Sib risks of anencephaly and spina bifida in British Columbia

The prevalence at birth of anencephaly or spina bifida cystica among sibs of individuals born in British Columbia with these defects was studied using routinely collected records of morbidity and mortality within the province. The population prevalence of these neural-tube defects in British Columbia is approximately 1.55 per thousand births, lower than in other areas where family studies have been carried out. A total of 1,028 affected individuals born in British Columbia during the period 1952–1970 was ascertained from health and vital documents collected on an ongoing basis by the Division of Vital Statistics of the British Columbia Ministry of Health. Information on the families of these cases was acquired using computer-linked groupings of British Columbia marriage, birth, and stillbirth records. The risk of affected individuals among the sibs was 2.4%, about 15 times the population prevalence at birth. The prevalence among subsequent sibs of the first affected individual in a family was 2.1%. There was no difference in risk when various factors that influence the population incidence of these conditions were considered. The risk of recurrence of either of these anomalies after two previously affected sibs was 4.8%, or double the risk after one affected sib. From these results and those of a recent New York survey of sib risks of neural-tube anomalies it would seem that the risk of anencephaly and spina bifida cystica to sibs of affected cases in North America is approximately half the risk in Great Britain, and it is this lower risk of 2% that should be used for genetic counseling in North America.     

Relationships among life stress, perceived family environment, and the psychological distress of spina bifida adolescents

Fifty-three teen-agers with spina bifida participated in a mail survey and completed measures of recent life events, perceived family environment, and psychological distress. Low levels of perceived family conflict and control served as life stress buffers in the prediction of distress, whereas a high level of perceived independence served as a life stress exacerbator. These interaction effects differ from those obtained for a normal sample of adolescents in the lone previous study (Burt, Cohen, & Bjorck, 1988) that reported comparable analyses. The results suggest that the process by which family environments moderate stress adjustment differs for able-bodied vs. spina bifida adolescents.     

Distribution of affected muscles and degree of neurogenic lesion in patients with spina bifida

Introduction

Patients with spina bifida in the lumbosacral region usually have various degrees of motor and sensory dysfunctions of the lower extremities and anal sphincter. The aim of our study was to evaluate the distribution and differences in frequencies of affected muscles, number of affected muscles and degree of neurogenic lesion between patients with spina bifida occulta (SBO) and spina bifida aperta (SBA).

Material and methods

In 100 patients with SB, 6 muscles in the lower limbs were separately analysed. Due to the number of affected muscles, we evaluated 5 groups of patients: with 1 affected muscle, 2 affected muscles, 3 affected muscles, 4 affected muscles and 5 affected muscles. Three degrees of neurogenic lesions were assessed: mild, moderate and severe.

Results

The tibialis anterior muscle was most frequently affected in SB patients. The outer anal sphincter was frequently affected in the group of SBA patients. Single muscle affection is frequent in the group of patients with SBO, while in the group of patients with SBA, 4 muscles were significantly frequently affected. The great majority of patients (45.46%) with affected outer anal sphincter (OAS) in the group of SBO were without affection of other muscles, while for the SBA group it was for every third patient. Mild neurogenic lesion was significantly frequent in SBO patients, while severe form was significantly frequent in SBA patients.

Conclusions

Patients with SBO usually present with mild to moderate clinical presentation, while multiple root involvement and severe degree of neurogenic lesion is associated more frequently with SBA.     

Degree of genetic homozygosity and distribution of AB0 blood types among patients with spina bifida occulta and spina bifida aperta

Introduction

Assuming that spina bifida (SB) is a genetically controlled disease, the aim of our study was to evaluate the degree of genetic homozygosity and the distribution of AB0 blood types among patients with SB occulta and SB aperta by the homozygously recessive characteristics (HRC) test.

Material and methods

Our study included an analysis of the presence, distribution and individual combination of 15 selected genetically controlled morpho-physiological traits in a sample of 100 patients with SB (SB occulta N = 50 and SB aperta N = 50) and a control group of individuals (N = 100).

Results

We found a statistically significant difference between the mean values for genetic homozygosity (SB 4.5 ±0.3; control 3.0 ±0.2, p < 0.001) and also differences in the presence of certain individual combinations of such traits. In 12 (80.0%) of the 15 observed characteristics, recessive homozygosity was expressed to a greater degree among the group of SB patients, while for 9 (60.0%) of the traits this level of difference was statistically significant (Σ_χ ² = 266.3, p < 0.001). There was no difference in average homozygosity of such genetic markers between groups of SB occulta and SB aperta patients, but the type of individual variation in the two studied groups significantly differed. In the group of patients with SB the frequency of 0 blood group was significantly increased while B blood group was significantly decreased.

Conclusions

Our results clearly show that there is a populational genetic difference in the degree of genetic homozygosity and variability between the group of patients with SB and individuals without clinical manifestations, indicating a possible genetic component in the aetiopathogenesis of spina bifida.     

Risk factors for latex allergy in patients with spina bifida and latex sensitization

BACKGROUND: Some subjects with spina bifida (SB) and latex sensitization (cutaneous and/or serum IgE) can have clinical reactions, while others may have no symptoms after the exposure to latex products. OBJECTIVE: This study was carried out to determine the risk factors associated with latex allergy in patients affected with SB and latex sensitization. METHODS: Fifty-nine consecutive subjects affected with SB, besides answering a questionnaire, underwent a skin-prick test (SPT) to latex and the determination of the specific serum IgE (RAST CAP) to latex. The total serum IgE concentration was determined and SPT to common aero- and food-allergens, skin tests (prick + prick) with fresh foods (kiwi, pear, orange, pineapple, tomato, banana) and RAST CAP to the same foods tested by the prick + prick technique, were also performed. RESULTS: Fifteen out of the 59 subjects (25%) were sensitized to latex according to the presence of IgE to latex detected by SPT (nine patients) and/or RAST CAP (13 patients). Five out of the 15 sensitized patients (33%) suffered from clinical reactions to latex (urticaria, conjunctivitis, angioedema, rhinitis, bronchial asthma) while they were using latex gloves and while inflating latex balloons. In the 15 sensitized patients, the presence of specific latex seric IgE > 3.5 kU/L (>/= class 3), a positive latex SPT, an elevated total serum IgE, and a positive prick + prick and/or a positive RAST CAP to foods, were significant (P < 0.05) risk factors associated with latex symptoms. The other factors tested (age, gender, months of intermittent bladder catheterization, surgical procedures, SPT reactivity and clinical reactions to aero-allergens and food-allergens, skin tests for fresh foods, positive RAST CAP to foods) were not significantly different in symptomatic and asymptomatic patients. CONCLUSION: Significant risk factors for symptoms to latex in patients with SB and latex sensitization were a presence of specific IgE to latex > 3.5 kU/L, a more frequent positive latex SPT, elevated total IgE, and one or more positive prick + prick and/or RAST CAP to fresh foods.     

Physical status and psychosocial adjustment in children with spina bifida

Investigated the relationship between the physical status and psychosocial adjustment of chronically physically handicapped children. The status of 61 children with spina bifida regarding six specific disease or disability parameters was determined from medical charts. Their mothers completed the Child Behavior Checklist as a measure of the children's psychosocial adjustment. Children with spina bifida were reported to display on the average significantly more behavior and social competence problems than expected for children in general. However, children with differing degrees of physical problems and disability did not differ significantly in their psychosocial adjustment. The general lack of relationship between physical status and adjustment as it relates to a conceptual model guiding this research is discussed.     

Psychological adaptation of mothers of children with spina bifida: association with dimensions of social relationships.

Investigated the hypothesis that dimensions of social relationships such as family support, conflict, and control; marital quality/support, social support, and social coping are associated with the psychological adjustment of mothers of children with spina bifida. A representative sample of 66 mothers answered a series of questionnaires including the Family Environment Scale. Dyadic Adjustment Scale, Social Support Questionnaire (6-item form), Social Coping Questionnaire, and SCL-90-R. Results indicated that mothers with more supportive families and marriages and less conflicted and controlling families reported lower levels of psychological symptoms. Coping strategies directed at friends were related to more symptoms.     

Attention and executive functions in adolescents with spina bifida

OBJECTIVE: This study was designed to examine attention processes and executive functioning in adolescents with spina bifida, and to explore whether impairment in these domains contributes to problems with social adjustment. METHODS: A sample of adolescents with spina bifida (n = 68) and a matched comparison group (n = 68) and their families were followed longitudinally. All participants completed questionnaires, and the adolescent participants underwent neurocognitive testing. RESULTS: The spina bifida sample showed greater impairment on objective and subjective measures of attention and executive functioning, even when differences in intellectual functioning were controlled. Additionally, attention and executive deficits were found to be predictive of social adjustment difficulties. A mediational analysis suggested the neurocognitive deficits mediate associations between spina bifida status and social adjustment difficulties. CONCLUSIONS: Adolescents with spina bifida appear to exhibit clear impairment in attention and executive functioning and this impairment may contribute to their well-established social difficulties.     

Loss of RAD9B impairs early neural development and contributes to the risk for human spina bifida

DNA damage response (DDR) genes orchestrating the network of DNA repair, cell cycle control, are essential for the rapid proliferation of neural progenitor cells. To date, the potential association between specific DDR genes and the risk of human neural tube defects (NTDs) has not been investigated. Using whole‐genome sequencing and targeted sequencing, we identified significant enrichment of rare deleterious RAD9B variants in spina bifida cases compared to controls (8/409 vs. 0/298; p = .0241). Among the eight identified variants, the two frameshift mutants and p.Gln146Glu affected RAD9B nuclear localization. The two frameshift mutants also decreased the protein level of RAD9B. p.Ser354Gly, as well as the two frameshifts, affected the cell proliferation rate. Finally, p.Ser354Gly, p.Ser10Gly, p.Ile112Met, p.Gln146Glu, and the two frameshift variants showed a decreased ability for activating JNK phosphorylation. RAD9B knockdowns in human embryonic stem cells profoundly affected early differentiation through impairing PAX6 and OCT4 expression. RAD9B deficiency impeded in vitro formation of neural organoids, a 3D cell culture model for human neural development. Furthermore, the RNA‐seq data revealed that loss of RAD9B dysregulates cell adhesion genes during organoid formation. These results represent the first demonstration of a DDR gene as an NTD risk factor in humans.     

The search of latex sensitization in spina bifida: diagnostic approach

BACKGROUND: Sensitization to latex has become a major problem in children with spina bifida. Life-threatening reactions may occur in these patients, therefore the search of latex sensitization must be an active task in all of these children. OBJECTIVE: To design an approach for the diagnosis of latex sensitization in children with spina bifida. METHODS: We studied 100 consecutive unselected patients. Skin prick tests with a commercial latex extract were performed, latex-specific serum immunoglobulin (Ig) E was determined by CAP test, and risk factors were studied. Originally, patients with an area of latex skin test > 50% of the area of histamine and/or CAP class > or = 3 were considered sensitized to latex. Diagnostic tests were also performed in a control group of 51 atopic and nonatopic children. RESULTS: After performing a receiver-operating characteristics curve for both tests we recommend skin tests > 25% of the area of histamine (sensitivity - SEN = 79%, specificity - SPE = 100%, positive predictive value - PPV = 100%, negative predictive value - NPV = 90%), or CAP class > or = 2 (SEN = 88%, SPE = 100%, PPV = 100%, NPV = 94%) as diagnostic cut-off points. The anamnesis had a SEN of 44% for diagnosis, and a SPE of 100%. Latex sensitization was associated with more than 5 operations (OR = 8, 95% CI = 3-21.3), a personal history of atopy (OR = 11.5, 95% CI = 2.3-57.1), and serum total IgE > or = 2 z-units (OR = 4, 95% CI = 1. 6-10). CONCLUSION: For the routine evaluation of children with spina bifida, we propose a diagnostic algorithm with skin prick tests as a first step and CAP second.     

Parents' social adjustment in families of children with spina bifida: a theory-driven review

OBJECTIVE: Five theoretical hypotheses about the impact of spina bifida (SB) on parents' social adjustment in the parent-child, the marital and the family-level relationship were tested. METHODS: PsycInfo, Medline and reference lists were searched. This yielded 27 eligible reports. Effect sizes (Hedges' d) were computed to estimate the impact of SB. RESULTS: Overall, the effects of SB were small to negligible on the affective dimensions of parents' relationships. The few effects that were found tended to be positive. The most important negative effects of SB were found in the parent-child relationship (parenting stress and overprotection). CONCLUSIONS: Support was found for the resilience-disruption hypothesis, the role-division hypothesis and the miscarried-helping hypothesis, but not for the marital-disruption hypothesis or the marginality hypothesis.     

Predictors of parenting behavior trajectories among families of young adolescents with and without spina bifida

OBJECTIVE: To evaluate the utility of familial and parental variables in predicting trajectories of parenting behaviors among families of young adolescents with and without spina bifida (SB). METHOD: Sixty-eight families with a child with SB and a demographically matched comparison group (CG) of 68 families of an able-bodied child participated. Observational and questionnaire assessments of parenting behavior were collected via home visits at three time points, as were reports of parent and family functioning. RESULTS: Family conflict was negatively associated with adaptive parenting behavior at Time 1 (T1), but positively associated with adaptive parenting change. Although the direction of this effect was the same across both groups, findings were more robust for the SB sample. Among fathers of children with SB, parenting stress was positively associated with adaptive parenting at T1 but negatively associated with adaptive parenting change. In contrast, within the CG, paternal parenting stress was negatively associated with adaptive parenting at T1 but showed no enduring negative effects in longitudinal analyses. CONCLUSIONS: Family conflict and parenting stress were significant predictors of parenting behaviors and longitudinal parenting change. Findings are interpreted within a developmental context such that variables associated with maladaptive (or adaptive) parenting in the short run, may facilitate adaptive (or maladaptive) parenting over time based on young adolescents' changing developmental needs.     

Determination of independent risk factors and comparative analysis of diagnostic methods for immediate type latex allergy in spina bifida patients

Background Development of allergy to natural rubber latex in spina bifida patients is determined by several risk factors, such as age, number of interventions and atopic disease that are, however, interdependent. Furthermore, several diagnostic procedures have been analysed, but a comprehensive analysis of their diagnostic significance is lacking. Objective To determine the independent major risk factor(s) for development of natural rubber latex allergy and the most valuable diagnostic procedure. Methods In aselectively collected spina bifida patients, we correlated existing natural rubber latex allergy with age, sex, atopy and the number of hospitalizations and of surgical interventions in appropriately matched subgroups. Allergy to natural rubber latex was established by application of a latex glove fragment on the skin. Skin-prick tests with glove eluate, a natural latex extract and a commercial latex extract were carried out as were specific IgE measurements by radioimmuno assay (RAST-CAP). The results of the latex application test are compared with the other diagnostic methods. Results Out of 74 fully evaluated patients, 17 had a positive application test. The number of surgical interventions correlates strongly with the presence of natural rubber latex allergy (P < 0.0002), independent of age, sex and presence of atopy. Skin-prick tests with unstandardized allergens made from known high allergenic latex gloves represent the most sensitive diagnostic method, with the highest negative predictive value and a specificity of 0.95. RAST-CAP was the next best method with a specificity of 0.93, a sensitivity of 0.89 and a negative predictive value of 0.97. Conclusion The number of surgical interventions is the major independent determining factor for allergy to natural rubber latex in spina bifida patients. Unstandardized skin-prick tests are the most sensitive and specific diagnostic tool, but RAST-CAP is almost equally performant and therefore a valid alternative.     

Observed and perceived dyadic and systemic functioning in families of preadolescents with spina bifida

OBJECTIVE: To examine dyadic and systemic family functioning across several domains (conflict, cohesion, and stress) in families of preadolescents with spina bifida in comparison to families of able-bodied preadolescents (8- and 9-year olds; n = 68 in each sample). METHODS: Mother-, father-, and child-reported questionnaire data and observational ratings of family behavior were employed. RESULTS: Findings revealed significant group and socioeconomic status (SES) differences, particularly for the observational family data. Compared to families of able-bodied children, families in the spina bifida sample were less cohesive and children from this sample were more passive during family interaction tasks. Additional analyses suggested that some of these significant associations between group status and family functioning were mediated by verbal IQ, indicating that a significant portion (42%-55%) of the overall group effect was due to variations in child cognitive functioning. Lower SES families demonstrated higher levels of observed mother-child conflict, less observed and perceived family cohesion, and more life events. Lower SES families from the spina bifida sample appear to be particularly at risk for lower levels of family cohesion. CONCLUSIONS: Findings for the spina bifida sample support a resilience-disruption view (Costigan, Floyd, Harter, & McClintock, 1997) of systemic functioning in families of children with pediatric conditions.     

A longitudinal study of pubertal timing,parent-child conflict,and cohesion in families of young adolescents with spina bifida

OBJECTIVE: To study longitudinal associations between perceived pubertal timing and family conflict and cohesion during the transition to adolescence in 68 families of children with spina bifida and 68 matched families with able-bodied children. Children were 8 or 9 years old at Time 1 and 10 or 11 years old at Time 2. METHODS: Family conflict and cohesion were assessed with observational data and maternal, paternal, and child reports on questionnaires. Perceived pubertal timing was assessed with maternal report. RESULTS: Consistent with the literature on typically developing young adolescents, prospective longitudinal analyses revealed that early maturity was associated with higher levels of conflict and decreases in cohesion in families with able-bodied children. Contrary to these findings, perceived pubertal timing had less of an impact (or the opposite impact) in families of children with spina bifida. Findings were robust across respondents and methods of data collection. CONCLUSIONS: Findings based on multimethod and multisource data suggest that familial response to developmental change differs across context (spina bifida vs. able-bodied). Possible reasons for differential responses to the adolescent transition are reviewed. Services are likely to be enhanced if health professionals routinely discuss adolescent developmental issues with parents and youths during clinic visits.     

Longitudinal study of observed and perceived family influences on problem-focused coping behaviors of preadolescents with spina bifida

OBJECTIVE: To study coping socialization longitudinally by examining reported and observed family environment and parenting variables in relation to children's problem-focused coping in a sample of 68 families of preadolescents with spina bifida and 68 matched able-bodied comparison families. METHODS: Family environment and parenting variables were assessed with mother and father reports and observational measures. Children's problem-focused coping was self-reported. RESULTS: Prospective analyses revealed that maternal responsiveness, paternal responsiveness, and family cohesion predicted an increase in children's use of problem-focused coping strategies, while change in paternal responsiveness and maternal responsiveness and demandingness was related concurrently to change in coping. Few group (spina bifida vs. able-bodied) or gender differences with respect to parenting and family influences on children's coping behaviors were found. CONCLUSIONS: Multimethod findings suggest that the quality of parenting and family environment is associated with children's problem-focused coping behaviors. We discuss clinical implications.     

Influencing clinical practice regarding the use of antiepileptic medications during pregnancy: Modeling the potential impact on the prevalences of spina bifida and cleft palate in the United States

Selected antiepileptic drugs (AEDs) increase the risk of birth defects. To assess the impact of influencing AED prescribing practices on spina bifida and cleft palate we searched the literature for estimates of the association between valproic acid or carbamazepine use during pregnancy and these defects and summarized the associations using meta-analyses. We estimated distributions of the prevalence of valproic acid and carbamazepine use among women of childbearing age based on analyses of four data sets. We estimated the attributable fractions and the number of children born with each defect that could be prevented annually in the United States if valproic acid and carbamazepine were not used during pregnancy. The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0–21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3–9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3–7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1–4.5) in the United States. Approximately 40 infants (95% UI: 10–100) with spina bifida and 35 infants (95% UI: 10–70) with cleft palate could be born without these defects each year if valproic acid were not used during pregnancy; 5 infants (95% UI: 0–15) with spina bifida and 5 infants (95% UI: 0–15) with cleft palate could be born without these defects each year if carbamazepine were not used during pregnancy. This modeling approach could be extended to other medications to estimate the impact of translating pharmacoepidemiologic data to evidence-based prenatal care practice. Published 2011 Wiley-Liss, Inc.