Longitudinal study of neonatal brain tissue volumes in preterm infants and their ability to predict neurodevelopmental outcome

&NA; Premature birth has been associated with poor neurodevelopmental outcomes. However, the relation between such outcomes and brain growth in the neonatal period has not yet been fully elucidated. This study investigates longitudinal brain development between birth and term‐equivalent age (TEA) by quantitative imaging in a cohort of premature infants born between 26 and 36 weeks gestational age (GA), to provide insight into the relation of brain growth with later neurodevelopmental outcomes. Longitudinal T2‐weighted magnetic resonance images (MRI) of 84 prematurely born infants acquired shortly after birth and TEA were automatically segmented into cortical gray matter (CGM), unmyelinated white matter (UWM), subcortical gray matter (SGM), cerebellum (CB) and cerebrospinal fluid (CSF). General linear models and correlation analysis were used to study the relation between brain volumes and their growth, and perinatal variables. To investigate the ability of the brain volumes to predict children's neurodevelopmental outcome at 18–24 months and at 5 years of age, a linear discriminant analysis classifier was tested and several general linear models were fitted and compared by statistical tests. From birth to TEA, relative volumes of CGM, CB and CSF with respect to total intracranial volume increased, while relative volumes of UWM and SGM decreased. The fastest growing tissues between birth and TEA were found to be the CB and the CGM. Lower GA at birth was associated with lower growth rates of CGM, CB and total tissue. Among perinatal factors, persistent ductus arteriosus was associated with lower SGM, CB and IC growth rates, while sepsis was associated with lower CSF and intracranial volume growth rates. Model comparisons showed that brain tissue volumes at birth and at TEA contributed to the prediction of motor outcomes at 18–24 months, while volumes at TEA and volume growth rates contributed to the prediction of cognitive scores at 5 years of age. The family socio‐economic status (SES) was not correlated with brain volumes at birth or at TEA, but was strongly associated with the cognitive outcomes at 18–24 months and 5 years of age. This study provides information about brain growth between birth and TEA in premature children with no focal brain lesions, and investigates their association with subsequent neurodevelopmental outcome. Parental SES was found to be a major determinant of neurodevelopmental outcome, unrelated to brain growth. However, further research is necessary in order to fully explain the variability of neurodevelopmental outcomes in this population. HighlightsPreterm infant longitudinal brain growth from birth to term age was investigated.Infant brain MRIs were automatically segmented and tissue volumes measured.Perinatal factors and gestational age affected tissue volumes and their growth.Volumes and growth rates were associated with later cognitive and motor outcomes.Family socio‐economic status was a major determinant of neurodevelopmental outcomes.

[1]  Deanne K. Thompson,et al.  Preterm infant hippocampal volumes correlate with later working memory deficits. , 2008, Brain : a journal of neurology.

[2]  M. Farah,et al.  Childhood poverty: Specific associations with neurocognitive development , 2006, Brain Research.

[3]  Richard L Robertson,et al.  Late Gestation Cerebellar Growth Is Rapid and Impeded by Premature Birth , 2005, Pediatrics.

[4]  A. Anderson,et al.  Regional brain volumes and their later neurodevelopmental correlates in term and preterm infants. , 2003, Pediatrics.

[5]  Courtney Stevens,et al.  Differences in the neural mechanisms of selective attention in children from different socioeconomic backgrounds: an event-related brain potential study. , 2009, Developmental science.

[6]  Alan Lucas,et al.  Hippocampal Volume and Everyday Memory in Children of Very Low Birth Weight , 2000, Pediatric Research.

[7]  B. E. Gridley,et al.  Review of the Bayley Scales of Infant Development—Second edition , 1994 .

[8]  Deanne K. Thompson,et al.  Examination of the Pattern of Growth of Cerebral Tissue Volumes From Hospital Discharge to Early Childhood in Very Preterm Infants. , 2016, JAMA pediatrics.

[9]  J. Oosterlaan,et al.  Meta-Analysis of Neurobehavioral Outcomes in Very Preterm and/or Very Low Birth Weight Children , 2009, Pediatrics.

[10]  T. Xiong,et al.  An overview of risk factors for poor neurodevelopmental outcome associated with prematurity , 2012, World Journal of Pediatrics.

[11]  Cyril Flamant,et al.  Neurodevelopmental Outcome at 2 Years of Age according to Patent Ductus Arteriosus Management in Very Preterm Infants , 2016, Neonatology.

[12]  Rebecca C. Knickmeyer,et al.  Regional Gray Matter Growth, Sexual Dimorphism, and Cerebral Asymmetry in the Neonatal Brain , 2007, The Journal of Neuroscience.

[13]  Laura E. Engelhardt,et al.  Socioeconomic disparities in neurocognitive development in the first two years of life. , 2015, Developmental psychobiology.

[14]  Steven P. Miller,et al.  Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. , 2005, The Journal of pediatrics.

[15]  Neil Marlow,et al.  Development of Executive Function and Attention in Preterm Children: A Systematic Review , 2009, Developmental neuropsychology.

[16]  Simon K Warfield,et al.  Intrauterine Growth Restriction Affects the Preterm Infant's Hippocampus , 2008, Pediatric Research.

[17]  Lianne J. Woodward,et al.  Cognitive Development Trajectories of Very Preterm and Typically Developing Children. , 2017, Child development.

[18]  N. Marlow,et al.  Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies , 2012, BMJ : British Medical Journal.

[19]  Frank Lindblad,et al.  Preterm Birth and Attention-Deficit/Hyperactivity Disorder in Schoolchildren , 2011, Pediatrics.

[20]  Hugo Lagercrantz,et al.  Brain Growth Gains and Losses in Extremely Preterm Infants at Term. , 2015, Cerebral cortex.

[21]  J. Volpe Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important , 2009, Journal of child neurology.

[22]  Max A. Viergever,et al.  Relation between clinical risk factors, early cortical changes, and neurodevelopmental outcome in preterm infants , 2016, NeuroImage.

[23]  Deanne K. Thompson,et al.  Reduction in Cerebellar Volumes in Preterm Infants: Relationship to White Matter Injury and Neurodevelopment at Two Years of Age , 2006, Pediatric Research.

[24]  Lynn T Singer,et al.  Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes. , 2003, Pediatrics.

[25]  L. Doyle,et al.  Neurodevelopmental outcome of bronchopulmonary dysplasia. , 2006, Seminars in perinatology.

[26]  Dieter Wolke,et al.  Effects of Gestational Age at Birth on Cognitive Performance: A Function of Cognitive Workload Demands , 2013, PloS one.

[27]  E. Sowell,et al.  Age-Related Differences in Cortical Thickness Vary by Socioeconomic Status , 2016, PloS one.

[28]  G. Breart,et al.  Survival of very preterm infants: Epipage, a population based cohort study , 2004, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[29]  Richard L Robertson,et al.  Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses , 2016, Pediatrics.

[30]  J. Hajnal,et al.  Abnormal Cortical Development after Premature Birth Shown by Altered Allometric Scaling of Brain Growth , 2006, PLoS medicine.

[31]  R. Bradley,et al.  Socioeconomic status and child development. , 2002, Annual review of psychology.

[32]  A. Lipp,et al.  SIGNIFICANCE OF PRENATAL, PERINATAL AND POSTNATAL FACTORS IN THE DEVELOPMENT OF AGA PRETERM INFANTS AT FIVE TO SEVEN YEARS , 1989, Developmental medicine and child neurology.

[33]  Jaap Oosterlaan,et al.  Brain development of very preterm and very low‐birthweight children in childhood and adolescence: a meta‐analysis , 2012, Developmental medicine and child neurology.

[34]  Petronella Anbeek,et al.  Brain Volumes at Term-Equivalent Age in Preterm Infants: Imaging Biomarkers for Neurodevelopmental Outcome through Early School Age. , 2016, The Journal of pediatrics.

[35]  Deanne K. Thompson,et al.  Object working memory deficits predicted by early brain injury and development in the preterm infant. , 2005, Brain : a journal of neurology.

[36]  Brigitte Vollmer,et al.  Sex differences in outcome and associations with neonatal brain morphology in extremely preterm children. , 2014, The Journal of pediatrics.

[37]  Richard Beare,et al.  Brain Volumes at Term-Equivalent Age Are Associated with 2-Year Neurodevelopment in Moderate and Late Preterm Children. , 2016, The Journal of pediatrics.

[38]  F. Lazeyras,et al.  Primary cortical folding in the human newborn: an early marker of later functional development. , 2008, Brain : a journal of neurology.

[39]  Wayne Lee,et al.  Longitudinal cerebellar growth following very preterm birth , 2016, Journal of magnetic resonance imaging : JMRI.

[40]  Gehan Roberts,et al.  Attention Difficulties in a Contemporary Geographic Cohort of Adolescents Born Extremely Preterm/Extremely Low Birth Weight , 2013, Journal of the International Neuropsychological Society.

[41]  Joel Fluss,et al.  Poor Reading in French Elementary School: The Interplay of Cognitive, Behavioral, and Socioeconomic Factors , 2009, Journal of developmental and behavioral pediatrics : JDBP.

[42]  Daniel Rueckert,et al.  Regional growth and atlasing of the developing human brain , 2016, NeuroImage.

[43]  J. Volpe Neurology of the Newborn , 1959, Major problems in clinical pediatrics.

[44]  N Marlow,et al.  The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth , 2005, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[45]  Petronella Anbeek,et al.  Cerebellar volume and proton magnetic resonance spectroscopy at term, and neurodevelopment at 2 years of age in preterm infants , 2012, Developmental medicine and child neurology.

[46]  Paul Aljabar,et al.  Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants. , 2016, The Journal of pediatrics.

[47]  E. Bancalari,et al.  Bronchopulmonary dysplasia. , 2001, American journal of respiratory and critical care medicine.

[48]  I. Evangelou,et al.  Complex Trajectories of Brain Development in the Healthy Human Fetus , 2016, Cerebral cortex.

[49]  Simon K Warfield,et al.  Early Alteration of Structural and Functional Brain Development in Premature Infants Born with Intrauterine Growth Restriction , 2004, Pediatric Research.

[50]  L. D. de Vries,et al.  Brain tissue volumes in preterm infants: prematurity, perinatal risk factors and neurodevelopmental outcome: A systematic review , 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[51]  Deanne K. Thompson,et al.  The predictive validity of neonatal MRI for neurodevelopmental outcome in very preterm children. , 2015, Seminars in perinatology.

[52]  Hong Wang,et al.  Abnormal Cerebral Structure Is Present at Term in Premature Infants , 2005, Pediatrics.

[53]  Hiroyuki Kidokoro,et al.  The impact of prenatal and neonatal infection on neurodevelopmental outcomes in very preterm infants , 2014, Journal of Perinatology.

[54]  Max A. Viergever,et al.  Prediction of cognitive and motor outcome of preterm infants based on automatic quantitative descriptors from neonatal MR brain images , 2017, Scientific Reports.

[55]  Christopher J. Cannistraci,et al.  Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. , 2000, JAMA.

[56]  K. Schneider,et al.  Analyse des Neugeborenenkollektivs der Bundesrepublik Deutschland , 2006 .

[57]  Ivana Isgum,et al.  Patent Ductus Arteriosus and Brain Volume , 2016, Pediatrics.

[58]  Deanne K. Thompson,et al.  Perinatal risk factors altering regional brain structure in the preterm infant. , 2006, Brain : a journal of neurology.

[59]  J. Volpe Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances , 2009, The Lancet Neurology.

[60]  Daniel Rueckert,et al.  Automatic anatomical brain MRI segmentation combining label propagation and decision fusion , 2006, NeuroImage.

[61]  Riitta Parkkola,et al.  Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children , 2011, Pediatric Radiology.

[62]  Deanna M Barch,et al.  Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms. , 2017, Journal of the American Academy of Child and Adolescent Psychiatry.

[63]  Franck Ramus,et al.  The Influence of Socioeconomic Status on Children’s Brain Structure , 2012, PloS one.

[64]  F. Rybicki,et al.  Regional Brain Development in Serial Magnetic Resonance Imaging of Low-Risk Preterm Infants , 2006, Pediatrics.

[65]  H. Wong,et al.  Nature or Nurture: A Systematic Review of the Effect of Socio-economic Status on the Developmental and Cognitive Outcomes of Children Born Preterm , 2013, Maternal and Child Health Journal.

[66]  Daniel Rueckert,et al.  Early growth in brain volume is preserved in the majority of preterm infants , 2007, Annals of neurology.

[67]  R. Kikinis,et al.  Quantitative magnetic resonance imaging of brain development in premature and mature newborns , 1998, Annals of neurology.

[68]  Simon K Warfield,et al.  Neonate hippocampal volumes: Prematurity, perinatal predictors, and 2‐year outcome , 2008, Annals of neurology.

[69]  Laura Gui,et al.  Morphology-driven automatic segmentation of MR images of the neonatal brain , 2012, Medical Image Anal..

[70]  L. Ment,et al.  Imaging biomarkers of outcome in the developing preterm brain , 2009, The Lancet Neurology.

[71]  Riitta Parkkola,et al.  Relations between brain volumes, neuropsychological assessment and parental questionnaire in prematurely born children , 2010, European Child & Adolescent Psychiatry.

[72]  Andrew Zalesky,et al.  Structural connectivity relates to perinatal factors and functional impairment at 7years in children born very preterm , 2016, NeuroImage.

[73]  J Hajnal,et al.  Perinatal cortical growth and childhood neurocognitive abilities , 2011, Neurology.