Regional cerebral development at term relates to school-age social-emotional development in very preterm children.

OBJECTIVE Preterm children are at risk for social-emotional difficulties, including autism and attention-deficit/hyperactivity disorder. We assessed the relationship of regional brain development in preterm children, evaluated via magnetic resonance imaging (MRI) at term-equivalent postmenstrual age (TEA), to later social-emotional difficulties. METHOD MR images obtained at TEA from 184 very preterm infants (gestation <30 weeks or birth weight <1,250 g) were analyzed for white matter abnormalities, hippocampal volume, and brain metrics. A total of 111 infants underwent diffusion tensor imaging, which provided values for fractional anisotropy and apparent diffusion coefficient. Social-emotional development was assessed with the Infant Toddler Social and Emotional Assessment (ITSEA) at age 2 and the Strengths and Difficulties Questionnaire (SDQ) at age 5 years. RESULTS Higher apparent diffusion coefficient in the right orbitofrontal cortex was associated with social-emotional problems at age 5 years (peer problems, p < .01). In females, smaller hippocampal volume was associated with increased hyperactivity (p < .01), peer problems (p < .05), and SDQ total score (p < .01). In males, a smaller frontal region was associated with poorer prosocial (p < .05) scores. Many of the hippocampal findings remained significant after adjusting for birthweight z score, intelligence, social risk, immaturity at birth, and parental mental health. These associations were present in children who had social-emotional problems in similar domains at age 2 and those who did not. CONCLUSIONS Early alterations in regional cerebral development in very preterm infants relate to specific deficits in social-emotional performance by school-age. These results vary by gender. Our results provide further evidence for a neuroanatomical basis for behavioral challenges found in very preterm children.

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

[2]  M. Kaminski,et al.  Behavioral Problems and Cognitive Performance at 5 Years of Age After Very Preterm Birth: The EPIPAGE Study , 2009, Pediatrics.

[3]  J. Allsop,et al.  Relationship Between White Matter Apparent Diffusion Coefficients in Preterm Infants at Term-Equivalent Age and Developmental Outcome at 2 Years , 2007, Pediatrics.

[4]  R. Goodman,et al.  The extended version of the Strengths and Difficulties Questionnaire as a guide to child psychiatric caseness and consequent burden. , 1999, Journal of child psychology and psychiatry, and allied disciplines.

[5]  J. Soul,et al.  Positive Screening for Autism in Ex-preterm Infants: Prevalence and Risk Factors , 2008, Pediatrics.

[6]  Deanne K. Thompson,et al.  Abnormal White Matter Signal on MR Imaging Is Related to Abnormal Tissue Microstructure , 2009, American Journal of Neuroradiology.

[7]  Diane C. Chugani,et al.  Diffusion Tensor Imaging of Frontal Lobe in Autism Spectrum Disorder , 2008, Cerebral cortex.

[8]  Jocelyne Bachevalier,et al.  The Orbitofrontal–amygdala Circuit and Self-regulation of Social–emotional Behavior in Autism , 2022 .

[9]  D. Stuss,et al.  The frontal lobes are necessary for 'theory of mind'. , 2001, Brain : a journal of neurology.

[10]  L. Doyle,et al.  A Novel Quantitative Simple Brain Metric Using MR Imaging for Preterm Infants , 2008, American Journal of Neuroradiology.

[11]  Carles Falcon,et al.  Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk , 2009, Pediatrics.

[12]  C. Limperopoulos.  Autism spectrum disorders in survivors of extreme prematurity. , 2009, Clinics in perinatology.

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

[14]  Ann-Mari Brubakk,et al.  Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities. , 2005, Pediatric neurology.

[15]  L. Doyle,et al.  Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. , 2003, JAMA.

[16]  Todd D. Little,et al.  The Infant–Toddler Social and Emotional Assessment (ITSEA): Factor Structure, Reliability, and Validity , 2003, Journal of abnormal child psychology.

[17]  Mario Schootman,et al.  Area-level poverty and preterm birth risk: A population-based multilevel analysis , 2008, BMC public health.

[18]  R. Goodman.  The Strengths and Difficulties Questionnaire: a research note. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[19]  Gehan Roberts,et al.  Social-emotional difficulties in very preterm and term 2 year olds predict specific social-emotional problems at the age of 5 years. , 2012, Journal of pediatric psychology.

[20]  Neil Marlow,et al.  Psychiatric Disorders in Extremely Preterm Children: Longitudinal Finding at Age 11 Years in the EPI , 2010 .

[21]  Matcheri S. Keshavan,et al.  Volumetric alterations of the orbitofrontal cortex in autism , 2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[22]  F. Cowan,et al.  Reduced development of cerebral cortex in extremely preterm infants , 2000, The Lancet.

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

[24]  Simon K Warfield,et al.  MR‐determined hippocampal asymmetry in full‐term and preterm neonates , 2009, Hippocampus.

[25]  L J Abernethy,et al.  Quantitative magnetic resonance imaging of the brain in survivors of very low birth weight , 2002, Archives of disease in childhood.

[26]  Steven P. Miller,et al.  Serial quantitative diffusion tensor MRI of the premature brain: Development in newborns with and without injury , 2002, Journal of magnetic resonance imaging : JMRI.

[27]  E. Bullmore,et al.  Differential activation of the amygdala and the ‘social brain’ during fearful face-processing in Asperger Syndrome , 2007, Neuropsychologia.

[28]  Russell Wilkins,et al.  Effect of neighbourhood income and maternal education on birth outcomes: a population-based study , 2006, Canadian Medical Association Journal.

[29]  C. Zahn-Waxler,et al.  Disorders of childhood and adolescence: gender and psychopathology. , 2008, Annual review of clinical psychology.

[30]  Indira Tendolkar,et al.  Amygdala and hippocampus enlargement during adolescence in autism. , 2010, Journal of the American Academy of Child and Adolescent Psychiatry.

[31]  T. Inder,et al.  White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term. , 2003, AJNR. American journal of neuroradiology.

[32]  Daniel Tranel,et al.  Asymmetric Functional Roles of Right and Left Ventromedial Prefrontal Cortices in Social Conduct, Decision-Making, and Emotional Processing , 2002, Cortex.

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

[34]  C. Boesch,et al.  Structural and Neurobehavioral Delay in Postnatal Brain Development of Preterm Infants1 , 1996, Pediatric Research.

[35]  D. Lamping,et al.  When to Use Broader Internalising and Externalising Subscales Instead of the Hypothesised Five Subscales on the Strengths and Difficulties Questionnaire (SDQ): Data from British Parents, Teachers and Children , 2010, Journal of abnormal child psychology.

[36]  T. Inder,et al.  Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. , 2006, The New England journal of medicine.

[37]  John B Carlin,et al.  Regression models for twin studies: a critical review. , 2005, International journal of epidemiology.

[38]  N. Tzavidis,et al.  Modeling risks: effects of area deprivation, family socio-economic disadvantage and adverse life events on young children’s psychopathology , 2010, Social Psychiatry and Psychiatric Epidemiology.

[39]  Rebecca Elliott,et al.  Neuronal correlates of theory of mind and empathy: A functional magnetic resonance imaging study in a nonverbal task , 2006, NeuroImage.

[40]  Gehan Roberts,et al.  High Rates of School Readiness Difficulties at 5 Years of Age in Very Preterm Infants Compared with Term Controls , 2011, Journal of developmental and behavioral pediatrics : JDBP.

[41]  L. Doyle,et al.  Parenting Behavior Is Associated With the Early Neurobehavioral Development of Very Preterm Children , 2009, Pediatrics.

[42]  R. Kikinis,et al.  Periventricular white matter injury in the premature infant is followed by reduced cerebral cortical gray matter volume at term , 1999, Annals of neurology.

[43]  Catherine Limperopoulos,et al.  Does Cerebellar Injury in Premature Infants Contribute to the High Prevalence of Long-term Cognitive, Learning, and Behavioral Disability in Survivors? , 2007, Pediatrics.

[44]  Eileen Luders,et al.  Sex differences in brain anatomy. , 2010, Progress in brain research.

[45]  A. Dale,et al.  Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. , 2007, Brain : a journal of neurology.

[46]  Philip Shaw,et al.  Cerebellar development and clinical outcome in attention deficit hyperactivity disorder. , 2007, The American journal of psychiatry.

[47]  J. Volpe,et al.  The encephalopathy of prematurity--brain injury and impaired brain development inextricably intertwined. , 2009, Seminars in pediatric neurology.

[48]  L. Doyle,et al.  Parental mental health and early social-emotional development of children born very preterm. , 2010, Journal of pediatric psychology.

[49]  R. Goodman,et al.  Psychometric properties of the strengths and difficulties questionnaire. , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[50]  F. Gonzalez-Lima,et al.  Adolescent female rats are more resistant than males to the effects of early stress on prefrontal cortex and impulsive behavior. , 2009, Developmental psychobiology.

[51]  M. Black,et al.  Cognitive development of children in poverty with failure to thrive: a prospective study through age 6. , 2003, Journal of child psychology and psychiatry, and allied disciplines.

[52]  N. Minich,et al.  Longitudinal outcomes of very low birth weight: Neuropsychological findings , 2004, Journal of the International Neuropsychological Society.

[53]  M. Joëls,et al.  Opposite Effects of Early Maternal Deprivation on Neurogenesis in Male versus Female Rats , 2009, PloS one.

[54]  Paul D. Williams,et al.  A user's guide to the General Health Questionnaire , 1988 .

[55]  L. Doyle,et al.  Early emergence of behavior and social-emotional problems in very preterm infants. , 2009, Journal of the American Academy of Child and Adolescent Psychiatry.

[56]  H Meltzer,et al.  Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample , 2003, International review of psychiatry.

[57]  John Pluta,et al.  Gender difference in neural response to psychological stress. , 2007, Social cognitive and affective neuroscience.

[58]  Moo K. Chung,et al.  Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism , 2007, Neuroscience Letters.

[59]  N Marlow,et al.  Attention deficit hyperactivity disorders and other psychiatric outcomes in very low birthweight children at 12 years. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[60]  M A Rutherford,et al.  Magnetic resonance imaging of the brain in a cohort of extremely preterm infants. , 1999, The Journal of pediatrics.

[61]  T. Inder,et al.  Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. , 2003, Jornal de Pediatria.

[62]  T. Schwartz,et al.  Depressive Symptoms in Mothers of Prematurely Born Infants , 2007, Journal of developmental and behavioral pediatrics : JDBP.

[63]  Peter J Cooper,et al.  Maternal depression and psychiatric outcomes in adolescent offspring: a 13-year longitudinal study. , 2007, Journal of affective disorders.

[64]  Marlon J. A. Jetten,et al.  Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress , 2011, European Neuropsychopharmacology.