Influenza and congenital anomalies: a systematic review and meta-analysis.

Luteijn JM, Brown MJ, Dolk H. (2013) Influenza and congenital anomalies: a systematic review and meta-analysis. Human Reproduction. 2013 Dec 22. [Epub ahead of print]

Abstract

STUDY QUESTION:

Does first trimester maternal influenza infection increase the risk of non-chromosomal congenital anomalies (CA)?

SUMMARY ANSWER:

First trimester maternal influenza exposure is associated with raised risk of a number of non-chromosomal CA, including neural tube defects, hydrocephaly, congenital heart defects, cleft lip, digestive system defects and limb reduction defects.

WHAT IS KNOWN ALREADY:

Hyperthermia is a well-established risk factor for neural tube defects. Previous studies suggest influenza may be a risk factor not only for neural tube defects, but also other CA. No systematic review has previously been undertaken.

STUDY DESIGN, SIZE, DURATION:

Systematic review and meta-analysis. A search of EMBASE and PUBMED was performed for English and Dutch studies published up to July 2013. A total of 33 studies (15 case-control, 10 cohort and 8 ecological) were included in the systematic review of which 22 studies were included in the meta-analysis.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS:

A total of 29 542 babies with congenital anomaly (1112 exposed) from case-control studies and 1608 exposed pregnancies resulting in 56 babies with congenital anomaly from cohort studies were included in the meta-analysis. Maternal influenza exposure was defined as any reported influenza, influenza-like illness or fever with flu, with or without serological or clinical confirmation during the first trimester of pregnancy. Data for 24 (sub)groups with congenital anomaly available from ≥3 studies were analysed using the DerSimonian-Laird random effects model. The hypothesis of publication bias was assessed using funnel plots and risk of bias of included studies was assessed using a slightly modified version of the Newcastle-Ottawa scale.

MAIN RESULTS AND THE ROLE OF CHANCE:

First trimester maternal influenza exposure was associated with an increased risk of any congenital anomaly [adjusted odds ratio (AOR) 2.00, 95% CI: 1.62-2.48], neural tube defects [odds ratio (OR) 3.33, 2.05-5.40], hydrocephaly (5.74, 1.10-30.00), congenital heart defects (1.56, 1.13-2.14), aortic valve atresia/stenosis (AOR 2.59, 1.21-5.54), ventricular septal defect (AOR 1.59, 1.24-2.14), cleft lip (3.12, 2.20-4.42), digestive system (1.72, 1.09-2.68) and limb reduction defects (2.03, 1.27-3.27). An increased risk for cleft lip (but not for cleft palate) was also reported by ecological studies not included in the meta-analysis. Study outcomes reported for 27 subgroups of congenital anomaly could not be included in the meta-analysis. Visual inspection of funnel plots did not suggest evidence for publication bias.

LIMITATIONS, REASONS FOR CAUTION:

This study enrolled observational studies that can be subject to limitations such as confounding, retrospective maternal exposure reports and non-response of intended participants. Influenza exposed pregnancies can also have been exposed to influenza related medication.

WIDER IMPLICATIONS OF THE FINDINGS:

Prevention of influenza in pregnant women may reduce congenital anomaly risk, and would be relevant to more than just neural tube defects. More research is needed to determine whether influenza and/or its related medication is teratogenic, to determine the role of hyperthermia in teratogenicity and the role of other environmental factors such as nutritional status in determining susceptibility.

STUDY FUNDING/ COMPETING INTERESTS:

Funded by the EC, under the framework of the EU Health Programme 2008-2013, Grant Agreement 2010 22 04 (Executive Agency for Health & Consumers). No competing interests.

KEYWORDS:

congenital anomalies, influenza, meta-analysis, observational studies, public health

PMID: 24365800

Longitudinal mediators of achievement in mathematics and reading in typical and atypical development.

Barnes MA, Raghubar KP, English L, Williams JM, Taylor H, Landry S. (2013) Longitudinal mediators of achievement in mathematics and reading in typical and atypical development. Journal of Expimental Child Psychology. 2014 Mar;119:1-16. 

Longitudinal studies of neurodevelopmental disorders that are diagnosed at or before birth and are associated with specific learning difficulties at school-age provide one method for investigating developmental precursors of later-emerging academic disabilities. Spina bifida myelomeningocele (SBM) is a neurodevelopmental disorder associated with particular problems in mathematics, in contrast to well-developed word reading. Children with SBM (n=30) and typically developing children (n=35) were used to determine whether cognitive abilities measured at 36 and 60months of age mediated the effect of group on mathematical and reading achievement outcomes at 8.5 and 9.5years of age. A series of multiple mediator models showed that: visual-spatial working memory at 36months and phonological awareness at 60months partially mediated the effect of group on math calculations, phonological awareness partially mediated the effect of group on small addition and subtraction problems on a test of math fluency, and visual-spatial working memory mediated the effect of group on a test of math problem solving. Groups did not differ on word reading, and phonological awareness was the only mediator for reading fluency and reading comprehension. The findings are discussed with reference to theories of mathematical development and disability and with respect to both common and differing cognitive correlates of math and reading.

doi: 10.1016/j.jecp.2013.09.006.

The prevalence of small intestinal bacterial overgrowth and methane production in patients with myelomeningocele and constipation.

Ojetti V, Bruno G, Paolucci V, Triarico S, D'aversa F, Ausili E, Gasbarrini A, Rendeli C. (2013) The prevalence of small intestinal bacterial overgrowth and methane production in patients with myelomeningocele and constipation. Spinal Cord. 2013 Nov 19.

Study design:Prospective study.Objectives:The objective of this study was to assess the prevalence of small intestinal bacterial overgrowth (SIBO), methane (CH₄) production and orocecal transit time (OCTT) in children affected by myelomeningocele.Setting:This study was conducted at the Catholic University in Rome, Italy.Methods:Eighteen (6M/12F; 16.4±7.6 years) children affected by myelomeningocele were enrolled. All subjects underwent H₂/CH₄ lactulose breath tests to assess SIBO and OCTT. All patients performed a visual analog scale to investigate abdominal pain, bloating and flatulence, and maintained a diary of the frequency and consistency of the stool during the previous 7 days. A nephro-urological clinical evaluation of the number of urinary tract infections (UTIs) and neurogenic bowel disease score were also performed.Results:Thirty-nine percent (7/18) of the children showed SIBO and 61% (11/18) presented a delayed OCTT. Moreover 44.4% (8/18) produced high levels of CH₄. Interestingly, all myelomeningocele children who produced CH₄ showed a delayed OCTT and a higher incidence of UTI, with a lower frequency of evacuation, compared with those with a normal or accelerated OCTT.Conclusion:The association between CH₄ and constipation suggests that CH₄ has an active role in the development of constipation. One of the most interesting features of our study is to identify a correlation between myelomeningocele, CH₄, delayed OCTT and UTI. The intestinal decontamination with locally acting drugs in these children may reduce the number of UTIs and improve intestinal motility.

doi: 10.1038/sc.2013.131.

Spina bifida grown up.

Liptak GS, Garver K, Dosa NP. (2013) Spina bifida grown up.  Journal of Developmental and Behavioral Pediatrics. 2013 Apr;34(3):206-15.



The majority of people with spina bifida in the United States are now older than 18 years of age. Health care delivery for adults with this condition should include routine surveillance for common conditions such as hypertension, hyperlipidemia and cancer. It should also address spina bifida-related complications such as pressure sores, lymphedema, sexual dysfunction and infertility, and hydrocephalus, as well as chiari-related symptoms such as sleep apnea and urologic and renal functioning. Almost all adults with spina bifida benefit from regular followup with specialists in urology, neurosurgery and physiatry. Health care providers for adults with spina bifida should recognize the impact of executive dysfunction and nonverbal learning disability on self management, independent living, and employment in adults with spina bifida.

doi: 10.1097/DBP.0b013e31828c5f88.

Young Adults with Spina Bifida May Have Higher Occurrence of Prehypertension and Hypertension.

Stepanczuk BC, Dicianno BE, Webb TS. (2013) Young Adults with Spina Bifida May Have Higher Occurrence of Prehypertension and Hypertension.  American Journal of Physical Medicine & Rehabilitation. 2013 Oct 1. 

Abstract

OBJECTIVE:

The aims of this study were to determine the occurrence of prehypertension and high blood pressure in adults with spina bifida (SB) and to examine relationships among blood pressure, cardiovascular disease risk factors, and SB-specific factors.

DESIGN:

This is a cross-sectional, retrospective analysis of adults with SB. SB-specific factors and cardiovascular disease risk factors were compared among subjects with high blood pressure, subjects with blood pressure in the prehypertensive range, and normotensive subjects using the χ, Kruskal-Wallis, or Fisher's exact tests.

RESULTS:

Of 225 subjects, the occurrence of prehypertension and high blood pressure was 27% (n = 22) and 27% (n = 22) for ages 18-29 yrs, 35% (n = 26) and 41% (n = 30) for ages 30-39 yrs, 18% (n = 8) and 66% (n = 29) for ages 40-49 yrs, and 21% (n = 5) and 67% (n = 16) for 50 yrs or older, respectively. Of the subjects with high blood pressure, 56% were men, 14% had obstructive sleep apnea, 14% had diabetes, 19% had renal dysfunction, 38% used tobacco, 16% had hydronephrosis, and 71% had a shunt. The groups differed significantly with respect to diabetes (P = 0.004), bladder procedures (P = 0.001), and renal dysfunction (P < 0.001), with higher proportions of subjects with high blood pressure having these comorbidities.

CONCLUSIONS:

Fewer than half of the subjects were considered normotensive. A greater proportion of young adults with SB appear to have high blood pressure compared with the general United States population. Because elevated blood pressure is an independent, modifiable risk factor of cardiovascular disease, these findings support early screening and intervention for elevated blood pressure in individuals with SB.

Goal Management Training improves everyday executive functioning for persons with spina bifida: Self-and informant reports six months post-training.

Stubberud J, Langenbahn D, Levine B, Stanghelle J, Schanke AK. (2013) Goal Management Training improves everyday executive functioning for persons with spina bifida: Self-and informant reports six months post-training. Neuropsycholical Rehabilitation. 2013 Oct 30

Executive dysfunction accounts for significant disability for many patients with spina bifida (SB), thus indicating the need for effective interventions aimed at improving executive functioning in this population. Goal Management Training™ (GMT) is a cognitive rehabilitation approach that targets disorganised behaviour resulting from executive dysfunction, and has received empirical support in studies of other patient groups. The purpose of this study was to determine if GMT would lead to perceived improved executive functioning in the daily lives of patients with SB, as evidenced by reduced report of dysexecutive problems in daily life on self- and informant questionnaires. Thirty-eight adults with SB were included in this randomised controlled trial (RCT). Inclusion was based upon the presence of executive functioning complaints. Experimental subjects (n = 24) received 21 hours of GMT, with efficacy of GMT being compared to results of subjects in a wait-list condition (n = 14). All subjects were assessed at baseline, post-intervention, and at six-month follow-up. Self-report measures indicated that the GMT group's everyday executive functioning improved significantly after training, lasting at least 6 months post-treatment.

There were no significant effects on informant-report questionnaires. Overall, these findings indicate that executive difficulties in everyday life can be ameliorated for individuals with congenital brain dysfunction.

doi: 10.1080/09602011.2013.847847

Folate-related gene variants in Irish families affected by neural tube defects.

Fisk Green R, Byrne J, Crider KS, Gallagher M, Koontz D, Berry RJ. (2013) Folate-related gene variants in Irish families affected by neural tube defects. Frontiers in Genetics. 2013 Nov 6;4:223.

 

Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19 bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative ("risk genotypes") and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p = 0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic mechanisms.

 

 

doi: 10.3389/fgene.2013.00223.

 

Free PMC Article

Serial casting versus stretching technique to treat knee flexion contracture in children with spina bifida: A comparative study.

Al-Oraibi S, Tariah HA, Alanazi A. (2013) Serial casting versus stretching technique to treat knee flexion contracture in children with spina bifida: A comparative study. Journal of Pediatric Rehabilitation Medicine. 2013 Jan 1;6(3):147-53. 

BACKGROUND:

Severe knee contractures that develop soon after muscle imbalance may not improve with stretching exercises and splinting. An alternative treatment is serial casting, which has been used to promote increased range of motion.

PURPOSE:

The purpose of this study was to compare the effectiveness of using serial casting and passive stretching approaches to treat knee flexion contracture in children with spina bifida.

METHODS:

In a pre/post randomized controlled study, ten participants were included in the serial casting group, while eight participants were included in the passive stretching intervention group. The degree of knee extension was measured at baseline, immediately after intervention, and at a one-year follow-up using a standard goniometer.

RESULTS:

Both groups showed significant improvements in the degree of flexion contracture at the post-treatment evaluation and the follow-up evaluation. The serial casting group showed significant improvements in knee flexion contracture at the post-treatment evaluation, t (9)=13.4, p < 0.001, and the one-year follow-up evaluation, t (9) = 7.46, p < 0.001. The passive stretching group also showed significant improvements in knee flexion contracture at the post-treatment evaluation, t (7) =2.6, p < 0.05, and the one-year follow-up evaluation, t (7) = 3.6, p < 0.05. However, statistically significant improvements in the serial casting group compared with passive stretching group in relation to the degree of flexion contracture were found at the immediate post-treatment evaluation, F(1, 15)=246, p=0.0001, and the one-year follow-up evaluation, F (1, 15)=51.5, p=0.0001.

CONCLUSION:

The outcomes of this study provide the first evidence that serial casting may be a useful intervention in treating knee flexion contracture in children with spina bifida. However, further investigations into serial casting, as well as investigations into the use of serial casting with other interventions, are warranted.

doi: 10.3233/PRM-130247.

Tumor in bladder reservoir after gastrocystoplasty.

Castellan M, Gosalbez R, Perez-Brayfield M, Healey P, McDonald R, Labbie A, Lendvay T. (2007)
Tumor in bladder reservoir after gastrocystoplasty. Journal of Urology. 2007 Oct;178(4 Pt 2):1771-4; discussion 1774.

PURPOSE:

To our knowledge the risk of malignancy in patients with previous bladder augmentation with stomach is unknown. We report 3 cases of gastric adenocarcinoma and 1 of transitional cell carcinoma after augmentation cystoplasty with stomach with long-term followup.

MATERIALS AND METHODS:

Between August 1989 and August 2002, 119 patients underwent augmentation cystoplasty with stomach at our 2 institutions (University of Miami School of Medicine, and Seattle Children's Hospital and Regional Medical Center). Medical records, urodynamic studies, radiographic imaging and laboratory evaluations were reviewed retrospectively and cases of malignancy were analyzed in detail.

RESULTS:

Four male patients had carcinoma after augmentation gastrocystoplasty. Preoperative diagnosis was neurogenic bladder in 3 patients and posterior urethral valve in 1. Three patients had gastric adenocarcinoma, while the other had poorly differentiated transitional cell carcinoma. Each case progressed to malignancy more than 10 years after augmentation (11, 12, 14 and 14 years, respectively).

CONCLUSIONS:

Patients who undergo bladder augmentation with a gastric remnant are at increased risk for malignancy, probably similar to that in patients with enterocystoplasty. Therefore, they require close long-term followup. Patients should be followed annually with ultrasound, and cystoscopy should be performed annually starting 10 years after gastrocystoplasty unless they have abnormal ultrasound, hematuria or another cancer risk factor. Any suspicious lesions should be biopsied, especially at the gastrovesical anastomotic site.

doi: 10.1016/j.juro.2007.05.100

Transitional cell carcinoma of the bladder following augmentation cystoplasty for the neuropathic bladder.

Soergel TM, Cain MP, Misseri R, Gardner TA, Koch MO, Rink RC. (2004) Transitional cell carcinoma of the bladder following augmentation cystoplasty for the neuropathic bladder.

Journal of Urology. 2004 Oct;172(4 Pt 2):1649-51; discussion 1651-2.

PURPOSE:

Patients with neurogenic bladder dysfunction due to spina bifida have been reported to be at increased risk for bladder cancer. Recent publications suggest that bladder augmentation is also a significant risk factor. We reviewed our experience with treating patients with spina bifida and bladder cancer.

MATERIALS AND METHODS:

Patients with spina bifida treated for bladder cancer between 1995 and 2005 were identified. Patient demographics, mode of bladder management, risk factors and presenting symptoms were recorded along with therapy, pathological findings and outcome. This patient cohort was combined with all prior known published studies for analysis.

RESULTS:

Eight patients with a median age of 41 years were treated. Only 1 patient (13%) had undergone bladder augmentation. Locally advanced stage (T3 or greater) or lymph node metastases were present in 88% of cases. Median survival was 6 months with only 1 patient alive with no evidence of recurrence at 20 months. A total of 11 prior published cases were identified and combined with this series. Transitional cell carcinoma was present in 58% of patients. Median survival was 6 months. Only 37% of patients had undergone bladder augmentation.

CONCLUSIONS:

Patients with spina bifida and bladder cancer present at a young age with variable tumor histology and advanced stage, and they have poor survival. Presenting symptoms are often atypical and bladder cancer should be a consideration in this patient population, even in young adults. Due to poor survival further study is warranted in this population to determine whether screening would be beneficial for earlier detection and improved outcomes.

doi: 10.1097/01.ju.0000140194.87974.56

Bladder cancer arising in a spina bifida patient.

Game X, Villers A, Malavaud B, Sarramon J. (1999) Bladder cancer arising in a spina bifida patient.

Urology. 1999 Nov;54(5):923.

We report the case of a 52-year-old patient with spina bifida, neurologic bladder, and a history of recurrent urinary tract infections (UTIs) in whom a bladder cancer was incidentally discovered. Cytology, cystoscopy, and cystography showed nonspecific, extensive inflammatory lesions. Cystography demonstrated a complex of diverticulae and cellules. Pathologic examination of a diverticulectomy specimen revealed a grade III pT3b transitional and squamous cell carcinoma. Because of the similar disease causation (recurrent UTIs, stones, and indwelling catheterization), we suggest extension of the guidelines proposed for patients with spinal cord injuries (ie, annual serial bladder biopsies) to patients with nontraumatic neurogenic bladder.

Patients with spina bifida and bladder cancer: atypical presentation, advanced stage and poor survival.

Austin JC, Elliott S, Cooper CS. (2007) Patients with spina bifida and bladder cancer: atypical presentation, advanced stage and poor survival. Journal of Urology. 2007 Sep;178(3 Pt 1):798-801.

PURPOSE:

Patients with neurogenic bladder dysfunction due to spina bifida have been reported to be at increased risk for bladder cancer. Recent publications suggest that bladder augmentation is also a significant risk factor. We reviewed our experience with treating patients with spina bifida and bladder cancer.

MATERIALS AND METHODS:

Patients with spina bifida treated for bladder cancer between 1995 and 2005 were identified. Patient demographics, mode of bladder management, risk factors and presenting symptoms were recorded along with therapy, pathological findings and outcome. This patient cohort was combined with all prior known published studies for analysis.

RESULTS:

Eight patients with a median age of 41 years were treated. Only 1 patient (13%) had undergone bladder augmentation. Locally advanced stage (T3 or greater) or lymph node metastases were present in 88% of cases. Median survival was 6 months with only 1 patient alive with no evidence of recurrence at 20 months. A total of 11 prior published cases were identified and combined with this series. Transitional cell carcinoma was present in 58% of patients. Median survival was 6 months. Only 37% of patients had undergone bladder augmentation.

CONCLUSIONS:

Patients with spina bifida and bladder cancer present at a young age with variable tumor histology and advanced stage, and they have poor survival. Presenting symptoms are often atypical and bladder cancer should be a consideration in this patient population, even in young adults. Due to poor survival further study is warranted in this population to determine whether screening would be beneficial for earlier detection and improved outcomes.

doi.org/10.1016/j.juro.2007.05.055

Risk of bladder cancer in patients with spina bifida: Case reports and review of the literature.

Mirkin K, Casey JT, Mukherjee S, Kielb SJ. (2013) Risk of bladder cancer in patients with spina bifida: Case reports and review of the literature. Journal of Pediatric Rehabilitation Medicine. 2013 Jan 1;6(3):155-62. 

PURPOSE:

This article presents four cases of patients with spina bifida who developed bladder cancer while under our care and provides a literature review on the incidence, initial presentation, possible etiologies, and role for screening for bladder cancer in the neurogenic bladder population.

METHODS:

Case reports of four patients are presented followed by a literature review of the current available studies.

RESULTS:

Patients with spina bifida present with bladder cancer at an atypically young age with very advanced disease. The dire prognosis associated with bladder cancer in these patients demands that we provide better treatment, diagnosis, and prevention modalities. However, the potential morbidity, financial burden, and lack of proven benefit discourage cystoscopic screening in this patient population. Until we have more data on how to best serve spina bifida patients, this population should receive careful and regular urologic follow-up.

CONCLUSION:

Given the atypical young age of presentation and very advanced nature of bladder cancer in the spina bifida population, the authors strongly recommend that any new bladder changes, such as including increased urinary leakage, pain, recurrent infections, or increased gross hematuria, prompt immediate urologic referral for endoscopic evaluation and biopsy as indicated.

doi: 10.3233/PRM-130254.

Vesicoureteric reflux in children.

Kari JA, El-Desoky SM, Basnawi F, Bahrawi O. (2013) Vesicoureteric reflux in children. Urology Annals. 2013 Oct;5(4):232-6.

 

AIM:

This study aimed to identify the differences between primary and secondary vesicoureteric reflux (VUR) and the effect of associated bladder abnormalities on kidney function.

PATIENTS AND METHODS:

We retrospectively reviewed the medical records of children with VUR who were followed up at King Abdulaziz University Hospital from January 2005 to December 2010. The review included results of radiological investigations and kidney function tests. We used Chi-square test for statistical analysis and paired t-test to compare group means for initial and last creatinine levels.

RESULTS:

Ninety-nine children were included in this study. Twenty (20.2%) had primary VUR, 11 had high-grade VUR, while 9 had low-grade reflux. All children with low-grade VUR had normal dimercaptosuccinic acid (DMSA). Renal scars were present in 72% of the children with high-grade VUR. The mean creatinine levels (initial and last) for both groups were normal. Seventy-nine (79.8%) children had secondary VUR, which was due to posterior urethral valves (PUV) (46.8%), neurogenic bladder caused by meningomyelocele (25.3%), non-neurogenic neurogenic bladder (NNB) (21.5%), or neurogenic bladder associated with prune belly syndrome (6.3%). Children with NNB, meningomyelocele and PUV had high creatinine at presentation with no considerable worsening of their kidney functions during the last visit. Renal scars were present in 49.4% of the children with secondary VUR.

CONCLUSION:

Children with primary VUR and normal bladder had good-functioning kidneys, while those with secondary VUR associated with abnormal bladder caused by NNB, spina bifida or PUV had abnormal kidney functions. DMSA scans were useful in predicting higher grades of VUR in children with primary reflux.

KEYWORDS:

Children, neurogenic bladder, posterior urethral valves, primary reflux, secondary reflux, vesicoureteric reflux

 

doi: 10.4103/0974-7796.120292.

 

Free PMC Article

Resilience, self-esteem and self-compassion in adults with spina bifida.

Hayter MR, Dorstyn DS. (2013) Resilience, self-esteem and self-compassion in adults with spina bifida.

Spinal Cord. 2013 Dec 10. 

Study design: Cross-sectional survey.

Objectives:T o examine factors that may enhance and promote resilience in adults with spina bifida.

Setting: Community-based disability organisations within Australia.

Methods: Ninety-seven adults with a diagnosis of spina bifida (SB) completed a survey comprising of demographic questions in addition to standardised self-report measures of physical functioning (Craig Handicap Assessment and Reporting Technique), resilience (Connor-Davidson Resilience Scale, 10 item), self-esteem (Rosenberg Self-esteem Scale), self-compassion (Self-compassion Scale) and psychological distress (Depression Anxiety Stress Scales, 21 item).

Results: The majority (66%) of respondents reported moderate to high resilience. Physical disability impacted on coping, with greater CD-RISC 10 scores reported by individuals who were functionally independent in addition to those who experienced less medical co-morbidities. Significant correlations between resilience and psychological traits (self-esteem r=0.36, P < 0.01; self-compassion r=0.40, P < 0.01) were also noted. However, the combined contribution of these variables only accounted for 23% of the total variance in resilience scores (R²=0.227, F(5,94)=5.23, P < 0.01).

Conclusion: These findings extend current understanding of the concept of resilience in adults with a congenital physical disability. The suggestion is that resilience involves a complex interplay between physical determinants of health and psychological characteristics, such as self-esteem and self-compassion. It follows that cognitive behavioural strategies with a focus on self-management may, in part, contribute to the process of resilience in this group. Further large-scale and longitudinal research will help to confirm these findings.

doi: 10.1038/sc.2013.152.

Genetic association analyses of nitric oxide synthase genes and neural tube defects vary by phenotype.

Soldano KL, Garrett ME, Cope HL, Rusnak JM, Ellis NJ, Dunlap KL, Speer MC, Gregory SG, Ashley-Koch AE. (2013) Genetic association analyses of nitric oxide synthase genes and neural tube defects vary by phenotype.  Birth defects research. Part B, Developmental and reproductive toxicology. Oct;98(5):365-73. 

Neural tube defects (NTDs) are caused by improper neural tube closure during the early stages of embryonic development. NTDs are hypothesized to have a complex genetic origin and numerous candidate genes have been proposed. The nitric oxide synthase 3 (NOS3) G594T polymorphism has been implicated in risk for spina bifida, and interactions between that single nucleotide polymorphism (SNP) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have also been observed. To evaluate other genetic variation in the NO pathway in the development of NTDs, we examined all three NOS genes: NOS1, NOS2, and NOS3. Using 3109 Caucasian samples in 745 families, we evaluated association in the overall dataset and within specific phenotypic subsets. Haplotype tagging SNPs in the NOS genes were tested for genetic association with NTD subtypes, both for main effects as well as for the presence of interactions with the MTHFR C677T polymorphism. Nominal main effect associations were found with all subtypes, across all three NOS genes, and interactions were observed between SNPs in all three NOS genes and MTHFR C677T. Unlike the previous report, the most significant associations in our dataset were with cranial subtypes and the AG genotype of rs4795067 in NOS2 (p = 0.0014) and the interaction between the rs9658490 G allele in NOS1 and MTHFR 677TT genotype (p = 0.0014). Our data extend the previous findings by implicating a role for all three NOS genes, independently and through interactions with MTHFR, in risk not only for spina bifida, but all NTD subtypes.

doi: 10.1002/bdrb.21079. 

Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: glial proteins associated with cell damage and loss.

Naureen I, Waheed KA, Rathore AW, Victor S, Mallucci C, Goodden JR, Chohan SN, Miyan JA. (2013) Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: glial proteins associated with cell damage and loss. Fluids Barriers CNS. 2013 Dec 18;10(1):34. 

BACKGROUND:

In hydrocephalus an imbalance between production and absorption of cerebrospinal fluid (CSF) results in fluid accumulation, compression and stretching of the brain parenchyma. In addition, changes in CSF composition have a profound influence on the development and function of the brain and together, these can result in severe life-long neurological deficits. Brain damage or degenerative conditions can result in release of proteins expressed predominantly in neurons, astroglia, or oligodendroglia into the brain interstitial fluid, CSF and blood. Determination of such products in the CSF might be of value in diagnosing cause, aetiology and/or assessing the severity of the neurological damage in patients with hydrocephalus. We therefore analysed CSF from human neonates with hydrocephalus for these proteins to provide an insight into the pathophysiology associated with different aetiologies.

METHODS:

CSF was collected during routine lumbar puncture or ventricular tap. Samples were categorized according to age of onset of hydrocephalus and presumed cause (fetal-onset, late-onset, post-haemorrhagic or spina bifida with hydrocephalus). Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), vimentin and 2[prime], 3[prime]-cyclic nucleotide 3[prime]-phosphodiesterase (CNPase) were analysed through Western blotting of hydrocephalic CSF samples (n = 17) and compared with data from CSF of normal infants without neurological deficits (n = 8).

RESULTS:

GFAP was significantly raised only in CSF from post-haemorrhagic hydrocephalus while MBP was significantly raised in post-haemorrhagic and in spina bifida with hydrocephalus infants. Vimentin protein was only detected in some CSF samples from infants with late-onset hydrocephalus but not from other conditions. Surprisingly, CNPase was found in all neonatal CSF samples, including normal and hydrocephalic groups, although it was reduced in infants with late onset hydrocephalus compared with normal and other hydrocephalic groups.

CONCLUSIONS:

Apart from CNPase, which is an enzyme, the markers investigated are intracellular intermediate filaments and would be present in CSF only if the cells are compromised and the proteins released. Raised GFAP observed in post-haemorrhagic hydrocephalus must reflect damage to astrocytes and ependyma. Raised MBP in post-haemorrhagic and spina bifida with hydrocephalus indicates damage to oligodendrocytes and myelin. Vimentin protein detected in some of the late-onset hydrocephalic samples indicates damage to glial and other progenitors and suggests this condition affects periventricular regions. The presence of CNPase in all CSF samples was unexpected and indicates a possible novel role for this enzyme in brain development/myelination. Less CNPase in some cases of late-onset hydrocephalus could therefore indicate changes in myelination in these infants. This study demonstrates differential glial damage and loss in the developing human neonatal hydrocephalic brain associated with different aetiologies.

 

Free Article

Cerebrospinal fluid leak masquerading as a decubitus ulcer in a patient with spina bifida.

Taylor EM, Klinge PM, Sullivan SR, Taylor HO. (2013) Cerebrospinal fluid leak masquerading as a decubitus ulcer in a patient with spina bifida. Eplasty. 2013 Nov 11;13:ic62.

A 38-year-old man with a history of spina bifida and T12 paraplegia presented with a nonhealing sacral wound that developed from a site adjacent to his myelomeningocele repair scar. Clear fluid drained from this pinpoint opening intermittently for years and was determined to be cerebrospinal fluid during a repeat debridement.

Free PMC Article

Investigations of single nucleotide polymorphisms in folate pathway genes in Chinese families with neural tube defects.

Liu J, Qi J, Yu X, Zhu J, Zhang L, Ning Q, Luo X. (2013) Investigations of single nucleotide polymorphisms in folate pathway genes in Chinese families with neural tube defects.

J Neurol Sci. 2013 Nov 19. pii: S0022-510X(13)03046-3. 

AIMS:

We investigated the hypothesis that there are interactions between SNPs in folate metabolism pathway genes and environmental risk factors to the etiology of neural tube defects (NTDs).

METHOD:

In 602 Chinese families, 609 aborted fetus tissues or blood samples were collected from NTD individuals, and 1106 parental blood samples were detected as controls. We analyzed 28 SNPs in 12 folate pathway genes. Folate supplementation, gestational diabetes mellitus (GDM) and medicine administration before and during pregnancy were investigated. Case-parental control study and transmission/disequilibrium tests were performed according to environmental cofactor stratification.

RESULTS:

Association between 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and NTDs was significant in all stratifications (all P<.05), and synergistic effects of no folate supplementation and GDM were shown on NTD occurrence. 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTHM) 501A>G in case of GDM, and betaine-homocysteine methyltransferase (BHMT) 716G>A in case of no folate supplementation significantly associated with NTDs (both P<.05), whereas the two genotypes alone did not significantly associate with NTDs (both P>.05).

CONCLUSIONS:

MTHFR 677C>T genotype, especially in case of no folate supplementation and GDM, promotes NTD occurrence. MTHM 501A>G only in case of GDM, and BHMT 716G>A only in case of no folate supplementation contribute to the etiology of NTDs.

doi: 10.1016/j.jns.2013.11.017. 

Physical Activity, Exercise, and Health-related Measures of Fitness in Adults With Spina Bifida: A Review of the Literature.

Crytzer TM, Dicianno BE, Kapoor R. (2013) Physical Activity, Exercise, and Health-related Measures of Fitness in Adults With Spina Bifida: A Review of the Literature. PM R. 2013 Dec;5(12):1051-62.

Spina bifida (SB) is the most common birth defect in United States that results in permanent lifelong disability according to the Spina Bifida Association. Advancements in medical care have led to a longer life span and an increase in the risk of secondary conditions, for example, obesity, with age. The need to maintain a healthy and active lifestyle is even stronger in adults with SB than the general population. Our objective was to fill a gap in the literature by highlighting the current state of the literature on health-related measures of fitness, exercise, and physical activity (PA) in adults with SB. PubMed and Ovid were searched for articles by using the terms "spina bifida or myelomeningocele and exercise," published between January 1, 1988 and May 10, 2012. Results of studies showed that adults with SB had an inactive lifestyle, lower aerobic capacity, decreased level of daily PA, higher prevalence of obesity, and lower health-related quality of life compared with reference groups. Therapeutic interventions reduced pain, increased biomechanical efficiency during wheelchair propulsion, and improved PA and balance. Overall, the quality of the evidence on PA, exercise, and health-related measures of fitness is low in SB. Given misdistribution of adipose tissue, short stature, scoliosis, and joint contractures, future research should be conducted to determine the most reliable and low-cost methods of measuring body composition and to establish norms. Other reference standards, for example, aerobic capacity, require further development. Studies are needed to investigate lifestyle interventions that facilitate PA and exercise, and to determine the amount of exercise required to reduce secondary conditions as people with SB age. 

doi: 10.1016/j.pmrj.2013.06.010.

Pediatric Neurosurgery Patients Need More than a Neurological Surgeon: A Clinical Experience.

James HE, Macgregor TL, Childers Jr DO, La Corte E, Aldana PR. (2013) Pediatric Neurosurgery Patients Need More than a Neurological Surgeon: A Clinical Experience. Pediatric Neurosurgery. 2013 Dec 5. 

The Division of Pediatric Neurosurgery of the University of Florida College of Medicine Jacksonville initiated and developed a multidisciplinary comprehensive team for the management of patients with a neurosurgical condition other than spina bifida. This report relates the rationale and stages of development of a multidisciplinary team to facilitate the health care and special needs of these children.

doi:10.1159/000356331

A description of spina bifida cases and co-occurring malformations, 1976-2011.

Parker SE, Yazdy MM, Mitchell AA, Demmer LA, Werler MM. (2013) A description of spina bifida cases and co-occurring malformations, 1976-2011. Am J Med Genet A. 2013 Dec 19. 

Mandatory folic acid fortification in the United States corresponded with a decline in the prevalence of spina bifida (SB). The aim of this study was to describe the epidemiologic characteristics of isolated versus non-isolated SB cases in both pre- and post-fortification periods. SB cases in the Slone Epidemiology Center Birth Defects Study from 1976 to 2011 without chromosomal anomalies and syndromes were included. A maternal interview, conducted within 6 months of delivery, collected information on demographics, reproductive history, diet, and supplement use. Daily folic acid intake in the periconceptional period was calculated using both dietary and supplement information and categorized as low intake
( < 400 µg/day) or high intake (≥400 µg/day). SB cases (n = 1170) were classified as isolated (80.4%) or non-isolated (19.1%). Non-isolated cases were further divided into subgroups based on accompanying major malformations (midline, renal, genital, heart, laterality). Compared to non-isolated cases, isolated cases were more likely to be white, non-Hispanic and have more than 12 years of education. Cases in the renal, genital, and heart subgroups had the lowest proportions of mothers with a high folic acid intake. The change from pre- to post-fortification was associated with a decrease in the proportion of isolated cases from 83% to 72%, though in both periods isolated cases were more likely to be female and their mothers were more likely to have high folic acid intake. These findings highlight the importance of separating isolated and non-isolated cases in etiologic research of SB.

doi: 10.1002/ajmg.a.36324.