Cognitive Developmental Delay Research Articles

Brain cell type specific proteomics approach to discover pathological mechanisms in the childhood CNS disorder mucolipidosis type IV.

Mucolipidosis IV (MLIV) is an ultra-rare, recessively inherited lysosomal disorder resulting from inactivating mutations in MCOLN1, the gene encoding the lysosomal cation channel TRPML1. The disease primarily affects the central nervous system (CNS) and manifests in the first year with cognitive and motor developmental delay, followed by a gradual decline in neurological function across the second decade of life, blindness, and premature death in third or fourth decades. Brain pathology manifestations in MLIV are consistent with hypomyelinating leukodystrophy with brain iron accumulation. Presently, there are no approved or investigational therapies for MLIV, and pathogenic mechanisms remain largely unknown. The MLIV mouse model, Mcoln1-/- mice, recapitulates all major manifestations of the human disease. Here, to better understand the pathological mechanisms in the MLIV brain, we performed cell type specific LC-MS/MS proteomics analysis in the MLIV mouse model and reconstituted molecular signatures of the disease in either freshly isolated populations of neurons, astrocytes, oligodendrocytes, and neural stem cells, or whole tissue cortical homogenates from young adult symptomatic Mcoln1-/- mice. Our analysis confirmed on the molecular level major histopathological hallmarks of MLIV universally present in Mcoln1-/- tissue and brain cells, such as hypomyelination, lysosomal dysregulation, and impaired metabolism of lipids and polysaccharides. Importantly, pathway analysis in brain cells revealed mitochondria-related alterations in all Mcoln1-/- brain cells, except oligodendrocytes, that was not possible to resolve in whole tissue. We also report unique proteome signatures and dysregulated pathways for each brain cell population used in this study. These data shed new light on cell-intrinsic mechanisms of MLIV and provide new insights for biomarker discovery and validation to advance translational studies for this disease.

Child neurodevelopmental disorders in armed conflict country, case of DR Congo: long-term trauma impact on brain development in childhood: review

Child neurodevelopmental disorders in armed conflict country, case of DR Congo: long-term trauma impact on brain development in childhood: review

Clinical and Molecular Aspects Associated with Defects in the Transcription Factor POU3F4: A Review.

X-linked deafness (DFNX) is estimated to account for up to 2% of cases of hereditary hearing loss and occurs in both syndromic and non-syndromic forms. POU3F4 is the gene most commonly associated with X-linked deafness (DFNX2, DFN3) and accounts for about 50% of the cases of X-linked non-syndromic hearing loss. This gene codes for a transcription factor of the POU family that plays a major role in the development of the middle and inner ear. The clinical features of POU3F4-related hearing loss include a pathognomonic malformation of the inner ear defined as incomplete partition of the cochlea type 3 (IP-III). Often, a perilymphatic gusher is observed upon stapedectomy during surgery, possibly as a consequence of an incomplete separation of the cochlea from the internal auditory canal. Here we present an overview of the pathogenic gene variants of POU3F4 reported in the literature and discuss the associated clinical features, including hearing loss combined with additional phenotypes such as cognitive and motor developmental delays. Research on the transcriptional targets of POU3F4 in the ear and brain is in its early stages and is expected to greatly advance our understanding of the pathophysiology of POU3F4-linked hearing loss.

Changes in the early communicative behaviors of young children with significant cognitive and motor developmental delays in a two-year span

IntroductionThis study examines longitudinal changes in communicative behavior of young children with significant cognitive and motor developmental delays (SDD) and determines their individual communicative trajectories. A second focus of this study is the relation of changes in communicative behavior with motor skills. MethodsData consists of codes resulting from a self-developed coding scheme used on observations of 23 children in three different settings and responses on a questionnaire. First, group trends were determined to find out whether communication-related variables tend to significantly change over the course of two years. Furthermore, these findings were contrasted with the individual trajectories of the children. Next, the association of initial communicative skills and (the acquisition of) specific motor skills with the change in their communicative functioning was studied. Wilcoxon Signed Ranks and correlational analyses were used to answer the research questions. ResultsOut of sixteen different variables related to communicative behavior, ten changed significantly over the course of two years. Children with more focus on prompt on the first datapoint showed a significantly larger increase of signs of functionality. Still, all children showed highly individual trajectories. Children with better motor skills on the first datapoint showed a significantly larger increase in communication rate. ConclusionsResults show that if a myriad of detailed variables are taken into account children with significant cognitive and motor developmental disabilities do change regarding their communicative functioning, but that they tend to all show unique developmental trajectories. Children with stronger skills in some aspects of communication and motor functioning, can be considered advantaged regarding their communicative development.

Long-term adverse neurodevelopmental outcomes of discordant twins delivered at term: A nationwide population-based study.

To evaluate long-term adverse neurodevelopmental outcomes of discordant twins delivered at term. Retrospective cohort study. Nationwide (Republic of Korea). All twin children delivered at term between 2007 and 2010. The study population was divided into two groups according to inter-twin birthweight discordancy: the 'concordant twin group', twin pairs with inter-twin birthweight discordancy less than 20%; and the 'discordant twin group', twin pairs with inter-twin birthweight discordancy of 20% or more. The risk of long-term adverse neurodevelopmental outcomes was compared between the concordant twin group and the discordant twin group. Long-term adverse neurodevelopmental outcomes between smaller and larger twin children within twin pairs were further analysed. The composite adverse neurodevelopmental outcome was defined as the presence of at least one of the following: motor developmental delay, cognitive developmental delay, autism spectrum disorders/attention deficit hyperactivity disorders, tics/stereotypical behaviour or epileptic/febrile seizure. Long-term adverse neurodevelopmental outcome. Of 22 468 twin children (11 234 pairs) included, 3412 (15.19%) twin children were discordant. The risk of composite adverse neurodevelopmental outcome was higher in the discordant twin group than in the concordant twin group (adjusted hazard ratio [HR] 1.13, 95% CI 1.03-1.24). The long-term adverse neurodevelopmental outcomes were not significantly different between smaller and larger twin children in discordant twin pairs (adjusted HR 1.01, 95% CI 0.81-1.28). In twin pairs delivered at term, an inter-twin birthweight discordancy of 20% or greater was associated with long-term adverse neurodevelopmental outcomes; and long-term adverse neurodevelopmental outcomes were not significantly different in smaller or larger twin children in discordant twin pairs.

Accelerazione improvvisa dell’età ossea nel bambino prepubere. Quali le possibili cause?

George is referred at age 6 years 6 months from family pediatrician to a pediatric endocrinologist for poor statural growth and some facial dysmorphic notes. Second child of non consanguineous parents. Older sister is in good health. Father 177 cm tall, mother 161 cm, menarche 11 1/2 years. Genetic target cm 175.5 (50° pc). No major pathologies in family history. Pregnancy passed regularly, induced delivery at 39 weeks due to fetal distress; neonatal period progressed without complications. At birth kg 2650, cm 49. Head circumference unknown. According to the mother, growth in the first years of life was regular. Modest delay in psychomotor development: first words after one year, independent walking at 17 months. He is followed in Child Neuropsychiatry for “developmental delay and mild intellectual disability (IQ :63) and behavioral problems” and is undergoing psycho-motor physiotherapy treatment. He is also being followed in Broncho Pneumology for episodes of bronchial asthma and by ophthalmologists for modest strabismus. The parents report that George, seen at age 5 years and 6 months, had a stature of 101.9 cm (3° pc), a weight of 17.5 kg, and a bone age 4 years and 6 months. Given the dysmorphic facial notes, two geneticists had been consulted who did not make a diagnostic suspicion. CGH array was negative. On objective examination (6 years and 6 months), general and nutritional conditions are good, preserved limb/trunk ratio. Some modest facial dysmorphia, mild strabismus and modest delay in cognitive development are noted. Examination of the various organs and apparatuses is negative. Height 107 cm (3° pc, 10 cm below genetic target), weight 21 kg, BMI 15 (25° pc). Bone age found to be 5 1/2 years (1 year below chronological age). The pediatric endocrinologist decides to recheck statural growth at 6 to 12 months. In fact, the child is revisited at ages 8 and 4 months. The period between the two visits has progressed without any particular events. Dysmorphia persists, regular trunk/limb ratio, prepubertal genitalia. Height 123 cm (10° pc, within genetic target), weight 25 kg, BMI 16.6 (25°-50° pc), head circumference 52.5 cm (50° pc). Bone age: 10 years, almost 2 years higher than chronological age. Conclusions: stature at low limits of normal, some dysmorphic notes, modest psychomotor and cognitive delay, rapid acceleration of bone age, which at age 5 ½ years and at 6 years 6/12) 1 year lower than chronological became at 8 years 4 months almost 2 years higher resulting in worsening prognosis of final stature (see Figure 1).

Describing the communicative profiles of young children with a significant cognitive and motor developmental delay

The communicative behavior of young children with significant cognitive and motor developmental delays is generally considered to be limited, idiosyncratic and non-intentional. At present, changes between and within children over time regarding their communicative behavior are hard to detect. This article describes an exploratory observational study that draws on data from the first data point of 38 children who are participating in a longitudinal project on the developmental trajectories of children with significant cognitive and motor developmental delays. The aims of this study were to (a) describe the participants’ communicative behavior in detail with communication-related variables that reflect differences across individuals, (b) create summarizing variables and (c) explore whether subgroups of children can be detected. A self-developed coding scheme and descriptive statistics combined with correlational analyses were used, followed by a principal component analysis and visual inspection of the outcome of this analysis. The within-group differences related to communicative behavior was characterized using 16 variables. Based on these variables, three overarching components were formulated: communication proficiency, Expressions of Discomfort and Rejection and Differentiation According to Focus. All participating children were found to be unique in terms of their component scores and the relationship among their component scores.

A pediatric near-infrared spectroscopy brain-computer interface based on the detection of emotional valence.

Brain-computer interfaces (BCIs) are being investigated as an access pathway to communication for individuals with physical disabilities, as the technology obviates the need for voluntary motor control. However, to date, minimal research has investigated the use of BCIs for children. Traditional BCI communication paradigms may be suboptimal given that children with physical disabilities may face delays in cognitive development and acquisition of literacy skills. Instead, in this study we explored emotional state as an alternative access pathway to communication. We developed a pediatric BCI to identify positive and negative emotional states from changes in hemodynamic activity of the prefrontal cortex (PFC). To train and test the BCI, 10 neurotypical children aged 8–14 underwent a series of emotion-induction trials over four experimental sessions (one offline, three online) while their brain activity was measured with functional near-infrared spectroscopy (fNIRS). Visual neurofeedback was used to assist participants in regulating their emotional states and modulating their hemodynamic activity in response to the affective stimuli. Child-specific linear discriminant classifiers were trained on cumulatively available data from previous sessions and adaptively updated throughout each session. Average online valence classification exceeded chance across participants by the last two online sessions (with 7 and 8 of the 10 participants performing better than chance, respectively, in Sessions 3 and 4). There was a small significant positive correlation with online BCI performance and age, suggesting older participants were more successful at regulating their emotional state and/or brain activity. Variability was seen across participants in regards to BCI performance, hemodynamic response, and discriminatory features and channels. Retrospective offline analyses yielded accuracies comparable to those reported in adult affective BCI studies using fNIRS. Affective fNIRS-BCIs appear to be feasible for school-aged children, but to further gauge the practical potential of this type of BCI, replication with more training sessions, larger sample sizes, and end-users with disabilities is necessary.

A systematic review of home-based records in maternal and child health for improving informational continuity, health outcomes, and perceived usefulness in low and middle-income countries.

BackgroundEvidence shows that a gap in the documentation of patients’ past medical history leads to errors in, or duplication of, treatment and is a threat to patient safety. Home-based or patient-held records (HBR) are widely used in low and middle-income countries (LMIC) in maternal and childcare. The aim is to systematically review the evidence on HBRs in LMICs for (1) improving informational continuity for providers and women/families across health care visits and facilities, (2) to describe the perceived usefulness by women/families and healthcare providers, and (3) maternal and child health outcomes of using HBRs for maternal and child health care.MethodsThe protocol was registered in PROSPERO (CRD42019139365). We searched MEDLINE, EMBASE, CINAHL, and Global Index Medicus databases for studies with home-based records from LMICs. Search terms pertained to women or parent-held records and LMICs. Two reviewers assessed studies for inclusion using a priori study selection criteria- studies explaining the use of HBRs in LMIC for maternal and child health care. The included study quality was appraised using the Mixed Methods Appraisal Tool (MMAT). Results from all study designs were summarised narratively.ResultsIn total, 41 papers were included in the review from 4514 potential studies. Included studies represented various study designs and 16 countries. The least evaluated function of HBR was information continuity across health care facilities (n = 6). Overall, there were limited data on the usefulness of HBRs to providers and mothers/families. Home-based records were mostly available for providers during health care visits. However, the documentation in HBRs varied. The use of HBRs is likely to lead to improved antenatal visits and immunisation uptake, and skilled birth delivery in some settings. Mothers’ knowledge of breastfeeding practices and danger signs in pregnancy improved with the use of HBRs. One randomised trial found the use of HBRs reduced the risk of cognitive development delay in children and another reported on trial lessened the risk of underweight and stunted growth in children.ConclusionThere is limited literature from LMICs on the usefulness of HBRs and for improving information transfer across healthcare facilities, or their use by women at home. Current HBRs from LMICs are sub-optimally documented leading to poor informational availability that defeats the point of them as a source of information for future providers.

Umbilical cord serum elementomics of 52 trace elements and early childhood neurodevelopment: Evidence from a prospective birth cohort in rural Bangladesh.

Prenatal exposures to neurotoxic metals and trace elements are associated with early childhood neurodevelopmental outcomes. However, consequences of simultaneous exposure to mixtures of elements remain unclear. To examine individual and joint effects of prenatal trace element exposure on early childhood neurodevelopment. Using a well-established Bangladesh prospective birth cohort (2008-2011), we measured concentrations of 52 trace elements in umbilical cord serum of 569 mother-infant pairs using inductively coupled plasma mass spectrometry. Neurodevelopment was evaluated at 20-40months of age using Bayley Scales of Infant and Toddler Development, Third Edition. Stability elastic net (ENET) was used to screen elements individually associated with the outcome; candidate exposures were combined by weighted linear combination to form a risk score representing their mixture effect on early childhood neurodevelopment. Stability ENET identified 15 trace elements associated with cognitive composite score and 14 associated with motor composite score, which were linearly combined to form the element risk score (ERS). Children with higher ERScognitive had lower probability of cognitive developmental delay (ORhighest vs lowest: 0.21; 95%CI: 0.10, 0.40; P<0.001; Ptrend<0.001). Children with ERSmotor in the top quintile had a significantly lower risk of motor developmental delay (OR: 0.16; 95%CI: 0.09, 0.31; P<0.001; Ptrend<0.001) versus the lowest quintile. In Bayesian kernel machine regression analyses, lithium [conditional posterior inclusion probability (cPIP)=0.68], aluminum (cPIP=0.83) and iron (cPIP=1.00) contributed most to the lower cognitive composite score; zinc (cPIP=1.00), silver (cPIP=0.81), and antimony (cPIP=0.65) mainly contributed to the change of motor composite score. Co-exposure to lithium/aluminum/iron or zinc/silver/antimony appears to impact children's neurodevelopment. ERS score reflecting maternal exposure could indicate children's risk of neurodevelopmental delay, warranting further studies to explore the underlying mechanism.

Nitric Oxide Attenuates Human Cytomegalovirus Infection yet Disrupts Neural Cell Differentiation and Tissue Organization.

Human cytomegalovirus (HCMV) is a prevalent betaherpesvirus that is asymptomatic in healthy individuals but can cause serious disease in immunocompromised patients. HCMV is also the leading cause of virus-mediated birth defects. Many of these defects manifest within the central nervous system and include microcephaly, sensorineural hearing loss, and cognitive developmental delays. Nitric oxide is a critical effector molecule produced as a component of the innate immune response during infection. Congenitally infected fetal brains show regions of brain damage, including necrotic foci with infiltrating macrophages and microglia, cell types that produce nitric oxide during infection. Using a 3-dimensional cortical organoid model, we demonstrate that nitric oxide inhibits HCMV spread and simultaneously disrupts neural rosette structures, resulting in tissue disorganization. Nitric oxide also attenuates HCMV replication in 2-dimensional cultures of neural progenitor cells (NPCs), a prominent cell type in cortical organoids that differentiate into neurons and glial cells. The multipotency factor SOX2 was decreased during nitric oxide exposure, suggesting that early neural differentiation is affected. Nitric oxide also reduced maximal mitochondrial respiration in both uninfected and infected NPCs. We determined that this reduction likely influences neural differentiation, as neurons (Tuj1+ GFAP- Nestin-) and glial populations (Tuj1- GFAP+ Nestin-) were reduced following differentiation. Our studies indicate a prominent, immunopathogenic role of nitric oxide in promoting developmental defects within the brain despite its antiviral activity during congenital HCMV infection. IMPORTANCE Human cytomegalovirus (HCMV) is the leading cause of virus-mediated congenital birth defects. Congenitally infected infants can have a variety of symptoms manifesting within the central nervous system. The use of 3-dimensional (3-D) cortical organoids to model infection of the fetal brain has advanced the current understanding of development and allowed broader investigation of the mechanisms behind disease. However, the impact of the innate immune molecule nitric oxide during HCMV infection has not been explored in neural cells or cortical 3-D models. Here, we investigated the effect of nitric oxide on cortical development during HCMV infection. We demonstrate that nitric oxide plays an antiviral role during infection yet results in disorganized cortical tissue. Nitric oxide contributes to differentiation defects of neuron and glial cells from neural progenitor cells despite inhibiting viral replication. Our results indicate that immunopathogenic consequences of nitric oxide during congenital infection promote developmental defects that undermine its antiviral activity.

Erratum to: Could Fetuin-A Be a Biomarker for Autism Spectrum Disorder and Cognitive Developmental Delay?

Erratum to: Could Fetuin-A Be a Biomarker for Autism Spectrum Disorder and Cognitive Developmental Delay?

Implementasi Teknik Scaffolding Untuk Mengembangkan Kecerdasan Kognitif Anak Usia Dini

This study departs from the problem where early childhood experiences delays in cognitive development. The delay in cognitive development is due to the learning model provided by parents or teachers which is still limited to providing advice and "warnings", even though early childhood in the pre-operational period needs an example of real actions so that children are easier to understand and take action. This study aims to develop AUD cognitive intelligence through scaffolding techniques so that children's cognitive development can develop well and quickly. This study uses descriptive qualitative research, where in this study the researcher provides clear and operational explanations and descriptions regarding the use of scaffolding techniques as an appropriate and fast way to develop children's cognitive intelligence. In this study, it was found that the use of scaffolding techniques can help parents and teachers in developing and training cognitive intelligence in children. Children's cognitive intelligence can be seen from children starting to be able to put on and take off shoes properly and correctly.

Structural Protein Effects Underpinning Cognitive Developmental Delay of the PURA p.Phe233del Mutation Modelled by Artificial Intelligence and the Hybrid Quantum Mechanics-Molecular Mechanics Framework.

A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA–Phe233del showed that the occurrence of the Phe233del affects between 220–320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein–DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA–Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics–Molecular Mechanics (QM–MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

Could Fetuin-A Be a Biomarker for Autism Spectrum Disorder and Cognitive Developmental Delay?

Early detection of cognitive developmental delay (CDD) and autism spectrum disorder (ASD) is challenging, despite the numerous scientific studies conducted and different therapeutic strategies. Lack of a biomarker for autism is a limiting factor for early diagnosis, which could provide better outcome with early start of therapy. Because of the high serum fetuin-A concentration during intrauterine life, it has been suggested that fetuin-A may have a role in brain development. The current study sought to determine if fetuin-A, a multifunctional glycoprotein thought to have a role in brain development, may be used as a biomarker for the diagnosis of ASD and developmental delay. The study involved 55 children with cognitive developmental delays and 40 healthy children. Two categories of children with cognitive developmental delays were identified. The participants were subjected to a psychiatric assessment as well as developmental testing. Only 54.5% of the 55 individuals had CDD, whereas 45.5% had ASD. Using an ELISA kit, the levels of serum fetuin-A were determined spectrophotometrically. The serum fetuin-A levels in the patients from the test group were found to be significantly lower than in the healthy individuals (p < 0.001). The cutoff value for the serum fetuin-A levels for cognitive developmental delay and autism spectrum disorder was 518 µg/liter, according to the results of ROC analysis (84.6% sensitivity and 91.4% specificity, AUC: 0.95, p < 0.001). The findings suggest that the serum fetuin-A level may be used to diagnose autism spectrum disorder and cognitive developmental delays.

Autism spectrum disorder: Comorbidity and demographics in a clinical sample

Objective: To determine the demographic and clinical characteristics of children followed up with the diagnosis of autism spectrum disorder (ASD) at a tertiary center in Southeeast Turkey. Methods: Children followed up with the diagnosis of ASD at a university hospital child psychiatry clinic between June 2016 and June 2021 were evaluated retrospectively for comorbidities, intellectual functioning and age at diagnosis. Results: In the preschool group, females displayed significantly more frequent cognitive developmental delay. Median age at diagnosis was 36 months (IQR= 22) regardless of gender. Approximately three-fourth (73.7%) of the cases had at least one psychiatric comorbid disorder while 22.8% had at least one medical diagnosis. Psychiatric comorbidity was found to be associated with later diagnosis. Conclusion: Although the age at first diagnosis in this study is relatively earlier than the studies in the literature, most of the children with ASD are still diagnosed very late. Psychiatric comorbidities may lead to later diagnosis due to overshadowing. Training of educational and primary healthcare workers on symptoms of ASD may enable earlier diagnosis.

Developmental Functioning Outcomes in Infants With Cystic Fibrosis: A 24- to 36-Month Follow-Up Study.

This study aimed to examine early motor repertoire using Prechtl General Movement Assessment (GMA) and later developmental functioning of infants with cystic fibrosis (CF). Early motor repetoire was evaluated using Prechtl GMA, and developmental functioning was assessed using Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) in infants with CF and their peers who were neurotypical, as the control group. Twelve infants with CF clinically stable and 12 infants who were neurotypical, with respective median post-term ages of 14 and 13weeks, were assessed using GMA. At 24 to 36months, the Bayley-III was applied to the CF group (median post-term age = 27.5months) and the control group (median post-term age = 27.0months). Fidgety movements were absent in 5 infants with CF, whereas all infants who were neurotypical had normal fidgety movements. The Motor Optimality Score was significantly lower in the CF group (median = 18.5) compared with the control group (median = 26). The CF group had significantly lower composite scores in the Bayley-III cognition, language, and motor domains compared with the control group. Cognitive, language, and motor development was delayed in infants with CF. Developmental functioning of infants with CF should be assessed as early as possible and monitored, and age-specific early intervention programs should be considered when necessary. Infants with CF may have motor, cognitive, and language developmental delays compared with peers who are neurotypical during early childhood, and hospitalization was negatively correlated with motor development at 24 to 36months of age. This study highlights the importance of early assessment of developmental functioning and age-specific, early intervention programs when necessary in infants with CF. It is important to assess developmental functioning as early as possible in infants with CF and to consider age-specific early intervention programs when necessary.

Is Serum Progranulin Level a Biomarker in Autism and Cognitive Development Disorders?

Cognitive developmental delay is a picture of the group of early-onset chronic diseases that affect 1.5-10% of children. Autism spectrum disorders are neurodevelopmental diseases with a genetic basis and abnormal brain development, characterized by disorders in areas that make up interpersonal relationships, such as communication, social cognition, and processing of emotional signals. Immune system dysfunction is thought to play a role in the pathogenesis of some neurological disorders, including autism. Progranulin is thought to be a regulator of the innate immune response. The purpose of this study was to look at plasma levels of progranulin, an anti-inflammatory neurotrophic factor, in children with autism spectrum disorder and cognitive developmental delay. The study was conducted on 52 children who were patients and 35 healthy children. Of the 52 children of the patient group, 32 were diagnosed with CDD and 20 were diagnosed with cognitive developmental delay-autism spectrum disorder. Serum progranulin concentrations were measured using a human-specific sandwich enzyme-linked immunosorbent assay. Serum progranulin concentration was statistically lower in the patient group (110.746 ± 26.04) than in the healthy control group (137.346 ± 30.02). There was a statistically significant difference between the groups in levels of serum progranulin (P=.000). Receiver operating characteristic analysis was performed to evaluate the potential of progranulin as a biomarker to distinguish patients with cognitive developmental delay-autism spectrum disorder from healthy children. It detected a moderate area under the curve (0.743 ± 0.06) value and a more significant P value for progranulin (P=.000). Progranulin deficiency in patients with autism spectrum disorder-cognitive developmental delay may result in decreased neurotrophic support for many years, with cumulative damage associated with unregulated inflammation that may play a role in autism spectrum disorder-cognitive developmental delay. We believe that low progranulin levels could be a biomarker for autism spectrum disorder-cognitive developmental delay.

372 Pediatric Abusive Head Trauma During the First Year of Covid-19

INTRODUCTION: During the Covid-19 pandemic parental burnout was associated with increases in child abuse. However, the effects of the pandemic on Abusive Head Trauma (AHT) have not yet been described. METHODS: We included all patients &lt;5 years old with expert-confirmed AHT at our freestanding children's hospital from 3/2018-2/2021. Demographic and clinical data were excerpted, and pediatric neuroradiologists reviewed neuroimaging. Descriptive and inferential analyses were conducted with RStudio. Early morbidity was assessed using gross-motor milestones and developmental quotients with the Capute Scales (CAT/CLAMS). RESULTS: 103 patients suffered AHT (64 pre-Covid-19, 39 Covid-19). The Covid-19 cohort was younger (median age 115 v. 152 days, p=0.027) and lived in homes with higher maternal unemployment (51% v. 22%, p=0.003), smaller spaces (apartments 56% v. 31%, p=0.043) and more people (median 5 v. 4, p=0.047). Clinical findings including Glasgow Coma Scale, Injury Severity Score, and multi-organ injury were similar. Neurosurgical intervention was similar (31% v. 20%, p=0.23). Neuroimaging found that during Covid-19 children suffered more extensive sub-arachnoid hemorrhage (32% v 14%, p=0.040) and spinal hemorrhage (6/39 v. 3/64 cases, p=0.046). Notably, mortality was 19% in both groups (p=0.92). During Covid-19 children removed from parental care were more likely to be placed with relatives (61% v. 36%, p=0.039) versus foster care (8.3% v. 30%, p=0.039). At 2-month follow-up, no differences were observed in new motor (43% v. 54%, p=0.45), language (33% v. 18%, p=0.59), or cognitive (36% v. 48%, p=0.36) developmental delays nor in severity of new deficits. CONCLUSION: Pediatric AHT is a serious public health problem and occurs especially at times of high family stress.(3) During Covid-19 children suffering AHT were younger and more likely to live in homes experiencing greater socioeconomic stressors compared with pre-pandemic levels.

The Relationship Between Family-Centered Stimulation And Cognitive Development Of Children Age 5-6 Years In Akad Village

The number of early childhood children in Kampung Akad, Pesisir Selatan Regency who experience delays in cognitive development is the background of this research. The cause of the slow cognitive development of children is thought to be due to the lack of stimulation provided by the family. This study aims to see an overview of stimulation in the family, a description of children's cognitive development, and the relationship between stimulation in the family and the cognitive development of children aged 5-6 years.his type of research is quantitative with a correlational approach. The population in this study were mothers who had children aged 5-6 years, while for the sampling using simple random sampling. Data collection techniques using a questionnaire, while for data analysis using the percentage formula and Spearmen Rho. The results showed that a) stimulation in the family was still low; b) children's cognitive development is still very low; and c) there is a significant relationship between stimulation in the family and the cognitive development of children aged 5-6 years.Keywords: Stimulation, cognitive development, family