Language Composite Scores Research Articles

Prenatal urinary metabolites of polycyclic aromatic hydrocarbons and toddler cognition, language, and behavior.

Animal and epidemiological studies suggest that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may negatively impact toddler neurodevelopment. We investigated this association in 835 mother-child pairs from CANDLE, a diverse pregnancy cohort in the mid-South region of the U.S. PAH metabolite concentrations were measured in mid-pregnancy maternal urine. Cognitive and Language composite scores at ages 2 and 3years were derived from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3). Behavior Problem and Competence scores at age 2 were derived from the Brief Infant and Toddler Social Emotional Assessment (BITSEA). We used multivariate linear or Poisson regression to estimate associations with continuous scores and relative risks (RR) of neurodevelopment delay or behavior problems per 2-fold increase in PAH, adjusted for maternal health, nutrition, and socioeconomic status. Secondary analyses investigated associations with PAH mixture using Weighted Quantile Sum Regression (WQS) with a permutation test extension. 1- hydroxypyrene was associated with elevated relative risk for Neurodevelopmental Delay at age 2 (RR=1.20, 95% CI: 1.03,1.39). Contrary to hypotheses, 1-hydroxynaphthalene was associated with lower risk for Behavior Problems at age 2 (RR=0.90, 95% CI: 0.83,0.98), and combined 1- and 9-hydroxyphenanthrene was associated with 0.52-point higher (95% CI: 0.11,0.93) Cognitive score at age 3. For PAH mixtures, a quintile increase in hydroxy-PAH mixture was associated with lower Language score at age 2 (βwqs=-1.59; 95% CI: -2.84, -0.34; ppermutation=0.07) and higher Cognitive score at age 3 (βwqs=0.96; 95% CI: 0.11, 1.82; ppermutation=0.05). All other estimates were consistent with null associations. In this large southern U.S. population we observed some support for adverse associations between PAHs and neurodevelopment.

White matter hyperintensities and regional tau‐PET signal independently contribute to cognitive deficits in symptomatic patients on the Alzheimer’s disease continuum

AbstractBackgroundWe examined the associations of white matter hyperintensities (WMH), amyloid‐PET, and tau‐PET with multi‐domain cognitive performance in symptomatic patients on the Alzheimer’s disease (AD) continuum.Method119 amyloid‐PET‐positive patients diagnosed with MCI or AD dementia underwent 3‐Tesla structural MRI, 18F‐flortaucipir (tau)‐PET,11C‐PIB (amyloid)‐PET, and neuropsychological assessment. Standardized uptake value ratio (SUVR) flortaucipir‐ and PIB‐PET images were created using tracer‐specific reference regions and warped to template space. Patients were split based on availability of FLAIR‐MRI (Figure 1). The exploratory sample (n=50; no FLAIR) was used to run voxelwise models to identify regions where flortaucipir‐ and PIB‐PET were associated with episodic memory, executive, language, semantic memory, and visuospatial composite scores. In the validation sample (n=69), WMH were segmented from FLAIR and T1‐MRIs using a two‐step supervised algorithm. Linear regression models assessed the independent contributions of global WMH volume (corrected for intracranial volume and log‐transformed) and cognitive domain‐specific regional PET‐SUVR (derived in the exploratory sample) to each cognitive domain.ResultThe two samples had comparable demographics and clinical characteristics, with relatively young age (mean ∼65.5) and moderate impairment (mean MMSE ∼ 22, Table 1). In the exploratory sample, cognitive scores were associated with regional flortaucipir‐SUVR patterns (Figure 2); PIB‐SUVR was not robustly associated with cognition. In the validation sample, global WMH volume was inversely correlated with global PIB‐SUVR (r=‐.25, p=.04) but not global cortical flortaucipir‐SUVR (r=‐.18, p=.15). Older age predicted lower cortical flortaucipir‐SUVR (r=‐.70, p<.001) and greater WMH volume (r=.46, p<.001). Female sex was specifically associated with greater cortical flortaucipir‐SUVR (d=0.64, p=.01; psdsps ConclusionIn patients at the early clinical stages of AD, tau‐PET and global WMH volume were not associated with each other, but independently contributed to cognitive impairment. These findings emphasize the clinical relevance of cerebrovascular injury in the context of AD pathology, even in younger patients.

Abstract 14202: Perioperative Metabolites Are Associated With Neurodevelopmental Outcomes at One Year in Neonates Undergoing Cardiopulmonary Bypass

Introduction: Improving neurodevelopmental (ND) outcomes for children with congenital heart disease has become a priority. Known clinical and surgical risk factors do not fully capture differences in ND outcomes. The objective of this study was to determine if plasma metabolites at the time of neonatal cardiac surgery were association with ND outcomes at 1 year. Methods: A secondary analysis of a clinical trial in 110 neonates undergoing cardiac surgery was performed. Plasma samples obtained pre-op, immediately post-op and at 12 hours post op had LC/MS/MS metabolomic profiling with a 193-plex targeted metabolite assay covering >366 metabolic pathways. Metabolite levels were compared to one-year neurodevelopmental outcomes measured by the Bayley Scales of Infant and Toddler Development III (BSID). Results: 40/193 metabolites were detected and quantified for analysis. Regression models utilizing metabolites and metabolite features identified associations with cognitive (n=5), language (n=4) and motor (n=10) BSID composite scores. Enrichment analysis disease pathways included seizures (tyrosine and isoleucine) and indoxyl sulfate, a known neurotoxic product from tryptophan synthesis. Conclusions: Perioperative metabolites may serve as biomarkers for prediction of 1-year ND outcomes and provide a scientific basis for targeted interventions to optimize perioperative care.

Disorders, Disabilities, and Differences: Reconciling the Medical Model with a Neurodiversity Perspective.

Zoe is a 25-month-old girl who presented to developmental-behavioral pediatrics with her parents for follow-up after receiving a diagnosis of autism spectrum disorder with global developmental delay and language impairment 3 months ago. Zoe was born by spontaneous vaginal delivery at term after an uncomplicated pregnancy, labor, and delivery. She had a routine newborn course and was discharged home with her parents 2 days after her birth.At 7 months, Zoe was not able to sit independently, had poor weight gain, and had hypertonia on physical examination. Her parents described her to tense her arms and have hand tremors when she held her bottle during feedings and reported that she had resisted their attempts to introduce pureed or other age-appropriate table foods into her diet. The Bayley Scales of Infant and Toddler Development Screening Test was administered and found a cognitive composite score of 70, language composite score of 65, and motor composite score of 67. Chromosomal microarray analysis, testing for fragile X syndrome, laboratory studies for metabolic disorders, magnetic resonance imaging of the brain, and an audiologic examination were normal. Zoe was referred to and received early intervention services including physical therapy, feeding therapy, and infant stimulation services. By 16 months, Zoe was walking independently and was gaining weight well but continued to have sensory aversions to some foods.At 22 months, Zoe was evaluated by a multidisciplinary team because of ongoing developmental concerns and concerning results on standardized screening for autism spectrum disorder completed at her 18-month preventive care visit. Her parents also reported concern about the possibility of autism spectrum disorder (ASD) because they both were diagnosed with ASD as young children. Both parents completed college and were employed full-time. Zoe's mother seemed to be somewhat anxious during the visit and provided fleeting eye contact throughout the evaluation. Zoe's father was assertive, but polite, and was the primary historian regarding parental concerns during the evaluation.Zoe was noted to have occasional hand flapping and squealing vocalizations while she roamed the examination area grabbing various objects and casting them to the floor while watching the trajectory of their movements. She did not use a single-finger point to indicate her wants or needs and did not initiate or follow joint attention. She met criteria for ASD. In discussing the diagnosis with Zoe's parents, they shared that they were not surprised by the diagnosis. They expressed feeling that Zoe was social and playful, although delayed in her language. Hence, they were more concerned about her disinterest in eating. They were not keen on behavioral intervention because they did not want Zoe to be "trained to be neurotypical." Although the mother did not receive applied behavior analysis (ABA), the father had received ABA for 3 years beginning at age 5 years. He believed that ABA negatively changed his personality, and he did not want the same for Zoe.How would you assist Zoe's parents in identification of priorities for her developmental care while ensuring respect for their perspective of neurodiversity?

Early Detection of Cognitive, Language, and Motor Delays for Low-Income Preterm Infants: A Brazilian Cohort Longitudinal Study on Infant Neurodevelopment and Maternal Practice.

Aim: This study examined the neurodevelopment trajectories, the prevalence of delays, and the risks and protective factors (adverse outcomes, environment, and maternal factors) associated with cognitive, motor, and language development for preterm infants from 4– to 24-months.Method: We assessed 186 preterm infants (24.7% extremely preterm; 54.8% very preterm; 20.4% moderate/late preterm) from 4– to 24-months using the Bayley Scales of Infant Development – III. Maternal practices and knowledge were assessed using the Daily Activities of Infant Scale and the Knowledge of Infant Development Inventory. Birth risks and adverse outcomes were obtained from infant medical profiles.Results: A high prevalence of delays was found; red flags for delays at 24-months were detected at 4– and 8-months of age. The neurodevelopmental trajectories showed steady scores across time for cognitive composite scores for extremely- and very-preterm infants and for language composite scores for the extremely- and moderate/late-preterm; a similar trend was observed for the motor trajectories of moderate/late preterm. Changes over time were restricted to motor composite scores for extremely- and very-preterm infants and for cognitive composite scores for moderate/late preterm; declines, stabilization, and improvements were observed longitudinally. Positive, strong, and significant correlations were for the neurodevelopment scores at the first year of life and later neurodevelopment at 18 and 24 months. The cognitive, language, and motor composite scores of extremely and very preterm groups were associated with more risk factors (adverse outcomes, environment, and maternal factors). However, for moderate/late preterm infants, only APGAR and maternal practices significantly explained the variance in neurodevelopment.Discussion: Although adverse outcomes were strongly associated with infant neurodevelopment, the environment and the parents’ engagement in play and breastfeeding were protective factors for most preterm infants. Intervention strategies for preterm infants should start at 4– to 8-months of age to prevent unwanted outcomes later in life.

Language function following preterm birth: prediction using machine learning

BackgroundPreterm birth can lead to impaired language development. This study aimed to predict language outcomes at 2 years corrected gestational age (CGA) for children born preterm.MethodsWe analysed data from 89 preterm neonates (median GA 29 weeks) who underwent diffusion MRI (dMRI) at term-equivalent age and language assessment at 2 years CGA using the Bayley-III. Feature selection and a random forests classifier were used to differentiate typical versus delayed (Bayley-III language composite score <85) language development.ResultsThe model achieved balanced accuracy: 91%, sensitivity: 86%, and specificity: 96%. The probability of language delay at 2 years CGA is increased with: increasing values of peak width of skeletonized fractional anisotropy (PSFA), radial diffusivity (PSRD), and axial diffusivity (PSAD) derived from dMRI; among twins; and after an incomplete course of, or no exposure to, antenatal corticosteroids. Female sex and breastfeeding during the neonatal period reduced the risk of language delay.ConclusionsThe combination of perinatal clinical information and MRI features leads to accurate prediction of preterm infants who are likely to develop language deficits in early childhood. This model could potentially enable stratification of preterm children at risk of language dysfunction who may benefit from targeted early interventions.ImpactA combination of clinical perinatal factors and neonatal DTI measures of white matter microstructure leads to accurate prediction of language outcome at 2 years corrected gestational age following preterm birth.A model that comprises clinical and MRI features that has potential to be scalable across centres. It offers a basis for enhancing the power and generalizability of diagnostic and prognostic studies of neurodevelopmental disorders associated with language impairment.Early identification of infants who are at risk of language delay, facilitating targeted early interventions and support services, which could improve the quality of life for children born preterm.

Maternal emotional and physical intimate partner violence and early child development: investigating mediators in a cross-sectional study in a South African birth cohort

ObjectivesThis study investigated associations between recent maternal intimate partner violence (IPV) (emotional, physical and sexual) and child development at 2 years as well as whether maternal depression or alcohol use...

Predictors of behavioural and emotional outcomes in toddlers with congenital heart disease.

Children with congenital heart disease (CHD) are at risk for psychological challenges, including internalising (e.g., depression, anxiety) and externalising (e.g., aggression, inattention) problems. The present study aimed to investigate the development of psychological concerns in early childhood by identifying predictors of behavioural and emotional problems in toddlers with CHD. Children with CHD who were seen for neurodevelopmental (ND) evaluation at 12 ± 3 months of age, who completed the Bayley Scales of Infant Development-III (BSID-III) and whose parents completed the Child Behavior Checklist (CBCL), a standardised measure of emotional/behavioural problems at age 24-36 months, were included in the study (n = 144). CBCL scores were compared to test norms and classified as normal or abnormal. A classification tree was used to assess the association between CBCL scores and demographic and clinical variables. Multi-variable tree analyses revealed lower BSID-III language composite scores at age 9-15 months predicted clinical CBCL internalising (p < 0.001), externalising (p = 0.004) and total scores (p < 0.001) at age 24-36 months. Lower maternal education levels also predicted clinical CBCL internalising (p < 0.0001), externalising (p < 0.001) and total scores (p < 0.0001). Lower language abilities and lower maternal education predict increased behavioural and emotional problems in toddlers with CHD. These risk factors should be considered during routine ND evaluations to allow for earlier identification of children with CHD and their families who may benefit from psychological support.

A-68 Neuropsychological Predictors of Seizure Freedom in Patients Undergoing Stereotactic Laser Ablation of the Hippocampus (SLAH) for Refractory Epilepsy

Abstract Objective Presurgical cognitive and psychiatric status can serve as predictors of surgical outcomes; however, there are no studies that assess the predictive nature of cognitive factors and psychiatric illness on seizure freedom following stereotactic laser ablation, a novel, minimally invasive surgical approach, of the hippocampus (SLAH). Therefore, this study aimed to assess whether neuropsychological factors were associated with long-term postoperative outcome, defined as time maintaining continuous postoperative seizure freedom (Engel Class I outcome persistently after surgery), after mesial temporal laser ablation surgery. Method Forty-one patients (Age M = 37.5 ± 12.6; 61% female; 63% left mesial temporal ablation; 37% right mesial temporal ablation) were selected from retrospective data collection of epilepsy surgery outcomes following mesial temporal laser ablation. Patients were assessed with a presurgical neuropsychological battery as part of Phase I work-up. Results Wilcoxon rank-sum tests revealed there were no significant differences between groups (seizure free and non-seizure free) across presurgical intellectual functioning, (seizure free M = 37.6; non-seizure free M = 40.6; p = 0.31), verbal memory (p = 0.59), visual memory (p = 0.39), and language composite scores (p = 0.87). There was also no significant difference in presurgical mean depression scores (p = 0.81). Conclusions There were no significant differences between groups in presurgical cognitive and psychiatric predictors on seizure outcomes; however, sample size is a limitation. Further investigations are needed given that cognitive and psychiatric predictors may be associated with SLAH outcomes. Additionally, these findings add to the absence of literature on cognitive and psychiatric predictors in SLAH.

Neonatal stroke: Clinical characteristics and neurodevelopmental outcomes

Neonatal stroke can potentially result in significant neurological sequelae in affected infants. Studies on neurodevelopmental outcomes and the need for rehabilitation therapies in the first two years are limited. We aimed to describe the clinical characteristics, diagnostic evaluation, and neurodevelopmental outcomes of a cohort of infants with neonatal stroke. A retrospective cohort study of infants with neonatal stroke, from 2011 to 2020. Maternal and infant characteristics were described. Placental pathology, echocardiogram results, and prothrombotic evaluations were reported. The neurodevelopmental outcomes using Bayley scale of infant development (BSID III), rates of epilepsy and cerebral palsy, and the need for rehabilitation therapies at two years were described. During the study period, 55 infants had neonatal stroke. Majority (93%) were term or late preterm infants. Maternal chorioamnionitis and perinatal HIE were diagnosed in about a third of the infants. Most (66%) of the infants presented with seizures. On brain MRI, the lesions were unilateral in 76% and arterial in origin in 86% of the infants. Meconium exposure (42%), intrauterine inflammation/infection (37%) and fetal vascular malperfusion (16%) were seen on placental histopathology. At two-year BSID III assessment, median (min, max) composite cognitive, language, and motor scores were 100 (55-145), 97 (47-124), and 100 (46-141), respectively. Among this cohort, epilepsy (27%), cerebral palsy (16%) and the need for rehabilitation therapies (physical -24%, occupational -18%, speech -21%) were reported at two years. Neonatal stroke presented commonly in term or late preterm infants with seizures. It was unilateral and arterial in origin in most infants. Maternal chorioamnionitis and perinatal HIE were the most commonly associated conditions at birth. About one-fifth of the infants had mild or severe developmental delays at two years. Epilepsy, cerebral palsy, and need for rehabilitation therapies were noted in a significant proportion of infants at two years.

Impact of Brain Malformations on Neurodevelopmental Outcome in Children with a History of Prenatal Surgery for Open Spina Bifida

Introduction: This retrospective study investigates brain malformations and their impact on neurodevelopmental outcome in children after prenatal surgery for spina bifida (SB). Methods: Sixty-one patients were included. On neonatal MRI, SB-associated brain malformations were assessed. Ventricular size, ventriculo-peritoneal shunt (VPS), and endoscopic third ventriculostomy (ETV) were also documented. Neurodevelopment was assessed with the Bayley-III and correlated with brain malformations, ventricular size, and VPS/ETV placement. Results: Chiari II malformation was detected in all patients. Corpus callosum (CC) abnormality was noted in 40%, heterotopies in 35%, and cerebellar parenchymal defects in 11%. 96% had ventriculomegaly; in 46%, VPS/ETV was performed. Cognitive and language testing yielded results in the low-average range (Bayley-III: Cognitive Composite Score 93.6, Language Composite Score 89.7), motor testing was below average (Motor Composite Score 77.4). CC abnormalities, heterotopies, and cerebellar defects were not associated with poorer Bayley-III scores, whereas patients with severe ventriculomegaly performed poorer in all subtests, significantly so for the language composite score. Patients requiring intervention for hydrocephalus had significantly lower scores in motor testing. Discussion/Conclusion: Additional brain malformations in open SB do not seem to have an impact on cognitive function at 2 years of age. Severe ventriculomegaly is a risk factor for poorer cognitive outcome; hydrocephalus surgery adds an additional risk for delayed motor function.

Happy Talk: A pilot effectiveness study of a targeted-selective speech-language and communication intervention for children from areas of social disadvantage.

Despite the public health implications of language difficulties associated with social disadvantage, there is a dearth of effectiveness studies investigating the effects of targeted speech and language programmes in this area. To determine the effects of a targeted selective community-based child language intervention programme (Happy Talk), which simultaneously engaged with parents and early childhood educators, in the Republic of Ireland. A mixed methods methodology was applied with quantitative outcome and qualitative process data collected. Effectiveness was examined using a quasi-experimental single blind study design comparing Happy Talk with 'usual care' across four preschools. Qualitative process data were also gathered to examine the acceptability and feasibility of the Happy Talk approach in practice, and to identify factors to improve the probability of successful wider implementation. Child language (PLS-5) and quality-of-life measures were administered pre- and immediately post- the 11-week intervention. Responsiveness was assessed as the parental outcome, and the oral language environment of preschools was measured using the Communication Supporting Classroom Observation Tool (CSCOT). Retrospective acceptability was analysed with reference to the theoretical framework of acceptability (v 2). Pre-/post-expressive and composite language scores were collected for 58 children, and receptive scores for 54 children. Multiple linear regression revealed significant intervention effects for comprehension and total language with large and moderate effect sizes, respectively (0.60 and 0.46 SD). No significant effect was shown for parental responsiveness. No effects were found for the preschool environment or children's quality of life. Preschool staff deemed the programme to be an acceptable method of enhancing children's speech and language skills and rated the intervention positively. The Happy Talk pilot effectiveness trial shows that comprehension can be improved (with a large effect) in preschool children from areas of social disadvantage, following an 11-week intervention, in which parents and preschool staff are simultaneously engaged. The ecological validity of the programme, as well as feasibility and acceptability to staff, make it a suitable programme to be delivered at scale. What is already known on the subject Up to 50% of children from socially disadvantaged areas enter preschool with speech and language difficulties. The majority of intervention studies are (1) researcher led; (2) efficacy trials carried out in ideal conditions; and (3) focus on working with parents or early childhood educators rather than engaging with both groups simultaneously. Many studies omit child language outcomes, and those that include them tend to show relatively modest effects for expressive language and negligible effects for receptive language. What this paper adds to existing knowledge This pilot study shows that the Happy Talk programme, which is embedded in the community and which simultaneously engages with parents and early childhood educators, is highly effective in improving children's receptive language skills. These findings are particularly important in the context of (1) the study taking place in real world conditions; and (2) the programme being designed and refined by speech and language therapy services, rather than one which is researcher led. What are the potential or actual clinical implications of this work? Implementing an 11-week targeted selective community-based language intervention can result in a large positive effect on receptive language for children from areas of social disadvantage. The study findings highlight the importance of embedding intervention programmes in the community and of simultaneously engaging with parents and preschool staff.

Left lateralization of neonatal caudate microstructure affects emerging language development at 24 months.

The complex interaction between brain and behaviour in language disorder is well established. Yet to date, the imaging literature in the language disorder field has continued to pursue heterogeneous and relatively small clinical cross‐sectional samples, with emphasis on cortical structures and volumetric analyses of subcortical brain structures. In our current work, we aimed to go beyond this state of knowledge to focus on the microstructural features of subcortical brain structures (specifically the caudate nucleus) in a large cohort of neonates and study its association with emerging language skills at 24 months. Variations in neonatal brain microstructure could be interpreted as a proxy for in utero brain development. As language development is highly dependent on cognitive function and home literacy environment, we also examined their effect on the caudate–language function relationship utilizing a conditional process model. Our findings suggest that emerging language development at 24 months is influenced by the degree of left lateralization of neonatal caudate microstructure, indexed by diffusion tensor imaging (DTI)‐derived fractional anisotropy (FA). FA is an indirect measure of neuronal and dendritic density within grey matter structures. We also found that the caudate–language function relationship is partially mediated by cognitive function. The conditional indirect effect of left caudate FA on language composite score through cognitive function was only statistically significant at low levels of home literacy score (−1 standard deviation [SD]). The authors proposed that this may be related to ‘compensatory’ development of cognitive skills in less favourable home literacy environments.

Family integrated care: very preterm neurodevelopmental outcomes at 18 months

ObjectiveTo examine whether the family integrated care (FICare) programme, a multifaceted approach which enables parents to be engaged as primary caregivers in the neonatal intensive care unit, impacts infant neurodevelopment...

Association between body composition at term equivalent age and Bayley scores at 2 years in preterm infants.

To evaluate whether in a historical cohort of preterm infants, body composition at term equivalent age (TEA) correlated with Bayley scores at 2 years of corrected age. Ninety-five preterm babies were admitted to our neonatal intensive unit and underwent air-displacement plethysmography assessment at TEA. Of these, 74 completed Bayley tests at 2 years. We used multiple linear regression analysis to assess the association of body composition with Bayley scores. Mean gestational age and birthweight of our population were respectively 29.8 (±2.2) weeks and 1150 (±330) grams. Higher fat-free mass (FFM) z-score was associated with higher language (adjusted r = 0.28, p = 0.03) and motor composite scores (adjusted r = 0.33, p = 0.03) in both univariate and multiple regression analysis including birth weight, sex, maternal university degree, mechanical ventilation, and bilingualism. In our study FFM at term equivalent age was associated with higher Bayley composite motor and language scores at 2 years.

Dual Effect of PER2 C111G Polymorphism on Cognitive Functions across Progression from Subjective Cognitive Decline to Mild Cognitive Impairment.

Background: Periodic circadian protein homolog 2 (PER2) has a role in the intracellular signaling pathways of long-term potentiation and has implications for synaptic plasticity. We aimed to assess the association of PER2 C111G polymorphism with cognitive functions in subjective cognitive decline (SCD). Methods: Forty-five SCD patients were included in this study. All participants underwent extensive neuropsychological investigation, analysis of apolipoprotein E (APOE) and PER2 genotypes, and neuropsychological follow-up every 12 or 24 months for a mean time of 9.87 ± 4.38 years. Results: Nine out of 45 patients (20%) were heterozygous carriers of the PER2 C111G polymorphism (G carriers), while 36 patients (80%) were not carriers of the G allele (G non-carriers). At baseline, G carriers had a higher language composite score compared to G non-carriers. During follow-up, 15 (34.88%) patients progressed to mild cognitive impairment (MCI). In this group, we found a significant interaction between PER2 G allele and follow-up time, as carriers of G allele showed greater worsening of executive function, visual-spatial ability, and language composite scores compared to G non-carriers. Conclusions: PER2 C111G polymorphism is associated with better language performance in SCD patients. Nevertheless, as patients progress to MCI, G allele carriers showed a greater worsening in cognitive performance compared to G non-carriers. The effect of PER2 C111G polymorphism depends on the global cognitive status of patients.

Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology

There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited. This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally. This retrospective cohort study included inborn, nonanomalous infants, born at <29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment. Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88). Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at <29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

Correlations between serum BDNF levels and neurodevelopmental outcomes in infants of mothers with gestational diabetes

Diabetes during pregnancy is associated with an increased risk of foetal and neonatal complications and long-term complications in the offspring. Brain-derived neurotrophic factor (BDNF), a neurotrophin that has a crucial role in neurogenesis modulation and neural pathway maturation during neurodevelopment, may have a role in protecting neurons against injury and diseases by modulating glucose metabolism. The aim of this study was to investigate the possible relationship between the serum BDNF levels of infants of mothers with gestational diabetes (IMGD) and neurodevelopmental outcomes of the children after birth. A total of 24 candidates, including 8 IMGD and 16 healthy infants, were recruited for the study. Medical records were reviewed. Serum BDNF levels of the study participants were collected at birth and at 6 and 12 months of age. Developmental outcomes of each candidate were assessed using the Bayley Scales of Infant Development III (BSID III) at 6 and 12 months of corrected age. Compared to non-IMGD, IMGD had greater mean body weight (p=0.04) and height (p<0.01) at age 12 months. The language composite score was significantly lower in IMGD at 12 months of age (p=0.038). The BDNF content was significantly higher in the non-IMGD than in the IMGD group at 12 months of age (p=0.013). In this study, we demonstrated that infants of mothers with gestational diabetes do worse in language development and have lower BDNF levels at 12 months of age. There may be a close correlation between language outcomes and serum BDNF levels at 12 months of age. A follow-up study on future developmental status is warranted.

Neonatal Encephalopathy Is Associated With Altered IL-8 and GM-CSF Which Correlates With Outcomes.

Aim: To investigate the relationship between cytokines associated with innate immune cell activation and brain injury and outcome in infants with NE compared to neonatal controls.Methods: Serum and CSF biomarkers associated with activated neutrophils and monocytes [Interleukin-8 (IL-8) and Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF)] were serially measured using duplex immunoassays on days 1, 3 and 7 in term newborns with NE and controls. Results were compared to grade of encephalopathy, seizures, MRI brain imaging, mortality and Bayley Score of Infant and Toddler Development (Bayley-III) at 2 years of age.Results: Ninety-four infants had serum samples collected with 34 CSF samples. NE Grade II/III was significantly associated with elevated on day 2 serum IL-8. Mortality was best predicted by elevated day 1 IL-8. GM-CSF was initially elevated on day 1 and abnormal MRI imaging was associated with decreased day 2 GM-CSF. Elevated GM-CSF at day of life 6–7 correlated negatively with composite cognitive, language and motor Bayley-III scores at 2 years.Conclusion: Moderate or severe NE and mortality was associated with elevated IL-8. Day 2 GM-CSF could predict abnormal MRI results in NE and Bayley-III. Therefore, these cytokines are altered in NE and may predict early outcomes and further implicate inflammatory processes in NE.

Neurodevelopmental outcomes following bevacizumab treatment for retinopathy of prematurity: a systematic review and meta-analysis.

To systematically review the studies exploring the association between bevacizumab and neurodevelopmental outcomes. Embase, Medline, CINAHL, and Cochrane Library databases were searched for studies examining neurodevelopmental outcomes of preterm infants treated with bevacizumab compared to laser ablation or cryotherapy for severe retinopathy of prematurity (ROP). Thirteen studies (clinical trial = 1; cohort studies = 12) were included. Random-effects model meta-analysis showed significant increased odds of cognitive impairment associated with bevacizumab treatment on both unadjusted (unadjusted odds ratio (OR) 1.61; 95% confidence interval (CI) 1.12, 2.30) and adjusted analyses (adjusted OR 1.90; 95% CI 1.22, 2.97). Infants treated with bevacizumab for severe ROP had significantly lower Bayley-III cognitive (mean difference (MD) -1.66; 95% CI -3.21, -0.12), and language composite scores (MD -5.50; 95% CI -8.24, -2.76) compared to infants treated with laser ablation or cryotherapy. Bevacizumab treatment for severe ROP is associated with increased risk of cognitive impairment and lower cognitive and language scores in preterm infants.