Automated assessment of EEG background for neurodevelopmental prediction in neonatal encephalopathy.

Objective: Assess the capacity of brain state of the newborn (BSN) to predict neurodevelopment outcomes in neonatal encephalopathy.

Methods: Trends of BSN, a deep learning-based measure translating EEG background to a continuous trend, were studied from a three-channel montage long-term EEG monitoring from a prospective cohort of 92 infants with neonatal encephalopathy and neurodevelopmental outcomes assessed by Bayley Scales of Infant Development, 3rd edition (Bayley-III) at 18 months. Outcome prediction used categories "Severe impairment" (Bayley-III composite score ≤70 or death) or "Any impairment" (score ≤85 or death).

Review of clinical trials and guidelines for children and youth with mucopolysaccharidosis: outcome selection and measurement.

Background: To inform the development of a core outcome set (COS) for children and youth with mucopolysaccharidoses (MPS), we aimed to identify all outcomes and associated outcome measurement instruments that are reported in recent clinical trials and recommended as measurements in clinical management guidelines.

Methods: To identify English-language clinical trials and guidelines pertaining to MPS published between 2011 and mid-2021, we applied a comprehensive peer-reviewed search strategy to relevant databases and registers on May 16, 2021. Two reviewers independently screened retrieved citations and then full-text articles to determine eligibility for inclusion.

Long-term neurodevelopmental outcomes following liver transplantation for metabolic disease-a single centre experience.

This study describes the neurodevelopmental outcome of children with urea cycle disorders (UCD) and organic acidemias (OA) preliver transplant (LT), 1-year, and 3-years post-LT. We performed a retrospective chart review of children with OA or UCD transplanted between January 2014 and December 2021. Standardized motor and cognitive assessment scores were collected from children who had ≥1 motor/cognitive assessment at any timepoint.

Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy.

Background: Evidence is needed to inform thresholds for glycemic management in neonatal encephalopathy (NE). We investigated how severity and duration of dysglycemia relate to brain injury after NE.

Methods: A prospective cohort of 108 neonates ≥36 weeks gestational age with NE were enrolled between August 2014 and November 2019 at the Hospital for Sick Children, in Toronto, Canada.

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy.

Background And Objectives: Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE.

Methods: This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU).

Deep intronic variant in MVK as a cause for mevalonic aciduria initially presenting as non-syndromic retinitis pigmentosa.

Non-syndromic retinitis pigmentosa (NSRP) is a clinically and genetically heterogeneous group of disorders characterized by progressive degeneration of the rod and cone photoreceptors, often leading to blindness. The evolving association of syndromic genes to cause NSRP and the increasing role of intronic variants in explaining missing heritability in genetic disorders present challenges in establishing conclusive clinical and genetic diagnoses. This study sought to identify and validate the causative genetic variant(s) in a 13-year-old male initially diagnosed with NSRP.

Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I.

Objective: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition.

Methods: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls.

Results: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC.

Establishing a core outcome set for mucopolysaccharidoses (MPS) in children: study protocol for a rapid literature review, candidate outcomes survey, and Delphi surveys.

Background: Mucopolysaccharidoses (MPS) are a group of inherited metabolic diseases characterized by chronic, progressive multi-system manifestations with varying degrees of severity. Disease-modifying therapies exist to treat some types of MPS; however, they are not curative, underscoring the need to identify and evaluate co-interventions that optimize functioning, participation in preferred activities, and quality of life. A Canadian pediatric MPS registry is under development and may serve as a platform to launch randomized controlled trials to evaluate such interventions.

Randomized Trial of Oral Iron and Diet Advice versus Diet Advice Alone in Young Children with Nonanemic Iron Deficiency.

Objective: To compare the effects of 2 treatment options on neurodevelopmental and laboratory outcomes in young children with nonanemic iron deficiency.

Study Design: A blinded, placebo-controlled, randomized trial of children 1-3 years with nonanemic iron deficiency (hemoglobin ≥110 g/L, serum ferritin <14 μg/L) was conducted in 8 primary care practices in Toronto, Canada. Interventions included ferrous sulfate or placebo for 4 months; all parents received diet advice.

Person Ability Scores as an Alternative to Norm-Referenced Scores as Outcome Measures in Studies of Neurodevelopmental Disorders.

Although norm-referenced scores are essential to the identification of disability, they possess several features which affect their sensitivity to change. Norm-referenced scores often decrease over time among people with neurodevelopmental disorders who exhibit slower-than-average increases in ability. Further, the reliability of norm-referenced scores is lower at the tails of the distribution, resulting in floor effects and increased measurement error for people with neurodevelopmental disorders.

Association between Serum Ferritin and Cognitive Function in Early Childhood.

In infants 1-3 years of age, we found higher serum ferritin values associated with higher cognitive function, as measured by the Mullen Scales of Early Learning (P = .02 for the nonlinear relationship). A serum ferritin of 17 μg/L corresponded to the maximum level of cognition, beyond which there was no meaningful improvement.

Attention and corpus callosum volumes in individuals with mucopolysaccharidosis type I.

Objective: Previous research suggests attention and white matter (WM) abnormalities in individuals with mucopolysaccharidosis type I (MPS I); this cross-sectional comparison is one of the first to examine the relationship of WM structural abnormalities as measured by corpus callosum (CC) volumes with attention scores to evaluate this relationship in a larger sample of patients with MPS I.

Methods: Volumetric MRI data and performance on a computerized measure of sustained attention were compared for 18 participants with the severe form of MPS I (MPS IH), 18 participants with the attenuated form of MPS I (MPS I), and 60 typically developing age-matched controls.

Results: The MPS I groups showed below-average mean attention scores ( < 0.

Long-term outcome of patients with X-linked adrenoleukodystrophy: A retrospective cohort study.

Background: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder associated with leukodystrophy, myeloneuropathy and adrenocortical insufficiency. We performed a retrospective cohort study to evaluate long-term outcome of patients with X-ALD.

Method: All patients with X-ALD diagnosed between 1989 and 2012 were included.

New Paradigm for the Treatment of Glucose Transporter 1 Deficiency Syndrome: Low Glycemic Index Diet and Modified High Amylopectin Cornstarch.

Objective: Glucose transporter 1 deficiency syndrome is an autosomal, dominantly inherited neurometabolic disorder caused by mutations in the SLC2A1 gene. Decreased glucose transport into the brain results in seizures and cognitive dysfunction. The ketogenic diet is the treatment of choice, but complicated with compliance problems.

An internal pilot study for a randomized trial aimed at evaluating the effectiveness of iron interventions in children with non-anemic iron deficiency: the OptEC trial.

Background: The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted.

Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment.

Objectives: Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden.

Methods: Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes.

Optimizing early child development for young children with non-anemic iron deficiency in the primary care practice setting (OptEC): study protocol for a randomized controlled trial.

Background: Three decades of research suggests that prevention of iron deficiency anemia (IDA) in the primary care setting may be an unrealized and unique opportunity to prevent poor developmental outcomes in children. A longitudinal study of infants with IDA showed that the developmental disadvantage persists long term despite iron therapy. Early stages of iron deficiency, termed non-anemic iron deficiency (NAID), provide an opportunity for early detection and treatment before progression to IDA.

Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II.

Unlabelled: The phenotype of attenuated mucopolysaccharidosis type II (MPS II), also called Hunter syndrome, has not been previously studied in systematic manner. In contrast to the "severe" phenotype, the "attenuated" phenotype does not present with behavioral or cognitive impairment; however, the presence of mild behavior and cognitive impairment that might impact long-term functional outcomes is unknown. Previously, significant MRI abnormalities have been found in MPS II.

Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: L-arginine supplementation alternative to lysine-restricted diet.

Background And Hypothesis: Pyridoxine dependent epilepsy (PDE) due to mutations in the ALDH7A1 gene (PDE-ALDH7A1) is caused by α-aminoadipic-semialdehyde-dehydrogenase enzyme deficiency in the lysine pathway resulting in the accumulation of α-aminoadipic acid semialdehyde (α-AASA). Classical presentation is neonatal intractable seizures with a dramatic response to pyridoxine. Pyridoxine therapy does not prevent developmental delays in the majority of the patients.

Long-term treatment outcome of two patients with pyridoxine-dependent epilepsy caused by ALDH7A1 mutations: normal neurocognitive outcome.

Pyridoxine-dependent epilepsy is an autosomal recessively inherited disorder of lysine catabolism caused by mutations in the ALDH7A1 gene. We report 2 patients with normal neurocognitive outcome (full-scale IQ of 108 and 74) and their more than 10 years' treatment outcome on pyridoxine monotherapy. Both patients had specific borderline impairments in visual processing speed.

The effects of maternal supplementation of polyunsaturated Fatty acids on visual, neurobehavioural, and developmental outcomes of the child: a systematic review of the randomized trials.

Polyunsaturated fatty acid (PUFA) use in pregnancy has been promoted as beneficial for visual and neurobehavioural development in the fetus. However, no systematic review of the randomized trials has been conducted. The objective of this review was to evaluate potential advantages of this regiment by reviewing all randomized trials in pregnancy.