviewed retrospectively. Eighteen had been treated with prednisone, 12 with deflazacort, and 19 had no drug treatment. All boys treated with steroids received medication for >2 yrs before losing their ambulation. Lower and upper limb motor functions, pulmonary function, prevalence of surgery for scoliosis, and side effects were compared. RESULTS: Boys in the steroid groups were significantly more functional and performed better on all tests than boys not treated (P < 0.05). There was no significant difference between the deflazacort- and prednisone-treated groups (P > 0.05). The number of boys having scoliosis surgery in treated groups was significantly less than nontreated boys (P < 0.05). The control group's pulmonary capacity was decreasing and significantly less than both prednisone- and deflazacort-treated boys. Both deflazacort and prednisone had beneficial effect on pulmonary function and scoliosis. Cataracts, hypertension, behavioral changes, excessive weight gain, and vertebral fracture were noted as serious side effects. CONCLUSIONS: Prednisone and deflazacort have a significant beneficial effect on slowing the disease progress. Their usage in Duchenne muscular dystrophy may prolong ambulation and upper limb function with similar potency. Both steroids also improve pulmonary function, in addition to delaying the need for spinal interventions, with similar therapeutic profiles.

E1A and E1B proteins inhibit inflammation induced by adenovirus.

Replication-defective human adenovirus (Ad) group C transducing vectors, most of which have the E1A, E1B, and E3 genes deleted, are highly inflammatory despite the fact that the parental viruses typically cause subclinical or mild infections. To investigate this paradox, the roles that the E1A, E1B, and E3 genes play in inflammation were tested by using replication-incompetent viruses carrying a deletion of the preterminal protein gene. The viruses were injected into BALB/c mouse ears, and edema was monitored as a sensitive surrogate marker of inflammation. A virus deleted for the E1A 289R (transcription activating) protein was noninflammatory, and inhibited edema induced by empty virus particles. The E1A 243R and E1B 55-kDa (p53 binding) proteins play the most important roles in inhibition of inflammation by the noninflammatory virus. The E1B 19-kDa antiapoptotic protein inhibited edema when both the E1A 243R and E1B 55-kDa proteins were expressed but strongly induced edema when only one was expressed. E3 proteins had their greatest effect on the inhibition of edema induced by the E1A 289R protein. The results support a model in which inflammation is countered through a mechanism that involves complex genetic interactions between Ad early region proteins and offer promise for the design and construction of noninflammatory Ad gene therapy vectors that are relatively easy to grow and purify.