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Moshtaghioon S, Elahi M, Ebrahim Soltani Z, Ahmadi E, Nabian MH. MicroRNA regulation in neural tube defects: Insights into pathogenesis and potential therapeutic targets. Gene 2025; 945:149311. [PMID: 39914791 DOI: 10.1016/j.gene.2025.149311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/30/2024] [Accepted: 02/03/2025] [Indexed: 02/22/2025]
Abstract
Neural tube defects (NTDs) represent a significant burden on global pediatric health, contributing to high rates of infant mortality and morbidity. Despite extensive research into their etiology, NTDs continue to pose challenges in diagnosis and treatment. MicroRNAs (miRNAs) have emerged as promising candidates for understanding the molecular mechanisms underlying NTDs and potentially offering avenues for improved diagnosis and therapeutic intervention. This review explores the multifaceted roles of miRNAs in the context of NTD pathogenesis. Studies have identified specific miRNA profiles associated with NTDs, providing insights into their potential as diagnostic biomarkers. Furthermore, dysregulation of certain miRNAs has been implicated in the pathophysiology of NTDs, highlighting their role as potential therapeutic targets. Additionally, animal models and deep sequencing approaches have expanded our understanding of the diverse miRNA expression patterns associated with NTDs. By unraveling the intricate molecular mechanisms underlying NTD pathogenesis, miRNAs offer promising avenues for early detection and intervention, ultimately improving outcomes for affected individuals.
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Affiliation(s)
- Seyedali Moshtaghioon
- Department of Orthopaedic and Trauma Surgery Dr. Shariaty Hospital Tehran University Medical Science Tehran Iran
| | - Mohammad Elahi
- Center for Orthopedic Trans-disciplinary Applied Research Tehran University of Medical Science Tehran Iran
| | | | - Elham Ahmadi
- School of Medicine Tehran University Medical Science Tehran Iran
| | - Mohammad Hossein Nabian
- Center for Orthopedic Trans-disciplinary Applied Research Tehran University of Medical Science Tehran Iran
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Dos Santos MA, Andrade F, Cruz de Souza M, Gerzson LR, Kobus-Bianchini K, Meireles ALF. Analysis of Commercial Instagram Content on Pediatric Neurological Physiotherapy Interventions and Products in Brazil. Phys Occup Ther Pediatr 2025:1-15. [PMID: 40207618 DOI: 10.1080/01942638.2025.2486111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 03/12/2025] [Accepted: 03/23/2025] [Indexed: 04/11/2025]
Abstract
AIMS To describe the content of commercial pediatric neurological physical therapy posts on Instagram and report the main interventions and products featured. METHODS A cross-sectional study was conducted using five pediatric neurological physical therapy hashtags on Brazilian commercial Instagram profiles, on three different days. The initial 50 posts for each hashtag were extracted by two independent reviewers. Data included the source of the posts, content characteristics, target populations, interventions featured in the posts and on the Instagram profiles, as well as the products promoted in the posts. RESULTS A total of 449 Instagram posts from 190 profiles were analyzed. Most posts were in video format (n = 278; 61.9%), categorized as service reports (n = 203; 45.2%), and posted by autonomous physical therapists (n = 195; 43.4%). The most frequent interventions were Suit therapy (n = 60; 15.9%) and mobility training (n = 59; 15.6%). Cerebral palsy (n = 90; 20%) and Down syndrome (n = 35; 7.7%) were the most frequently represented health conditions. CONCLUSIONS Instagram offers various interventions and products for pediatric neurological rehabilitation. Excess information may cause indecision and adherence to ineffective treatments by families. Future research should assess the evidence behind services on social media and their impact on parents' decision-making.
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Affiliation(s)
| | - Francine Andrade
- Department of Physical Therapy, Universidade do Estado de Santa Catarina, Florianópolis, SC, Brazil
| | - Marinna Cruz de Souza
- Department of Physical Therapy, Unversidade do Sul de Santa Catarina, Florianópolis, SC, Brazil
| | - Laís Rodrigues Gerzson
- Department of Physical Therapy, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Karoline Kobus-Bianchini
- Department of Physical Therapy, Universidade do Estado de Santa Catarina, Florianópolis, SC, Brazil
| | - André Luís Ferreira Meireles
- Department of Physical Therapy, Universidade do Estado de Santa Catarina, Florianópolis, SC, Brazil
- Department of Physical Therapy, Unversidade do Sul de Santa Catarina, Florianópolis, SC, Brazil
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Benabdderrahmane K, Stirnemann J, Ramtani S, Falentin-Daudré C. Biodegradation study in FBS media of polycaprolactone patch as a potential prenatal treatment for myelomeningocele. J Biomater Appl 2025; 39:1097-1114. [PMID: 39880383 DOI: 10.1177/08853282251316894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
Myelomeningocele (MMC) is a congenital defect of the spine characterized by meningeal and spinal cord protrusion through open vertebral archs, and its exposure to the amniotic fluid. Given that the progression of neuronal loss begins early in fetal life, an early coverage of the defect is required to improve the neurological outcomes. Several studies have proposed patches as an alternative to full surgical repair, to achieve an early protection of the spine and possibly reduce the rate of complications of current prenatal surgical procedures. In our previous work, we developed a biocompatible, watertight and biodegradable patch to improve in utero MMC repair. This patch offers an anti-adhesive internal surface to prevent adhesion to spinal cord tissue, and a bioactive external surface to promote tissue coverage. The aim of this study is to assess the patch's in vitro degradation in an amniotic-fluid-like medium and investigate the surface functionalization effect, to understand its mechanism and predict the patch's behavior over time. The study was carried out for 24 weeks in FBS medium and after each period the samples were characterized by differential scanning calorimetry, scanning electron microscopy, steric exclusion chromatography, toluidine blue assay and contact angle measurement. The results revealed a progression of PCL hydrolysis over time, characterized by a decrease in molar mass and evidence of erosion as observed by SEM. Furthermore, this process appears to be accelerated by ozonation, compared to surface functionalization without ozonation. The latter can be considered as the most suitable technique to preserve the patch structure over time, while benefiting from the grafting polymers properties during the first weeks of implantation.
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Affiliation(s)
- K Benabdderrahmane
- BEST/CB3S, UMR CNRS 7244, Institut Galilée, Université Sorbonne Paris Nord, Villetaneuse, France
| | - J Stirnemann
- Obstetrics and Maternal-Fetal Medicine, Hôpital Necker Enfants Malades, AP-HP, Paris, France
- EA7328, Institut IMAGINE, Université de Paris-Cité, Paris, France
| | - S Ramtani
- BEST/CB3S, UMR CNRS 7244, Institut Galilée, Université Sorbonne Paris Nord, Villetaneuse, France
| | - C Falentin-Daudré
- BEST/CB3S, UMR CNRS 7244, Institut Galilée, Université Sorbonne Paris Nord, Villetaneuse, France
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Reis OAF, Ito HN, de Oliveira Otávio J, de Oliveira Filho DJ, Lima EM, de Bessa J, da Silva PLL, de Almeida Vasconcelos MM, de Carvalho Mrad FC. Clinical and urodynamic findings in children and adolescents with neurogenic bladder undergoing augmentation cystoplasty: a systematic review. Pediatr Nephrol 2025; 40:355-365. [PMID: 39249128 DOI: 10.1007/s00467-024-06499-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/06/2024] [Accepted: 08/06/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND Augmentation cystoplasty (AC) is a procedure to improve the clinical and urodynamic parameters of neurogenic bladder (NB) in children and adolescents refractory to other treatments. We performed a systematic review to investigate these parameters in children and adolescents with NB undergoing AC. METHODS We followed PRISMA guidelines and searched electronic databases until March 2024 for studies involving patients aged three to 19 years diagnosed with NB undergoing AC. We assessed clinical and urodynamic parameters before and after surgery, focusing on improvements in urinary incontinence, vesicoureteral reflux (VUR), bladder capacity, compliance, and end filling detrusor pressure (EFP). RESULTS A total of 212 NB patients underwent AC and were evaluated for urinary incontinence before and after surgery. Two studies showed a 76.5% to 78.9% improvement in incontinence without bladder outlet procedures (BOP). Another study found no significant difference in incontinence improvement rates between AC with and without BOP. The VUR resolution rate assessed in three studies ranged from 12.5 to 64%. Three studies showed a variation in bladder capacity from 52.8 to 70% of the expected bladder capacity pre-AC to 95.9 to 119%, post-AC. A fourth study showed a variation in bladder capacity from 87 ml pre-AC to 370 ml post-AC. Two studies showed a variation from 3.2 to 4.6 ml/cm H2O pre-AC to 13.7 to 41.3 ml/cm H2O post-AC in bladder compliance. The EFP in three studies varied from 37.2 to 47.6 cm H2O pre-AC to 11 to 17.4 cm H2O post-AC. CONCLUSION After AC, urinary incontinence, bladder capacity, EFP, and bladder compliance improved in children and adolescents with NB.
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Affiliation(s)
- Otávio Augusto Fonseca Reis
- Faculty of Medicine, Department of Pediatric, Pediatric Nephrology Unit, Hospital das Clínicas (UFMG), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Avenida Alfredo Balena 190. Sala 267, Santa Efigênia, Belo Horizonte, 30130-100, Brazil
- Urology Unit, Hospital Felicio Rocho, Belo Horizonte, Brazil
| | - Hilton Naoto Ito
- Faculty of Medicine, Department of Pediatric, Pediatric Nephrology Unit, Hospital das Clínicas (UFMG), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Avenida Alfredo Balena 190. Sala 267, Santa Efigênia, Belo Horizonte, 30130-100, Brazil
| | - Juliana de Oliveira Otávio
- Faculty of Medicine, Department of Pediatric, Pediatric Nephrology Unit, Hospital das Clínicas (UFMG), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Avenida Alfredo Balena 190. Sala 267, Santa Efigênia, Belo Horizonte, 30130-100, Brazil
| | - Diniz José de Oliveira Filho
- Faculty of Medicine, Department of Pediatric, Pediatric Nephrology Unit, Hospital das Clínicas (UFMG), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Avenida Alfredo Balena 190. Sala 267, Santa Efigênia, Belo Horizonte, 30130-100, Brazil
| | - Eleonora Moreira Lima
- Faculty of Medicine, Department of Pediatric, Pediatric Nephrology Unit, Hospital das Clínicas (UFMG), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Avenida Alfredo Balena 190. Sala 267, Santa Efigênia, Belo Horizonte, 30130-100, Brazil
| | - José de Bessa
- Department of Urology, Universidade Estadual de Feira de Santana (UEFS), Feira de Santana, Brazil
| | | | - Mônica Maria de Almeida Vasconcelos
- Faculty of Medicine, Department of Pediatric, Pediatric Nephrology Unit, Hospital das Clínicas (UFMG), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Avenida Alfredo Balena 190. Sala 267, Santa Efigênia, Belo Horizonte, 30130-100, Brazil
| | - Flávia Cristina de Carvalho Mrad
- Faculty of Medicine, Department of Pediatric, Pediatric Nephrology Unit, Hospital das Clínicas (UFMG), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Avenida Alfredo Balena 190. Sala 267, Santa Efigênia, Belo Horizonte, 30130-100, Brazil.
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Sánchez-Romero M, Tlaxcala-Castillo L, Pichardo-Rojas PS, Valencia-Melo MA, Paz-López ÁA, Sánchez-Sagastegui F, Wegman-Ostrosky T. Sacral Agenesis. Pediatr Neurol 2025; 163:27-34. [PMID: 39642685 DOI: 10.1016/j.pediatrneurol.2024.10.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 10/28/2024] [Accepted: 10/29/2024] [Indexed: 12/09/2024]
Abstract
Sacral agenesis (SA) is a rare congenital neurological disorder characterized by the incomplete development of the sacral spine. This work summarizes the scientific literature on SA, including the following sections: pathogenesis, epidemiology, risk factors, genetics, clinical manifestations, radiological classification, diagnosis, and management. The aim of this work is to provide the most up-to-date and comprehensive medical narrative literature review for this rare congenital disease. This narrative review used PubMed, MEDLINE, Science Direct, and Embase databases. Between December 2022 and September 2023, the following terms were used for the inclusion of original articles: "rare disease," "caudal regression," "diabetic embryopathy," and "sacral agenesis.? The International Sacral Agenesis/Caudal Regression Association participated in reviewing this manuscript and drafting a paragraph on behalf of those living with this condition. The clinical manifestations of SA are heterogeneous. The most prevalent manifestations involve peripheral neurological, motor, urinary, and digestive issues. The prognosis depends on the severity and associated abnormalities. Patients usually exhibit normal mental function but require a multidisciplinary evaluation and largely supportive treatment that enables them to live successful lives. More awareness and research are needed.
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Affiliation(s)
| | | | - Pavel Salvador Pichardo-Rojas
- Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston, Houston, Texas
| | | | | | | | - Talia Wegman-Ostrosky
- Subdirection of Basic Research, Instituto Nacional de Cancerología, Mexico City, Mexico; ABC Medical Center, Mexico City, Mexico.
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Parajuli YG, Sinclair M. Cognitive, Behavioral and Educational Outcomes in Children Aged 5-11 Years With Spina Bifida in Northern Ireland. Birth Defects Res 2025; 117:e2434. [PMID: 39825676 PMCID: PMC11742512 DOI: 10.1002/bdr2.2434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 06/28/2024] [Accepted: 12/10/2024] [Indexed: 01/20/2025]
Abstract
INTRODUCTION While improved medical and surgical care for children with pina bifida has improved their survival, some may have lower cognitive, behavioral and educational performance. The paper assesses the effect of spina bifida on cognitive, behavioral, and educational outcomes in 5-11 year olds. METHODS A cross-sectional study design was used where data were collected from parents/guardians and teachers using Behavior Rating Inventory of Executive Function, second edition (BRIEF2), Strengths and Difficulties Questionnaire (SDQ), and Teacher Academic Attainment Scale (TAAS). RESULTS Nineteen parental and 13 teacher responses were received for children with spina bifida, and 8 parental and seven teacher responses for children without Spina Bifida. Overall, the majority of the sample were female. Children in both groups performed at a similar level across subscales of BRIEF2 with the exception of Working Memory. No group differences were found in SDQ scales as assessed by parents; teacher assessment of conduct problems. Hyperactivity/inattention and peer problems were higher for children with spina bifida. Anticipated matched analysis was not possible due to unequal number of participants between the groups. Children with spina bifida performed similarly as peers without spina bifida in all subjects across the curriculum with the exception of English, Mathematics, and History. DISCUSSION Based on this small sample, a potential need for evidence-based interventions to assist children with spina bifida in the cognitive area of working memory and also in English, Mathematics and History is postulated. Larger longitudinal studies are required to confirm these findings.
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Affiliation(s)
| | - Marlene Sinclair
- School of NursingUlster University BelfastBelfastNorthern IrelandUK
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Aguayo-Gómez A, Luna-Muñoz L, Svyryd Y, Muñoz-Téllez LÁ, Mutchinick OM. Bayesian polygenic risk estimation approach to nuclear families with discordant sib-pairs for myelomeningocele. PLoS One 2024; 19:e0316378. [PMID: 39774454 PMCID: PMC11684611 DOI: 10.1371/journal.pone.0316378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Myelomeningocele (MMC) is the most severe and disabling form of spina bifida with chronic health multisystem complications and social and economic family and health systems burden. In the present study, we aimed to investigate the genetic risk estimate for MMC in a cohort of 203 Mexican nuclear families with discordant siblings for the defect. Utilizing a custom Illumina array, we analyzed 656 single nucleotide polymorphisms (SNPs) of 395 candidate genes to identify a polygenic risk profile for MMC. Through a family-based analysis employing the transmission disequilibrium test (TDT) and Bayesian analysis, we assessed risk alleles transmission and calculated conditional probabilities estimating a polygenic risk for MMC. Our findings reveal significant associations of six genes related to neural tube closure (PSMB4, ATIC, DKK2, PSEN2, C2CD3, and PLCB2), showing differences in risk allele transmission between affected and unaffected siblings. Bayesian analysis identified changes in the risk profile after initiating folic acid fortification in Mexico, showing an evident decline in the conditional risk from 1/156 to 1/304 respectively. Despite the decline, this represents a 5.84-fold increase in risk before fortification and a 2.99-fold increase post-fortification compared to the baseline risk level (1/910). Our study highlights the advantage of incorporating a Bayesian analytical methodology in families with discordant sib-pairs, offering insights into the polygenic risk estimate for MMC and, most probably, for other congenital malformations.
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Affiliation(s)
- Adolfo Aguayo-Gómez
- Department of Genetics, National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), Mexico City, Mexico
| | - Leonora Luna-Muñoz
- Department of Genetics, National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), Mexico City, Mexico
| | - Yevgeniya Svyryd
- Department of Genetics, National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), Mexico City, Mexico
| | - Luis Ángel Muñoz-Téllez
- Department of Genetics, National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), Mexico City, Mexico
| | - Osvaldo M. Mutchinick
- Department of Genetics, National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), Mexico City, Mexico
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Arabzadeh H, Jenabi E, Masoumi SZ. Maternal factors for neural tube defects in offspring: An umbrella review. Open Med (Wars) 2024; 19:20241061. [PMID: 39434859 PMCID: PMC11491881 DOI: 10.1515/med-2024-1061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 08/31/2024] [Accepted: 09/13/2024] [Indexed: 10/23/2024] Open
Abstract
Objective We conducted an umbrella review focusing on maternal risk factors during pregnancy associated with neural tube defects (NTDs). Methods Our search was in databases PubMed, Scopus, and Web of Science. We specifically targeted meta-analyses examining maternal factors during pregnancy in relation to NTDs. The comparison involved assessing metrics such as odds ratio (OR) or related risk ratios reported in the included studies, as well as parameters like heterogeneity (I²), 95% prediction interval, small-study effects, excess significance biases, and sensitivity analysis. Results Three risk factors for fetal NTDs, namely hyperthermia with an OR of 1.92, obesity with an OR of 1.68, and passive smoking with an OR of 1.90, were classified as highly suggestive evidence (Class II). Influenza, with an OR of 3.33, was considered a risk factor with suggestive evidence (Class III). Multivitamin supplementation during pregnancy, with an OR of 0.76, and low maternal vitamin B12, with an OR of 2.41, were categorized as weak evidence (Class IV). Conclusion We identified four risk factors including hyperthermia, influenza, obesity, and passive smoking as suggestive or highly suggestive evidence for NTDs. Low maternal vitamin B12 was identified as a risk factor for NTDs, supported by weak evidence.
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Affiliation(s)
- Hoda Arabzadeh
- Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ensiyeh Jenabi
- Mother and Child Care Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
- Autism Spectrum Disorders Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Seyedeh Zahra Masoumi
- Department of Midwifery, School of Nursing and Midwifery, Mother and Child Care Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
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Eriks-Hoogland I, Schwethelm M, Müller L, Stoyanov J, Pannek J, Glisic M. Health status, functioning and risk profiles for secondary health conditions in adolescents and young adults with spina bifida: a cross-sectional study at time of transition. Swiss Med Wkly 2024; 154:3836. [PMID: 39462478 DOI: 10.57187/s.3836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2024] Open
Abstract
INTRODUCTION The transition from paediatric to adult medical care is a critical period for adolescents with spina bifida, often marked by deteriorating health and functional status. OBJECTIVES To describe the health status and functioning of individuals with spina bifida at the time of transition from paediatric to adult care and to identify risk profiles for potentially modifiable secondary health conditions (urinary tract infections, pressure injuries, respiratory problems and obesity). METHODS Descriptive study of data (derived from medical records) from all adolescents and young adults with spina bifida aged 15-25 years who were referred to a single specialised spinal cord injury centre as part of the transition programme during the period from 1 September 2015 to 31 May 2022. Descriptive statistics were used to describe the study population and to analyse the frequency and co-occurrence of congenital and acquired secondary health conditions. The equality of proportions test was used to test the prevalence of secondary health conditions based on important personal and clinical characteristics. RESULTS We included 43 adolescents with spina bifida with a mean age of 18.4 years (SD 2.5); in 63% of them the neurological level was lumbar, and around 50% of them were wheelchair-dependent. The median Spinal Cord Injury Measure (SCIM) III score was 72 (IQR 61-89). The mean number of secondary health conditions at time of transition was 8.8. The most prevalent secondary health conditions were lower urinary tract dysfunction, bowel dysfunction, sexual dysfunction and contractures. Respiratory problems were more prevalent in females and in individuals with lower SCIM III scores, whereas no differences were observed in the prevalence of other modifiable secondary health conditions. Clustering of secondary health conditions was mainly seen for urinary tract infection + pressure injury and for urinary tract infection + pressure injury + obesity. CONCLUSION The prevalence of secondary health conditions among individuals with spina bifida at time of transition is alarmingly high and functional profiles underscore the need for supporting adolescents and young adults with daily medical issues. The study highlights the critical role of transition programmes and interdisciplinary follow-up care in preventing health problems and improving functioning and independence in everyday life.
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Affiliation(s)
- Inge Eriks-Hoogland
- Swiss Paraplegic Centre, Nottwil, Switzerland
- Faculty of Health Sciences and Medicine at the University of Lucerne, Lucerne, Switzerland
- Swiss Paraplegic Research, Nottwil, Switzerland
- International National Spinal Injuries Centre (ISCoS), Paediatric Special Interest Group, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, United Kingdom
| | | | | | - Jivko Stoyanov
- Swiss Paraplegic Research, Nottwil, Switzerland
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
| | - Jürgen Pannek
- Swiss Paraplegic Centre, Nottwil, Switzerland
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Marija Glisic
- Swiss Paraplegic Research, Nottwil, Switzerland
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
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Rüegg L, Vonzun L, Zepf J, Strübing N, Möhrlen U, Mazzone L, Meuli M, Spina Bifida Study Group, Ochsenbein-Kölble N. Gestational Diabetes in Women with Fetal Spina Bifida Repair-Influence of Perioperative Management. J Clin Med 2024; 13:5029. [PMID: 39274242 PMCID: PMC11395906 DOI: 10.3390/jcm13175029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/20/2024] [Accepted: 08/23/2024] [Indexed: 09/16/2024] Open
Abstract
Background/Objectives: Fetal spina bifida (fSB) is the most common neural tube defect, and intrauterine repair has become a valid treatment option for selected cases. If fSB repair is offered, the ideal time for surgery is from 24 to 26 gestational weeks (GWs). The preoperative steroids for lung maturation and preoperative tocolytics that are administered are known to increase the prevalence of gestational diabetes (GD), which normally occurs in about 10-15% of all pregnant women. This study assessed the prevalence, possible influencing factors, and consequences on the course of pregnancy regarding GD in this cohort. Methods: Between 2010 and 2022, 184 fSB cases were operated. Those patients operated on after 24 0/7 GWs received steroids before surgery. All the patients received tocolysis, and an oral glucose tolerance test was performed between 26 and 28 GWs at least 7 days after steroid administration. In 2020, we established an early postoperative mobilization protocol. The perioperative management procedures of those patients with and without GD were compared to each other, and also, the patients treated according to the early mobilization protocol were compared to the remaining cohort. Results: Nineteen percent were diagnosed with GD. Corticosteroids were administered in 92%. Neither the corticoid administration nor the interval between the administration and glucose tolerance test was different in patients with or without GD. Further, 99.5% received postoperative tocolytics for at least 48 h. The women with GD had significantly longer administration of tocolytics. The length of stay (LOS) was higher in those patients with GD. The gestational age (GA) at delivery was significantly lower in the cohort with GD. In the early mobilized group, we found a significantly higher GA at delivery (37.1 GWs vs. 36.2 GWs, p = 0.009) and shorter LOS (p < 0.001), and their GD rate was lower (10% vs. 20%), although not statistically significant. Conclusions: The GD incidence in the women after fSB repair was higher than in the usual pregnant population. Early mobilization, rapid tocolytics decrease, and shorter LOS could benefit the pregnancy course after fSB repair and may decrease the risk for GD in this already high-risk cohort without increasing the risk for preterm delivery.
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Affiliation(s)
- Ladina Rüegg
- Department of Obstetrics, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
| | - Ladina Vonzun
- Department of Obstetrics, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, 8006 Zurich, Switzerland
| | - Julia Zepf
- Department of Obstetrics, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
| | - Nele Strübing
- Department of Obstetrics, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, 8006 Zurich, Switzerland
| | - Ueli Möhrlen
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, 8006 Zurich, Switzerland
- Department of Pediatric Surgery, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
- Spina Bifida Center, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - Luca Mazzone
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, 8006 Zurich, Switzerland
- Department of Pediatric Surgery, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
- Spina Bifida Center, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - Martin Meuli
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
- Spina Bifida Center, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | | | - Nicole Ochsenbein-Kölble
- Department of Obstetrics, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Rämistrasse 71, 8006 Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, 8006 Zurich, Switzerland
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11
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Peiffer S, Gyimah M, Powell P, Lepard JR, King C, Passoni N, Whitehead WE, King A. Characteristics and Outcomes of Patients With Spina Bifida in Texas by Patient Age. J Surg Res 2024; 300:231-240. [PMID: 38824853 DOI: 10.1016/j.jss.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 03/20/2024] [Accepted: 05/03/2024] [Indexed: 06/04/2024]
Abstract
INTRODUCTION Spina bifida (SB) occurs in 3.5/10,000 live births and is associated with significant long-term neurologic and urologic morbidity. We explored the characteristics and outcomes of pediatric patients with SB and the facilities that treat them in Texas. METHODS We retrospectively reviewed a statewide hospital inpatient discharge database (2013-2021) to identify patients aged <18 y with SB using International Classification of Diseases 9/10 codes. Patients transferred to outside hospitals were excluded to avoid double-counting. Descriptive statistics and chi-square test were performed. RESULTS Seven thousand five hundred thirty one inpatient hospitalizations with SB were analyzed. Most SB care is provided by a few facilities. Two facilities (1%) averaged >100 SB admissions per year (33% of patients), while 15 facilities (8%) treat 10-100 patients per year (51% of patients). Most facilities (145/193, 75%) average less than one patient per year. Infants tended to be sicker (17% extreme illness severity, P < 0.001). Overall mortality is low (1%), primarily occurring in the neonatal period (8%, P < 0.001). Most admissions are associated with surgical intervention, with 63% of encounters having operating room charges with an average cost of $25,786 ± 24,884. Admissions for spinal procedures were more common among infants, whereas admissions for genitourinary procedures were more common among older patients (P < 0.001). The average length of stay was 8 ± 16 d with infants having the longest length of stay (19 ± 33, P < 0.001). CONCLUSIONS Patients have significant long-term health needs with evolving pediatric surgical indications as they grow. Pediatric SB care is primarily provided by a small number of facilities in Texas. Longitudinal care coordination of their multidisciplinary surgical care is needed to optimize patient care.
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Affiliation(s)
- Sarah Peiffer
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas
| | - Mike Gyimah
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas
| | - Paulina Powell
- Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas
| | - Jacob R Lepard
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas; Department of Neurosurgery, Texas Children's Hospital, Houston, Texas; Department of Neurosurgery, Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Cyrus King
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
| | - Niccolo Passoni
- Scott Department of Urology, Baylor College of Medicine, Houston, Texas; Department of Urology, Texas Children's Hospital, Houston, Texas
| | - William E Whitehead
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas; Department of Neurosurgery, Texas Children's Hospital, Houston, Texas
| | - Alice King
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas.
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12
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Lemin S, van Bosse HJP, Hutka L, Soberdash S, Patibandla J. Prenatal diagnosis (or lack thereof) of arthrogryposis multiplex congenita and its impact on the perinatal experience of parents: A retrospective survey. Prenat Diagn 2024; 44:614-622. [PMID: 38578615 DOI: 10.1002/pd.6569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 03/23/2024] [Accepted: 03/25/2024] [Indexed: 04/06/2024]
Abstract
OBJECTIVE To examine parental experiences during pregnancies affected by Arthrogryposis Multiplex Congenita (AMC) by identifying commonalities, risk factors, and areas for improvement in detection rates, care protocols, and patient experience. STUDY DESIGN An online survey was distributed via AMC support groups on Facebook. Topics included demographics, risk factors, parental recall of sonographic findings, delivery characteristics and neonatal findings. Responses were divided into antenatally detected cases (ADCs) and postnatally detected cases (PDCs). Quantitative responses were analyzed with the Fisher exact test. Qualitative data were analyzed with thematic analysis. RESULTS The antenatal detection rate of arthrogryposis was 37%. Decreased fetal movement was reported by 53% and early bleeding by 21%. Sonographic findings in ADCs included clubfoot (83%), clenched hand (51%), decreased fetal movement (50%), elbow contracture (51%), and knee contracture (46%). Among ADCs, 29% delivered vaginally and 71% delivered by cesarean versus PDCs (44% vaginal, 56% cesarean). Neonatal intensive care unit admission rate was 63%. Bone fracture occurred in 9%. Detection led to a planned change in delivery mode in 33% and location in 50%. Among ADCs, 17% felt their concerns were not adequately addressed versus 43% of PDCs. CONCLUSIONS Antenatal detection of arthrogryposis was low. We propose enhanced screening criteria to aid prenatal diagnosis and promote utilization of more robust practice guidelines.
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Affiliation(s)
- Sara Lemin
- Department of Obstetrics and Gynecology, Aultman Hospital/Northeast Ohio Medical University, Canton, Ohio, USA
| | - Harold J P van Bosse
- Department of Orthopaedic Surgery, Cardinal Glennon Children's Hospital/SSM Health/St. Louis University, St. Louis, Missouri, USA
| | - Lauren Hutka
- Department of Obstetrics and Gynecology, Aultman Hospital/Northeast Ohio Medical University, Canton, Ohio, USA
| | - Shea Soberdash
- Department of Obstetrics and Gynecology, Aultman Hospital/Northeast Ohio Medical University, Canton, Ohio, USA
| | - Jay Patibandla
- Department of Obstetrics and Gynecology, Aultman Hospital/Northeast Ohio Medical University, Canton, Ohio, USA
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13
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Benabdderrahmane K, Stirnemann J, Ramtani S, Falentin-Daudré C. Development of a double-layer electrospun patch as a potential prenatal treatment for myelomeningocele. Wound Repair Regen 2024; 32:246-256. [PMID: 37957136 DOI: 10.1111/wrr.13123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 09/05/2023] [Accepted: 10/12/2023] [Indexed: 11/15/2023]
Abstract
Myelomeningocele (MMC) is a congenital defect of the spine characterised by meningeal and spinal cord protrusion through the open vertebral arches. This defect causes progressive prenatal damage of the spinal cord, leading to lifelong handicap. Although mid-trimester surgical repair may reduce part of the handicap, an earlier and less invasive approach would further improve the prognosis, possibly minimising maternal and foetal risks. Several studies have proposed an alternative approach to surgical repair by covering the defect with a patch and protecting the exposed neural tissue. Our study aims to elaborate on a waterproof and biodegradable bioactive patch for MMC prenatal foetal repair. We developed a double-layer patch that can provide a waterproof coverage for the spinal cord, with a bioactive side, conducive to cell proliferation, and an antiadhesive side to avoid its attachment to the medulla.
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Affiliation(s)
- K Benabdderrahmane
- LBPS/CSPBAT, UMR CNRS 7244, Institut Galilée, Université Sorbonne Paris Nord, Villetaneuse, France
| | - J Stirnemann
- Obstetrics and Maternal-Fetal Medicine, Hôpital Necker Enfants Malades, AP-HP, Paris, France
- EA7328 Institut Imagine & Université de Paris-Cité, Paris, France
| | - S Ramtani
- LBPS/CSPBAT, UMR CNRS 7244, Institut Galilée, Université Sorbonne Paris Nord, Villetaneuse, France
| | - C Falentin-Daudré
- LBPS/CSPBAT, UMR CNRS 7244, Institut Galilée, Université Sorbonne Paris Nord, Villetaneuse, France
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14
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Doğan ÇS, Taner S, Tiryaki BD, Alaygut D, Özkayın N, Kara A, Gençler A, Pınarbaşı AS, Nalçacıoğlu H, Yüksel S, Akacı O, Yılmaz EK, Yavuz S, Doğan K, Gülşan RYÇ, Aksoy GK, Çiçek N, Aksu B, Küçük N, Altugan FŞ, Selçuk ŞZ, Baştuğ F, Erfidan G, Atmış B, Gökçeoğlu AU, Önder ENA, Elmacı AM, Cengiz N, Gülleroğlu K, Yılmaz EB, Tayfur AÇ, Yılmaz GG, Yel Sİ, Pehlivanoğlu C, Akgün C, Kara MA, Kılıç BD, Şimşek ÖÖ, Yucal M, Ağar BE, Gürgöze MK, Yağmur İ, Madsar Ö, Karalı DT, Girişgen İ, Bodur ED, Çomak E, Gökçe İ, Kaya M, Tabel Y, Günay N, Gülmez R, Çalışkan S. Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study. Pediatr Nephrol 2024; 39:1509-1519. [PMID: 38040872 DOI: 10.1007/s00467-023-06212-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 10/06/2023] [Accepted: 10/18/2023] [Indexed: 12/03/2023]
Abstract
BACKGROUND Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. METHODS Data from children aged 0-19 years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1 year of age without pre-existing kidney abnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15 ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. RESULTS A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13 years old (range 2-18 years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15 years old. CONCLUSION MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.
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Affiliation(s)
- Çağla Serpil Doğan
- Division of Pediatric Nephrology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey.
| | - Sevgin Taner
- Division of Pediatric Nephrology, Adana City Hospital, Adana, Turkey
| | - Betül Durucu Tiryaki
- Division of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Demet Alaygut
- Division of Pediatric Nephrology, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Neşe Özkayın
- Division of Pediatric Nephrology, Faculty of Medicine, Trakya University, Edirne, Turkey
| | - Aslıhan Kara
- Division of Pediatric Nephrology, Faculty of Medicine, Fırat University, Elazığ, Turkey
| | - Aylin Gençler
- Division of Pediatric Nephrology, Faculty of Medicine, Harran University, Şanlıurfa, Turkey
| | - Ayşe Seda Pınarbaşı
- Division of Pediatric Nephrology, Diyarbakır Children's Hospital, Diyarbakır, Turkey
| | - Hülya Nalçacıoğlu
- Division of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
| | - Selçuk Yüksel
- Division of Pediatric Nephrology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Okan Akacı
- Division of Pediatric Nephrology, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey
| | - Esra Karabağ Yılmaz
- Division of Pediatric Nephrology, Cerrahpaşa Medical Faculty, İstanbul University - Cerrahpaşa, İstanbul, Turkey
| | - Sevgi Yavuz
- Division of Pediatric Nephrology, Başakşehir Çam and Sakura City Hospital, İstanbul, Turkey
| | - Kenan Doğan
- Division of Pediatric Nephrology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Rumeysa Yasemin Çiçek Gülşan
- Division of Pediatric Nephrology, University of Health Sciences, Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey
| | - Gülşah Kaya Aksoy
- Division of Pediatric Nephrology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Neslihan Çiçek
- Division of Pediatric Nephrology, Faculty of Medicine, Marmara University, İstanbul, Turkey
| | - Bağdagül Aksu
- Division of Pediatric Nephrology, İstanbul Faculty of Medicine, İstanbul University, İstanbul, Turkey
| | - Nuran Küçük
- Division of Pediatric Nephrology, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey
| | - Fatma Şemsa Altugan
- Division of Pediatric Nephrology, University of Health Sciences, Bilkent City Hospital, Ankara, Turkey
| | - Şenay Zırhlı Selçuk
- Division of Pediatric Nephrology, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Funda Baştuğ
- Division of Pediatric Nephrology, Kayseri City Hospital, Kayseri, Turkey
| | - Gökçen Erfidan
- Division of Pediatric Nephrology, University of Health Sciences, Gazi Yaşargil Training and Research Hospital, Diyarbakir, Turkey
| | - Bahriye Atmış
- Division of Pediatric Nephrology, Faculty of Medicine, Çukurova University, Adana, Turkey
| | - Arife Uslu Gökçeoğlu
- Division of Pediatric Nephrology, Faculty of Medicine, Alanya Alaaddin Keykubat University, Antalya, Turkey
| | | | - Ahmet Mithat Elmacı
- Division of Pediatric Nephrology, Faculty of Medicine, Karamanoğlu Mehmetbey University, Karaman, Turkey
| | - Nurcan Cengiz
- Division of Pediatric Nephrology, Faculty of Medicine, Sıtkı Koçman University, Muğla, Turkey
| | - Kaan Gülleroğlu
- Division of Pediatric Nephrology, Faculty of Medicine, Başkent University, Ankara, Turkey
| | - Ebru Bekiroğlu Yılmaz
- Division of Pediatric Nephrology, University of Health Sciencies, Dr. Behçet Uz Children's Hospital, Izmir, Turkey
| | - Aslı Çelebi Tayfur
- Division of Pediatric Nephrology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey
| | | | - Sİbel Yel
- Division of Pediatric Nephrology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Cemile Pehlivanoğlu
- Division of Pediatric Nephrology, Faculty of Medicine, Koç University, İstanbul, Turkey
| | - Cihangir Akgün
- Division of Pediatric Nephrology, Faculty of Medicine, İstanbul Medipol University, İstanbul, Turkey
| | - Mehtap Akbalık Kara
- Division of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | | | - Özgür Özdemir Şimşek
- Division of Pediatric Nephrology, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Melike Yucal
- Division of Pediatric Nephrology, Faculty of Medicine, Trakya University, Edirne, Turkey
| | - Buket Esen Ağar
- Division of Pediatric Nephrology, Faculty of Medicine, Fırat University, Elazığ, Turkey
| | - Metin Kaya Gürgöze
- Division of Pediatric Nephrology, Faculty of Medicine, Fırat University, Elazığ, Turkey
| | - İsmail Yağmur
- Division of Pediatric Urology, Faculty of Medicine, Harran University, Urfa, Turkey
| | - Ömer Madsar
- Department of Urology, Faculty of Medicine, Harran University, Urfa, Turkey
| | - Demet Tekcan Karalı
- Division of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
| | - İlknur Girişgen
- Division of Pediatric Nephrology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Ece Demirci Bodur
- Division of Pediatric Nephrology, Başakşehir Çam and Sakura City Hospital, İstanbul, Turkey
| | - Elif Çomak
- Division of Pediatric Nephrology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - İbrahim Gökçe
- Division of Pediatric Nephrology, Faculty of Medicine, Marmara University, İstanbul, Turkey
| | - Mehtap Kaya
- Division of Pediatric Nephrology, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey
| | - Yılmaz Tabel
- Division of Pediatric Nephrology, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Neslihan Günay
- Division of Pediatric Nephrology, Kayseri City Hospital, Kayseri, Turkey
| | - Rüveyda Gülmez
- Division of Pediatric Nephrology, University of Health Sciences, Gazi Yaşargil Training and Research Hospital, Diyarbakir, Turkey
| | - Salim Çalışkan
- Division of Pediatric Nephrology, Cerrahpaşa Medical Faculty, İstanbul University - Cerrahpaşa, İstanbul, Turkey
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Mirzaei S, Khoshkholghsima M, Sabaghzadeh A, Kurdkandi HZ. Cervicothoracic (C 6, C 7 & T 1) spina bifida occulta - A case report. Int J Surg Case Rep 2024; 117:109477. [PMID: 38452644 PMCID: PMC10926287 DOI: 10.1016/j.ijscr.2024.109477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 02/29/2024] [Accepted: 03/01/2024] [Indexed: 03/09/2024] Open
Abstract
INTRODUCTION Spina bifida (SB), as one of the spine abnormalities, is caused by incomplete closure of the neural tube and generally includes two types: open and closed. This study aims to introduce one of the rare cases of closed SB. CASE PRESENTATION A 34-year-old male patient was admitted to the hospital with neck pain. Radiographic and computed tomography (CT) imaging revealed bifid spinous processes from C6 to T1 vertebrae, indicative of a rare case of closed SB in the cervicothoracic region. CLINICAL DISCUSSION Closed SB, while often regarded as benign, can be associated with various pathologies that require follow-up. CONCLUSION Diagnosing this abnormality is crucial for addressing potential complications that may arise from it.
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Affiliation(s)
- Soheil Mirzaei
- Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Radiology, Shahid Sattari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maryam Khoshkholghsima
- Department of Radiology, Shahid Sattari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sabaghzadeh
- Department of Orthopedic Surgery, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hooshmand Zarei Kurdkandi
- Bone, Joint and Related Tissue Research Center, Akhtar Orthopedic Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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16
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Koch VH, Lopes M, Furusawa E, Vaz K, Barroso U. Multidisciplinary management of people with spina bifida across the lifespan. Pediatr Nephrol 2024; 39:681-697. [PMID: 37501019 DOI: 10.1007/s00467-023-06067-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 06/09/2023] [Accepted: 06/19/2023] [Indexed: 07/29/2023]
Abstract
The average worldwide prevalence of neural tube defects (NTDs) is 1.0 per 1000 births. Its development is multifactorial due to genetic and non-genetic factors. Spina bifida (SB) is one of main representatives of NTD. The spinal cord lesion level is the main determinant of the level of paralysis, numbness, and difficulties with bladder/bowel functions. Myelomeningocele prenatal repair reduces hydrocephalus and hindbrain herniation and improves motor function. The severity of hydrocephalus is associated with poorer neurodevelopmental outcomes whether operated on prenatally or after birth. People with SB tend to have a lower IQ and cognitive difficulties. Early diagnosis, proactivity, and lifelong multidisciplinary follow-up are key protective issues. Invasive urological interventions should be considered in selected patients after failure of conservative treatment. Transition to adult care should be well planned as it is challenging. Health literacy is directly associated with success at transition. Sexuality and fertility should be addressed before/during puberty. Overall, the rates of fecal and urinary continence and skin breakdown increase with age, whereas the ability to ambulate declines with age. Bowel and urinary incontinence are independent predictors of lower health-related quality of life (HRQoL) in adults with SB. Bowel incontinence has negative impact on HRQoL regardless of frequency or amount. Long-term caregiver support should be offered at diagnosis. Survival at a mean of 50 years is poor, at 32%, due to central nervous system deaths, cancer, urological disease, and sepsis. Challenges to implementation of recommended practices exist, especially in low and middle-income countries.
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Affiliation(s)
- Vera H Koch
- Pediatric Nephrology Unit, Department of Pediatrics, University of São Paulo Medical School, Children's Hospital, Hospital das Clinicas, Sau Paulo, Brazil.
| | - MarcosTomasin Lopes
- Pediatric Nephrology Unit, Department of Pediatrics, University of São Paulo Medical School, Children's Hospital, Hospital das Clinicas, Sau Paulo, Brazil
| | - Erika Furusawa
- Pediatric Nephrology Unit, Department of Pediatrics, University of São Paulo Medical School, Children's Hospital, Hospital das Clinicas, Sau Paulo, Brazil
| | - Katharinne Vaz
- Division of Urology, Federal University of Bahia - UFBA, Salvador, BA, Brazil
| | - Ubirajara Barroso
- Division of Urology - Federal University of Bahia, Bahiana School of Medicine, Salvador, BA, Brazil
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17
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Hifny MA, Park TH, Yagi S, Abdelmegeed AG, El-Shazly M. Myelomeningocele Defects Reconstruction With Various Types of Keystone Flaps: An Algorithmic Approach Based on Defect Shape. J Craniofac Surg 2024; 35:626-629. [PMID: 37830806 DOI: 10.1097/scs.0000000000009779] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 08/21/2023] [Indexed: 10/14/2023] Open
Abstract
The keystone flap has become an established option that has been utilized recently to close significant myelomeningocele defects. Although the keystone flaps can be adapted to repair myelomeningocele defects of different sizes, the shape of the defect is also an essential factor to consider. In this study, the authors proposed an algorithmic approach for reconstructing significant meningomyelocele defects utilizing different types of keystone flaps based on the shape of the resulting defect. From September 2016 to March 2022, the authors retrospectively reviewed the medical records of 28 patients with meningomyelocele who underwent repair with the keystone flaps. The mean age was 28 days (3 days to 4.5 months). Twenty-one meningomyelocele defects were in the lumbosacral (75%) and 7 in the thoracolumbar regions (25%). The defect sizes ranged from 3.5×5 cm (area, 13.4 cm 2 ) to 9×7 cm (area, 49.5 cm 2 ), with an average of 26.2 cm 2 . Ten meningomyelocele defects were a vertically oriented oval shape, 16 defects were a transversely oriented oval shape, and 2 defects were circular. In addition, unilateral keystone flap was used in 7.1% of the patients (2 patients), bilateral keystone flap in 28.6% (8 patients), and rotation advancement keystone flaps in 64.3% (18 patients). According to these findings, an algorithm was created based on the defect shape. This algorithmic approach is used as a decision-making guide to select the correct type of keystone flaps to repair myelomeningocele according to the defect shape.
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Affiliation(s)
- Mahmoud A Hifny
- Department of Plastic Surgery, Faculty of Medicine, Qena University Hospital, South Valley University, Qena, Egypt
| | - Tae Hwan Park
- Department of Plastic and Reconstructive Surgery, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Shunjiro Yagi
- Department of Plastic and Reconstructive Surgery, Tottori University Hospital, Yonago, Japan
| | | | - Mohamed El-Shazly
- Department of Plastic Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt
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Zepf J, Vonzun L, Rüegg L, Strübing N, Krähenmann F, Meuli M, Mazzone L, Moehrlen U, Ochsenbein-Kölble N. Fetal Spina Bifida Repair in Obese Mothers: Is Maternal and Fetal Safety Compromised? Fetal Diagn Ther 2024; 51:175-183. [PMID: 38190813 PMCID: PMC10994580 DOI: 10.1159/000536071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 12/20/2023] [Indexed: 01/10/2024]
Abstract
INTRODUCTION The Management of Myelomeningocele Study (MOMS) eligibility criteria preclude in utero surgery for fetal spina bifida (fSB) when the maternal body mass index (BMI) is ≥35 kg/m2. Some centers still respect this criterion, while others, like ours, do not. This study aimed to assess whether maternal and fetal safety is compromised with higher maternal BMIs. METHODS Data of 192 patients with open fSB repair at our center were retrospectively analyzed. According to their BMI, patients were divided into three groups: group 1 (BMI <30 kg/m2), group 2 (BMI 30-35 kg/m2), and group 3 (BMI >35 kg/m2). Subgroup analysis was performed to assess differences in maternal and fetal outcomes. Additionally, complications were divided into grades 1 to 5 according to their severity and outcome consequences and compared among groups. RESULTS Out of 192 patients, 146 (76.0%) had a BMI <30 kg/m2, 28 (14.6%) had a BMI 30-35 kg/m2, and 18 (9.4%) had a BMI >35 kg/m2. Significant differences occurring more often in either group 2 or 3 compared to group 1 were maternal wound seroma (50% or 56% vs. 32%, p = 0.04), amniotic fluid leakage (14% or 6% vs. 2%, p = 0.01) as well as vaginal bleeding (11% or 35% vs. 9%, p = 0.01). On the contrary, duration of tocolysis with atosiban was shorter in patients with BMI >30 kg/m2 (4 or 5 vs. 6 days, p = 0.01). When comparing severity of maternal or fetal complications, grade 1 intervention-related complications occurred significantly more often in group 3 compared to group 1 or 2 (78% vs. 45% or 57%, p = 0.02). Gestational age at delivery was around 36 weeks in all groups without significant differences. CONCLUSION This investigation did not identify clinically relevant maternal and/or fetal outcome problems related to BMIs >35 kg/m2. Additional studies are however needed to confirm our results.
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Affiliation(s)
- Julia Zepf
- Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
| | - Ladina Vonzun
- Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Ladina Rüegg
- Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
| | - Nele Strübing
- Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Franziska Krähenmann
- Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Martin Meuli
- University of Zurich, Zurich, Switzerland
- Department of Pediatric Surgery, University Children’s Hospital Zurich, Zurich, Switzerland
- Spina Bifida Center, University Children’s Hospital Zurich, Zurich, Switzerland
| | - Luca Mazzone
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
- Department of Pediatric Surgery, University Children’s Hospital Zurich, Zurich, Switzerland
- Spina Bifida Center, University Children’s Hospital Zurich, Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland
| | - Ueli Moehrlen
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
- Department of Pediatric Surgery, University Children’s Hospital Zurich, Zurich, Switzerland
- Spina Bifida Center, University Children’s Hospital Zurich, Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland
| | - Nicole Ochsenbein-Kölble
- Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Spina Bifida Study Group Zurich
- Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland
- The Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
- Department of Pediatric Surgery, University Children’s Hospital Zurich, Zurich, Switzerland
- Spina Bifida Center, University Children’s Hospital Zurich, Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland
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19
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Ledet Iii LF, Plaisance CJ, Daniel CP, Wagner MJ, Alvarez I, Burroughs CR, Rieger R, Siddaiah H, Ahmadzadeh S, Shekoohi S, Kaye AD, Varrassi G. Spina Bifida Prevention: A Narrative Review of Folic Acid Supplements for Childbearing Age Women. Cureus 2024; 16:e53008. [PMID: 38406082 PMCID: PMC10894015 DOI: 10.7759/cureus.53008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 01/26/2024] [Indexed: 02/27/2024] Open
Abstract
Neural tube defects (NTDs) are malformations that occur during embryonic development, and they account for most central nervous system birth anomalies. Genetic and environmental factors have been shown to play a role in the etiology of NTDs. The different types of NTDs are classified according to anatomic location and severity of the defect, with most of the neural axis anomalies occurring in the caudal spinal or cranial areas. Spina bifida is a type of NTD that is characterized by an opening in the vertebral arch, and the level of severity is determined by the extent to which the neural tissue protrudes through the opened arch(es). Prevention of NTDs by administration of folic acid has been studied and described in the literature, yet there are approximately 300,000 cases of NTDs that occur annually, with 88,000 deaths occurring per year worldwide. A daily intake of at least 400 μg of folic acid is recommended especially for women of childbearing age. To provide the benefits of folic acid, prenatal vitamins are recommended in pregnancy, and many countries have been fortifying foods such as cereal grain products with folic acid; however, not all countries have instituted folic acid fortification programs. The present investigation includes a description of the pharmacology of folic acid, neural tube formation, defects such as spina bifida, and the relevance of folic acid to developing spina bifida. Women's knowledge and awareness of folic acid regarding its importance in the prevention of spina bifida is a major factor in reducing incidence worldwide.
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Affiliation(s)
- Lloyd F Ledet Iii
- School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Connor J Plaisance
- School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Charles P Daniel
- School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Maxwell J Wagner
- School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Ivan Alvarez
- School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Caroline R Burroughs
- School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Ross Rieger
- Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Harish Siddaiah
- Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Shahab Ahmadzadeh
- Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Sahar Shekoohi
- Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Alan D Kaye
- Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
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20
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Manso MT, Matos VMJ. Spina bifida, the normal, the pathological and the in-between: first evidence from a forensic osteological collection. Int J Legal Med 2024; 138:249-258. [PMID: 37522954 PMCID: PMC10771999 DOI: 10.1007/s00414-023-03066-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 07/17/2023] [Indexed: 08/01/2023]
Abstract
Spina bifida (SB), a rare congenital disorder, is often mentioned as an individualizing factor in Forensic Anthropology. A lack of empirical data regarding SB is noticed in the scientific literature. Moreover, within the scope of anthropological research on SB disparities in terminology, classification systems, and methodological approaches result in incomparable results. The wide range (1,2%-50%) of "spina bifida occulta" reported prevalences is a good example. This research aims to analyze and debate the standard diagnostic criteria of SB on human skeletal remains, and attempts to elaborate on an universal system, premised on the distinction between SB as a pathology, and cleft neural arch (CNA) as an anatomical variant, according to Barnes (1994, p. 360 [1). A study-base of 209 individuals (88 males; 121 females; 44-99 years old) from the 21st Century Identified Skeletal Collection from the University of Coimbra (CEI/XXI) was macroscopically analyzed, focusing on the sacrum and remaining vertebrae. Four individuals presented complete posterior opening of the sacral canal (2,6%[4/156]). The observed bone changes, combined with the analysis of the entire skeleton, indicate that CNA, rather than SB linked to a neural tube defect, is the most reliable explanation for these cases. Overall, CNA was observed on 11 skeletons (7.05% of 156). The viability and applicability of the developed methodology for the identification of SB/CNA in forensic and/or osteological contexts are discussed, as well as the possibility of a lower prevalence of SB occulta, in the general population, than speculated before. HIGHLIGHTS: • Spina bifida has been studied so far under different methodologies, classification systems and nomenclature, leading to unstandardized and incomparable data. • Spina bifida as a pathological manifestation of a neural tube defect, as opposed to cleft neural arch as a simple form of skeletal variation. • Both spina bifida and complete sacral cleft fit the criteria of an individualizing trait in Forensic Anthropology.
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Affiliation(s)
- Maria Torres Manso
- Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal.
| | - Vitor M J Matos
- Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal
- Research Centre for Anthropology and Health, Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal
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21
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Narang K, Wyatt M, O'Leary P, Qureshi MY, Kolbe A, Stephens EH, Dearani JA, Ruano R. Novel approach to prenatal predictors of outcomes for fetuses with severe Ebstein anomaly. J Matern Fetal Neonatal Med 2023; 36:2271626. [PMID: 37904503 DOI: 10.1080/14767058.2023.2271626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 10/11/2023] [Indexed: 11/01/2023]
Abstract
OBJECTIVE Ebstein anomaly (EA) is a cardiac malformation with highly variable presentation and severity with limited perinatal management options. We present incorporation of fetal lung measurements into a multidisciplinary evaluation for counseling and predicting postnatal outcomes in patients with severe EA. METHODS Five fetuses with severe fetal EA were reviewed. Third trimester sonographic observed/expected total lung area (O/E TLA) and lung to head ratio (O/E LHR), fetal MRI total fetal lung volume ratio (O/E-TFLV), echocardiographic cardio-thoracic ratio (CT ratio), sonographic estimated fetal weight (EFW) by Hadlock formula and presence of hydrops, were used to guide perinatal management. RESULTS Three of five had appropriate fetal growth, were delivered at term in a cardiac operative suite, and underwent immediate intervention with good neonatal outcomes. Two had severe fetal growth restriction (FGR), CT ratios > 0.8 and O/E LHR and TLA < 25%. One of which delivered prematurely with neonatal demise and one suffered in utero demise at 34 weeks. CONCLUSIONS FGR, hydrops, increased CT ratio and reduced O/E LHR and TFLV are potential prognosticators of poor outcomes in severe EA, and should be validated in larger cohorts that would allow for a statistical analysis of the predictive utility of these measurements.
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Affiliation(s)
- Kavita Narang
- Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Michelle Wyatt
- Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Patrick O'Leary
- Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - M Yasir Qureshi
- Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Amy Kolbe
- Pediatric Radiology Division, Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Elizabeth H Stephens
- Department of Cardiovascular Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Joseph A Dearani
- Department of Cardiovascular Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Rodrigo Ruano
- Division Chief of Maternal-Fetal Medicine, Director UHealth Jackson Fetal Care, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
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22
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Mammadov M, Emon ST, Akar E, Akakin D, Şener D. Effects of sodium fluoride on neural tube development in chick embryos. Neurochirurgie 2023; 69:101502. [PMID: 37741361 DOI: 10.1016/j.neuchi.2023.101502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 08/29/2023] [Accepted: 09/12/2023] [Indexed: 09/25/2023]
Abstract
OBJECTIVE Various environmental factors encountered in daily life are associated with the development of neural tube defects. This study aims to investigate the effects of fluoride on neural tube development in chick embryos. METHODS A total of 60 specific pathogen-free, fertile, zero-day Leghorn-type eggs were used in the study. Group 1 was the control group, in which only saline was administered. Group 2 was the low-dose group, in which 0.003 mg of fluoride was administered, and Group 3 was the high-dose group, in which 0.006 mg of fluoride was administered. After 72 h of incubation, the embryonic disc was evaluated microscopically. RESULTS In the control group, the surface ectoderm of all sections was intact, the neural tube was closed, and the neuroepithelium, the basement membrane surrounding the neuroepithelium, the somites, and the notochord displayed standard structure. Neural tube defects were observed in 3 of the chick embryos, that was given low-dose fluoride. In Group 3, which was administered high doses of fluoride, neural tube defects were observed in 4 embryos. It was observed that the development of neural tube defects was no statistically significantly higher in low and high-dose fluoride group compared to the control group. CONCLUSION Low and high-dose fluoride exposure was associated with developing neural tube defects, but there was no statisticaly significance.
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Affiliation(s)
- Mazhar Mammadov
- Haydarpaşa Numune Training and Research Hospital, Department of Neurosurgery, Istanbul, Turkey
| | - Selin Tural Emon
- Haydarpaşa Numune Training and Research Hospital, Department of Neurosurgery, Istanbul, Turkey
| | - Ezgi Akar
- Haydarpaşa Numune Training and Research Hospital, Department of Neurosurgery, Istanbul, Turkey.
| | - Dilek Akakin
- Marmara University, School of Medicine, Department of Histology and Embryology, İstanbul, Turkey
| | - Dila Şener
- Bahcesehir University, School of Medicine, Department of Histology and Embryology, Istanbul, Turkey
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23
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Hakim WS, Aljanabi AS. The Aperta type of neural tube defect: The relevant experience in a local community with the diversity of the presentation. J Med Life 2023; 16:1499-1502. [PMID: 38313183 PMCID: PMC10835562 DOI: 10.25122/jml-2023-0190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 08/10/2023] [Indexed: 02/06/2024] Open
Abstract
A series of birth defects known as neural tube defects (NTDs) appear when the neural tube fails to fully or partially close during fetal development. In nations without folic acid supplementation, their incidence ranges from 0.5 to 2 per 1,000 births. The purpose of our study is to estimate the prevalence of NTDs and define the workup for newborn infants with an open neural tube in Al-Qadissiyah, Iraq. This 18-year descriptive retrospective analysis included all babies with NTD diagnoses at the Maternity and Child Teaching Hospital in Al-Qadissiyah Governorate, Iraq. Over the research period, 187 cases of NTDs were evaluated. NTDs presented a male predominance and an incidence rate of 9.4 per 1,000 births, with spina bifida (67.9%), encephalocele (24.02%), and anencephaly (8.02%) being the most prevalent defects. The typical gestational age was 36±5, whereas the typical maternal age was 30±5. It should be noted that 29.9% of women did not take folic acid supplements during the first trimester, while one-third of moms did not benefit from medical supervision during pregnancy. In 65.2% of instances, an antenatal diagnosis was made, and cesarean section was the mode of delivery in 87,8% of cases. Other than that, 64.7% of women lived in low socioeconomic conditions, and 67.9% were from rural areas. The relevance of reinforcing and maximizing folic acid measures throughout the periconceptional phase is emphasized by the fact that NTDs require high intensity and advanced care.
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Affiliation(s)
- Wissam Saleh Hakim
- Department of Surgery, College of Medicine, University of Al-Qadisiyah, Iraq
| | - Ali Saleh Aljanabi
- Department of Surgery, College of Medicine, University of Al-Qadisiyah, Iraq
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24
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Vanbelleghem E, Muyshond V, Colman R, Vanden Meerschaut F, Stoop D, Janssens S, Tilleman K. Incidence of and indications for sperm donor restriction - analysis of patients continuing treatment: a retrospective single-centre study. Reprod Biomed Online 2023; 47:103224. [PMID: 37244865 DOI: 10.1016/j.rbmo.2023.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/18/2023] [Accepted: 04/26/2023] [Indexed: 05/29/2023]
Abstract
RESEARCH QUESTION What are the incidence of and indications for sperm donor restriction due to suspected/confirmed disease risk, and the future treatment choices of patients using these sperm donors? DESIGN This single-centre retrospective study involved donors who had restrictions on the use of their imported spermatozoa from January 2010 to December 2019, and current or previous recipients. Indications for sperm restriction and the characteristics of patients undergoing medically assisted reproduction (MAR) treatment with these specimens at the time of restriction were collected. Differential characteristics of women who decided on whether or not to contintue the procedure were assessed. Characteristics potentially leading to treatment continuation were identified. RESULTS Of 1124 sperm donors identified, 200 (17.8%) were restricted, most commonly for multifactorial (27.5%) and autosomal recessive (17.5%) disorders. The spermatozoa had been used for 798 recipients, of whom 172, receiving spermatozoa from 100 donors, were informed about the restriction and constituted the 'decision cohort'. The specimens from the restricted donors were accepted by 71 (approximately 40%) patients, with 45 (approximately 63%) eventually using the restricted donor for their future MAR treatment. The odds of accepting the restricted spermatozoa decreased with increasing age (OR 0.857, 95% CI 0.800-0.918, P < 0.001) and the time between MAR treatment and the restriction date (OR 0.806, 95% CI 0.713-0.911, P < 0.001). CONCLUSION Donor restriction due to suspected/confirmed disease risk is relatively frequent. This affected a relevant number of women (around 800), of whom 172 (approximately 20%) had to decide whether or not to use these donors further. Although donor screening is being performed thoroughly, there remain health risks for donor children. Realistic counselling of all stakeholders involved is necessary.
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Affiliation(s)
- Eva Vanbelleghem
- Department for Medical Genetics, Ghent University Hospital, Belgium
| | - Vanessa Muyshond
- Department for Reproductive Medicine, Ghent University Hospital, Belgium
| | - Roos Colman
- Biostatistics Unit, Department of Public Health and Primary Care, Ghent University, Belgium
| | | | - Dominic Stoop
- Department for Reproductive Medicine, Ghent University Hospital, Belgium
| | - Sandra Janssens
- Department for Medical Genetics, Ghent University Hospital, Belgium
| | - Kelly Tilleman
- Department for Reproductive Medicine, Ghent University Hospital, Belgium..
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25
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Hassan MH, Raslan MA, Tharwat M, Sakhr HM, El-Khateeb EES, Sakr SF, Ameen HH, Hamdan AR. Metabolic Analysis of Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms (MTHFR 677C<T and MTHFR 1298A<C), Serum Folate and Vitamin B12 in Neural Tube Defects. Indian J Clin Biochem 2023; 38:305-315. [PMID: 37234187 PMCID: PMC10205924 DOI: 10.1007/s12291-022-01049-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 04/17/2022] [Indexed: 10/18/2022]
Abstract
Neural tube defects (NTDs) are among the most prevalent and debilitating birth defects with their causes are still unknown, despite mounting evidence that genetic and/or environmental factors may play a role. We aimed to analyze two single nucleotide polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene, serum folate and vitamin B12 status among a cohort of Egyptian children with NTDs and their mothers. A case-control study has been conducted on 50 Egyptian children with various types of NTDs and their mothers. They were comparable with 50 unrelated healthy, age and sex matched children and their mothers (50) selected as controls. Pediatric and neurosurgical assessments were performed to the included cases. Serum folate and vitamin B12 were measured using ELISA kits. MTHFR 677C
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Affiliation(s)
- Mohammed H. Hassan
- Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523 Egypt
| | - Mohamed A. Raslan
- Department of Chemistry, Faculty of Science, Aswan University, Aswan, 81528 Egypt
| | - Mena Tharwat
- Department of Chemistry, Faculty of Science, Aswan University, Aswan, 81528 Egypt
| | - Hala M. Sakhr
- Department of Pediatrics, Faculty of Medicine, South Valley University, Qena, 83523 Egypt
| | | | - Shimaa Fathy Sakr
- Molecular Biology Unit, Medical Technology Center, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Hesham H. Ameen
- Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt
| | - Ali R. Hamdan
- Department of Neurosurgery, Faculty of Medicine, South Valley University, Qena, 83523 Egypt
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26
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Cheng C, Cong Q, Liu Y, Hu Y, Liang G, Dioneda KMM, Yang Y. Yap controls notochord formation and neural tube patterning by integrating mechanotransduction with FoxA2 and Shh expression. SCIENCE ADVANCES 2023; 9:eadf6927. [PMID: 37315133 PMCID: PMC10266736 DOI: 10.1126/sciadv.adf6927] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 05/04/2023] [Indexed: 06/16/2023]
Abstract
Correct notochord and neural tube (NT) formation is crucial to the development of the central nervous system and midline structures. Integrated biochemical and biophysical signaling controls embryonic growth and patterning; however, the underlying mechanisms remain poorly understood. Here, we took the opportunities of marked morphological changes during notochord and NT formation and identified both necessary and sufficient roles of Yap, a key mechanosensor and mechanotransducer, in biochemical signaling activation during formation of notochord and floor plate, the ventral signaling centers that pattern the dorsal-ventral axis of NT and the surrounding tissues. We showed that Yap activation by a gradient of mechanical stress and tissue stiffness in the notochord and ventral NT induces FoxA2 and Shh expression. Hedgehog signaling activation rescued NT patterning defects caused by Yap deficiency, but not notochord formation. Therefore, mechanotransduction via Yap activation acts in feedforward mechanisms to induce FoxA2 expression for notochord formation and activate Shh expression for floor plate induction by synergistically interacting with FoxA2.
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Affiliation(s)
| | | | - Yuchen Liu
- Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, 188 Longwood Ave., Boston, MA 02115, USA
| | - Yizhong Hu
- Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, 188 Longwood Ave., Boston, MA 02115, USA
| | - Guoyan Liang
- Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, 188 Longwood Ave., Boston, MA 02115, USA
| | - Kevin Marc Manquiquis Dioneda
- Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, 188 Longwood Ave., Boston, MA 02115, USA
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27
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Dell'Apa D, Fumeo M, Volta A, Bernardini M, Fidanzio F, Buffagni V, Christen M, Jagannathan V, Leeb T, Bianchi E. Case report: Sacral agenesis in two boxer dogs: clinical presentation, diagnostic investigations, and outcome. Front Vet Sci 2023; 10:1201484. [PMID: 37303726 PMCID: PMC10248164 DOI: 10.3389/fvets.2023.1201484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 05/09/2023] [Indexed: 06/13/2023] Open
Abstract
Two boxer dogs from the same litter were presented at 3 months of age for urinary and fecal incontinence. Both dogs had an abnormal tail consisting of a small stump, an atonic anal sphincter, and absent perineal reflex and sensation. Neurological evaluation was indicative of a lesion of the cauda equina or sacral spinal cord. Radiology and CT scan of the spine displayed similar findings in the two dogs that were indicative of sacral agenesis. Indeed, they had 6 lumbar vertebrae followed by a lumbosacral transitional vertebra, lacking a complete spinous process, and a hypoplastic vertebra carrying 2 hypoplastic sacral transverse processes as the only remnant of the sacral bone. Caudal vertebrae were absent in one of the dogs. On MRI, one dog had a dural sac occupying the entire spinal canal and ending in a subfascial fat structure. In the other dog, the dural sac finished in an extracanalar, subfascial, well-defined cystic structure, communicating with the subarachnoid space, and consistent with a meningocele. Sacral agenesis-that is the partial or complete absence of the sacral bones-is a neural tube defect occasionally reported in humans with spina bifida occulta. Sacral agenesis has been described in human and veterinary medicine in association with conditions such as caudal regression syndrome, perosomus elumbis, and Currarino syndrome. These neural tube defects are caused by genetic and/or environmental factors. Despite thorough genetic investigation, no candidate variants in genes with known functional impact on bone development or sacral development could be found in the affected dogs. To the best of the authors' knowledge, this is the first report describing similar sacral agenesis in two related boxer dogs.
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Affiliation(s)
- Diletta Dell'Apa
- Department of Veterinary Science, University of Parma, Parma, Italy
| | - Martina Fumeo
- Department of Veterinary Science, University of Parma, Parma, Italy
| | - Antonella Volta
- Department of Veterinary Science, University of Parma, Parma, Italy
| | - Marco Bernardini
- Neurodiagnostic Unit, Anicura Portoni Rossi Veterinary Hospital, Bologna, Italy
- Department of Animal Medicine, Production and Health, Clinical Section, University of Padua, Legnaro, Italy
| | | | | | - Matthias Christen
- Vetsuisse Faculty, Institute of Genetics, University of Bern, Bern, Switzerland
| | - Vidhya Jagannathan
- Vetsuisse Faculty, Institute of Genetics, University of Bern, Bern, Switzerland
| | - Tosso Leeb
- Vetsuisse Faculty, Institute of Genetics, University of Bern, Bern, Switzerland
| | - Ezio Bianchi
- Department of Veterinary Science, University of Parma, Parma, Italy
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28
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Pastora Bucardo DM, González F, Montes Pastora M, Pimienta Ramirez PA, Bonilla IL, Vielot NA, Finnell RH. Neural tube defects: Prevalence, mortality, and maternal characteristics in two departmental hospitals in the northwestern region of Nicaragua, 2006-2018. Birth Defects Res 2023; 115:945-953. [PMID: 37025002 DOI: 10.1002/bdr2.2174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 03/20/2023] [Accepted: 03/23/2023] [Indexed: 04/08/2023]
Abstract
BACKGROUND Congenital anomalies are the fifth most common cause of neonatal mortality in Nicaragua, and neural tube defects (NTDs) are the most common of all cases of lethality associated with a birth defect. Prevalence and mortality estimates are needed to propose effective intervention strategies that prevent NTDs over time. METHODS A cross-sectional study was carried out in northwestern Nicaragua from January 2006 to December 2018. All cases of NTDs (anencephaly, spina bifida, and encephalocele) were registered in hospital surveillance systems, and the medical histories of the mothers and newborns were reviewed. Prevalence was calculated by considering the number of live births and stillbirths older than 20 weeks of gestation with NTDs, divided by the total number of live births and stillbirths in each study year. Neonatal mortality rate (NMR) for NTD, and case fatality for spina bifida was calculated. RESULTS Two hundred fifty cases of NTDs were identified from 178,498 deliveries (177,316 live births and 1,182 stillbirths). The prevalence of NTDs during this time period was 14.01 (95% CI: 12.27-15.74) per 10,000 births. The prevalence of spina bifida (n = 140), anencephaly (n = 97), and encephalocele (n = 13) was 7.84, (95% CI: 6.54-9.14), 5.43 (95% CI: 4.30-6.45), and 0.73 (95% CI: 0.33-1.12) per 10,000 births, respectively. Mothers with fetus or newborns affected with NTDs did not use folic acid prior to conception, and 11% experienced periods of hyperthermia during the first trimester of pregnancy. NMR for NTDs was 0.55 per 1.000 livebirths. Case fatality for all NTDs and for spina bifida were 55% and 18%, respectively. CONCLUSION The prevalence and mortality of NTDs in the northwestern region of Nicaragua present peaks and troughs during the study period. Spina bifida was the most frequent type of NTD. We believe that these findings could be of use by health policy makers to strengthen the primary prevention of NTDs in the region through the monitoring of the food fortification policy and folic acid supplementation to women of childbearing age. Additional etiologic studies of NTDs should be considered to identify additional prevention measures.
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Affiliation(s)
| | - Fredman González
- Department of Microbiology, Faculty of Medical Sciences, National Autonomous University of Nicaragua-León, León, Nicaragua
| | - María Montes Pastora
- Department of Public Health, National Autonomous University of Nicaragua, León, Nicaragua
| | - Paula Andrea Pimienta Ramirez
- Center for Precision Environmental Health, Departments of Molecular and Human Genetics, Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Indiana López Bonilla
- Department of Public Health, National Autonomous University of Nicaragua, León, Nicaragua
| | - Nadja A Vielot
- Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Richard H Finnell
- Center for Precision Environmental Health, Departments of Molecular and Human Genetics, Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas, USA
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Hosseini-Siyanaki MR, Liu S, Dagra A, Reddy R, Reddy A, Carpenter SL, Khan M, Lucke-Wold B. Surgical Management of Myelomeningocele. NEONATAL 2023; 4:08. [PMID: 38179156 PMCID: PMC10766379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 01/06/2024]
Abstract
Myelomeningocele (MMC) is one of the most common abnormalities of the central nervous system that causes significant neurological impairment. Traditionally, treatment consisted of postnatal closure with the management of the complications, such as ventricular shunting. MMC is a plausible candidate for in-utero surgery because of the mechanism of neurologic damage that begins with abnormal neurulation and continues throughout gestation. Researchers discussed the benefits of in-utero closure prior to the publication of the prospective randomized multicenter Management of Myelomeningocele Study (MOMS trial). Compared to postnatal repair with maternal complications and prematurity as trade-offs, prenatal repair reduced shunting, reversed hindbrain herniation, and improved neurological function. This article discusses the diagnosis, evaluation, long-term follow-up, surgical options, and innovative treatment for fetal myelomeningocele.
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Affiliation(s)
| | - Sophie Liu
- Department of Neuroscience, University of Johns Hopkins, Baltimore, MD, USA
| | - Abeer Dagra
- University of Florida, College of Medicine, Gainesville, FL, USA
| | - Ramya Reddy
- University of Florida, College of Medicine, Gainesville, FL, USA
| | - Akshay Reddy
- University of Florida, College of Medicine, Gainesville, FL, USA
| | | | - Majid Khan
- University of Nevada, Reno School of Medicine, Reno, NV, USA
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Rizzo G, Pavjola M, Pietrolucci ME. Expert ultrasonographic evaluation in fetuses with spina bifida: An essential prerequisite to select candidate to fetal surgery. JOURNAL OF CLINICAL ULTRASOUND : JCU 2023; 51:415-416. [PMID: 36893036 DOI: 10.1002/jcu.23363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 09/29/2022] [Indexed: 06/18/2023]
Abstract
Suggested management flowchart in presence of a prenatal diagnosis of open spina bifida.
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Affiliation(s)
- Giuseppe Rizzo
- Departement of Obstetrics and Gynecology, Università di Roma Tor Vergata, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Maqina Pavjola
- Departement of Obstetrics and Gynecology, Università di Roma Tor Vergata, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Maria Elena Pietrolucci
- Departement of Obstetrics and Gynecology, Università di Roma Tor Vergata, Fondazione Policlinico Tor Vergata, Rome, Italy
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Acosta-Medina E, Zorro-Guío OF, Abdala-Vargas NJ, Jacomussi-Alzate L, Figueredo LF, Johnson JM, Patiño-Gómez JG, Ordóñez-Rubiano EG. Postnatal Surgical Correction of Myelomeningoceles: Preoperative and Intraoperative Risk Factors Associated with Postoperative Neurologic Outcomes. World Neurosurg 2023; 170:e629-e638. [PMID: 36410703 DOI: 10.1016/j.wneu.2022.11.079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 11/17/2022] [Indexed: 11/21/2022]
Abstract
OBJECTIVE Open spina bifida or myelomeningocele (MMC) is a congenital defect that results from failure of caudal neurulation. We present a case series of patients who were treated with postnatal surgical correction for MMC, evaluating the possible preoperative and intraoperative risk factors associated with neurologic outcomes. METHODS A retrospective chart review of patients who underwent postnatal surgical correction for MMCs over 11 years at our institution was performed. MMCs were classified based on their morphologic configuration into 3 types. Type I includes defects without a sac and there is cerebrospinal fluid (CSF) leak. Type II includes where there is a sac ≤4 cm, with or without CSF leak. Type III includes defects with a sac that are greater than 4 cm. RESULTS Fifty patients were included. The median age of gestation at surgery was 37.4 weeks. There were 30 females (60%). All mothers received adequate folate supplementation. All patients underwent surgical correction in the first 48 hours. Lower extremity motor function at the last clinical follow-up was normal in 34 patients (68%). CSF leak, infection, and mortality were 8%, 2%, and 0%, respectively. Twenty-one patients (42%) underwent ventriculoperitoneal shunt for hydrocephalus. CONCLUSIONS Despite there being no statistically significant associations with a timely closure, all cases were treated within the first 48 hours and this could influence the low complication rate. Individuals of Hispanic background who received appropriate folate supplementation still had high rates of MMC and we posit that this may be caused in part by a genetic/molecular predisposition.
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Affiliation(s)
- Enrique Acosta-Medina
- Department of Neurological Surgery, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital de San José, Bogotá, Colombia
| | - Oscar F Zorro-Guío
- Department of Neurological Surgery, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital de San José, Bogotá, Colombia
| | - Nadin J Abdala-Vargas
- Department of Neurological Surgery, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital de San José, Bogotá, Colombia
| | - Lorena Jacomussi-Alzate
- Department of Neurological Surgery, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital de San José, Bogotá, Colombia
| | - Luisa F Figueredo
- Department of Neurosurgery, Brain Tumor Stem Cell Laboratory, Mayo Clinic Florida, Jacksonville, Florida, USA
| | - Jason M Johnson
- Neuroradiology, Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Javier G Patiño-Gómez
- Department of Neurological Surgery, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital de San José, Bogotá, Colombia
| | - Edgar G Ordóñez-Rubiano
- Department of Neurological Surgery, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital de San José, Bogotá, Colombia; Research Institute, Fundación Universitaria de Ciencias de la Salud (FUCS), Hospital de San José, Bogotá, Colombia; Department of Biomedical Engineering, Universidad de los Andes, Bogotá, Colombia.
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Cao R, Xie J, Zhang L. Abnormal methylation caused by folic acid deficiency in neural tube defects. Open Life Sci 2022; 17:1679-1688. [PMID: 36589786 PMCID: PMC9784971 DOI: 10.1515/biol-2022-0504] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/27/2022] [Accepted: 09/01/2022] [Indexed: 12/24/2022] Open
Abstract
Neural tube closure disorders, including anencephaly, spina bifida, and encephalocele, cause neural tube defects (NTDs). This congenital disability remained not only a major contributor to the prevalence of stillbirths and neonatal deaths but also a significant cause of lifelong physical disability in surviving infants. NTDs are complex diseases caused by multiple etiologies, levels, and mechanisms. Currently, the pathogenesis of NTDs is considered to be associated with both genetic and environmental factors. Here, we aimed to review the research progress on the etiology and mechanism of NTDs induced by methylation modification caused by folic acid deficiency. Folic acid supplementation in the diet is reported to be beneficial in preventing NTDs. Methylation modification is one of the most important epigenetic modifications crucial for brain neurodevelopment. Disturbances in folic acid metabolism and decreased S-adenosylmethionine levels lead to reduced methyl donors and methylation modification disorders. In this review, we summarized the relationship between NTDs, folic acid metabolism, and related methylation of DNA, imprinted genes, cytoskeletal protein, histone, RNA, and non-coding RNA, so as to clarify the role of folic acid and methylation in NTDs and to better understand the various pathogenesis mechanisms of NTDs and the effective prevention.
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Affiliation(s)
- Rui Cao
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, No. 56, Xinjian South Road, Yingze District, Taiyuan, Shanxi Province, China,Shanxi Key Laboratory of Pharmaceutical Biotechnology, Shanxi Biological Research Institute Co., Ltd, Taiyuan, China
| | - Jun Xie
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, No. 56, Xinjian South Road, Yingze District, Taiyuan, Shanxi Province, China
| | - Li Zhang
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, No. 56, Xinjian South Road, Yingze District, Taiyuan, Shanxi Province, China,Department of Hepatobiliary and Pancreatic Surgery and Liver Transplant Center, The First Hospital of Shanxi Medical University, No. 56, Xinjian South Road, Yingze District, Taiyuan, Shanxi Province, China
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Han X, Cao X, Aguiar-Pulido V, Yang W, Karki M, Ramirez PAP, Cabrera RM, Lin YL, Wlodarczyk BJ, Shaw GM, Ross ME, Zhang C, Finnell RH, Lei Y. CIC missense variants contribute to susceptibility for spina bifida. Hum Mutat 2022; 43:2021-2032. [PMID: 36054333 PMCID: PMC9772115 DOI: 10.1002/humu.24460] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 08/29/2022] [Accepted: 08/30/2022] [Indexed: 01/29/2023]
Abstract
Neural tube defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to the cerebral folate deficiency syndrome by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased risk for NTDs by depressing embryonic folate concentrations. In this study, we examined CIC variants from whole-genome sequencing (WGS) data of 140 isolated spina bifida cases and identified eight missense variants of CIC gene. We tested the pathogenicity of the observed variants through multiple in vitro experiments. We determined that CIC variants decreased the FOLR1 protein level and planar cell polarity (PCP) pathway signaling in a human cell line (HeLa). In a murine cell line (NIH3T3), CIC loss of function variants downregulated PCP signaling. Taken together, this study provides evidence supporting CIC as a risk gene for human NTD.
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Affiliation(s)
- Xiao Han
- Department of Reproductive Medicine Center, Henan
Provincial People’s Hospital, People’s Hospital of Zhengzhou
University, Zhengzhou, Henan Province, People’s Republic of China
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
| | - Xuanye Cao
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
| | - Vanessa Aguiar-Pulido
- Center for Neurogenetics, Brain and Mind Research
Institute, Weill Cornell Medicine, New York, NY, USA
- Department of Computer Science, University of Miami, Coral
Gables, FL 33146, USA
| | - Wei Yang
- Department of Pediatrics, Stanford University School of
Medicine, Stanford, CA, USA
| | - Menuka Karki
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
| | - Paula Andrea Pimienta Ramirez
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
| | - Robert M. Cabrera
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
| | - Ying Linda Lin
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
| | - Bogdan J. Wlodarczyk
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
| | - Gary M. Shaw
- Department of Pediatrics, Stanford University School of
Medicine, Stanford, CA, USA
| | - M. Elizabeth Ross
- Center for Neurogenetics, Brain and Mind Research
Institute, Weill Cornell Medicine, New York, NY, USA
| | - Cuilian Zhang
- Department of Reproductive Medicine Center, Henan
Provincial People’s Hospital, People’s Hospital of Zhengzhou
University, Zhengzhou, Henan Province, People’s Republic of China
| | - Richard H. Finnell
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
- Departments of Molecular and Human Genetics and Medicine,
Baylor College of Medicine, Houston, TX 77031, USA
| | - Yunping Lei
- Center for Precision Environmental Health, Department of
Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031,
USA
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Uy MNAR, Tantengco OAG. Investigating the landscape and trajectory of spina bifida research in Asia: a bibliometric analysis. Childs Nerv Syst 2022; 38:1581-1591. [PMID: 35474541 DOI: 10.1007/s00381-022-05527-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 04/10/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Spina bifida is a type of a neural tube defect which affects 243.14 per 100,000 babies in Asia. Research articles on spina bifida have increased in the recent years. However, no study has focused on the research trends in this field in Asia. METHODS A systematic review of literature on spina bifida in Asia was performed using the Scopus database from inception to 2020. All published studies on spina bifida conducted in or published by authors from Asia were included in our analysis. Bibliometric information was obtained from Scopus and bibliometrics diagrams were created using VOSviewer software. RESULTS A total of 652 articles were obtained in this study. The number of publications showed an upward trend starting 2000s. The country with the greatest number of publications was Japan while All India Institute of Medical Sciences was the most productive institution in spina bifida research in Asia. The current focus of this field in Asia was prevalence of spina bifida, prenatal diagnosis, folic acid supplementation, and complications of spina bifida. Future areas of research in spina bifida include the genetic basis of neural tube defects and the use of stem cell technology as therapies for spina bifida. CONCLUSION This is the first bibliometric analysis on spina bifida in Asia. It showed the trend and future areas of research on spina bifida in Asia. Despite the increase in scientific literature on spina bifida research, more research outputs and collaborations are needed especially in developing countries in Asia.
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Affiliation(s)
| | - Ourlad Alzeus G Tantengco
- College of Medicine, University of the Philippines Manila, Pedro Gil Street, Ermita, Manila, Philippines.
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Sacral Spina Bifida Occulta: A Frequency Analysis of Secular Change. ANTHROPOLOGICAL REVIEW 2022. [DOI: 10.18778/1898-6773.85.2.02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Substantial relaxation of natural selection beginning around 1900 changed the mutation/selection balance of modern genetic material, producing an increase in variable anatomical structures. While multiple structures have been affected, the temporal increase in variations of the sacrum, specifically, ‘Sacral Spina Bifida Occulta,’ have been reliably demonstrated on a localised scale. Calculation of largescale frequency has been hindered by the localised nature of these publications, the morphological variability of this variation, and potential pathological associations, which have produced divergent classifications, and conflicting reported rates of occurrence. A systematic review of the reported literature was conducted to provide an objective analysis of Sacral Spina Bifida Occulta frequency from 2500 BCE to the present. This review was designed to compensate for observed inconsistencies in reporting and to ascertain, for the first time, the temporal trajectory of this secular trend. A systematic review of Sacral Spina Bifida Occulta literature was conducted through the strict use of clinical meta-analysis criteria. Publications were retrieved from four databases: PubMed, Embase, the Adelaide University Library database, and Google Scholar. Data were separated into three historical groups, (1 = <1900, 2 = 1900 to 1980 and 3 = >1980), and frequency outcomes compared, to determine temporal rates of occurrence.
A total of 39/409 publications were included in the final analysis, representing data for 16,167 sacra, spanning a period of 4,500 years. Statistically significant results were obtained, with total open S1 frequency increasing from 2.34%, (79 to 1900CE), to 4.80%, (1900 to 1980CE) and to 5.43% (>1980CE). These increases were significant at p<0.0001, with Chi-squared analysis. A clear secular increase in the global frequency of Sacral Spina Bifida Occulta has been demonstrated from 1900 to the present. This research provides a novel and adaptable framework for the future assessment of variation distribution, with important implications for the fields of biological anthropology and bioarchaeology.
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Hifny MA, Hamdan AR, Tayel AM, El Khateeb EES, Yagi S, Park TH. Rotation Advancement Keystone Flap for Closure of Large Myelomeningocele Defects. Ann Plast Surg 2022; 89:77-81. [PMID: 35502970 DOI: 10.1097/sap.0000000000003150] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Myelomeningocele is the most common form of neural tube anomalies. Early reliable skin coverage should be achieved to reduce central nervous system infections. The keystone flaps are gaining popularity for myelomeningocele defect reconstruction. However, the use of a traditional keystone flap is limited in very wide or transversely oriented myleomeningocele defects with inadequate lateral tissue laxity. In this study, we present our successful experience using modified rotation advancement keystone flaps for closure of the transversely oriented myelomeningocele defects. PATIENTS AND METHODS Between April 2019 and April 2020, the modified rotation advancement keystone flap was used for reconstruction of transversely oriented myelomeningocele defect in 7 patients (5 males and 2 females) with average age of 14 days. The localization of the lesions was lumbosacral in 5 patients and thoracolumbar in 2 patient. The average myelomeningocele defect width was 6.4 cm, whereas the average defect length was 5.7 cm. The following information was evaluated: the flap dimensions, operative time, and postoperative complications. RESULTS All patients had uneventful operations, except for 1 case of superficial epidermolysis over flap tip, which settled with conservative wound management. Immediate venous congestion was detected in 2 patients that completely resolved. Otherwise, all wounds healed without any evidence of complications. The mean follow-up was 4 months. CONCLUSIONS Although the conventional keystone flap seems to have geometric constraints to close a transversally oriented myelomeningocele defect, the modified rotation advancement keystone flap serves as a superior alternative and effective option for closure transversally oriented defect.
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Affiliation(s)
| | - Ali R Hamdan
- Neurosurgery, Faculty of Medicine, Qena University Hospital, South Valley University, Qena, Egypt
| | - Amr M Tayel
- Neurosurgery, Faculty of Medicine, Qena University Hospital, South Valley University, Qena, Egypt
| | | | - Shunjiro Yagi
- Department of Plastic and Reconstructive Surgery, Tottori University Hospital, Yonago, Japan
| | - Tae Hwan Park
- Department of Plastic and Reconstructive Surgery, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
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Zhao T, McMahon M, Reynolds K, Saha SK, Stokes A, Zhou CJ. The role of Lrp6-mediated Wnt/β-catenin signaling in the development and intervention of spinal neural tube defects in mice. Dis Model Mech 2022; 15:275313. [PMID: 35514236 PMCID: PMC9194482 DOI: 10.1242/dmm.049517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 04/27/2022] [Indexed: 01/09/2023] Open
Abstract
Neural tube defects (NTDs) are among the common and severe birth defects with poorly understood etiology. Mutations in the Wnt co-receptor LRP6 are associated with NTDs in humans. Either gain-of-function (GOF) or loss-of-function (LOF) mutations of Lrp6 can cause NTDs in mice. NTDs in Lrp6-GOF mutants may be attributed to altered β-catenin-independent noncanonical Wnt signaling. However, the mechanisms underlying NTDs in Lrp6-LOF mutants and the role of Lrp6-mediated canonical Wnt/β-catenin signaling in neural tube closure remain unresolved. We previously demonstrated that β-catenin signaling is required for posterior neuropore (PNP) closure. In the current study, conditional ablation of Lrp6 in dorsal PNP caused spinal NTDs with diminished activities of Wnt/β-catenin signaling and its downstream target gene Pax3, which is required for PNP closure. β-catenin-GOF rescued NTDs in Lrp6-LOF mutants. Moreover, maternal supplementation of a Wnt/β-catenin signaling agonist reduced the frequency and severity of spinal NTDs in Lrp6-LOF mutants by restoring Pax3 expression. Together, these results demonstrate the essential role of Lrp6-mediated Wnt/β-catenin signaling in PNP closure, which could also provide a therapeutic target for NTD intervention through manipulation of canonical Wnt/β-catenin signaling activities. Summary: Conditional ablation of Lrp6 in dorsal neural folds causes spinal neural tube defects that can be rescued by genetic activation of β-catenin or maternal supplementation of Wnt signaling agonists.
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Affiliation(s)
- Tianyu Zhao
- Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California, Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Moira McMahon
- Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California, Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Kurt Reynolds
- Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California, Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Subbroto Kumar Saha
- Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California, Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Arjun Stokes
- Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California, Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
| | - Chengji J Zhou
- Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California, Department of Biochemistry and Molecular Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
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Kucha W, Seifu D, Tirsit A, Yigeremu M, Abebe M, Hailu D, Tsehay D, Genet S. Folate, Vitamin B12, and Homocysteine Levels in Women With Neural Tube Defect-Affected Pregnancy in Addis Ababa, Ethiopia. Front Nutr 2022; 9:873900. [PMID: 35464038 PMCID: PMC9033285 DOI: 10.3389/fnut.2022.873900] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 03/08/2022] [Indexed: 11/21/2022] Open
Abstract
Background Neural tube defects (NTDs) are prevalent congenital defects associated with pre-pregnancy diet with low levels of maternal folate. They are linked to severe morbidity, disability, and mortality, as well as psychological and economic burdens. Objective The goal of this study was to determine the levels of folate, vitamin B12, and homocysteine in the blood of women who had a pregnancy impacted by NTDs. Subjects and Methods A hospital-based case–control study was undertaken between September 2019 and August 2020. The study comprised a total of 100 cases and 167 controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of folate, vitamin B12, and homocysteine in the serum. Results Only 39% of the cases and 54.5% of control mothers reported periconceptional use of folic acid/multivitamin, which indicated a statistically significant difference (p = 0.014). Logistic regression indicated that periconceptional use of folic acid/multivitamin was associated with NTDs (p = 0.015, OR = 1.873, 95% CI: 1.131–3.101). We found that 57% of the cases and 33.5% of controls, as well as 43% of cases and 20.4% of controls had serum folate and vitamin B12 levels below the cut-off value, respectively. Twenty-seven percent of the cases and 6.6% of controls had hyperhomocysteinemia (HHcy). The median concentrations of folate, vitamin B12, and homocysteine in cases and controls were 4.78 and 8.86 ng/ml; 266.23 and 455 pg/ml; 13.43 and 9.7 μmol/l, respectively. The median concentration of folate (p < 0.001) and vitamin B12 (p < 0.001) were significantly lower in the cases than controls, while the homocysteine concentration (p < 0.001) was significantly lower in the controls than cases. Folate [OR (95% CI) = 1.652 (1.226–2.225; p = 0.001)], vitamin B12 [OR (95% CI) = 1.890 (1.393–2.565; p < 0.001], and homocysteine [OR (95% CI) = 0.191 (0.09–0.405; p < 0.001)] levels were associated with NTDs. Conclusion Folate and vitamin B12 are deficient in both cases and control mothers. The lower levels of folate and vitamin B12 with an elevated homocysteine level in NTD-affected pregnancy may be an indication that these biochemical variables were risk factors for NTDs. Folate/multivitamin supplementation and/or food fortification should be promoted.
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Affiliation(s)
- Winner Kucha
- Department of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
- *Correspondence: Winner Kucha
| | - Daniel Seifu
- Biochemistry Division of Basic Sciences, University of Global Health Equity, Kigali, Rwanda
| | - Abenezer Tirsit
- Neurosurgery Unit, School of Medicine, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Mahlet Yigeremu
- Department of Obstetrics and Gynecology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Markos Abebe
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - Dawit Hailu
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | | | - Solomon Genet
- Department of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Biodegradation of poly(L-lactic acid) and poly(ε-caprolactone) patches by human amniotic fluid in an in-vitro simulated fetal environment. Sci Rep 2022; 12:3950. [PMID: 35273223 PMCID: PMC8913814 DOI: 10.1038/s41598-022-07681-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/04/2022] [Indexed: 11/17/2022] Open
Abstract
Open spina bifida or myelomeningocele (MMC) is a devastating neurologic congenital defect characterized by primary failure of neural tube closure of the spinal column during the embryologic period. Cerebrospinal fluid leak caused by the MMC spinal defect in the developing fetus can result in a constellation of encephalic anomalies that include hindbrain herniation and hydrocephalus. The exposure of extruded spinal cord to amniotic fluid also poses a significant risk for inducing partial or complete paralysis of the body parts beneath the spinal aperture by progressive spinal cord damage in-utero. A randomized trial demonstrated that prenatal repair by fetal surgery, sometimes using patches, to cover the exposed spinal cord with a watertight barrier is effective in reducing the postnatal neurologic morbidity as evidenced by decreased incidence and severity of postnatal hydrocephalus and the reduced need for ventricular-peritoneal shunting. Currently, the use of inert or collagen-based patches are associated with high costs and inadequate structural properties. Specifically, the inert patches do not degrade after implantation, causing the need for a post-natal removal surgery associated with trauma for the newborn. Our present study is aimed towards in-vitro degradation studies of a newly designed patch, which potentially can serve as a superior alternative to existing patches for MMC repair. This novel patch was fabricated by blending poly(l-lactic acid) and poly(ε-caprolactone). The 16-week degradation study in amniotic fluid was focused on tracking changes in crystallinity and mechanical properties. An additional set of designed patches was exposed to phosphate-buffered saline (PBS), as a time-paired control. Crystallinity studies indicate the progress of hydrolytic degradation of the patch in both media, with a preference to bulk erosion in phosphate buffered saline and surface erosion in amniotic fluid. Mechanical testing results establish that patch integrity is not compromised up to 16 weeks of exposure either to body fluids analog (PBS) or to amniotic fluid.
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Soleimani-Jadidi S, Meibodi B, Javaheri A, Tabatabaei RS, Hadadan A, Zanbagh L, Abbasi H, Bahrami R, Mirjalili SR, Karimi-Zarchi M, Neamatzadeh H. Association between Fetal MTHFR A1298C (rs1801131) Polymorphism and Neural Tube Defects Risk: A Systematic Review and Meta-Analysis. Fetal Pediatr Pathol 2022; 41:116-133. [PMID: 32536231 DOI: 10.1080/15513815.2020.1764682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
BACKGROUND The association of the fetal MTHFR A1298C (rs1801131) polymorphism and neural tube defects (NTDs) susceptibility has been widely demonstrated, but the results remain inconclusive. Thus, we performed a meta-analysis to investigate the association between fetal MTHFR A1298C polymorphism and NTDs risk. METHODS An electronic search of PubMed, web of science, SciELO, CNKI database for studies on the fetal MTHFR A1298C polymorphism and NTDs risk was performed up to March 30, 2020. RESULTS A total of 22 case-control studies with 3,224 fetuses with NTDs and 3,295 controls were selected. Overall, pooled data showed that the fetal MTHFR A1298C polymorphism was not significantly associated with risk an increased risk of NTDs in the global population. When stratified analysis by ethnicity, country of origin and NTDs type, still no statistically significant association was found. CONCLUSIONS Our pooled data emerged no evidence for significant association between fetal MTHFR A1298C polymorphism and NTDs risk.
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Affiliation(s)
- Sara Soleimani-Jadidi
- Department of Obstetrics and Gynecology, Lorestan University of Medical Sciences, Lorestan, Iran
| | - Bahare Meibodi
- Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Atiyeh Javaheri
- Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Razieh Sadat Tabatabaei
- Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amaneh Hadadan
- Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Leila Zanbagh
- Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Obstetrics and Gynecology, Yazd Branch, Islamic Azad University, Yazd, Iran
| | - Hajar Abbasi
- Department of Obstetrics and Gynecology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Bahrami
- Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Reza Mirjalili
- Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mojgan Karimi-Zarchi
- Department of Obstetrics and Gynecology, Iran University of Medical Sciences, Tehran, Iran.,Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Neamatzadeh
- Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Starowicz J, Cassidy C, Brunton L. Health Concerns of Adolescents and Adults With Spina Bifida. Front Neurol 2021; 12:745814. [PMID: 34867728 PMCID: PMC8633437 DOI: 10.3389/fneur.2021.745814] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/20/2021] [Indexed: 11/13/2022] Open
Abstract
Due to advancements in medical care, people with spina bifida (SB) are surviving well into adulthood, resulting in a growing number of patients transitioning to an adult sector unequipped to care for people with chronic rehabilitative and medical needs. The Transitional and Lifelong Care (TLC) program is a multidisciplinary clinical service that compensates for this gap, providing comprehensive, coordinated care to adolescents, and adults with SB. As a relatively new clinical service, objective data about the patients using the service and their needs is scant. This study sought to identify the most common health concerns among TLC patients with SB at initial clinical consultation. A retrospective chart review of 94 patient charts was performed. Following data extraction, descriptive analyses were completed. The mean age of the sample was 29.04 ± 13.8 years. One hundred individual concerns and 18 concern categories were identified. On average, patients or care providers identified nine health concerns across various spheres of care, with care coordination being the most prevalent concern identified (86%). Patients also commonly had concerns regarding neurogenic bladder (70%), medications (66%), assistive devices (48%), and neurogenic bowel (42%). The numerous and wide-ranging health concerns identified support the need for individualised, coordinated care and a "medical home" for all adolescents and adults with SB during and following the transition to adult care. Health care providers caring for this population should continue to address well-documented health concerns and also consider raising discussion around topics such as sexual health, mental health, and bone health. Further research is required to understand how best to address the complex medical issues faced by adults with SB to maximise health and quality of life and improve access to healthcare.
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Affiliation(s)
- Jessica Starowicz
- Faculty of Health Sciences, Health and Rehabilitation Sciences, Western University, London, ON, Canada
| | - Caitlin Cassidy
- Schulich School of Medicine and Dentistry, Physical Medicine and Rehabilitation and Paediatrics, Western University, London, ON, Canada
| | - Laura Brunton
- Faculty of Health Sciences, School of Physical Therapy, Western University, London, ON, Canada
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Huang W, Gu H, Yuan Z. Identifying biomarkers for prenatal diagnosis of neural tube defects based on "omics". Clin Genet 2021; 101:381-389. [PMID: 34761376 DOI: 10.1111/cge.14087] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 11/05/2021] [Accepted: 11/06/2021] [Indexed: 11/27/2022]
Abstract
Neural tube defects (NTDs) are the most severe birth defects and the main cause of newborn death; posing a great challenge to the affected children, families, and societies. Presently, the clinical diagnosis of NTDs mainly relies on ultrasound images combined with certain indices, such as alpha-fetoprotein levels in the maternal serum and amniotic fluid. Recently, the discovery of additional biomarkers in maternal tissue has presented new possibilities for prenatal diagnosis. Over the past 20 years, "omics" techniques have provided the premise for the study of biomarkers. This review summarizes recent advances in candidate biomarkers for the prenatal diagnosis of fetal NTDs based on omics techniques using maternal biological specimens of different origins, including amniotic fluid, blood, and urine, which may provide a foundation for the early prenatal diagnosis of NTDs.
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Affiliation(s)
- Wanqi Huang
- Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China
| | - Hui Gu
- Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China
| | - Zhengwei Yuan
- Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China
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Sadhukhan S, Maity S, Chakraborty S, Paul S, Munian D, Pattanayak AK, Jana B, Das M. Molecular Insight into the Effect of a Single-Nucleotide Polymorphic Variation on the Structure and Dynamics of Methionine Synthase Reductase and Its Association with Neural Tube Defects. ACS OMEGA 2021; 6:26372-26380. [PMID: 34667917 PMCID: PMC8519501 DOI: 10.1021/acsomega.1c03563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/17/2021] [Indexed: 06/13/2023]
Abstract
Neural tube defects (NTDs) are among the common and severe congenital malformations in neonates. According to a WHO report, nearly three lakh babies are affected per year worldwide by NTDs. Most studies revealed that folate deficiency is the key element to promote NTD with other oligogenic and multifactorial elements. This folate is metabolized by the FOCM (folate one-carbon metabolism) pathway. The most important step in the FOCM pathway is the conversion of methionine to homocysteine, which is guided by the enzyme MTRR. Several single-nucleotide polymorphisms (SNPs) in the MTRR gene are strongly associated with the progression of NTD. A nonsynonymous allelic variant (rs1532268) of the protein leads to a missense mutation at the 202nd position from serine to leucine (S202L) and is associated with a higher disease prevalence in different populations. In our study, this SNP indicates a 2-fold increase in the risk of disease progression (p-value of 0.03; OR 2.76; 95% CI 1.08-7.11). Here, extensive molecular dynamics simulations and interaction network analysis reveal that the change of 202nd serine to leucine alters the structures of the FAD and NAD binding domains, which restricts the ligand binding. The S202L variation alters the functional dynamics that might impede the electron transport chain along the NADP(H)→ FAD→ FMN pathway and hamper phosphorylation by kinases like GSK-3 and CaM-II during the posttranscriptional modification of the protein. The present study provides functional insights into the effect of the genetic variations of the MTRR gene on the NTD disease pathogenesis.
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Affiliation(s)
- Susanta Sadhukhan
- Department of Zoology, University of
Calcutta, Kolkata, 700019 India
| | - Subhajit Maity
- Department of Zoology, University of
Calcutta, Kolkata, 700019 India
- Department of Zoology, Ramakrishna
Mission Vivekananda Centenary College, Kolkata, 700118
India
| | - Sandipan Chakraborty
- Amity Institute of Biotechnology, Amity
University Kolkata, Kolkata, 700135 India
| | - Silpita Paul
- Department of Zoology, University of
Calcutta, Kolkata, 700019 India
| | - Dinesh Munian
- Department of Neonatology, Institute of
Post Graduate Medical Education Research (IPGMER), Kolkata 700020,
India
| | | | - Biman Jana
- School of Chemical Sciences, Indian
Association for Cultivation of Science, Kolkata, 700032
India
| | - Madhusudan Das
- Department of Zoology, University of
Calcutta, Kolkata, 700019 India
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Guéant JL, Guéant-Rodriguez RM, Kosgei VJ, Coelho D. Causes and consequences of impaired methionine synthase activity in acquired and inherited disorders of vitamin B 12 metabolism. Crit Rev Biochem Mol Biol 2021; 57:133-155. [PMID: 34608838 DOI: 10.1080/10409238.2021.1979459] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Methyl-Cobalamin (Cbl) derives from dietary vitamin B12 and acts as a cofactor of methionine synthase (MS) in mammals. MS encoded by MTR catalyzes the remethylation of homocysteine to generate methionine and tetrahydrofolate, which fuel methionine and cytoplasmic folate cycles, respectively. Methionine is the precursor of S-adenosyl methionine (SAM), the universal methyl donor of transmethylation reactions. Impaired MS activity results from inadequate dietary intake or malabsorption of B12 and inborn errors of Cbl metabolism (IECM). The mechanisms at the origin of the high variability of clinical presentation of impaired MS activity are classically considered as the consequence of the disruption of the folate cycle and related synthesis of purines and pyrimidines and the decreased synthesis of endogenous methionine and SAM. For one decade, data on cellular and animal models of B12 deficiency and IECM have highlighted other key pathomechanisms, including altered interactome of MS with methionine synthase reductase, MMACHC, and MMADHC, endoplasmic reticulum stress, altered cell signaling, and genomic/epigenomic dysregulations. Decreased MS activity increases catalytic protein phosphatase 2A (PP2A) and produces imbalanced phosphorylation/methylation of nucleocytoplasmic RNA binding proteins, including ELAVL1/HuR protein, with subsequent nuclear sequestration of mRNAs and dramatic alteration of gene expression, including SIRT1. Decreased SAM and SIRT1 activity induce ER stress through impaired SIRT1-deacetylation of HSF1 and hypomethylation/hyperacetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), which deactivate nuclear receptors and lead to impaired energy metabolism and neuroplasticity. The reversibility of these pathomechanisms by SIRT1 agonists opens promising perspectives in the treatment of IECM outcomes resistant to conventional supplementation therapies.
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Affiliation(s)
- Jean-Louis Guéant
- UMR Inserm 1256 N-GERE (Nutrition, Génetique et Exposition aux Risques Environmentaux), Université de Lorraine, Vandoeuvre-lès-Nancy, France.,Departments of Digestive Diseases and Molecular Medicine and National Center of Inborn Errors of Metabolism, University Hospital Center, Université de Lorraine, Vandoeuvre-lès-Nancy, France
| | - Rosa-Maria Guéant-Rodriguez
- UMR Inserm 1256 N-GERE (Nutrition, Génetique et Exposition aux Risques Environmentaux), Université de Lorraine, Vandoeuvre-lès-Nancy, France.,Departments of Digestive Diseases and Molecular Medicine and National Center of Inborn Errors of Metabolism, University Hospital Center, Université de Lorraine, Vandoeuvre-lès-Nancy, France
| | - Viola J Kosgei
- UMR Inserm 1256 N-GERE (Nutrition, Génetique et Exposition aux Risques Environmentaux), Université de Lorraine, Vandoeuvre-lès-Nancy, France
| | - David Coelho
- UMR Inserm 1256 N-GERE (Nutrition, Génetique et Exposition aux Risques Environmentaux), Université de Lorraine, Vandoeuvre-lès-Nancy, France
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Azzarà A, Rendeli C, Crivello AM, Brugnoletti F, Rumore R, Ausili E, Sangiorgi E, Gurrieri F. Identification of new candidate genes for spina bifida through exome sequencing. Childs Nerv Syst 2021; 37:2589-2596. [PMID: 33855610 DOI: 10.1007/s00381-021-05153-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 03/29/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE Neural tube defects are a group of birth defects caused by failure of neural tube closure during development. The etiology of NTD, requiring a complex interaction between environmental and genetic factors, is not well understood. METHODS We performed whole-exome sequencing (WES) in six trios, with a single affected proband with spina bifida, to identify rare/novel variants as potential causes of the NTD. RESULTS Our analysis identified four de novo and ten X-linked recessive variants in four of the six probands, all of them in genes previously never implicated in NTD. Among the 14 variants, we ruled out six of them, based on different criteria and pursued the evaluation of eight potential candidates in the following genes: RXRγ, DTX1, COL15A1, ARHGAP36, TKTL1, AMOT, GPR50, and NKRF. The de novo variants where located in the RXRγ, DTX1, and COL15A1 genes while ARHGAP36, TKTL1, AMOT, GPR50, and NKRF carry X-linked recessive variants. This analysis also revealed that four patients presented multiple variants, while we were unable to identify any significant variant in two patients. CONCLUSIONS Our preliminary conclusion support a major role for the de novo variants with respect to the X-linked recessive variants where the X-linked could represent a contribution to the phenotype in an oligogenic model.
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Affiliation(s)
- Alessia Azzarà
- Dipartimento di Scienze della Vita e di Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Roma, Italia. .,Unità di Genetica Medica, Università Campus Bio-Medico, Roma, Italia.
| | - Claudia Rendeli
- Spina Bifida Center, Dipartimento di Scienze della Vita e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Anna Maria Crivello
- Dipartimento di Scienze della Vita e di Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Fulvia Brugnoletti
- Dipartimento di Scienze della Vita e di Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Roberto Rumore
- Dipartimento di Scienze della Vita e di Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Emanuele Ausili
- Spina Bifida Center, Dipartimento di Scienze della Vita e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Eugenio Sangiorgi
- Dipartimento di Scienze della Vita e di Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Roma, Italia.,Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Fiorella Gurrieri
- Unità di Genetica Medica, Università Campus Bio-Medico, Roma, Italia
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Peake JN, Knowles RL, Shawe J, Rankin J, Copp AJ. Maternal ethnicity and the prevalence of British pregnancies affected by neural tube defects. Birth Defects Res 2021; 113:968-980. [PMID: 33754462 PMCID: PMC7611580 DOI: 10.1002/bdr2.1893] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/06/2021] [Accepted: 03/06/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Few data are available on the prevalence of neural tube defects (NTDs) within different ethnic communities of the United Kingdom. This study aimed to calculate prevalence estimates for NTD-affected pregnancies, classified by maternal ethnicity, and to explore why variations in prevalence might exist. METHODS A cross-sectional study was performed with data from regional congenital anomaly registers in England and Wales, for NTD-affected pregnancies between 2006 and 2011. Using binomial regression models, we examined NTD-affected pregnancy prevalence estimates and rate ratios (PRRs), by maternal ethnicity. RESULTS The prevalence of NTDs was 12.14 per 10,000 births, with no differences between study years. Anencephaly, encephalocele and spina bifida occurred at 4.98, 1.37 and 5.80 per 10,000 births respectively. Mothers of Indian ethnicity were 1.84 times more likely (95% CI: 1.24, 2.73) and Bangladeshi mothers 2.86 times more likely (95% CI: 1.48, 5.53) than White mothers to have an NTD-affected pregnancy, after adjusting for maternal deprivation and maternal age. The excess prevalence in Indian mothers was specifically for anencephaly (PRR 2.57; 95% CI: 1.52, 4.34), and in Bangladeshi mothers the trend was for increased spina bifida (PRR 3.86; 95% CI: 0.72, 8.69). Anencephaly in Indian mothers was especially associated with other congenital anomalies (non-isolated NTDs). CONCLUSIONS Different British ethnic groups vary in NTD prevalence. The excess prevalence of anencephaly as a non-isolated NTD in pregnancies of Indian mothers could indicate involvement of genetic or other unmeasured behavioral factors. Future work is needed to seek etiological explanations for the ethnicity differences and to develop improved methods for primary prevention.
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Affiliation(s)
- Jordana N Peake
- Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Rachel L Knowles
- Population, Policy and Practice Department, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Jill Shawe
- Faculty of Health, University of Plymouth, Devon, UK
| | - Judith Rankin
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Andrew J Copp
- Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK
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Nahal MSH, Wigert H, Imam A, Axelsson ÅB. Assessment of health status in adolescents with spina bifida in the West Bank, Palestine: sense of coherence and self-perceived health. Disabil Rehabil 2021; 44:5479-5486. [PMID: 34106796 DOI: 10.1080/09638288.2021.1936660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE To assess self-perceived health and sense of coherence (SOC) in adolescents with spina bifida (SB) in the West Bank, Palestine, compared to a healthy reference group. Further, to assess the association between impairment levels in the adolescents with SB and their self-perceived health and SOC. METHODS Fifty adolescents with SB and 150 healthy adolescents completed measures of self-perceived health - the Pediatric Quality of Life Inventory (PedsQLTM 4.0) - and SOC. The rehabilitation center nurses identified the physical impairments of the adolescents with SB from their medical records, and classified them by impairment severity. RESULTS Adolescents with SB reported lower self-perceived health (PedsQL median 55, IQR 42-67), than the reference group (median 85, IQR 74-90), p < 0.001, and lower SOC (median 47, IQR 44-50) than the reference group (median 55, IQR 44-61), p < 0.001. Impairment level was inversely associated with both self-perceived health and SOC. CONCLUSIONS The low self-perceived health and SOC among adolescents with SB in Palestine indicate the need for collaboration between policy makers and providers to improve these adolescents' physical and social environment and to promote the rehabilitation services provided for them.Implications for rehabilitationThe low self-perceived health and SOC among adolescents with SB in Palestine highlight the need to develop appropriate interventions to promote their health, independency, and self-care management.Collaboration of the caregivers and health care providers is required to develop, implement, and evaluate intervention programs that might promote coping abilities of the adolescents with SB.A multidisciplinary approach is needed to set goals that have a meaningful impact on social, emotional, behavioral, and educational conditions of the adolescents with SB and in different settings, for example, home, school, and community.The environment in Palestine presents barriers to the social engagement of adolescents with SB, and new ways are needed to enhance their participation in the society to promote their self-concept and wellbeing.
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Affiliation(s)
- Maha Sudki Hmeidan Nahal
- Faculty of Nursing, College of Health Professions, Al-Quds University, Abu Dies Campus, Jerusalem, Palestine
| | - Helena Wigert
- Faculty of Nursing, Institute of Health and Care Sciences, Sahlgrenska Academy at Gothenburg University and Division of Neonatology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Asma Imam
- Health and Community Studies, School of Public Health at Al-Quds University, Abu Dies Campus, Jerusalem, Palestine
| | - Åsa B Axelsson
- Nursing, Institute of Health and Care Sciences, Sahlgrenska Academy at Gothenburg University and Division of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Pregnancy-Related Extracellular Vesicles Revisited. Int J Mol Sci 2021; 22:ijms22083904. [PMID: 33918880 PMCID: PMC8068855 DOI: 10.3390/ijms22083904] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/20/2021] [Accepted: 04/07/2021] [Indexed: 12/14/2022] Open
Abstract
Extracellular vesicles (EVs) are small vesicles ranging from 20–200 nm to 10 μm in diameter that are discharged and taken in by many different types of cells. Depending on the nature and quantity of their content—which generally includes proteins, lipids as well as microRNAs (miRNAs), messenger-RNA (mRNA), and DNA—these particles can bring about functional modifications in the receiving cells. During pregnancy, placenta and/or fetal-derived EVs have recently been isolated, eliciting interest in discovering their clinical significance. To date, various studies have associated variations in the circulating levels of maternal and fetal EVs and their contents, with complications including gestational diabetes and preeclampsia, ultimately leading to adverse pregnancy outcomes. Furthermore, EVs have also been identified as messengers and important players in viral infections during pregnancy, as well as in various congenital malformations. Their presence can be detected in the maternal blood from the first trimester and their level increases towards term, thus acting as liquid biopsies that give invaluable insight into the status of the feto-placental unit. However, their exact roles in the metabolic and vascular adaptations associated with physiological and pathological pregnancy is still under investigation. Analyzing peer-reviewed journal articles available in online databases, the purpose of this review is to synthesize current knowledge regarding the utility of quantification of pregnancy related EVs in general and placental EVs in particular as non-invasive evidence of placental dysfunction and adverse pregnancy outcomes, and to develop the current understanding of these particles and their applicability in clinical practice.
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Gomar-Alba M, Vargas-López AJ, Narro-Donate JM, Castelló-Ruiz MJ, García-Pérez F, Masegosa-González J. Rotation flap closure of a giant dorsolumbar myelomeningocele: technical note. Childs Nerv Syst 2021; 37:1323-1326. [PMID: 33454814 DOI: 10.1007/s00381-020-05021-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 12/17/2020] [Indexed: 11/30/2022]
Abstract
PURPOSE Myelomeningocele (MMC) is the most prevalent form of spina bifida aperta. Here we present the surgical repair technique of a dorsolumbar myelomeningocele with a large associated soft tissue defect. METHODS Data concerning the anamnesis and complementary studies were obtained from the clinical history. Surgical images were obtained in the operation room during surgery. RESULT We describe the case of a newborn with a dorsal myelomeningocele with a placode in the central area and a large associated skin defect of 12 x× 12 cm. Urgent intervention was carried out on the day of birth with placode reconstruction. Dorsal and gluteus maximus muscle rotation and skin rotation flap were performed in order to achieve complete closure of the myocutaneous defect. The patient presented a good recovery with no new neurological deficit. CONCLUSION Myelomeningocele may be associated with large myocutaneous defects that can be difficult to correct by primary closure. In these cases, rotation flaps may be necessary to achieve complete closure.
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Affiliation(s)
- Mario Gomar-Alba
- Department of Neurosurgery, Hospital Universitario Torrecárdenas, Almería, Spain.
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Rotation advancement V-Y posterior thigh flap combined with a biceps femoris muscle flap for reconstruction of a recurrent ischial pressure sore in pediatric patients. EUROPEAN JOURNAL OF PLASTIC SURGERY 2021. [DOI: 10.1007/s00238-020-01684-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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