A Pilot Study of Continuous Limited-Channel aEEG in Term Infants with Encephalopathy

ObjectiveTo evaluate the accuracy, feasibility, and impact of limited-channel amplitude integrated electroencephalogram (aEEG) monitoring in encephalopathic infants. Study design Encephalopathic infants were placed on limited-channel aEEG with a software-based seizure event detector for 72 hours. A 12-hour epoch of conventional EEG-video (cEEG) was simultaneously collected. Infants were randomly assigned to monitoring that was blinded or visible to the clinical team. If a seizure detection event occurred in the visible group, the clinical team interpreted whether the event was a seizure, based on review of the limited-channel aEEG. EEG data were reviewed independently offline. Results In more than 68 hours per infant of limited-channel aEEG monitoring, 1116 seizures occurred (>90% clinically silent), with 615 detected by the seizure event detector (55%). Detection improved with increasing duration of seizures (73% >30 seconds, 87% >60 seconds). Bedside physicians were able to accurately use this algorithm to differentiate true seizures from false-positives. The visible group had a 52% reduction in seizure burden (P = .114) compared with the blinded group. Conclusions Monitoring for seizures with limited-channel aEEG can be accurately interpreted, compares favorably with cEEG, and is associated with a trend toward reduced seizure burden

Neurodevelopmental and Perinatal Correlates of Simple Brain Metrics in Very Preterm Infants

OBJECTIVE: To explore perinatal correlates of 3 simple measures of brain size, known as metrics, in very preterm infants at term-equivalent age and their relationship to 2-year neurodevelopmental outcomes.DESIGN: Prospective cohort study of preterm infants born at a gestational age of less than 30 weeks or a weight of less than 1250 g between April 1, 2001, and December 31, 2003, and followed up at 2 years of corrected age. SETTING: The Royal Women\u27s Hospital and the magnetic resonance imaging unit at the Royal Children\u27s Hospital. PATIENTS: Two hundred thirty-six preterm infants. INTERVENTIONS: Brain metrics--biparietal, bifrontal, and transverse cerebellar diameters--on magnetic resonance imaging for preterm infants at term-equivalent age and neurodevelopmental assessments at 2 years of corrected age. MAIN OUTCOME MEASURES: Mental Development Index and the Psychomotor Development Index of the Bayley Scales of Infant Development-Revised. RESULTS: Higher birth weight z score, shorter duration of assisted ventilation, and postmenstrual age at magnetic resonance imaging were independently associated with increases in the 3 brain metrics, and male sex was associated with larger bifrontal and biparietal diameters. Only the biparietal diameter was predictive of cognitive and motor indices after adjustment for perinatal variables and social risk. CONCLUSION: This study provides further evidence of altered brain growth in preterm infants, relating to growth restriction and severity of illness, that in turn relate to neurodevelopmental outcome

A Novel Quantitative Simple Brain Metric Using MR Imaging for Preterm Infants

BACKGROUND AND PURPOSE: The application of volumetric techniques to preterm infants has revealed brain volume reductions. Such quantitative data are not available in routine neonatal radiologic care. The objective of this study was to develop simple brain metrics to compare brain size in preterm and term infants and to correlate these metrics with brain volumes from volumetric MR imaging techniques.MATERIALS AND METHODS: MR images from 189 preterm infants <30 weeks’ gestational age or <1250 g birthweight scanned at term-equivalent age and 36 term infants were studied. Fifteen tissue and fluid measures were systematically evaluated on 4 selected sections. The results were correlated with total brain, gray matter, white matter, and CSF volumes. RESULTS: The mean bifrontal, biparietal, and transverse cerebellar diameters were reduced (−11.6%, 95% confidence interval [CI], −13.8% to −9.3%; −12%, 95% CI, −14% to −9.8%; and −8.7%, 95% CI, −10.5% to −7% respectively) and the mean left ventricle diameter was increased (+22.3%, 95% CI, 2.9%–41.6%) in preterm infants (P < .01). Strong correlations were found between the bifrontal and biparietal measures with total brain tissue volume, whereas the size of the ventricles and the interhemispheric measure correlated with CSF volume. Intraobserver reliability was high (intraclass correlation coefficients [ICC], >0.7), where interobserver agreement was acceptable for tissue measures (ICC, >0.6) but lower for fluid measures (ICC, <0.4) CONCLUSIONS: Simple brain metrics at term-equivalent age showed smaller brain diameters and increased ventricle size in preterm infants compared with full-term infants. These measures represent a reliable and easily applicable method to quantify brain growth and assess brain atrophy in this at-risk population

Brain tissue microstructural and free-water composition 13 years after very preterm birth

There have been many studies demonstrating children born very preterm exhibit brain white matter microstruc- tural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (<30 weeks’ gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and in- creased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and concurrent adverse cognitive and motor outcomes in very preterm children. The findings demonstrate brain microstructural and free-water alterations up to thirteen years from neonatal brain abnormalities in very preterm children that relate to adverse neurodevelopmental outcomes.Claire Kelly, Thijs Dhollander, Ian H Harding, Wasim Khan, Richard Beare, Jeanie LY Cheong, Lex W Doyle, Marc Seal, Deanne K Thompson, Terrie E Inder, Peter J Anderso

Impaired language abilities and white matter abnormalities in children born very preterm and/or very low birth weight

To investigate language abilities in children born very preterm (VPT; <32 weeks' gestational age) or very low birth weight (VLBW; <1500 g) at 7 years of age and compare their performances with children born at term, and to determine whether group differences could be explained by cerebral white matter abnormality on neonatal magnetic resonance imaging.A cohort of 198 children born <30 weeks' gestational age and/or <1250 g, and 70 term controls were examined. White matter abnormalities were rated quantitatively on brain magnetic resonance imaging at term-equivalent age. Language was assessed at age 7 years using standardized language tests. Differences between groups were tested in the 5 language subdomains of phonological awareness, semantics, grammar, discourse, and pragmatics. A mediation effect was tested between birth group, white matter abnormality, and language subdomains.The VPT/VLBW group performed significantly worse than controls on all language subdomains (all P < .001). White matter abnormality mediated the effect of group differences on phonological awareness, and partly mediated this effect for semantics, grammar, and discourse. White matter abnormality was not significantly associated with pragmatics (P = .13).Language is an important area of concern in children born VPT/VLBW. Neonatal white matter abnormality is an important predictor of outcome; however, different language abilities are differentially associated with neonatal white matter abnormality.Natalie Reidy, Angela Morgan, Deanne K. Thompson, Terrie E. Inder, Lex W. Doyle, Peter J. Anderso

Parenting behavior at 2 years predicts school-age performance at 7 years in very preterm children

Background Parenting influences child development, but it is unclear whether early parenting behaviour can influence school-age outcomes in very preterm (VPT) children, and/or if certain groups of VPT children may be more affected by early parenting behaviour. These research questions were examined. Methods Participants were 147 children born <30 weeks’ gestation or birth weight <1250 g and their primary caregiver. At term corrected age (CA), magnetic resonance imaging (MRI) was used to determine presence and severity of brain abnormality and medical data collected. High medical risk was defined as the presence of at least one of sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, moderate to severe white matter abnormality on MRI, or postnatal corticosteroids. At 2 years CA, parent–child interaction was assessed, and at 7 years CA, general intelligence (IQ), language, executive function, academic skills, and social-emotional functioning were assessed. Results Higher levels of parent–child synchrony, and parent facilitation, sensitivity and positive affect at 2 years were associated with better child outcomes at 7 years, while higher levels of intrusiveness and negative affect were associated with poorer outcomes. Many of these relationships remained after controlling for early child cognitive development. Interactions between child medical risk (higher/lower) and parenting were limited to child reading, math, and executive functioning outcomes, with stronger relationships for lower medical risk children. Conclusions The contribution of early parenting to VPT children's school-age performance is significant, with stronger effects for lower medical risk children in some outcomes. These findings support the premise that parenting strategies should be included in the NICU and early interventions programs for VPT infants.Karli Treyvaud, Lex W. Doyle, Katherine J. Lee, Alexandra Ure, Terrie E. Inder, Rod W. Hunt, Peter J. Anderso

Corpus callosum alterations in very preterm infants: Perinatal correlates and 2 year neurodevelopmental outcomes

The aim of this study was to relate altered corpus callosum (CC) integrity in 106 very preterm (VPT) infants (<30 weeks' gestational age or <1250 g birth weight) at term equivalent to perinatal predictors and neurodevelopmental outcomes at two years. T1 and diffusion magnetic resonance images were obtained. The CC was traced, and divided into six sub-regions for cross-sectional area and shape analyses. Fractional anisotropy, mean, axial and radial diffusivity were sampled within the CC, and probabilistic tractography was performed. Perinatal predictors were explored. The Bayley Scales of Infant Development (BSID-II) was administered at two years. Intraventricular hemorrhage was associated with a smaller genu and altered diffusion values within the anterior and posterior CC of VPT infants. White matter injury was associated with widespread alterations to callosal diffusion values, especially posteriorly, and radial diffusivity was particularly elevated, indicating altered myelination. Reduced CC tract volume related to lower gestational age, particularly posteriorly. Reduced posterior callosal skew was associated with postnatal corticosteroid exposure. This more circular CC was associated with delayed cognitive development. Higher diffusivity, particularly in splenium tracts, was associated with impaired motor development. This study elucidates perinatal predictors and adverse neurodevelopmental outcomes associated with altered callosal integrity in VPT infants.Deanne K.Thompson, Terrie E.Inder, Nathan Faggian, Simon K.Warfieldd, Peter J.Anderson, Lex W.Doyle, Gary F.Ega