Neurodevelopmental Assessment Research Articles

Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.

The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72mol/L), ZD7288 (50μmol/L), and KN-62 (10μmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.

Brain volume and neurodevelopment at 13 years following sepsis in very preterm infants.

Associations of neonatal infection with brain growth and later neurodevelopmental outcomes in very preterm (VP) infants are unclear. This study aimed to assess associations of neonatal sepsis in VP infants with (1) brain growth from term-equivalent age to 13 years; and (2) 13-year brain volume and neurodevelopmental outcomes. 224 infants born VP ( < 30 weeks' gestation/<1250 g birthweight) were recruited. Longitudinal brain volumes for 68 cortical and 14 subcortical regions were derived from MRI at term-equivalent, 7 and/or 13 years of age for 216 children (79 with neonatal sepsis and 137 without). 177 children (79%) had neurodevelopmental assessments at age 13. Of these, 63 with neonatal sepsis were compared with 114 without. Brain volumetric growth trajectories across time points were compared between sepsis and no-sepsis groups using mixed effects models. Linear regressions compared brain volume and neurodevelopmental outcome measures at 13 years between sepsis and no sepsis groups. Growth trajectories were similar and there was little evidence for differences in brain volumes or neurodevelopmental domains at age 13 years between those with or without sepsis. Neonatal sepsis in children born VP does not appear to disrupt subsequent brain development, or to have functional consequences in early adolescence. Neonatal sepsis has been associated with poorer short-term neurodevelopmental outcomes and reduced brain volumes in very preterm infants. This manuscript provides new insights into the long-term brain development and neurodevelopmental outcomes of very preterm-born children who did or did not have neonatal sepsis. We found that regional brain volumes up to 13 years, and neurodevelopmental outcomes at age 13, were similar between those with and without neonatal sepsis. The links between neonatal sepsis and long-term neurodevelopment remain unclear.

Inpatient Skin-to-Skin Care Predicts 12-month Neurodevelopmental Outcomes in Very Preterm Infants

To examine the relationship between inpatient skin-to-skin care rates and neurodevelopmental scores measured at 12 months in very preterm infants. From a retrospective review of medical records of 181 very preterm infants (<32 weeks gestational age [GA]at birth), we derived skin-to-skin care rate, ie, total minutes of skin-to-skin care each infant received over the number of days of hospital stay. We used scores on the Capute Scales from routine follow-up assessments at 12 months to measure neurodevelopmental outcomes. Families averaged approximately 17 minutes/day of skin-to-skin care (2 days/week, 70 minutes/session), although there was substantial variability. Variation in skin-to-skin rate was positively associated with outcomes at 12 months corrected age (r = 0.25, p < .001). Skin-to-skin rate significantly predicted 6.2% unique variance in 12-month neurodevelopmental outcomes, after adjusting for GA, socioeconomic status (SES), health acuity, and visitation frequency. A 20-minute increase in skin-to-skin care per day was associated with a 10-point increase (0.67 SDs) in neurodevelopmental outcomes at 12 months. GA, and infant health acuity did not moderate these relations. Very preterm infants who experienced more skin-to-skin care during hospitalization demonstrated higher scores on 12-month neurodevelopmental assessments. Results provide evidence that skin-to-skin care confers extended benefits to very preterm infants through the first year of life. Skin-to-skin care offers promise as part of family-centered interventions designed to promote positive developmental outcomes in at-risk infants.

Sleep Disturbance in Children with Fetal Alcohol Spectrum Disorder and the Relationship to the Neurodevelopmental Profile.

Sleep disturbance is an important feature of fetal alcohol spectrum disorder (FASD). We sought to describe sleep patterns in school-aged children with FASD, in comparison with a typically developing community group, and investigate the relationship between sleep and neurodevelopmental profiles. The FASD cohort (N = 36) was recruited from a tertiary Australian FASD diagnostic center, and the typically developing group (N = 36) was previously recruited as a control cohort for a separate study. Sleep disturbance was assessed with the caregiver-completed Sleep Disturbance Scale for Children (SDSC) questionnaire. Neurodevelopmental assessment results for the 10 domains impaired in FASD were used for correlations with sleep disturbance. In the FASD group, 80% of children scored above the SDSC cutoff, compared with 22% of the control group (p < 0.001). Statistically significant group differences were seen for all 6 subscales of the SDSC (p < 0.05). The most frequently affected domains in the FASD group related to difficulties with initiating and maintaining sleep (58%), sleep-wake transition disorders (44%), and disorders of arousal (42%). A statistically significant relationship was not found between sleep and the severity of neurodevelopmental impairment or impairment of a particular domain, acknowledging the limitations of our small sample size. Half of the FASD sample (52%) were taking a pharmaceutical agent to support sleep, which was not associated with lower SDSC scores. In this small study, sleep disturbances were frequently reported by carers of children with FASD, independent of the severity of their neurodevelopmental impairments. Persistent sleep disturbance despite the use of sleep medications highlights the need for prospective studies exploring sleep interventions in this population. Integration of behavioral sleep medicine into management is recommended for all children with FASD.

Neurodevelopment Outcome among Preterm Infants Admitted in Neonatal Intensive Care Unit

Introduction: With increasing the survival rates of premature babies, the management of long term complications, especially neurodevelopmental disorder is becoming an important issue for a better life. Aims: To assess the factors associated with adverse neurodevelopment outcome among preterm infants admitted in Neonatal Intensive Care Unit (NICU). Methods and Material: This prospective cohort study was conducted in Department of Neonatology, BSMMU, Dhaka, Bangladesh. Premature infants (&lt;34 weeks) discharged from the NICU were enrolled and followed up for neurodevelopmental assessment at 6 months of age. Prenatal, perinatal, and postnatal features of the babies were recorded. The Bayley-III scale was used to assess the composite scores. Continuous variables were analyzed using an independent t-test and categorical variables with chi-square test. Logistic regression analysis was performed to find out the relationship of risk factors with neurodevelopmental scores. Results: A total 47 patients were analysed at 6 months of age using Bayley scale III. Mean birth weight and gestational age was 1595.11 ± 377.17g and 32.43 ± 1.48 weeks respectively. Mean cognitive, motor and language score were 80.79±14.51, 82.87±14.53 and 82.98±13.72 respectively. Despite the fact that all mean scores were normal, 27.7% of infants in cognition, 23.4% in motor, and 31.9% in language had a BSID-III value &lt; 70. Variables like gestational age &lt; 30 weeks, birth weight &lt;1500 grams, and convulsion have been linked to poor neurodevelopmental outcomes. However, regression analysis revealed none of them were significant. Conclusions: In our study, at six months of age, the cognitive, language, and motor scores of preterm newborns (less than 34 weeks of gestation) were within normal limits. Of the newborns, we observed that 27.7% had cognitive delay and 31.9% experienced language delay. J Dhaka Med Coll. 2022; 31(2) : 251-257

Prediction of Cerebral Palsy and Other Motor Developmental Trajectories in High-Risk Neonate Using the Rapid Neurodevelopmental Assessment (RNDA)

Background: Cerebral Palsy (CP) is a prevalent motor disability affecting children globally, emphasizing the need for early identification and intervention. The Rapid Neurodevelopmental Assessment (RNDA) offers a comprehensive approach to predict CP and other motor developmental trajectories in high-risk neonates. Objective: This longitudinal cohort study aims to evaluate the effectiveness of RNDA in predicting CP and motor developmental trajectories. Method: Seventy term neonates from Dhaka Shishu (Children) Hospital were included, with neurodevelopmental assessments conducted using RNDA. Assessments were performed at 3 months and 6-9 months, with CP evaluation at 12 months using clinical examinations. Results: Prolonged labor (44.3%) and delayed cry after birth (31.4%) were common among the study patients (n=70), with varying modes of delivery including normal vaginal delivery (50.0%), vaginal delivery with complications (12.9%), and lower uterine cesarean section (37.1%). Muscle tone, primitive reflexes, gross and fine motor skills, epilepsy, and microcephaly were evaluated across visits to identify impending CP. Significant associations were found between hypertonicity, primitive reflex impairment, gross motor impairment, and fine motor impairment with impending CP across visits, particularly in the 3rd visit (p&lt;0.05). Sensitivity, specificity, accuracy, and predictive values varied across parameters and visits, with fine motor skills and gross motor skills showing the highest sensitivity in the 3rd visit (86.4% and 100.0%, respectively). Additionally, abnormal EEG, USG of the brain, and MRI findings were significantly associated with impending CP, with USG of the brain demonstrating the highest sensitivity (93.3%) and MRI showing the highest specificity (70.0%). Conclusion: RNDA emerges as a valuable tool for early prediction of CP and motor developmental trajectories in high-risk neonates. Early identification through RNDA facilitates timely interventions, optimizing long-term neurodevelopmental outcomes.

Feasibility and success of a non-sedated brain MRI training protocol in 7-year-old children from rural and semi-rural Colombia.

Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.

Long-term developmental outcomes of children with congenital Zika syndrome.

Eight years after the epidemics in Brazil, children with congenital Zika syndrome (CZS) and their families confront ongoing health challenges. This study aims to characterize how virally induced prenatal brain injury impacts development and functional outcomes among children diagnosed with CZS. We performed a cross-sectional study of a consecutive series of children diagnosed with CZS. Using validated neurodevelopmental assessments, we evaluated gross motor function, manual ability, communication, eating and drinking, and visual function. Sixty children (29 males, and 31 females) met the inclusion criteria for the study. Comorbidities such as epilepsy (90.0%) and undernutrition (38.3%), along with clinical conditions including dysphagia (68.3%) and dependence on tube feeding (31.7%), were observed. Our results demonstrate a majority of children at level V - the most severe level within a five-tier system - in the Gross Motor Function (86.7%), Manual Ability (85.0%), Communication Function (68.3%), Eating and Drinking Ability (40.0%) Classification Systems, and level IV in the Visual Function Classification System (38.3%). CZS is associated with severe functional impairments and comorbidities, adversely impacting child development and quality of life. These findings reveal persistent challenges affecting the functioning of children with CZS, underscoring the need for continued support and specialized care. This study aimed to characterize the long-term clinical and functional characteristics of a subset of children with Congenital Zika Syndrome (CZS). We found that eight years after the Brazilian Zika epidemic, this subset of children with CZS continues to demonstrate major functional limitations impacting mobility, vision, and the ability to eat and drink. Our analysis documented a very high level of disability in several key functional classification systems. Notably, applying a new instrument for visual ability among children diagnosed with cerebral palsy, we found that more than 60% of the study group have poor or very poor visual function.

Doxapram for apnoea of prematurity and neurodevelopmental outcomes at age 5–6 years

ObjectiveTo assess the long-term neurodevelopmental impact of doxapram for treating apnoea of prematurity.DesignSecondary analysis of the French national cohort study EPIPAGE-2. Recruitment took place in 2011. A standardised neurodevelopmental assessment...

Parent-reported health outcomes at preschool age in preterm survivors: a population-based cohort study

ObjectiveLiterature on health status (HS) and health-related quality of life of preterm survivors at preschool age is sparse. Further, little is known about the relationship between parent-reported HS outcomes and...

Early cognitive assessment in premature infants: the discriminatory value of eye-tracking vs. Bayley Scales.

The testing of visuocognitive development in preterm infants shows strong interactions between perinatal characteristics and cognition, learning and overall neurodevelopment evolution. The assessment of anticipatory gaze data of object-location bindings via eye-tracking can predict the neurodevelopment of preterm infants at the age of 3 years; little is known, however, about the early cognitive function and its assessment methods during the first year of life. The current study presents data from a novel assessment tool, a Delayed Match Retrieval (DMR) paradigm via eye-tracking was used to measure visual working memory (VWM) and attention skills. The eye-tracking task that was designed to measure infants' ability to actively localize objects and to make online predictions of object-location bindings. 63 infants participated in the study, 39 preterm infants and 24 healthy full term infants - at a corrected age of 8-9 months for premature infants and similar chronological age for full term infants. Infants were also administered the Bayley Scales of Infant and Toddler Development. The analysis of the Bayley scores showed no significant difference between the two groups while the eye-tracking data showed a significant group effect on all measurements. Moreover, preterm infants' VWM performance was significantly lower than full term's. Birth weight affected the gaze time on all Areas Of Interest (AOIs), overall VWM performance and the scores at the Cognitive Bayley subscale. Furthermore, preterm infants with fetal growth restriction (FGR) showed significant performance effects in the eye-tracking measurements but not on their Bayley scores verifying the high discriminatory value of the eye gaze data. Visual working memory and attention as measured via eye-tracking is a non-intrusive, painless, short duration procedure (approx. 4-min) was found to be a significant tool for identifying prematurity and FGR effects on the development of cognition during the first year of life. Bayley Scales alone may not pick up these deficits. Identifying tools for early neurodevelopmental assessments and cognitive function is important in order to enable earlier support and intervention in the vulnerable group of premature infants, given the associations between foundational executive functional skills and later cognitive and academic ability.

Does surgery affect the neurodevelopmental outcome of moderate laryngomalacia?

BackgroundModerate laryngomalacia lies in the grey zone where the parents and treating team might hesitate to decide the treatment plan for the child. Neurodevelopmental assessment of the child was neither assessed nor incorporated in surgical decision-making in the past. ObjectivesTo evaluate the neurodevelopmental outcome of moderate laryngomalacia treatment strategies (surgery versus conservative). MethodsWe conducted an observational multicentric cohort study. We compared two groups of patients according to their moderate laryngomalacia treatment strategy: surgical treatment and no treatment. The neurodevelopmental outcome was assessed by Griffiths-III developmental scales. ResultsA total of 150 children were diagnosed with moderate laryngomalacia of which 56 were successfully treated with surgery and 94 improved without intervention. The median Griffiths-III developmental quotients (DQs) of subscales A, B, C, E, and general development were significantly higher in the surgically treated group compared to conservatively treated ones. ConclusionUntreated moderate laryngomalacia cases have worse neurodevelopmental outcomes than surgically treated cases.

Risk factors for PDA ligation and neurodevelopmental outcomes at corrected 18–24 months in very low birth weight infants

BackgroundPatent ductus arteriosus (PDA) is commonly encountered morbidity which often occurs as up to 60% of extremely preterm infants born at < 29 weeks gestational age (GA).PurposeThis study aims to assess the clinical risk factors associated with PDA ligation among very low birth weight infants (VLBWI) and evaluate the neurodevelopmental outcomes of those who underwent PDA ligation.MethodsA total of 540 VLBWI were initially diagnosed with PDA in our 50-bed level IV NICU at Seoul St. Mary’s Hospital, The Catholic University of Korea, between January 2015 and June 2023. Among these 540 VLBWI with PDA, only 221 had consistent hemodynamically significant (hs) PDA which required intervention including fluid restriction, medical treatment, or surgical ligation. In this study, only those 221 VLBWI with hsPDA who underwent neurodevelopmental assessment at corrected 18–24 months of age were included in this study analysis.ResultsOut of 221 VLBWI diagnosed with hemodynamically significant (hs) PDA, 133 (60.2%) underwent PDA ligation, while the remaining 88 (39.8%) had their hs PDAs closed either medically or with fluid restriction. The mean gestational age and birth weight were significantly lower in PDA ligation group compared to no PDA ligation group (27.02 ± 2.17 vs. 27.98 ± 2.36, 907.31 ± 258.36 vs. 1006.07 ± 283.65, p = 0.001, 0.008). Resuscitation including intubation at delivery and intraventricular hemorrhage (IVH) (grade ≥ 3) were significantly higher in PDA ligation group. The clinical outcomes in the PDA ligation group revealed significantly worse oucomes compared to the no PDA ligation group. Both resuscitation, including intubation at delivery, and IVH (grade ≥ 3), consistently exhibited an increased risk for PDA ligation in a multivariable logistic regression analysis. Concerning neurodevelopmental outcomes, infants who underwent PDA ligation demonstrated significantly lower cognitive scores. However, only IVH (grade ≥ 3) and PVL were consistently associated with an increased risk of abnormal neurodevelopment at the corrected age of 18–24 months.ConclusionIn our study, despite the consistent association between cognitive developmental delays in VLBWI who underwent PDA ligation, we observed that sicker and more vulnerable VLBWIs, specifically those experincing severe IVH, consistently exhibited an increased risk for both PDA ligation and abnormal neurodevelopment at the corrected age of 18–24 months.

Validating cognitive screening in young people with first-episode psychosis: The CogScreen protocol.

Cognitive impairments are a core feature of first-episode psychosis (FEP) and one of the strongest predictors of long-term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support. However, there are currently no validated screening measures for young people with FEP. CogScreen is a hybrid effectiveness-implementation study which aims to evaluate the classification accuracy (relative to a neuropsychological assessment as a reference standard), test-retest reliability and acceptability of two cognitive screening tools in young people with FEP. Participants will be 350 young people (aged 12-25) attending primary and specialist FEP treatment centres in three large metropolitan cities (Adelaide, Sydney, and Melbourne) in Australia. All participants will complete a cross-sectional assessment over two sessions including two cognitive screening tools (Screen for Cognitive Impairment in Psychiatry and Montreal Cognitive Assessment), a comprehensive neuropsychological assessment battery, psychiatric and neurodevelopmental assessments, and other supplementary clinical measures. To determine the test-retest reliability of the cognitive screening tools, a subset of 120 participants will repeat the screening measures two weeks later. The protocol, rationale, and hypotheses for CogScreen are presented. CogScreen will provide empirical evidence for the validity and reliability of two cognitive screening tools when compared to a comprehensive neuropsychological assessment. The screening measures may later be incorporated into clinical practice to assist with rapid identification and treatment of cognitive deficits commonly experienced by young people with FEP.

Phenylbutyrate Treatment in a Boy with MCT8 Deficiency: Improvement of Thyroid Function Tests and Possible Livertoxicity.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare X-chromosomal inherited disease leading to severe cognitive impairment, muscular hypotonia and symptoms of peripheral thyrotoxicosis. Experimental approaches aiming to functionally rescue mutant MCT8 activity by the chemical chaperone phenylbutyrate (PB) demonstrated promising effects in vitro for several MCT8 missense mutations. The objective was to evaluate biochemical and clinical effects of PB in doses equivalent to those approved for the treatment of urea cycle disorders in a boy with MCT8 deficiency due to a novel MCT8 missense mutation c.703G > T (p.V235L). During a treatment period of 13 months, PB led to a significant decrease of elevated TSH and T3 serum concentrations, while fT4 increased. Weight z-score of the toddler remained remarkably stable during the treatment period. Neurodevelopmental assessments (BSID-III) revealed a slight increase of gross motor skills from developmental age 4 to 6 months. However, increasing liver enzyme serum activities and accumulation of phenylacetate (PAA) in urine led to treatment interruptions and dose alterations. In vitro analyses in MDCK1 cells confirmed the pathogenicity of MCT8 p.V235L. However, while PB increased expression of the mutant protein, it did not rescue T3 transport, suggesting a PB effect on thyroid function tests independent of restoring MCT8 activity. In a clinical attempt of PB treatment in MCT8 deficiency we observed a significant improvement of thyroid hormone function tests, tendencies towards body weight stabilization and slight neurodevelopmental improvement. Hepatotoxicity of PB may be a limiting factor in MCT8 deficiency and requires further investigation.

Research gaps in the neurodevelopmental assessment of children with complex congenital heart defects: a scoping review

BackgroundChildren with congenital heart defects (CHD) are at risk for a range of developmental disabilities that challenge cognition, executive functioning, self-regulation, communication, social-emotional functioning, and motor skills. Ongoing developmental surveillance is therefore key to maximizing neurodevelopmental outcome opportunities. It is crucial that the measures used cover the spectrum of neurodevelopmental domains relevant to capturing possible predictors and malleable factors of child development.ObjectivesThis work aimed to synthesize the literature on neurodevelopmental measures and the corresponding developmental domains assessed in children aged 1−8 years with complex CHD.MethodsPubMed was searched for terms relating to psycho-social, cognitive and linguistic-communicative outcomes in children with CHD. 1,380 papers with a focus on complex CHD that reported neurodevelopmental assessments were identified; ultimately, data from 78 articles that used standardized neurodevelopmental assessment tools were extracted.ResultsThirty-nine (50%) of these excluded children with syndromes, and 9 (12%) excluded children with disorders of intellectual development. 10% of the studies were longitudinal. The neurodevelopmental domains addressed by the methods used were: 53% cognition, 16% psychosocial functioning, 18% language/communication/speech production, and 13% motor development-associated constructs.ConclusionsData on social communication, expressive and receptive language, speech motor, and motor function are underrepresented. There is a lack of research into everyday use of language and into measures assessing language and communication early in life. Overall, longitudinal studies are required that include communication measures and their interrelations with other developmental domains.

Postnatal Growth Assessment and Prediction of Neurodevelopment and Long-Term Growth in Very Low Birth Weight Infants: A Nationwide Cohort Study in Korea.

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18-24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04-2.65), NDI (aOR, 2.09; 95% CI, 1.71-2.55), and growth failure (aOR, 1.57; 95% CI, 1.16-2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03-1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77-3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18-24 months.

Neurodevelopmental outcomes following possible serious bacterial infection in early infancy in Karachi, Pakistan: a prospective cohort study

BackgroundPakistan reports a significant burden of neonatal mortality, with infections as one of the major causes. We aim to assess the long-term impact of early infancy infections on neurodevelopmental outcomes during later childhood.MethodsWe conducted a prospective follow-up study of the cohort enrolled at the Karachi site of the Aetiology of Neonatal Infection in South Asia (ANISA) during 2019–2020. Children with a possible serious bacterial infection (based on the WHO IMCI algorithm) at early infancy were assessed for neurodevelopment at 6–9 years of age and compared with healthy controls. The Ten Questions (TQS) questionnaire, Strengths and Difficulties Questionnaire (SDQ), and Parent’s Evaluation of Developmental Stage Assessment Level (PEDS: DM-AL) neurodevelopmental assessment tools, were administered and scored by the research staff who were blinded to the child’s exposure status. Generalized Structural Equation Modelling (GSEM) was employed to verify relationships and associations among developmental milestones, anthropometry, and sociodemographic variables.ResultsA total of 398 children (241 cases and 157 controls) completed neurodevelopmental and growth assessments. Cases had a significantly higher rate of abnormal TQS scores (54.5% vs. 35.0%, p-value 0.001), greater delays in motor milestones (21.2% vs. 12.1%, p-value 0.02), lower fine motor skills (78.4 ± 1.4 vs. 83.2 ± 1.5, p-value 0.02). The receptive language skills were well-developed in both groups. According to the logistic regression model, exposure to infection during the first 59 days of life was associated with delayed TQS milestones (β = -0.6, 95% CI -1.2,-0.04), TQS hearing domain (β = -0.3, 95% CI: -1.2 to 0.7), PEDS: DM-AL fine motor domain (β = -1.3, 95% CI: -4.4 to 1.7), PEDS: DM-AL receptive language development (β = -1.1, 95% CI: -3.7 to 1.4) and child anthropometric measurements such as weight and height (β = -0.2, 95% CI: -0.4 to 0.01 and β = -0.2, 95% CI: -0.4 to -0.01, respectively). Early pSBI exposure was positively associated with PEDS: DM-AL self-help domain (β = 0.6, 95% CI: -1.2 to 2.4) and SDQ-P overall score (β = 0.02, 95% CI: -0.3 to 0.3).ConclusionChildren exposed to PSBI during early infancy have higher rates of abnormal development, motor delays, and lower fine motor skills during later childhood in Pakistan. Socioeconomic challenges and limited healthcare access contribute to these challenges, highlighting the need for long-term follow-ups with integrated neurodevelopment assessments.

Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD.

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

Neurodevelopmental Outcomes Following Childhood Viral Meningitis in Canterbury New Zealand.

Most childhood meningitis is viral in countries with widespread conjugate vaccine use. This study assessed clinical features and neurodevelopmental outcomes in preschool children following enteroviral and parechoviral meningitis. Children 18-42 months of age in Canterbury, New Zealand were included, who had enterovirus (EV) or parechovirus (HPEV) meningitis from 2015 to 2021. Comprehensive neurodevelopmental assessments were completed by a psychologist using the Bayley Scale for Infant Development-3 (BSID-3). Mean composite and scaled scores and proportion below the cutoff were assessed in each domain. Clinical data was analyzed. There were 79 children 18-42 months old with previous EV or HPEV meningitis. BSID assessments were completed for 33 children (55% male), median age 32 months, from 2019 to 2022 including 23 with EV and 10 HPEV meningitis. At diagnosis, 32 (97%) received intravenous/intramuscular antibiotics, and 6 received a fluid bolus. Parents reported developmental speech concerns in 6 children, and delayed motor milestones in 1 child. There was no reported sensorineural hearing loss. BSID mean composite scores were in the expected range for cognition 102 (confidence interval: 98-106), language 96 (93-100) and motor 102 (98-106) domains. Overall, 12/33 (36%) children had below expected scores in 1 developmental domain, including scores 1-2 SD below the normative mean for cognition (2/33; 6%), receptive language (6/33; 18%), expressive language (5/33; 15%) and gross motor (6/33; 18%). There were no differences between scores in EV and HPEV meningitis. Following viral meningitis, more than a third of preschool children had a mild developmental delay with comprehensive neurodevelopmental assessment, suggesting targeted follow-up should be considered.