Cognitive Delay Research Articles

Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh.

There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1β, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders. 248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants,elevated concentrations (>75%)of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevatedIL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1β with lower expressive communication and motor z-scores. In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetalgrowth restriction. Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh. 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants. Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

31 A clinical trial using exergaming with augmented reality to promote physical activity in children with Cerebral Palsy at Children’s Hospital Los Angeles

OBJECTIVES/GOALS: Cerebral palsy (CP) is the most common motor disability in childhood in the US1. Augmented reality (AR) has promise enhancing engagement of rehabilitation2. We developed adaptive games for children with CP using Augment Therapy™. The goal of this study was to obtain user experience in the orthopedic clinic to inform a home-based clinical trial. METHODS/STUDY POPULATION: Participants were recruited at a pediatric center from July 1 to September 20, 2023. Inclusion criteria werediagnosis of CP, ages 5-10 years, English/Spanish speaking. Exclusion criteria were cognitive delay, audio or visual impairment, seizures, or recent surgery. The Augment Therapy™ app was delivered through a clinic iPad. The electronic medical record was used to screen eligible patients. 22 patients were screened; 14 were not eligible based on exclusion criteria. 2 patients refused based on not having enough time to participate. Children played 5 games and their movements were tracked using augmented reality. To evaluate the quality of the app, participants were asked to complete a validated questionnaire, the modified Mobile App Rating Scale. Descriptive statistics were used to analyze responses. RESULTS/ANTICIPATED RESULTS: Six participants were eligible and completed phase I. Eighty-three percent (5/6) of participants reported the character was mostly matching their child’s movements and easy for their child to follow instructions. Thirty three percent (2/6) reported there were technical issues where the app did not track or froze. 100% reported being interested in participating in the home clinical trial. Parent reported their child’s favorite games were flying and obstacle course. The mean and median MARS score was 3.8/5 and 4/5, respectively. Regarding engagement, 66.7% (4/6) reported the app was fun to use. DISCUSSION/SIGNIFICANCE: Families of children with CP reported positive experiences overall with Augment Therapy™ mobile app. The technical issues will need to be addressed. Future studies will need to establish efficacy and dosing time of use of the app for adherence to a program using these modules and engagement with the app to increase habitual physical activity.

130 Heterotopia and Neurodevelopmental Outcomes Patients With Prenatal Diagnosis of Myelomeningocele or Myeloschisis

INTRODUCTION: Gray matter heterotopia is a cortical malformation and a known risk factor for seizures and epilepsy. Historically, presence of heterotopia in one or both cerebral ventricles was a concern for postnatal neurological status in patients undergoing fetal closure of myelomeningocele/myeloschisis. There is little information known regarding the overall impact of heterotopia in this patient population. METHODS: A retrospective chart review was conducted for all patients evaluated at the Center of Fetal Diagnosis and Treatment with a diagnosis of myelomeningocele or myeloschisis between June 2016 to March 2023. Gray matter heterotopia was determined from prenatal US and confirmed with prenatal and postnatal MRI. The Bayley Scales of Infant and Toddler Development (edition III and IV) were used for neurodevelopmental assessments. RESULTS: Of 497 patients evaluated with a prenatal diagnosis of myelomeningocele or myeloschisis, 99 were found to have gray matter heterotopia on prenatal MRI. In the postnatal period, 347 patients ultimately delivered at our institution, of which 26 had confirmed gray matter heterotopia on postnatal MRI as well as underwent neurodevelopmental testing. The median age at neurodevelopmental assessment was 13.3 months. The median cognitive and language scores (95 and 99, respectively) were average in those patients with gray matter heterotopia. CONCLUSIONS: This study suggests that the presence of gray matter heterotopia in patients with prenatal diagnosis of myelomeningocele or myeloschisis is not associated with increased cognitive or language delay on neurodevelopmental testing at approximately 1 year of age. These findings can aid clinicians during prenatal consultation regarding fetal repair of spina bifida.

Insight into Insulin-like Growth Factor-1 Receptor (IGF-1R) gene mutations: Implications for growth disorders and treatment: A review of the literature and case report

Background: Insulin-like Growth Factor -1 Receptor (IGF-1R) and its ligand, IGF-1, are crucial for human tissue growth and development. Mutations in IGF-1R and, to a lesser extent, IGF-1 genes lead to diverse growth disorders, characterized by intrauterine growth retardation and postnatal growth challenges. Case report: We present a case of a 6-year-old girl with speech and mild cognitive delays, exhibiting normal motor skills, no neurological issues, and standard vital signs. Her growth parameters indicated significant retardation, with a height standard deviation score (Ht-SDS) of -2 and an IGF-1 level of +1.8 SDS, normal thyroid function and delayed bone age. Genetic analysis identified a 3335 mbp interstitial loss in 15q26.1, encompassing the IGF-1R gene, critical for growth and development. Literature review: Analysis of 34 papers provided insight into the genetic complexities of IGF-1R and IGF-1 mutations. Studies ranged from familial cases to cohort studies, uncovering mutations including missense mutations, deletions, and copy number variations (CNVs), each associated with unique growth disorder phenotypes. Advances in diagnostic techniques like multiplex ligation-dependent probe amplification (MLPA) and whole exome sequencing (WES) have been pivotal in identifying these mutations, facilitating more targeted management approaches. Conclusions: This case and review of literature underscore the importance of an integrated genetic, endocrine, and developmental approach in managing growth hormone deficiency (GHD) and IGF-1 resistance. The variability in growth disorders and response to therapy highlights the need for personalized treatment plans, informed by genetic insights, to optimize outcomes for patients with these complex conditions.

Prediction of short- and long-term outcomes using pre-operative ventricular size in infants with post-hemorrhagic ventricular dilation.

Post-hemorrhagic ventricular dilation (PHVD) leads to developmental delays in premature infants, yet the optimal timing of neurosurgical interventions is unknown. Neuroimaging modalities have emerged to delineate injury and follow the progression of PHVD. Fronto-temporal horn ratio (FTHR) is used as a marker of ventricular dilation and can be a standardized tool to direct the timing of neurosurgical intervention. Our study determined a pre-operative FTHR measurement threshold to predict short- and long-term outcomes. This is a retrospective cohort study of premature infants with severe intraventricular hemorrhage (IVH) who developed PHVD requiring neurosurgical intervention and were treated in a level IV NICU between 2012 and 2019. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were performed to evaluate the accuracy of pre-operative FTHR for predicting developmental delay. In-hospital outcomes and developmental assessments were analyzed. We reviewed 121 charts of infants with IVH and identified 43 infants with PHVD who required neurosurgical intervention. We found FTHR measurements were an excellent predictor of cognitive and motor delay with an AUC of 0.89 and 0.88, respectively. An average pre-operative FTHR of ≥ 0.67 was also associated with worse lung and feeding outcomes. There was excellent inter-observer reliability of individual components of FTHR measurements. Early intervention for PHVD is ideal but not always practical. Identification of ventricular size thresholds associated with better outcomes is needed to direct timing of neurosurgical intervention.

Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease

BackgroundFetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes. ObjectivesThis study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD. MethodsIn this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content. Superior vena cava (SVC) flow was used as a proxy for cerebral blood flow. Primary outcomes were 18-month mortality and Bayley Scales of Infant Development-III assessment. ResultsA total of 144 fetuses with cyanotic CHD were assessed. By 18 months, 18 patients (12.5%) died. Early mortality was associated with reduced combined ventricular output (P = 0.01), descending aortic flow (P = 0.04), and umbilical vein flow (P = 0.03). Of the surviving patients, 71 had ND outcomes assessed. Cerebral oxygen delivery was the fetal hemodynamic variable most strongly associated with cognitive, language, and motor outcomes (P < 0.05). Fetal SVC flow was also associated with cognitive, language, and motor outcomes (P < 0.01), and it remained an independent predictor of cognitive (P = 0.002) and language (P = 0.04) outcomes after adjusting for diagnosis. Diminished SVC flow also performed better than other fetal CMR and echocardiographic predictors of cognitive ND delay (receiver-operating characteristic curve area: 0.85; SE 0.05). ConclusionsAmong fetuses with cyanotic CHD, diminished fetal combined ventricular output is associated with mortality, whereas cerebral blood flow and oxygen delivery are associated with early cognitive, language, and motor development at 18 months of age. These results support the inclusion of fetal CMR to help identify patients at risk of adverse ND outcomes.

Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Comparison of combined intravenous and inhalation anesthesia and total intravenous anesthesia in laparoscopic surgery and the identification of predictive factors influencing the delayed recovery of neurocognitive function.

Compare the anesthesia effects of combined intravenous and inhalation anesthesia (CIVIA) and total intravenous anesthesia (TIVA) in laparoscopic surgery. Furthermore, our objective is to examine the elements that contribute to the delay in postoperative recovery of neurocognitive function and anticipate the manifestation of delayed recovery by analyzing serum cytokines. The CIVIA group and the TIVA group both consisted of 130 patients who were scheduled to have elective major abdominal surgery through laparoscopy. The criteria taken into account by the observational and record-keeping study were the patients' ages, sexes, body masses, heights, and the presence or absence of any preexisting problems. Both groups also had their anesthetic depth, duration, and per-unit-of-time muscle relaxant and analgesic dosages recorded. Finally, the length of each patient's stay in the hospital as well as their overall length of stay were tracked. By using the Mini-Mental State Examination (MMSE) to measure cognitive function, we assessed the mental states of the subjects. Additionally, we wanted to identify any biomarkers that could be linked to postoperative cognitive decline or delays in neurocognitive recovery. A total of 51 participants from the CIVIA group and 53 participants from the TIVA group satisfactorily completed the necessary neuropsychological exam for identifying delayed neurocognitive recovery at the study's completion. In the initial data of the two groups, no significant discrepancies were found (p > 0.05). The CIVIA group exhibited noteworthy reductions in the quantity of administered analgesics and muscle relaxants per unit of time in comparison to the TIVA group (p < 0.05). In addition to this, the duration from the sevoflurane tank being closed to the extubation period demonstrated a significant reduction in the CIVIA group compared to the TIVA group (p < 0.05). Moreover, no statistically notable distinction was observed in terms of postoperative hospitalization duration and overall hospitalization duration among both groups (p > 0.05). According to the study, both the CIVIA group and the TIVA group had a total of 7 (13.72%) and 17 (32.07%) individuals, respectively, who met the criteria for neurocognitive delayed recovery (Odds Ratio: 0.336; 95% CI: 0.134-0.864; p = 0.026). According to the research findings, it is indicated that there is a possibility for an increased presence of IL-6 in the bloodstream within 60 min following the incision made on the skin. This occurrence subsequently leads to the prolonged restoration of neurocognitive capabilities. The CIVIA technique outperforms the TIVA method in terms of overall assessment in the setting of laparoscopic surgery. It's also important to remember that an increased blood IL-6 level during laparoscopy may operate as a separate risk factor for a delay in the restoration of neurocognitive function.

Molecular basis of neurocognitive dysfunction and psychosis in Alpha-Mannosidosis

A significant portion of patients who are afflicted with lysosomal storage diseases (LSDs) encounter neurological manifestations, including cognitive issues and developmental delay, seizures, psychiatric issues, and an overall neurodegenerative decline. In order to enhance the development of effective therapies for these symptoms, it is imperative that we allude to the neuropathophysiology that underlies these manifestations. These distinct neurological and developmental features are particularly evident in patients with Alpha-Mannosidosis (AM), a type of LSD. However, there is limited published information regarding the mechanisms and pathophysiology of these presentations in patients with this condition. Although the precise impact of lysosomal storage on the biogenesis and functioning of neuronal cells has not been clearly defined, recent studies have placed emphasis on the significance of synaptic defects influencing this dysfunction. These defects encompass changes in synaptic spines, proteins, and vesicles, as well as postsynaptic densities that potentially precipitate functional disruptions in synaptic transmission and neurodegeneration. Ultimately, this cascade is thought to result in extensive neuronal loss and, consequently, the onset of cognitive manifestations. Uncovering the effects on synaptic components in LSDs with neurological symptoms like AM will enable a better understanding of disease progression. It will also allow us to identify critical targets for therapeutic intervention and the determination of optimal time frames for targeted treatments, as well as the effects of these treatments on mitochondrial function. The available therapeutic modalities in AM are not a definitive cure for affected patients, but rather an attempt to reduce the symptomatic severity in their presentation, while aiming to regress/slow down disease progression. This review will aim to discuss and rationalize the current treatment approaches in place for AM patients in relation to their effects on the improvement of neurocognitive symptoms in affected AM individuals.

Differential cognitive and behavioral development from 6 to 24 months in autism and fragile X syndrome

BackgroundSpecifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants.MethodsThe current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls.ResultsInfants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD.ConclusionsOur results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.

Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain.

A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse brain, combining short- and long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum of age-related changes, including differences in isoform usage, decreased mRNA dynamics and a module showing increased expression of neuronal genes. Notably, our results indicate a reduced abundance of mRNA isoforms leading to nonsense-mediated RNA decay and suggest a regulatory role for RNA-binding proteins, indicating that their regulation may be altered leading to the reshaping of the aged brain transcriptome. Collectively, our study highlights the importance of studying mRNA splicing events during brain aging.

A 5-year-old girl case of spastic paraplegia type 56, a mutation in the CYP2U1 gene

This case report details the presentation, diagnosis, and management of a 5-year-old girl from Saudi Arabia with Spastic Paraplegia Type 56 (SPG56) resulting from a novel mutation in the CYP2U1 gene. SPG56, a rare form of hereditary spastic paraplegia, exhibits genetic variability, impacting neurological and extra-neurological functions. The patient's clinical course involved a fall at age 2, subsequent motor deterioration, cognitive delays, and spasticity. Comprehensive diagnostic evaluations, including genetic testing, identified a homozygous likely pathogenic variant in CYP2U1. Despite outpatient therapy, the patient underwent a four-week intensive rehabilitation course to address spasticity and enhance daily living activities. This case highlights the challenges in diagnosing and managing SPG56 and underscores the importance of genetic testing in complex neurodegenerative cases.

Socio-familial environment influence on cognitive and language development in very preterm children.

Preterm children are at increased risk of cognitive and language delay compared with term-born children. While many perinatal factors associated with prematurity are well established, there is limited research concerning the influence of the socio-familial environment on the development of preterm children. This study aims to assess the relative impact of perinatal and socio-familial risk factors on cognitive and language development at 2years corrected age (CA). This retrospective cross-sectional study included preterm infants with a gestational age <32 weeks and/or a birth weight <1500 g, who underwent neurodevelopmental assessment at 2years CA. Cognitive and language scores were assessed using the Bayley Scales of Infant-Toddler Development, third edition. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated using a multivariable model to examine the relationship between developmental delays and perinatal and socio-familial factors. The prevalence of language delay was negatively associated with daycare attendance (aOR: 0.25, 95% CI: 0.07-0.85, p < 0.05) and high maternal educational levels (aOR: 0.24, 95% CI: 0.05-0.93, p < 0.05) and positively associated with bilingual environments (aOR: 5.62, 95% CI: 1.46-24.3, p < 0.05). Perinatal and postnatal risk factors did not show a significant impact on cognitive or language development. The development of language appears to be more influenced by the socio-familial environment than by early perinatal and postnatal factors associated with prematurity. These findings highlight the importance of considering socio-familial factors in the early identification and intervention of language delay among preterm children.

Developing a practical neurodevelopmental prediction model for targeting high-risk very preterm infants during visit after NICU: a retrospective national longitudinal cohort study

BackgroundFollow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability.MethodsWe developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score < 85 at 24 months CA. We used an evolutionary-derived machine learning method (EL-NDI) to develop models and compared them to those built by lasso regression, random forest, and support vector machine.ResultsOne thousand two hundred forty-four VPI were in the developmental set and the two validation cohorts had 763 and 1347 VPI, respectively. EL-NDI used only 4–10 variables, while the others required 29 or more variables to achieve similar performance. For models at 6 months CA, the area under the receiver operating curve (AUC) of EL-NDI were 0.76–0.81(95% CI, 0.73–0.83) for cognitive regress with 4 variables and 0.79–0.83 (95% CI, 0.76–0.86) for motor regress with 4 variables. For models at 12 months CA, the AUC of EL-NDI were 0.75–0.78 (95% CI, 0.72–0.82) for cognitive delay with 10 variables and 0.73–0.82 (95% CI, 0.72–0.85) for motor delay with 4 variables.ConclusionsOur EL-NDI demonstrated good performance using simpler, transparent, explainable models for clinical purpose. Implementing these models for VPI during follow-up visits may facilitate more informed discussions between parents and physicians and identify high-risk infants more effectively for early intervention.

Factors that influence performance in pediatric cochlear implant recipients with cochlear nerve deficiency

Objectives Children with cochlear nerve deficiency (CND) have wide variability in outcomes with cochlear implant (CI) use. The current study aims to report a large cohort of pediatric CI recipients with CND and to evaluate for factors that may predict improved performance. Methods The current study is a retrospective review of pediatric CI recipients with CND at a tertiary academic hospital. Variables including cochlear nerve status (hypoplasia vs aplasia), age at implantation, cochleovestibular malformation, bony cochlear nerve aperture, internal auditory canal aperture, and cognitive delay were evaluated for predictors of postoperative performance. A stepwise multinomial regression analysis was performed. Results Forty-seven CI recipients (54 ears) were included in the analysis. A majority (59%) showed auditory capabilities with their CI. Twenty percent of recipients achieved some level of open-set speech perception with their CI. The regression analysis identified cochlear nerve status and cognitive delay as predictors of performance. CI recipients with cochlear nerve hypoplasia had significantly improved performance compared to those with aplasia (p = 0.003). Recipients with cognitive delay had more limited benefit than those without cognitive delay (p = 0.033). Conclusions Children with CND can benefit from CI use, with outcomes spanning from non-use to development of spoken language. Predictive factors for improved performance include a lack of cognitive delay and cochlear hypoplasia rather than aplasia. These can be important considerations for parent counseling and decision making.

Supporting cognitive catch-up: The effects of cluster-randomized psychosocial stimulation interventions on preterm low birthweight children in rural China.

Improved survival of preterm low birthweight (LBW) infants due to advances in neonatal care has brought issues such as postnatal development trajectories to the foreground. This study pools evidence from three cluster-randomized experiments evaluating community-based psychosocial stimulation programs conducted from 2014 to 2017 that included 3571 rural Chinese children aged 6-24 months (51.1% male, 96.2% Han Chinese). The risk of severe cognitive delay was found to be 26.5 percentage points higher for preterm LBW children than for their peers at age 2.5, with a prevalence rate of 48.3%. Results show that psychosocial stimulation interventions can improve child cognitive development at scale, with beneficial impacts on child cognition disproportionately larger for preterm LBW children, helping them to catch up developmentally.

Investing in disadvantaged children for common prosperity in China

Despite rapid economic growth in China since 1978, rural-urban inequality has widened. High levels of socioeconomic inequality can have profound implications for child development and lifelong educational equity. Using a dataset containing early childhood development (ECD) outcomes of 0- to 3-year-olds (N = 9,053) from study sites in Eastern, Central, and Western China, the study finds that the risks of cognitive, language, and motor delay are, respectively, 43.2, 18.3, and 20.7 percentage points higher in rural study sites than in urban Shanghai (ps < .01). Impact evaluation of cluster-randomized experiments shows that parental training (focusing on child psychosocial stimulation and caregiver-child interaction) can improve parenting beliefs and practices (or investments) and ECD outcomes of disadvantaged rural children (p<.01). Such programs can play an important role in advancing progress toward more social equality and economic equity, the stated goals of China’s “Common Prosperity” policy.

Late Neonatal Sepsis in Very-low-birth-weight Premature Newborns Is Associated With Alterations in Neurodevelopment at Twenty-five Months of Age.

To evaluate the impact of late-onset sepsis (LOS) on the neurodevelopment of very-low-birth-weight (VLBW) premature infants. This is a retrospective cohort study of VLBW premature infants. The Mental Development Index (MDI) was determined for a population of 546 VLBW infants, at 14 and 25 months of age, and evaluated using the Bayley test. A history of meningitis or early neonatal sepsis was considered an exclusion criterion. The study parameters analyzed included perinatal variables, the development of neonatal comorbidities and a history of LOS. Multivariate linear regression and multinomial logistic regression analyses were performed. LOS was observed in 115 newborns, among whom microbiological testing showed that 65.0% presented Gram-positive bacteria, with Staphylococcus epidermidis being responsible for 55.4%. There was a significant association between the 25-month MDI and a history of LOS. This represents a decrease of 7.9 points in the MDI evaluation of newborns with a history of LOS. The latter history is also associated with the following neurodevelopmental alternations: mild motor disorders [odds ratio (OR): 2.75; 95% confidence intervals (CI): 1.07-7.05], moderate cognitive delay (OR: 3.07; 95% CI: 1.17-8.00) and cerebral palsy (OR: 2.41; 95% CI: 1.09-5.35). In our study cohort, LOS was associated with alterations in neurodevelopment, including reduced MDI, together with motor and cognitive disorders and cerebral palsy. To improve neurodevelopmental outcomes in this group of newborns, neonatal intensive care unit personnel should focus attention on preventing hospital-acquired infections.

The Relationship between Sleep Disturbance and Early Alzheimer's Disease – Mild Cognitive Impairment

During sleep, the brain can clear toxins related to Alzheimer's disease. Compared with the baseline without sleep disorder, subjects with sleep disorder have a 1.49-fold increased risk of Alzheimer's disease. There is a two-way relationship between sleep/wakefulness disorder and Alzheimer's disease pathology. Sleep plays an important role in memory consolidation. Research shows that sleep disorder may have an important impact on the symptoms and course of Alzheimer's disease. Therefore, we need to better understand the mechanism of cognitive and behavioral impairment related to Alzheimer's disease, and delay the progress of the disease by improving sleep. The risk of Alzheimer's disease in individuals with sleep disorder is higher than that in individuals without sleep disorder; Improving sleep can improve cognitive level and delay the development of cognitive impairment; DORA is an effective strategy to improve sleep disorder, neurodegeneration and cognitive impairment in patients with Alzheimer's disease.

Parent Fidelity Mediates the Effect of Project ImPACT on Vocal Complexity

Younger siblings of autistic children are at a high likelihood (HL) of autism, language, and/or cognitive delays. Vocal complexity, a continuous measure of the developmental maturity of vocal communication, is facilitated by parent-child interaction and predicts language outcomes. This study examined whether parents’ intervention fidelity to Project ImPACT, a 12-week, parent-mediated, naturalistic developmental behavioral intervention (NDBI), mediated the effect of Project ImPACT on parents’ verbal responsiveness (post-intervention) and children’s vocal complexity (3 months post-intervention). Participants were 54 12- to 24-month-old HL child-parent dyads who received 12 weeks of Project ImPACT ( n = 28) or business-as-usual ( n = 26) . Project ImPACT indirectly improved both parents’ verbal responsiveness and children’s vocal complexity by improving parents’ use of the intervention techniques. The efficacy of Project ImPACT in supporting early social communication might be attributed to how Project ImPACT helps parents improve the quality and frequency of their use of the intervention strategies across children’s everyday settings.