The Genesis of Schizophrenia: An Origin Story.

Schizophrenia is routinely referred to as a neurodevelopmental disorder, but the role of brain development in a disorder typically diagnosed during early adult life is enigmatic. The authors revisit the neurodevelopmental model of schizophrenia with genomic insights from the most recent schizophrenia clinical genetic association studies, transcriptomic and epigenomic analyses from human postmortem brain studies, and analyses from cellular models that recapitulate neurodevelopment. Emerging insights into schizophrenia genetic risk continue to converge on brain development, particularly stages of early brain development, that may be perturbed to deviate from a typical, normative course, resulting in schizophrenia clinical symptomatology. As the authors explicate, schizophrenia genetic risk is likely dynamic and context dependent, with effects of genetic risk varying spatiotemporally, across the neurodevelopmental continuum. Optimizing therapeutic strategies for the heterogeneous collective of individuals with schizophrenia may likely be guided by leveraging markers of genetic risk and derivative functional insights, well before the emergence of psychosis. Ultimately, rather than a focus on therapeutic intervention during adolescence or adulthood, principles of prediction and prophylaxis in the pre- and perinatal and neonatal stages may best comport with the biology of schizophrenia to address the early-stage perturbations that alter the normative neurodevelopmental trajectory.

Is neurodevelopment impaired in Brazilian children with intestinal failure on prolonged parenteral nutrition? A single center study.

PURPOSE: To assess the neurodevelopment outcomes of children younger than 42 months of age with intestinal failure (IF) using prolonged parenteral nutrition (PN) followed by a Pediatric Multidisciplinary Intestinal Rehabilitation Program from a public tertiary hospital in Brazil. METHODS: Bayley III scale was administered in children aged 2 to 42 months with IF and receiving PN for more than 60 days. Composite scores in cognitive, motor, and language domains were analyzed. Developmental delay was defined as a performance 2 standard deviations (SD) below the average at the 3 domains. Association between Bayley III composite scores and clinical variables related to IF were tested. RESULTS: Twenty-four children with median (IQR) age of 17.5 months (9-28.5) were studied, 58.3% were male. Developmental delay was found in 34%, 33% and 27% of the patients in cognitive, motor, and language domains, respectively. There was no significant association between the Bayley-III composite scores and length of hospitalization, prematurity, and number of surgical procedures with anesthesia. CONCLUSION: The study demonstrated impairments in the cognitive, motor and language domains in approximately one-third of young patients with IF on prolonged PN.

Early Neurodevelopmental Assessments for Predicting Long-Term Outcomes in Infants at High Risk of Cerebral Palsy.

Importance: Studies suggest that early neurodevelopmental assessments are beneficial for identifying cerebral palsy, yet their effectiveness in practical scenarios and their ability to detect cognitive impairment are limited. Objective: To assess the effectiveness of early neurodevelopmental assessments in identifying cerebral palsy and cognitive and other neurodevelopmental impairments, including their severity, within a multidisciplinary clinic. Design, Setting, and Participants: This diagnostic study was conducted at Monash Children's Hospital, Melbourne, Australia. Participants were extremely preterm infants born at less than 28 weeks' gestation or extremely low birth weight infants less than 1000 g and term encephalopathic infants who received therapeutic hypothermia, attending the early neurodevelopmental clinic between January 2019 and July 2021. Data were analyzed from December 2023 to January 2024. Exposures: Early cerebral palsy or high risk of cerebral palsy, the absence of fidgety movements, and Hammersmith Infant Neurological Examination (HINE) scores at corrected age (CA) 3 to 4 months. Early cerebral palsy or high risk of cerebral palsy diagnosis was based on absent fidgety movements, a low HINE score (<57), and medical neurological examination. Main Outcome and Measures: The outcomes of interest were cerebral palsy, cognitive and neurodevelopmental impairments and their severity, diagnosed at 24 to 36 months' CA. Results: A total of 116 infants (median [IQR] gestational age, 27 [25-29] weeks; 65 [56%] male) were included. Diagnosis of early cerebral palsy or high risk of cerebral palsy demonstrated a sensitivity of 92% (95% CI, 63%-99%) and specificity of 84% (95% CI, 76%-90%) for predicting cerebral palsy and 100% (95% CI, 59%-100%) sensitivity and 80% (95% CI, 72%-87%) specificity for predicting moderate to severe cerebral palsy. Additionally, the accuracy of diagnosis of early cerebral palsy or high risk of cerebral palsy was 85% (95% CI, 77%-91%) for predicting cerebral palsy and 81% (95% CI, 73%-88%) for predicting moderate to severe cerebral palsy. Similarly, the absence of fidgety movements had an 81% (95% CI, 73%-88%) accuracy in predicting cerebral palsy, and HINE scores exhibited good discriminatory power with an area under the curve of 0.88 (95% CI, 0.79-0.97) for cerebral palsy prediction. However, for cognitive impairment, the predictive accuracy was 44% (95% CI, 35%-54%) for an early cerebral palsy or high risk of cerebral palsy diagnosis and 45% (95% CI, 36%-55%) for the absence of fidgety movements. Similarly, HINE scores showed poor discriminatory power for predicting cognitive impairment, with an area under the curve of 0.62 (95% CI, 0.51-0.73). Conclusions and Relevance: In this diagnostic study of infants at high risk for cerebral palsy or other cognitive or neurodevelopmental impairment, early neurodevelopmental assessments at 3 to 4 months' CA reliably predicted cerebral palsy and its severity at 24 to 36 months' CA, signifying its crucial role in facilitating early intervention. However, for cognitive impairment, longer-term assessments are necessary for accurate identification.

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

BACKGROUND: Pakistan 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. METHODS: We 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. RESULTS: A 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 (ß = -0.6, 95% CI -1.2,-0.04), TQS hearing domain (ß = -0.3, 95% CI: -1.2 to 0.7), PEDS: DM-AL fine motor domain (ß = -1.3, 95% CI: -4.4 to 1.7), PEDS: DM-AL receptive language development (ß = -1.1, 95% CI: -3.7 to 1.4) and child anthropometric measurements such as weight and height (ß = -0.2, 95% CI: -0.4 to 0.01 and ß = -0.2, 95% CI: -0.4 to -0.01, respectively). Early pSBI exposure was positively associated with PEDS: DM-AL self-help domain (ß = 0.6, 95% CI: -1.2 to 2.4) and SDQ-P overall score (ß = 0.02, 95% CI: -0.3 to 0.3). CONCLUSION: Children 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.

Continuous epileptiform discharges are associated with worse neurodevelopmental findings in a congenital Zika syndrome prospective cohort.

PURPOSE: This study aimed to identify continuous epileptiform discharges (CEDs) on electroencephalograms (EEG) and to determine their clinical significance in children with congenital Zika syndrome (CZS). METHODS: This prospective cohort study included 75 children diagnosed with CZS born from March 2015 and followed up until September 2018 (age up to 36 months). EEG was performed to detect CEDs up to 24 months old. Data on obstetric, demographic, and clinical signs; cranial computed tomography (CT); ophthalmology examination; anti-seizure medication; growth; and motor development were collected. Fisher's exact test was used to verify the associations between categorical variables, and the T- test was used to compare the mean z-scores of anthropometric measurements between the groups with and without CED. RESULTS: CEDs were identified in 41 (54.67 %) children. The mean age of CEDs identification was 12.24 ± 6.86 months. Bilateral CEDs were shown in 62.89 % of EEGs. CEDs were associated with severe congenital microcephaly, defined by z-score >3 standard deviation of head circumference (HC) below the mean for sex and age (p = 0.025), and worse outcomes, including first seizure before 6 months (p = 0.004), drug-resistant epilepsy (p < 0.001), chorioretinal scarring or mottling (p = 0.002), and severe CT findings (p = 0.002). The CED group had lower mean z-scores of HC up to 24 months of age. CONCLUSION: This is the first description of the prevalence and significance of CEDs that also remains during wakefulness in patients with CZS. New investigations may suggest that it is more appropriate to classify the EEG not as a CED, but as a periodic pattern. Anyway, CEDs may be a marker of neurological severity in children with CSZ.

[Extremely preterm infants with severe intraventricular hemorrhage: neurological evolution and long term and educational status]. / Niños muy prematuros con hemorragia intraventricular extensa: evolución neurológica y escolaridad a largo plazo.

Extensive intraventricular hemorrhage (IVH) in very preterm newborns (VPNB) is associated with mortality and severe long-term neurological sequelae. OBJECTIVES: To know the most frequent neurological pathologies associated with extensive IVH, to determine the functional outcomes of mobility in the motor area and intellectual capacity in the cognitive area, to analyze the association between both areas and to know the schooling achieved. PATIENTS AND METHOD: Descriptive and longitudinal study in VPNB with extensive IVH born between 2001 and 2014. They underwent protocolized neurological follow-up until school age. The functional outcomes in mobility and intellectual capacity were categorized into 4 levels: level 1 corresponds to good functionality and autonomy; level 2, functionality that allows independence, with support in some tasks; level 3 requires constant external support; and level 4 where there is total dependence. The association was analyzed using Chi-square and Cramer's V coefficient. RESULTS: 74 children completed the follow-up; the most frequent associated neurological pathologies were neurodevelopmental disorders, hypertensive hydrocephalus, and epilepsy. Independent mobility (normal or with limitations) reached 74.4% while 24.3% used wheelchairs. 51.3% was categorized as normal to borderline intellectual range, 12.2% as mild intellectual disability (ID), 17.6% as moderate ID, and 19.9% as severe to profound ID. There was a strong statistical association between functional levels of mobility and intellectual capacity (p < 0.000 and V = 0.62). Schooling was proportional to intellectual capacity: 56.8% attended regular schools, 27.0% attended special schools, and 16.2% had no schooling. CONCLUSIONS: 2/3 VPNB with extensive IVH showed positive functional outcomes, from normal to mild limitations that allow an almost autonomous life; in 1/3 the outcomes were unfavorable in mobility and cognitive performance, and there was a strong statistical correlation between both areas studied. Schooling was consistent with the intellectual level.

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

BACKGROUND: Patent 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). PURPOSE: This 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. METHODS: A 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. RESULTS: Out 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. CONCLUSION: In 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.

Long-term visual and neurodevelopmental outcomes in children with Congenital Zika Syndrome after undergoing strabismus surgery.

Purpose: To assess long-term visual and neurodevelopmental outcomes in children with congenital Zika syndrome (CZS) after strabismus surgery. Methods: A consecutive sample of five children with CZS who underwent strabismus surgery was enrolled. All children underwent a standardized pre- and postoperative protocol including binocular best-corrected visual acuity (BCVA) using the Teller Acuity Cards II (TAC II), ocular alignment, functional vision using the functional vision developmental milestones test (FVDMT), and neurodevelopmental milestone evaluation using the Bayley Scales of Infant Development-Third Edition (BSID-III). Scores of the FVDMT outcomes considering the child's developmental age based on the BSID-III score were compared with scores from postoperative assessment. Results: Five children with CZS (3 girls, 2 boys) were enrolled with a mean age at baseline (preoperative) of 35.0 ± 0.7 months (range, 34-36 months) and at final assessment of 64.4 ± 0.5 months (range, 64-65 months). Preoperative BCVA was 1.2 ± 0.5 logMAR and at final assessment 0.7 ± 0.1 logMAR. Successful strabismus surgery outcome was maintained in 4/5 (80.0%) of children at final assessment. The children's BSID-III scores showed significant neurodevelopment delay at the initial assessment (corresponding developmental mean age was 4.7 months) and at their final assessment (corresponding developmental mean age was 5.1 months). There was improvement or stability in 34/46 items evaluated in the FVDMT (73.9%) when comparing baseline with 2-year follow-up. Conclusions: Strabismus surgery resulted in long-term ocular alignment in the majority of children with CZS. All the children showed improvement or stability in more than 70.0% of the functional vision items assessed. Visual and neurodevelopmental dysfunction may be related to complex condition and associated disorders seen in CZS including ocular, neurological, and skeletal abnormalities.

Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder.

BACKGROUND: Succinic semialdehyde dehydrogenase deficiency (SSADHD) represents a model neurometabolic disease at the fulcrum of translational research within the Boston Children's Hospital Intellectual and Developmental Disabilities Research Centers (IDDRC), including the NIH-sponsored natural history study of clinical, neurophysiological, neuroimaging, and molecular markers, patient-derived induced pluripotent stem cells (iPSC) characterization, and development of a murine model for tightly regulated, cell-specific gene therapy. METHODS: SSADHD subjects underwent clinical evaluations, neuropsychological assessments, biochemical quantification of γ-aminobutyrate (GABA) and related metabolites, electroencephalography (standard and high density), magnetoencephalography, transcranial magnetic stimulation, magnetic resonance imaging and spectroscopy, and genetic tests. This was parallel to laboratory molecular investigations of in vitro GABAergic neurons derived from induced human pluripotent stem cells (hiPSCs) of SSADHD subjects and biochemical analyses performed on a versatile murine model that uses an inducible and reversible rescue strategy allowing on-demand and cell-specific gene therapy. RESULTS: The 62 SSADHD subjects [53% females, median (IQR) age of 9.6 (5.4-14.5) years] included in the study had a reported symptom onset at ∼ 6 months and were diagnosed at a median age of 4 years. Language developmental delays were more prominent than motor. Autism, epilepsy, movement disorders, sleep disturbances, and various psychiatric behaviors constituted the core of the disorder's clinical phenotype. Lower clinical severity scores, indicating worst severity, coincided with older age (R= -0.302, p = 0.03), as well as age-adjusted lower values of plasma γ-aminobutyrate (GABA) (R = 0.337, p = 0.02) and γ-hydroxybutyrate (GHB) (R = 0.360, p = 0.05). While epilepsy and psychiatric behaviors increase in severity with age, communication abilities and motor function tend to improve. iPSCs, which were differentiated into GABAergic neurons, represent the first in vitro neuronal model of SSADHD and express the neuronal marker microtubule-associated protein 2 (MAP2), as well as GABA. GABA-metabolism in induced GABAergic neurons could be reversed using CRISPR correction of the pathogenic variants or mRNA transfection and SSADHD iPSCs were associated with excessive glutamatergic activity and related synaptic excitation. CONCLUSIONS: Findings from the SSADHD Natural History Study converge with iPSC and animal model work focused on a common disorder within our IDDRC, deepening our knowledge of the pathophysiology and longitudinal clinical course of a complex neurodevelopmental disorder. This further enables the identification of biomarkers and changes throughout development that will be essential for upcoming targeted trials of enzyme replacement and gene therapy.

The impact of excessive maternal weight on the risk of neuropsychiatric disorders in offspring-a narrative review of clinical studies.

The global prevalence of overweight and obesity is a significant public health concern that also largely affects women of childbearing age. Human epidemiological studies indicate that prenatal exposure to excessive maternal weight or excessive gestational weight gain is linked to various neurodevelopmental disorders in children, including attention deficit hyperactivity disorder, autism spectrum disorder, internalizing and externalizing problems, schizophrenia, and cognitive/intellectual impairment. Considering that inadequate maternal body mass can induce serious disorders in offspring, it is important to increase efforts to prevent such outcomes. In this paper, we review human studies linking excessive maternal weight and the occurrence of mental disorders in children.

Epileptic encephalopathies and progressive neurodegeneration.

Developmental encephalopathies (DE), epileptic encephalopathies (EE) and developmental and epileptic encephalopathies (DEE) are overlapping neurodevelopmental disorders characterized by early-onset, often severe epileptic seizures, developmental delay, or regression and have multiple etiologies. Classical nosology in child neurology distinguished progressive and nonprogressive conditions. A progressive course with global cognitive worsening in DEE is usually attributed to severe seizures and electroencephalographic abnormalities whose deleterious effects interfere with developmental processes both in an apparently healthy brain and in an anatomically compromised one. Next generation sequencing and functional studies have helped identifying and characterizing clinical conditions, each with a broad spectrum of clinical and anatomic severity corresponding to a variable level of neurodegeneration, such that both a rapidly progressive course and considerably milder phenotypes with no obvious deterioration can be configured with mutations in the same gene. In this mini review, we present examples of genetic DEE that draw connections between neurodevelopmental and neurodegenerative disorders.

Autism and neurodevelopmental disability risks in children with tracheostomies and ventilators.

BACKGROUND/OBJECTIVE: Infants who survive prematurity and other critical illnesses and require continued invasive mechanical ventilation (IMV) postdischarge (at home) are at high risk of developmental delays and disabilities. Studies of extremely preterm cohorts (<28-week gestation) demonstrate rates of 25% for intellectual disability (ID) and 7% for autism spectrum disorder (ASD). Rates of ASD and ID in children with IMV are unknown. This study aimed to determine neurodevelopmental disability risk in a cohort of children with postdischarge IMV. DESIGN/METHODS: A consecutive series of children with IMV were assessed 1 month, 6 months, and 1 year after discharge. Cognitive, social, and communicative domains were assessed by a Developmental and Behavioral Pediatrician using (1) clinical adaptive test/clinical linguistic and auditory milestone scale (CAT/CLAMS) of the capute scales; (2) pediatric evaluation of disability inventory computer adaptive test (PEDI-CAT); and (3) modified checklist for autism in toddlers, revised (MCHAT-R). Red flag signs and symptoms of ASD using DSM-V criteria were noted. Longitudinal testing was reviewed. Expert consensus impressions of evolving ASD and/or ID were determined. RESULTS: Eighteen children were followed for 1 year; at 1 year, the median age (range) was 23 (17-42) months. Children were 44% male, 33% non-Hispanic White, 39% non-Hispanic Black, and 28% Hispanic. Fifteen (83%) children were prematurity survivors. Median (range) developmental quotients (DQs): full-scale DQ 59 (11-86), CAT DQ 66.5 (8-96), and CLAMS DQ 49.5 (13-100). Twelve (67%) children were highly suspicious for ASD and/or evolving ID. CONCLUSIONS/SIGNIFICANCE: This cohort of children with at-home IMV demonstrates a higher risk of ASD and ID than prior premature cohorts. Larger investigations with longer follow-up are needed.

Understanding neurodevelopmental trajectories and behavioral profiles in SCN1A-related epilepsy syndromes.

BACKGROUND: A pathogenic variant in SCN1A can result in a spectrum of phenotypes, including Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS + ) syndrome. Dravet syndrome (DS) is associated with refractory seizures, developmental delay, intellectual disability (ID), motor impairment, and challenging behavior(1,2). GEFS + is a less severe phenotype in which cognition is often normal and seizures are less severe. Challenging behavior largely affects quality of life of patients and their families. This study describes the profile and course of the behavioral phenotype in patients with SCN1A-related epilepsy syndromes, explores correlations between behavioral difficulties and potential risk factors. METHODS: Data were collected from questionnaires, medical records, and semi-structured interviews. Behavior difficulties were measured using the Adult/Child Behavior Checklist (C/ABCL) and Adult self-report (ASR). Other questionnaires included the Pediatric Quality of Life Inventory (PedsQL), the Functional Mobility Scale (FMS) and the Sleep Behavior Questionnaire by Simonds & Parraga (SQ-SP). To determine differences in behavioral difficulties longitudinally, paired T-tests were used. Pearson correlation and Spearman rank test were used in correlation analyses and multivariable regression analyses were employed to identify potential risk factors. RESULTS: A cohort of 147 participants, including 107 participants with DS and 40 with genetic epilepsy with febrile seizures plus (GEFS + ), was evaluated. Forty-six DS participants (43.0 %) and three GEFS + participants (7.5 %) showed behavioral problems in the clinical range on the A/CBCL total problems scale. The behavioral profile in DS exists out of withdrawn behavior, aggressive behavior, and attention problems. In DS patients, sleep disturbances (ß = 1.15, p < 0.001) and a lower age (ß = -0.21, p = 0.001) were significantly associated with behavioral difficulties. Between 2015 and 2022, behavioral difficulties significantly decreased with age (t = -2.24, CI = -6.10 - -0.15, p = 0.04) in DS participants aging from adolescence into adulthood. A decrease in intellectual functioning (ß = 3.37, p = 0.02) and using less antiseizure medications in 2022 than in 2015, (ß = -1.96, p = 0.04), were identified as possible risk factors for developing (more) behavioral difficulties. CONCLUSIONS: These findings suggest that, in addition to epilepsy, behavioral difficulties are a core feature of the DS phenotype. Behavioral problems require personalized management and treatment strategies. Further research is needed to identify effective interventions.

Relationships of Severity of Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes and Poor Respiratory Function at 7-8 Years of Age.

OBJECTIVE: To clarify the relationships of 3 definitions of severity of bronchopulmonary dysplasia (BPD) with adverse neurodevelopmental and respiratory outcomes at early school-age. STUDY DESIGN: Participants comprised 218 consecutive survivors to 7-8 years of age born either <28 weeks' gestation or weighing <1000 g in Victoria, Australia, in 2005. BPD was classified as none, grade 1 (mild), grade 2 (moderate), or grade 3 (severe), using 2 commonly accepted definitions: 1) Jobe2001, and 2) Higgins2018, and our own 3) Victorian Infant Collaborative Study (VICS) 2005, adapted from Jensen2019. Outcomes included major neurodevelopmental disability, low IQ and academic achievement, poor motor function, and poor respiratory function as assessed by spirometry. Outcomes for children with each grade of BPD were compared with children with no BPD. RESULTS: Of the 218 survivors, 132 (61%) had BPD on Jobe2001 criteria, and 113 (52%) had BPD on both Higgins2018 and VICS2005 criteria. Grade 1 on any criteria was not associated with any adverse neurodevelopmental outcomes. Grade 1 on both Higgins2018 and VICS2005 was associated with reduced spirometry, grade 2 on both Higgins2018 and VICS2005, and grade 3 on all criteria were associated with increased risk for both adverse neurodevelopmental and respiratory outcomes. CONCLUSIONS: Compared with no BPD, receiving additional oxygen up to 29% but no positive pressure support at 36 weeks' postmenstrual age increased the risk of abnormal respiratory function but not adverse neurodevelopment. Receiving ≥30% oxygen or any positive pressure support at 36 weeks increased the risk of both adverse outcomes.

2024 United States Elections: Air Pollution, Neurodegeneration, Neuropsychiatric, and Neurodevelopmental Disorders. Who Cares?

Air pollution exposures ought to be of significant interest for the United States (US) public as health issues will play a role in the 2024 elections. Citizens are not aware of the harmful brain impact of exposures to ubiquitous anthropogenic combustion emissions and friction-derived nanoparticles, industrial nanoplastics, the growing risk of wildfires, and the smoke plumes of soot. Ample consideration of pediatric and early adulthood hallmarks of Alzheimer's disease, Parkinson's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis and associations with neuropsychiatric and neurodevelopmental disorders in the process of setting, reviewing, and implementing standards for particulate matter (PM)2.5, ultrafine PM, and industrial nanoparticles must be of interest to US citizens.

Two-year neurodevelopmental outcome in extremely preterm-born children: The Austrian Preterm Outcome Study Group.

AIM: The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. METHODS: All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. RESULTS: 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. CONCLUSION: In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources.