Bayley-III scales at 12 months of corrected age in preterm infants: Patterns of developmental performance and correlations to environmental and biological influences

Background and aims: Premature infants are at high risk for neurodevelopmental impairment (NDI) even in the absence of known brain complications of prematurity. Evaluation of the effectiveness of therapeutic interventions in association to neurodevelopmental outcome is required to improve or prevent the neurodevelopmental consequences of prematurity. The Bayley-III is currently the most commonly applied measurement tool for assessing early development both in clinical practice and research settings. Objective: To evaluate the relationship between known risk factors and early performance on the Bayley Scales of Infant Development-Third Edition at 12 months adjusted age in premature infants. Methods. Prospective study in a cohort of premature infants with gestational age ≤32 weeks, who underwent comprehensive developmental assessment using the five domains of Bayley Scales, cognitive, language, motor, social emotional and adaptive behavior at 12 months corrected age. Developmental scores were evaluated in relation to environmental influences, therapeutic interventions or practices and complications of prematurity. Results: Composite and Subscale scores for the cognitive, language and motor scales were below the 50th percentile, with no significant differences among them. Scores for the social-emotional and adaptive behavior, which are derived from the parent-report questionnaires, were near the average and significantly higher than the scores derived by the examiners. Multiple regression analyses showed that blood transfusions, apart from severely abnormal head ultrasound, gender, being small for gestational age and duration of invasive mechanical ventilation and oxygen administration were consistently related to neurodevelopmental outcome. Conclusions: Bayley-III assessments are important for getting early information about development following premature birth. Parents may overestimate children's performance. Neurodevelopmental outcome is related to several environmental, biological or medical conditions associated with prematurity. Adoption of therapeutic strategies targeting known neonatal risk factors could positively affect neurodevelopmental outcome. © 2015 Elsevier Ltd

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.Published version, accepted versionThis article is freely available online. Click on the 'Additional Link' above to access the full-text via the publisher's site

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

Abstract We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue. Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care