Risk For Delays In Development Research Articles

Extremely preterm children demonstrate hyperconnectivity during verb generation: A multimodal approach

Children born extremely preterm (EPT, <28 weeks gestation) are at risk for delays in development, including language. We use fMRI-constrained magnetoencephalography (MEG) during a verb generation task to assess the extent and functional connectivity (phase locking value, or PLV) of language networks in a large cohort of EPT children and their term comparisons (TC). 73 participants, aged 4 to 6 years, were enrolled (42 TC, 31 EPT). There were no significant group differences in age, sex, race, ethnicity, parental education, or family income. There were significant group differences in expressive language scores (p < 0.05). Language representation was not significantly different between groups on fMRI, with task-specific activation involving bilateral temporal and left inferior frontal cortex. There were group differences in functional connectivity seen in MEG. To identify a possible subnetwork contributing to focal spectral differences in connectivity, we ran Network Based Statistics analyses. For both beta (20–25 Hz) and gamma (61–70 Hz) bands, we observed a subnetwork showing hyperconnectivity in the EPT group (p < 0.05). Network strength was computed for the beta and gamma subnetworks and assessed for correlation with language performance. For the EPT group exclusively, strength of the subnetwork identified in the gamma frequency band was positively correlated with expressive language scores (r = 0.318, p < 0.05). Thus, hyperconnectivity is positively related to language for EPT children and might represent a marker for resiliency in this population.

Pediatric neurodevelopment by prenatal Zika virus exposure: a cross-sectional study of the Microcephaly Epidemic Research Group Cohort.

BackgroundThe implications of congenital Zika Virus (ZIKV) infections for pediatric neurodevelopment and behavior remain inadequately studied. The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related microcephaly and children with prenatal ZIKV exposure in the absence of microcephaly.MethodsWe conducted a cross-sectional study, nested in a cohort, of 274 children (aged 10–45 months) who were born during the peak and decline of the microcephaly epidemic in Northeast Brazil. Participants were evaluated between February 2017 and August 2019 at two tertiary care hospitals in Recife, Pernambuco, Brazil. We analyzed the children in four groups assigned based on clinical and laboratory criteria: Group 1 had severe microcephaly; Group 2 had moderate microcephaly; Group 3 had prenatal ZIKVexposure confirmed by maternal RT-PCR testing but no microcephaly; and Group 4 was a neurotypical control group. Groups were evaluated clinically for neurological abnormalities and compared using the Survey of Wellbeing of Young Children (SWYC), a neurodevelopment and behavior screening instrument validated for use in Brazil. Children with severe delays underwent further evaluation with an adapted version of the SWYC.ResultsBased on the SWYC screening, we observed differences between the groups for developmental milestones but not behavior. Among the 114 children with severe microcephaly of whom 98.2% presented with neurological abnormalities, 99.1% were ‘at risk of development delay’ according to the SWYC instrument. Among the 20 children with moderate microcephaly of whom 60% presented with neurological abnormalities, 65% were ‘at risk of development delay’. For children without microcephaly, the percentages found to be ‘at risk of developmental delay’ were markedly lower and did not differ by prenatal ZIKV exposure status: Group 3 (N = 94), 13.8%; Group 4 (N = 46), 21.7%.ConclusionsAmong children with prenatal ZIKV exposure, we found a gradient of risk of development delay according to head circumference. Children with severe microcephaly were at highest risk for delays, while normocephalic ZIKV-exposed children had similar risks to unexposed control children. We propose that ZIKV-exposed children should undergo first-line screening for neurodevelopment and behavior using the SWYC instrument. Early assessment and follow-up will enable at-risk children to be referred to a more comprehensive developmental evaluation and to multidisciplinary care management.

Prevalence and socioeconomic determinants of development delay among children in Ceará, Brazil: A population-based study

ObjectiveTo assess the prevalence of child development delay and to identify socioeconomic determinants.Study designWe conducted a population-based cross-sectional study of children 2 to 72 months of age residing in the state of Ceará, Brazil. In total, 3200 households were randomly selected for participation in the study and had child development assessed with the Ages and Stages Questionnaire (ASQ) version 3. Development delay was defined as a score of less than -2 standard deviations below the median of the Brazilian ASQ standard. We present population-level prevalence of delay in five development domains and assess socioeconomic determinants.ResultsA total of 3566 children completed the ASQ development assessment of which 9.2% (95% CI: 8.1–10.5) had at least one domain with development delay. The prevalence of delay increased with age in all domains and males were at higher risk for communication, gross motor and personal-social development delays as compared to females (p-values <0.05). We found robust associations of indicators of socioeconomic status with risk of development delay; increasing monthly income and higher social class were associated with reduced risk of delay across all domains (28,2% in the poorest and 21,2% in richest for any delay, p-values <0.05 for all domains). In addition, children in poor households that participated in conditional cash transfer (CCT) programs appeared to have reduced risk of delay as compared to children from households that were eligible, but did not participate, in CCT programs.ConclusionsThere is a relatively high population-level prevalence of development delay in at least one domain among children 0–6 years of age in Ceará, Brazil. Integrated child development, social support, and poverty reduction interventions may reduce the population-level prevalence of development delay in Ceará and similar settings.

Peptide Optimization at the Drug Discovery-Development Interface: Tailoring of Physicochemical Properties Toward Specific Formulation Requirements

Physicochemical properties of peptides need to be compatible with the manufacturing process and formulation requirements to ensure developability toward the commercial drug product. This aspect is often disregarded and only evaluated late in discovery, imposing a high risk for delays in development, increased costs, and finally for the project in general. Here, we report a case study of early physicochemical peptide characterization and optimization of dual glucagon-like peptide 1/glucagon receptor agonists toward specific formulation requirements. Aggregation issues which were observed at acidic pH in the presence of phenolic preservatives could be eliminated by modification of the peptide sequence, and chemical stability issues were significantly improved by addition of stabilizing formulation excipients. We describe structural, analytical, and biophysical characterization in different compositions to analyze the effect of pH and formulation excipients on physical and chemical stability. Molecular models have been generated to rationalize peptide stability behavior based on computed physicochemical descriptors and interactions with excipients. To conclude these studies, a general roadmap is proposed how to assess and optimize early physicochemical peptide properties in a sophisticated way by combining experimental and in silico profiling to provide stable peptide drugs under relevant formulation conditions at the end of discovery.

Predictive Value of Midline Spikes on Pediatric EEG for Seizure and Developmental Outcome.

Midline spikes are epileptiform discharges localized to the midsagittal regions of the brain. Isolated midline spikes are rare, but more common in children. Our objective was to determine whether midline spikes are predictive of seizure characteristics and neurodevelopment. EEGs and clinical information of 123 children with isolated midline spikes, and EEG follow-up within 12 to 24 months, were reviewed and compared with controls. Most children with midline spikes had seizures (91%), with an equal predisposition to focal or generalized seizure semiology. There was no difference between the midline spike and control groups in terms of neonatal complications, seizure characteristics (type, frequency, and etiology), and neurologic examination findings. In patients with abnormal neuro-maging, deep gray or white matter abnormalities were more frequent in the midline group (41% vs. 13%, P = 0.02). The midline group had a higher risk of development delay (DD) than controls (43% vs. 29%, odds ratio: 1.8, 95% CI [1.1-3.2], P = 0.03). A higher risk of DD was also noted in the midline group in those aged less than 4 years (52% vs. 26%, odds ratio: 3.1, 95% CI [1.0-9.2], P = 0.04) and in those without seizures (40% vs. 17%, odds ratio: 3.16, 95% CI [1.1-8.8], P = 0.03). This is the largest reported group of patients with midline spikes. Midline spikes have a strong association with seizures and DD. Our data suggest that midline spikes result from heterogeneous etiologies, are more common in young children, and are not benign.

Efficacy of Early Yakson Touch and Kinaesthetic Stimulation (Yakin) on the Development of High Risk Neonates: A Randomized Controlled Trial Protocol

Introduction: About 15 million babies are born preterm annually, with every year almost 1 million dying from complications and survivors prone to lifetime disability. Yakson touch and kinaesthetic stimulation techniques have proven effective in minimizing the complications and disability of preterm delivery, but presently there is no standardized protocol for their application. The aim is to investigate the efficacy of Yakson touch in combination with kinaesthetic stimulation (YAKIN) on the motor and behavioural development of neonates at high risk of development delay in comparison to conventional handling.Material and Methods: Neonates will be recruited via parental consent from a recognized tertiary care teaching hospital for this two-group pretest-posttest design of randomized controlled trial (RCT), with allocation into either a control group (n=14) or experimental group (n=14) by block randomization method. The experimental group will receive Yakson touch and kinaesthetic stimulation, whilst the control group will receive conventional handling inclusive of developmental positioning and Kangaroo mother care. The duration of intervention will be five out of seven days. Neonatal behavioural assessment scale (NBAS) will be performed at baseline and then on the 7th day to ascertain the intervention effectiveness.Results: Data analysis will be done by Wilcoxon signed rank test/paired t-test and Mann Whitney U test/independent t-test will be done to compare the pre and post intervention score of NBAS within and between groups. The level of significance will be set as p&lt;0.05.Conclusion: The present study may provide valuable information about early intervention to the neonatal physiotherapist, intensivist, nursing staff and parents of neonates.

Early intervention for infants and toddlers: Applications for pediatric oncology.

Young children (<3 years) with cancer are at risk for delays in development due to their disease and its required treatments and restrictions. In the United States, Part C of the Individuals with Disabilities Education Act describes a system of early intervention (EI) services for young children with delays or the potential for delays in development. Children with cancer may be eligible for EI but are rarely referred. Our objectives are to describe the critical impact of early childhood development on long-term outcomes, review current considerations for EI, and advocate for the referral to EI for young children with cancer.

Prevalencia De Alteraciones En El Desarrollo Psicomotor Para Niños De 1 Mes A 5 Años Valorados Con La Prueba EDI En Un Centro De Salud En México En El Periodo Febrero A Noviembre De 2015

Objective: To establish the prevalence of the psychomotor development alterations in children from a month old up to 5 years old tested with EDI test. Methodology: Transversal study with a non probabilistic sample of children who entered to be evaluated with EDI test for the first time in a period from February to November 2015. It took 204 evaluations through the SPSS V program. Results: 54 (26.47%) children resulted with some alert data, in which 32 (59.26%) referred lag in their development and 22 (40.74%) with risk of development delay. The rest were 150 (73.53%) tests with normal development. Conclusions: The high index of urinary tract infections during the prenatal period such as the preterm births stimulates the prevalence of psychomotor development alterations, which is why it is important the correct manage during pregnancy.

Identification of neurodevelopmental disabilities in underserved children using telehealth (INvesT): Clinical trial study design

BackgroundChildren living in poverty are at high risk for delays in development of language and behavior and they experience a discrepancy in diagnosis and access to intervention services. This gap is partially caused by barriers in access as well as traits that are specific to each child and family. The Identification of Neurodevelopmental Disabilities in Underserved Children using Telehealth (INvesT) trial is a novel intervention approach that was specifically designed to address these barriers. AimsThe INvesT trial has three primary aims: 1) to reduce the age of identification of neurodevelopmental disability for high-risk, low-income children. 2) To validate the INvesT protocol as a service delivery model that will decrease age of identifications of neurodevelopmental disability for high-risk, low-income children; and 3) to identify important child-specific factors, family-specific factors, and environmental factors that impact feasibility and success of the INvesT trial for high-risk, low-income children. MethodsThe INvesT trial is an open-label, double-blinded, placebo-controlled multi-level study that includes telehealth risk assessment, telehealth screening, traditional full assessment, and follow through to enrollment in early intervention. The trial is conducted in partnership with an urban community health clinic that largely serves a low-income patient population. ConclusionsThe results of the INvesT trial will provide evidence for the use of a telehealth service delivery model to improve access to care for neurodevelopmental disabilities for high-risk, low-income children.