Evaluation of the Neurodevelopmental Outcome of Toddlers with Spinal Dysraphism after Surgical Repair Using ASQ-3™ Scores

Background: Spinal dysraphism represents a wide spectrum of congenital abnormalities of the spine. Myelomeningocele is considered the most common malformation and the most common we saw in our community, with its morbidity problems seen commonly in the postoperative period. ASQ-3TM Scores are the ages and stages questionnaire, third edition, and represent a tool to assess the development progress, especially in toddlers. Objectives: Evaluation of neurodevelopmental outcome among Sudanese toddlers with spinal dysraphism after surgical closure with or without a VP shunt using ASQ-3TM Scores. Methodology: This is a retrospective hospital-based study of 84 patients who underwent myelomeningocele repair at the National Center for Neurological Sciences (NCNS) during the period from 2017 up to 2019. Data were collected through a constructed questionnaire, including ASQ-3TM Scores. Data were processed and analyzed using the Statistical Package for Social Science (SPSS) computer program. Version 25. Results: 84 patients were included in this study;all patients were diagnosed with spinal dysraphism. Out of them, 51 (60.7%) were 2 years old, 33 (39.3%) were 3 years old, 45 (53.6%) were male, 45 (53.6%) of patients mothers attended ANC irregularly, and 54 (64.3%) their mothers didn’t receive folate supplements. 44 (52.3%) of patients underwent MMC repair only, while 40 (47.7%) underwent MMC repair and VP shunt. The commonest postoperative complication was infection, reported in 12 (14.3%) of patients, followed by VP shunt revision in 9 (10.7%) of patients. Neurological assessment showed that the majority of patients need further assessment with a professional, 57 (67.9%) of children don’t walk, run, or climb like other toddlers as their parent’s state;also, half of patients (42, 50%) had medical problems, and 27 (32.1%) of their parent’s state that they do not talk like other toddlers their age. There was a statistically significant association between post-operative complications and communication development, problem-solving development, and personal social development (P value = 0.05), and a statistically significant association was found between age at repair and neurological development (P value = 0.05). Conclusion: The majority of patients had motor deficiency (particularly gross motor) and poor personal and social skills. Age at repair and postoperative complications significantly influenced the neurological development.

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

Perinatal Morbidity, Mortality, and Neurodevelopmental Outcomes of Neonates with Fetal Growth Restriction

Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliveries between 2013 and 2019, 109 cases of FGR were reviewed retrospectively for causes, indications for pregnancy termination, perinatal death, overall neonatal outcomes, and long-term prognosis. Results: Excluding FGR due to congenital anomalies (n = 17), the mortality rate was 3.3% (3/92). One neonate delivered at 23 weeks developed cerebral palsy (1.1%). Retinopathy of prematurity occurred in four neonates (4.3%). Neurodevelopmental disorders were present in six neonates (6.5%), all of whom were delivered at 32 - 38 weeks. Significantly lower gestational age at delivery, lower birth weight, and higher umbilical artery resistance indices were observed in neonates with neurodevelopmental disorders. Conclusions: Intact survival before 27 weeks of gestation at delivery with FGR is uncommon. Neurodevelopmental disorders may still develop after delivery at 32 - 38 weeks;consideration should be given to the timing of delivery usingfetal ductus venosus Doppler waveforms measurements to reduce neurodevelopmental disorders.

Network biology:A promising approach for drug target identification against neurodevelopmental disorders

Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrative and systems-level approach for understanding and interpreting these complex interactions.Biological network analysis is one method for reducing enormous data sets to clinically useful knowledge for disease diagnosis,prognosis,and treatment.The network of biological entities can help us predict drug targets for several diseases.The drug targets identified through the systems biology approach help in targeting the essential biological pathways that contribute to the progression and development of the disease.The novel strategical approach of system biologyassisted pharmacology coupled with computer-aided drug discovery(CADD)can help drugs fight multifactorial diseases efficiently.In the present review,we have summarized the role and application of network biology for not only unfolding the mechanism of complex neurodevelopmental disorders but also identifying important drug targets for diseases like ADHD,Autism,Epilepsy,and Intellectual Disability.Systems biology has emerged as a promising approach to identifying drug targets and aiming for targeted drug discovery for the precise treatment of neurodevelopmental disorders.

Neurodevelopmental Outcomes of Extremely Premature Infants with Extremely Low and Very Low Birth Weight at Three Years of Age: A Retrospective Study

Introduction: The purpose of this retrospective study is to identify medical conditions impacting neurodevelopmental outcomes of extremely low birth weight and very low birth weight preterm infants at three years of age. Methods: Infants born in Banner Diamond Children’s University Medical Center, receiving services in the Newborn Intensive Care Unit, and attending Neonatal Developmental Follow-Up Clinic were identified. Participants received developmental assessment and follow-up from August 2012 through December 2018. Relevant clinical conditions during initial hospital stay and up to three years of age were obtained by reviewing medical and developmental records. Bayley Scales of Infant Toddler Development (Bayley III) was used to evaluate skill development at 6, 9, 12, 18, 24, 30, 36 months. Results: Data analysis did not reveal significant p-values;it did demonstrate that some predictor variables impact neurodevelopmental outcomes in cognitive, language and motor skill development. Conclusion: This retrospective study reports significant association between birth weight and low cognitive scores. Correlations were also found between gestational age and Total Language, and the longer an infant stayed in the NICU, the poorer the Total Language Scaled Scores at 8 to 12 months, 15 to 18 months, and 24 to 36 months. Birth weight was found to be the greatest predictor of poor motor scores.

Neural stem cell replacement: a possible therapy for neurodevelopmental disorders?

Neurodevelopmental disorders are characterized by an abnormal development of the central nervous system, leading to a myriad of symptoms and diseases, including intellectual disability, attention deficits, impairments in learning and memory, speech disorders and repetitive behavior （Telias and Ben-Yosef, 2014）. Common major neurodevelopmental disorders include autism and autism spectrum disorders （ASDs）, fragile X syndrome （FXS）, Down syndrome （DS）, and Rett syndrome （RTT）. They can be collectively described as disorders in which the plasticity of the brain has been severely impaired. The concept of plasticity refers to the brain＇s ability to adapt to and process new information and react accordingly, and it can be classified into three categories： a） molecular plasticity, whenever specific receptors, ion channels, enzymes,

VEGF in the nervous system: an important target for research in neurodevelopmental and regenerative medicine

Vascular endothelial growth factor（VEGF）in neurodevelopment and regeneration：VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the VEGF-receptor （VEGFR）-inhibitor axitinib.

Ultrasonic vocalizations in mice: relevance for ethologic and neurodevelopmental disorders studies

Mice use ultrasonic vocalizations(USVs)to communicate each other and to convey their emotional state.USVs have been greatly characterized in specific life phases and contexts,such as mother isolation-induced USVs for pups or female-induced USVs for male mice during courtship.USVs can be acquired by means of specific tools and later analyzed on the base of both quantitative and qualitative parameters.Indeed,different ultrasonic call categories exist and have already been defined.The understanding of different calls meaning is still missing,and it will represent an essential step forward in the field of USVs.They have long been studied in the ethological context,but recently they emerged as a precious instrument to study pathologies characterized by deficits in communication,in particular neurodevelopmental disorders(NDDs),such as autism spectrum disorders.This review covers the topics of USVs characteristics in mice,contexts for USVs emission and factors that modulate their expression.A particular focus will be devoted to mouse USVs in the context of NDDs.Indeed,several NDDs murine models exist and an intense study of USVs is currently in progress,with the aim of both performing an early diagnosis and to find a pharmacological/behavioral intervention to improve patients’quality of life.

Okur-Chung neurodevelopmental综合征1例并文献复习

Okur-Chung neurodevelopmental综合征的发生与CSNK2A1基因突变有关,患儿以特殊面容和多系统受累为主要表现。本文通过文献复习Okur-Chung neurodevelopmental综合征,提高临床对本病的认识和诊断。此外,Okur-Chung neurodevelopmental综合征由于缺乏确切的临床诊断标准,确诊仍有赖于基因突变分析。

Preterm nutrition and neurodevelopmental outcomes

Survival of preterm infants has been steadily improving in recent years because of many recent advances in perinatal and neonatal medicine.Despite these advances,the growth of survivors does not reach the ideal target level of the normal fetus of the same gestational age.Postnatal weight gain is often not achieved because extrauterine growth has higher energy requirements than intrauterine growth,due to the intensive care environment,illness and inadequate nutrition.Although many other factors influence infant brain development,including family socioeconomic and educational background,the role of nutrition is considerable and fortunately,amenable to intervention.In the preterm neonate,the brain is the most metabolically demanding organ,consuming the largest proportions of energy and nutrient intake for its function and programmed growth and maturation.Weight gain,linear and head circumference growth are all markers of nutritional status and are independently associated with long-term neurodevelopment.Brain development is not only the result of nutrients intake,but in addition,of the interaction with growth factors which depend on adequate nutrient supply and overall health status.This explains why conditions such as sepsis,necrotizing enterocolitis and chronic lung disease alter the distribution and accretion of nutrients thereby suppressing growth factor synthesis.In this review,we will focus on the direct role of nutrition on neurodevelopment,emphasizing why it should be started without delay.The nutritional requirements of the preterm infant will be discussed,followed by the effects of general nutritional interventions and specific nutrients,as well as the role of nutritional supplements on neurodevelopment.The primordial role of human breast milk,breast milk fortifiers and human milk oligosaccharides will be discussed in detail.We will also examine the role of nutrition in preventing neonatal complications which can affect neurodevelopment in their own right.

Neurodevelopmental disorders:An innovative perspective via the response to intervention model

Neurodevelopmental disorders are a group of conditions classified together by the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders which include intellectual disability,communication disorders,autism spectrum disorder,attention-deficit/hyperactivity disorder,specific learning disorder(SLD),and motor disorders.SLD is present in many students,who exhibit significant difficulties in the acquisition of reading,written expression,and mathematics,mostly due to problems with executive functions(EF).The present study is a review of the current situation of neurodevelopmental disorders and SLD focusing on the benefits of the response to intervention model(RtI),which allows the combination of evaluation and intervention processes.It also addresses the key role of EF.The importance of adapting RtI to new possibilities such as the use of virtual reality is discussed and a theoretical framework for carrying that out is provided.

Classification,prevalence and integrated care for neurodevelopmental and child mental health disorders:A brief overview for paediatricians

‘Neurodevelopmental disorders’comprise a group of congenital or acquired longterm conditions that are attributed to disturbance of the brain and or neuromuscular system and create functional limitations,including autism spectrum disorder,attention deficit/hyperactivity disorder,tic disorder/Tourette’s syndrome,developmental language disorders and intellectual disability.Cerebral palsy and epilepsy are often associated with these conditions within the broader framework of paediatric neurodisability.Co-occurrence with each other and with other mental health disorders including anxiety and mood disorders and behavioural disturbance is often the norm.Together these are referred to as neurodevelopmental,emotional,behavioural,and intellectual disorders(NDEBIDs)in this paper.Varying prevalence rates for NDEBID have been reported in developed countries,up to 15%,based on varying methodologies and definitions.NDEBIDs are commonly managed by either child health paediatricians or child/adolescent mental health(CAMH)professionals,working within multidisciplinary teams alongside social care,education,allied healthcare practitioners and voluntary sector.Fragmented services are common problems for children and young people with multi-morbidity,and often complicated by subthreshold diagnoses.Despite repeated reviews,limited consensus among clinicians about classification of the various NDEBIDs may hamper service improvement based upon research.The recently developed“Mental,Behavioural and Neurodevelopmental disorder”chapter of the International Classification of Diseases-11 offers a way forward.In this narrative review we search the extant literature and discussed a brief overview of the aetiology and prevalence of NDEBID,enumerate common problems associated with current classification systems and provide recommendations for a more integrated approach to the nosology and clinical care of these related conditions.

Postnatal therapeutic approaches in genetic neurodevelopmental disorders

Genetic neurodevelopmental disorders are characterized by abnormal neurophysiological and behavioral phenotypes,affecting individuals worldwide.While the subject has been heavily researched,current treatment options relate mostly to alleviating symptoms,rather than targeting the altered genome itself.In this review,we address the neurogenetic basis of neurodevelopmental disorders,genetic tools that are enabling precision research of these disorders in animal models,and postnatal gene-therapy approaches for neurodevelopmental disorders derived from preclinical studies in the laboratory.

Neurodevelopmental in Relation to Breastfeeding–Experiences among Hungarian Preterm Infants at 12 Months of Corrected Age:Empirical Study

Preterm and low birth weight infants are at higher risk of neurodevelopmental outcomes;breastfeeding offers sev-eral beneficial aspects for them.This study aimed to describe the average neurodevelopmental outcomes of pre-term infants and examine the associations between neurodevelopment and breastfeeding among Hungarian preterm infants at 12 months of corrected age.154 preterm infants with low birth weight(<2500 g)and their mothers were participated in this study.Bayley-III Screening Test(Bayley Scales of Infant and Toddler Develop-ment Screening Test,Third Edition)was administered to measure the cognitive,language and motor skills of infants;breastfeeding data was obtained through parental anamnesis.To analyze data,independent sample t-test or the Welch t-test,Mann-Whitney tests,Chi-square tests of independence and Spearman’s rank correlation test were used to.Concerning the risk of developmental delay,Receptive and Expressive language and Fine motor subscales were the lowest.Examination of the associations between breastfeeding and neurodevelopmental per-formance identified significantly higher cognitive(U=2047.5;P=0.023)andfine motor(U=2096.0;P=0.037)skills in infants who were breastfed.We found significant positive correlations between the duration of breastfeeding and cognitive,expressive language andfine motor skills.The study draws the attention to the importance of breastfeeding and early screening.Further research is required to examine the casual relationship between neurodevelopmental outcomes and breastfeeding.

Management of sleep disorders among children and adolescents with neurodevelopmental disorders: A practical guide for clinicians

There is a complex relationship between sleep disorders and childhood neurodevelopmental,emotional,behavioral and intellectual disorders(NDEBID).NDEBID include several conditions such as attention deficit/hyperactivity disorder,autism spectrum disorder,cerebral palsy,epilepsy and learning(intellectual)disorders.Up to 75%of children and young people(CYP)with NDEBID are known to experience different types of insomnia,compared to 3%to 36%in normally developing population.Sleep disorders affect 15%to 19%of adolescents with no disability,in comparison with 26%to 36%among CYP with moderate learning disability(LD)and 44%among those with severe LD.Chronic sleep deprivation is associated with significant risks of behavioural problems,impaired cognitive development and learning abilities,poor memory,mood disorders and school problems.It also increases the risk of other health outcomes,such as obesity and metabolic consequences,significantly impacting on the wellbeing of other family members.This narrative review of the extant literature provides a brief overview of sleep physiology,aetiology,classification and prevalence of sleep disorders among CYP with NDEBIDs.It outlines various strategies for the management,including parenting training/psychoeducation,use of cognitive-behavioral strategies and pharmacotherapy.Practical management including assessment,investigations,care plan formulation and follow-up are outlined in a flow chart.

Neurodevelopmental Timing of Ethanol Exposure May Contribute to Observed Heterogeneity of Behavioral Deficits in a Mouse Model of Fetal Alcohol Spectrum Disorder (FASD)

Maternal drinking during pregnancy can result in a wide spectrum of cognitive and behavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The heterogeneity observed in FASD-related phenotypes can be attributed to a number of environmental and genetic factors;however, ethanol dose and timing of exposure may have significant influences. Here, we report the behavioral effects of acute, binge-like ethanol exposure at three neurodevelopmental times corresponding to the first, second, and third trimester of human development in C57BL/6J mice. Results show that developmental ethanol exposure consistently delays the development of basic motor skill reflexes and coordination as well as impairs spatial learning and memory. Observed changes in activity and anxiety-related behaviors, however, appear to be dependent on timing of alcohol exposure. The variability in behaviors between different treatment models suggests that these may be useful in evaluating the mechanisms disrupted by ethanol at specific neurodevelopmental times. The results provide further evidence that, regardless of developmental stage, the developing brain is acutely sensitive to alcohol exposure.

Neurodevelopmental outcome in congenital diaphragmatic hernia: Evaluation, predictors and outcome

To review the reported neurodevelopmental outcome of congenital diaphragmatic hernia(CDH) survivors, identify important predictors of developmental disabilities, and describe the pathophysiological mechanisms contributing to adverse outcome. A Medline search was performed for English-language articles cross-referencing CDH with pertinent search terms. Retrospective, prospective, and longitudinal follow-up studies were examined. The reference lists of identified articles were also searched. Neurodevelopmental dysfunction has been recognized as one of most common and potentially most disabling outcome of CDH. Intelligence appears to be in the low normal to mildly delayed range. Neuromotor dysfunction is common during early childhood. Behavioral problems, hearing impairment, and quality of life related issues are frequently encountered in older children and adolescence. Disease severity correlates with the degree of neurological dysfunction. Neurodevelopmental follow-up in CDH children should become standard of care to identify those who would benefit from early intervention services and improve neurological outcomes.

The cytokine hypothesis: A neurodevelopmental explanation for the emergence of schizophrenia later in life

There is increasing evidence for the cytokine hypothesis, which states that exposure to elevated cytokines in utero due to maternal immune activation is a major risk factor for the development of schizophrenia later in life. This is supported by numerous epidemicologic studies that connect multiple infections with schizophrenia emergence. Furthermore, cytokines are critically involved in early neurodevelopment and deviations from the norm can result in abnormal neuroanatomy and brain chemistry. Animal models of schizophrenia also support the critical role of developmental neuroinflammation in predisposing the brain to anatomical and behavioral abnormalities. Although there is strong evidence for the critical role of cytokines, they most likely work with other contributing risk factors such as genetic predisposition. New evidence indicates that cytokine exposure in utero may prime the brain and that a second stressor during adolescence, referred to as a second hit, may activate existing developmental vulnerabilities resulting in the emergence of clinical schizophrenia. Further knowledge of these pathogenic processes and risk factors could be very instrumental in reducing risk and slowing emergence of schizophrenia.

Multisystem Inflammatory Syndrome-Neonate: Biochemical Parameters as Early Marker of Adverse Neurodevelopmental Outcome

Background: Pregnant women and newborns are highly susceptible to Covid-19, manifesting as multisystem inflammatory syndrome-New-born (MISC-N) in many babies born to Covid positive mothers. The relationship between Covid-19 infection during pregnancy and neonatal neurodevelopmental outcome, if any, is unclear necessitating a follow-up study in this aspect. Methods: 16 babies with MIS-N, born to symptomatic Covid antibody positive mothers were enrolled. Demographic profile, treatment details and biochemical parameters were analyzed with neurodevelopmental follow-up. Results: 25% mothers received 2 doses of Covid vaccine;50% had oligohydramnios and 75% received antenatal steroids. 87.5% were preterm of which 62.5% required surfactant with ventilator support and 75% required ionotropic support. Significant association was found between the antibody level and D-dimer levels with the ferritin and LDH levels of the baby (p 0.05);gestational age with LDH and D-dimer levels (p 0.05) and Covid antibody level of the baby vs the duration of ventilator requirement (P-value-0.0009). D-dimer values of babies were positively associated with both maternal antibody and D-dimer levels. Neurodevelopmental follow-up done at 6 months of corrected gestational age showed 37.5% were normal, 37.5% hypertonic and 25% hypotonic. HINE score was below 60 in 62.5%. Development assessment using Bayley-III showed a delay in the motor domain (62.5%), cognitive domain (56.25%) and language domain (62.5%). Conclusion: Neurodevelopmental problems occur in babies born to Covid positive mothers and should be stratified as “high risk”. Anticipatory guidance to prospective mothers for preterm care should be given. Covid antibody titre and D-dimer levels may help to predict the NICU stay, ventilator requirement and the adverse neurodevelopmental outcomes in these babies.

Eeffect of super early comprehensive rehabilitationon neurodevelopmental prognosis of high-risk infants

Objective: To observe the effect of super-early comprehensive rehabilitation intervention on neurodevelopmental prognosis of premature high-risk infants;Methods: Premature high-risk infantsmet the inclusion criteria were divided into control group (n=30) and treatment group (n=30) according to parental willingness. The control group was given routine treatment, while the treatment group was treated with comprehensive rehabilitationon the basis of the control group. The course of treatment for both groups was 10 d. The changes of body weight, milk consumption, NBNA score, GMFM score and Gesell score were observed. Results:After treatment, the body weight and milk consumption of the treatment group increased significantly compared with those before treatment (P<0.01), which was significantly better than that of the control group (P<0.01);the NBNA score of the treatment group was higher than that of the control group at 40 weeks of gestational age (P<0.05), and the abnormal rate of NBNA was lower than that of the control group (P<0.01). The GMFM scores of A-energy and B-energy areas and the five dimensions of social adaptation, big exercise, fine exercise, language and personal social interaction in the treatment group increased significantly in 1 month, 2 months and 3 months after birth,which were significantly better than those in the control group (P<0.05 or P<0.01). Conclusion: Super-early comprehensive rehabilitation can improve the physical quality of high-risk infants and promote the development of the nervous system, with remarkable effect.