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

Caffeine for apnea of prematurity and brain development at 11 years of age

Objective Caffeine therapy for apnea of prematurity has been reported to improve brain white matter microstructure at term-equivalent age, but its long-term effects are unknown. This study aimed to investigate whether caffeine affects (1) brain structure at 11 years of age, and (2) brain development from term-equivalent age to 11 years of age, compared with placebo. Methods Preterm infants born ≤1250 g were randomly allocated to caffeine or placebo. Magnetic resonance imaging (MRI) was performed on 70 participants (33 caffeine, 37 placebo) at term-equivalent age and 117 participants (63 caffeine, 54 placebo) at 11 years of age. Global and regional brain volumes and white matter microstructure were measured at both time points. Results In general, there was little evidence for differences between treatment groups in brain volumes or white matter microstructure at age 11 years. There was, however, evidence that the caffeine group had a smaller corpus callosum than the placebo group. Volumetric brain development from term-equivalent to 11 years of age was generally similar between treatment groups. However, there was evidence that caffeine was associated with slower growth of the corpus callosum, and slower decreases in axial, radial, and mean diffusivities in the white matter, particularly at the level of the centrum semiovale, over time than placebo. Interpretation This study suggests any benefits of neonatal caffeine therapy on brain structure in preterm infants weaken over time and are not clearly detectable by MRI at age 11 years, although caffeine may have long-term effects on corpus callosum development.Claire E. Kelly, Wenn Lynn Ooi, Joseph Yuan-Mou Yang, Jian Chen, Chris Adamson, Katherine J. Lee ... et al

White matter microstructure correlates with mathematics but not word reading performance in 13-year-old children born very preterm and full-term

Individuals born very preterm (VPT; 1 standard deviation below FT mean) had significantly reduced neurite density compared with VPT children without an impairment. Reading performance was not significantly associated with any of the white matter microstructure parameters. Additionally, the associations between white matter microstructure and mathematics and reading performance did not differ significantly between VPT and FT groups. Our findings suggest that alterations in white matter microstructure, and more specifically lower neurite density, are associated with poorer mathematics performance in 13-year-old VPT and FT children. More research is required to understand the association between reading performance and white matter microstructure in 13- year-old children.Simonne E. Collins, Megan Spencer-Smith, Ines Mürner-Lavanchy, Claire E. Kellya, Philippa Pyman, Leona Pascoe, Jeanie Cheong, Lex W. Doyle, Deanne K. Thompson, Peter J. Anderso

Long-term development of white matter fibre density and morphology up to 13 years after preterm birth: a fixel-based analysis

Background It is well documented that infants born very preterm (VP) are at risk of brain injury and altered brain development in the neonatal period, however there is a lack of long-term, longitudinal studies on the effects of VP birth on white matter development over childhood. Most previous studies were based on voxel-averaged, non-fibre-specific diffusion magnetic resonance imaging (MRI) measures, such as fractional anisotropy. In contrast, the novel diffusion MRI analysis framework, fixel-based analysis (FBA), enables whole-brain analysis of microstructural and macrostructural properties of individual fibre populations at a sub-voxel level. We applied FBA to investigate the long-term implications of VP birth and associated perinatal risk factors on fibre development in childhood and adolescence. Methods Diffusion images were acquired for a cohort of VP (born <30 weeks' gestation) and full-term (FT, ≥37 weeks' gestation) children at two timepoints: mean (SD) 7.6 (0.2) years (n ​= ​138 VP and 32 FT children) and 13.3 (0.4) years (n ​= ​130 VP and 45 FT children). 103 VP and 21 FT children had images at both ages for longitudinal analysis. At every fixel (individual fibre population within an image voxel) across the white matter, we compared FBA metrics (fibre density (FD), cross-section (FC) and a combination of these properties (FDC)) between VP and FT groups cross-sectionally at each timepoint, and longitudinally between timepoints. We also examined associations between known perinatal risk factors and FBA metrics in the VP group. Results Compared with FT children, VP children had lower FD, FC and FDC throughout the white matter, particularly in the corpus callosum, tapetum, inferior fronto-occipital fasciculus, fornix and cingulum at ages 7 and 13 years, as well as the corticospinal tract and anterior limb of the internal capsule at age 13 years. VP children also had slower FDC development in the corpus callosum and corticospinal tract between ages 7 and 13 years compared with FT children. Within VP children, earlier gestational age at birth, lower birth weight z-score, and neonatal brain abnormalities were associated with lower FD, FC and FDC throughout the white matter at both ages. Conclusions VP birth and concomitant perinatal risk factors are associated with fibre tract-specific alterations to axonal development in childhood and adolescence.Claire E.Kelly, Deanne K.Thompson, Sila Genc, Jian Chen, Joseph YM.Yang, Chris Adamson ... et al

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

Origin and Evolution of Saturn's Ring System

The origin and long-term evolution of Saturn's rings is still an unsolved problem in modern planetary science. In this chapter we review the current state of our knowledge on this long-standing question for the main rings (A, Cassini Division, B, C), the F Ring, and the diffuse rings (E and G). During the Voyager era, models of evolutionary processes affecting the rings on long time scales (erosion, viscous spreading, accretion, ballistic transport, etc.) had suggested that Saturn's rings are not older than 100 My. In addition, Saturn's large system of diffuse rings has been thought to be the result of material loss from one or more of Saturn's satellites. In the Cassini era, high spatial and spectral resolution data have allowed progress to be made on some of these questions. Discoveries such as the ''propellers'' in the A ring, the shape of ring-embedded moonlets, the clumps in the F Ring, and Enceladus' plume provide new constraints on evolutionary processes in Saturn's rings. At the same time, advances in numerical simulations over the last 20 years have opened the way to realistic models of the rings's fine scale structure, and progress in our understanding of the formation of the Solar System provides a better-defined historical context in which to understand ring formation. All these elements have important implications for the origin and long-term evolution of Saturn's rings. They strengthen the idea that Saturn's rings are very dynamical and rapidly evolving, while new arguments suggest that the rings could be older than previously believed, provided that they are regularly renewed. Key evolutionary processes, timescales and possible scenarios for the rings's origin are reviewed in the light of tComment: Chapter 17 of the book ''Saturn After Cassini-Huygens'' Saturn from Cassini-Huygens, Dougherty, M.K.; Esposito, L.W.; Krimigis, S.M. (Ed.) (2009) 537-57

Changing consumption of resources for respiratory support and short-term outcomes in four consecutive geographical cohorts of infants born extremely preterm over 25 years since the early 1990s

OBJECTIVES:It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN:Prospective longitudinal cohort study. SETTING:The State of Victoria, Australia. PARTICIPANTS:All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES:Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS:Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS:Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.Jeanie L Y Cheong, Joy E Olsen, Li Huang, Kim M Dalziel, Rosemarie A Boland, Alice C Burnett ... et al

Nonlinear effects in resonant layers in solar and space plasmas

The present paper reviews recent advances in the theory of nonlinear driven magnetohydrodynamic (MHD) waves in slow and Alfven resonant layers. Simple estimations show that in the vicinity of resonant positions the amplitude of variables can grow over the threshold where linear descriptions are valid. Using the method of matched asymptotic expansions, governing equations of dynamics inside the dissipative layer and jump conditions across the dissipative layers are derived. These relations are essential when studying the efficiency of resonant absorption. Nonlinearity in dissipative layers can generate new effects, such as mean flows, which can have serious implications on the stability and efficiency of the resonance

Protocol for assessing whether cognition of preterm infants <29 weeks' gestation can be improved by an intervention with the omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA): a follow-up of a randomised controlled trial

INTRODUCTION: Docosahexaenoic acid (DHA) is an omega-3 (n-3) fatty acid that accumulates into neural tissue during the last trimester of pregnancy, as the fetal brain is undergoing a growth spurt. Infants born <29 weeks' gestation are deprived the normal in utero supply of DHA during this period of rapid brain development. Insufficient dietary DHA postnatally may contribute to the cognitive impairments common among this population. This follow-up of the N-3 fatty acids for improvement in respiratory outcomes (N3RO) randomised controlled trial aims to determine if enteral DHA supplementation in infants born <29 weeks' gestation during the first months of life improves cognitive development at 5 years of age corrected for prematurity. METHODS AND ANALYSIS: N3RO was a randomised controlled trial of enteral DHA supplementation (60 mg/kg/day) or a control emulsion (without DHA) in 1273 infants born <29 weeks' gestation to determine the effect on bronchopulmonary dysplasia (BPD). We showed that DHA supplementation did not reduce the risk of BPD and may have increased the risk.In this follow-up at 5 years' corrected age, a predefined subset (n=655) of children from five Australian sites will be invited to attend a cognitive assessment with a psychologist. Children will be administered the Wechsler Preschool and Primary Scale of Intelligence (fourth edition) and a measure of inhibitory control (fruit stroop), while height, weight and head circumference will be measured.The primary outcome is full-scale IQ. To ensure 90% power, a minimum of 592 children are needed to detect a four-point difference in IQ between the groups.Research personnel and families remain blinded to group assignment. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/17/WCHN/187). Caregivers will give informed consent prior to taking part in this follow-up study. Findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12612000503820.Jacqueline F Gould, Maria Makrides, Thomas R Sullivan, Peter J Anderson, Robert A Gibson, Karen P Best ... et al