First lessons 6 13

First Lessons

The Value of Healthy Regulation for Parent & Baby

Paige Terrien Church, MD

Neonatologist & Developmental Behavioral Pediatrician

Assistant Professor, Paediatrics

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DisclosureDisclosure

• I have no actual or potential conflict of interest in relation I have no actual or potential conflict of interest in relation to this program.to this program.

• I also assume responsibility for ensuring the scientific I also assume responsibility for ensuring the scientific validity, objectivity, and completeness of the content of validity, objectivity, and completeness of the content of my presentationmy presentation

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ObjectivesObjectives

At the end of this session you will be able to:At the end of this session you will be able to:

1.1. Understand neurosensory development and critical Understand neurosensory development and critical periodsperiods

2.2. Explain normal attachmentExplain normal attachment

3.3. Recognize impact of interrupted neurodevelopment on Recognize impact of interrupted neurodevelopment on outcomeoutcome

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Introduction

• “It is easier to build strong children than to repair broken men.” (Frederick Douglas)

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ProblemProblem

• 50-70% of very preterm infants have difficulty 50-70% of very preterm infants have difficulty with school performancewith school performance

• Proposed factor: complex amalgam of minor Proposed factor: complex amalgam of minor challengeschallenges– Behavioral Behavioral – Motor (fine, gross, visual)Motor (fine, gross, visual)

– Cognitive (intellect, processing)Cognitive (intellect, processing)

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Behavioral PhenotypeBehavioral Phenotype

• Describes a constellation of behavioral, Describes a constellation of behavioral, cognitive, motor, and social difficulties observed cognitive, motor, and social difficulties observed in a population with a common biological in a population with a common biological disorderdisorder

• Premature survivors have a phenotypePremature survivors have a phenotype– Common biological disorder=alterations in Common biological disorder=alterations in

brain developmentbrain development

Hodapp RM, Fidler DJ. Special Education and Genetics: Connections for the 21Hodapp RM, Fidler DJ. Special Education and Genetics: Connections for the 21 stst Century. The J Spec Educ Century. The J Spec Educ 1999; 33: 130-137.1999; 33: 130-137.

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Behavioral Phenotype of Prematurity Behavioral Phenotype of Prematurity

• Majority of preterms with Majority of preterms with resolution of medical resolution of medical issues by school ageissues by school age

• Motor delays commonMotor delays common

• Dystonia=early sign Dystonia=early sign

• Breslau N, Chilcoat EO, Johnson EO, Andreski P, Lucia VC. Breslau N, Chilcoat EO, Johnson EO, Andreski P, Lucia VC. Neurologic Soft Signs and Low Birthweight: Their Association and Neurologic Soft Signs and Low Birthweight: Their Association and Neuropsychiatric Implications. Biol Psychiatry 2000; 47: 71-79.Neuropsychiatric Implications. Biol Psychiatry 2000; 47: 71-79.

• Bracewell M, Marlowe N. Patterns of Motor Disability in the Very Bracewell M, Marlowe N. Patterns of Motor Disability in the Very Preterm Children. Ment Dev Disabil Res Rev 2002; 8: 241-248.Preterm Children. Ment Dev Disabil Res Rev 2002; 8: 241-248.

• Goyen T-A, Lui K. Developmental Coordination Disorder in Goyen T-A, Lui K. Developmental Coordination Disorder in “apparently normal” schoolchildren born extremely preterm. Arch Dis “apparently normal” schoolchildren born extremely preterm. Arch Dis Child 2009; 94: 298-302.Child 2009; 94: 298-302.

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• Social emotional dys-regulation Social emotional dys-regulation greater in pretermgreater in preterm– LabileLabile

• Internalizing conditionsInternalizing conditions– AnxietyAnxiety– WithdrawnWithdrawn– Socially awkwardSocially awkward– Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS. Cognitive and Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS. Cognitive and

Behavioral Outcomes of School-Aged Children Who Were Born Preterm: A Behavioral Outcomes of School-Aged Children Who Were Born Preterm: A Meta-Analysis. JAMA. 2002; 288: 728-737.Meta-Analysis. JAMA. 2002; 288: 728-737.

– Spittle AJ, Treyvaud K, Doyle LW, Spittle AJ, Treyvaud K, Doyle LW, et alet al. Early Emergence of Behavior and Social-. Early Emergence of Behavior and Social-Emotional Problems in the Very Preterm Infants. J. Am Acad Child Adolesc Emotional Problems in the Very Preterm Infants. J. Am Acad Child Adolesc Psychiatry 2009; 48: 909-918.Psychiatry 2009; 48: 909-918.

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• Preterms with greater:Preterms with greater:– Executive dysfunctionExecutive dysfunction– Hyperactivity, inattentionHyperactivity, inattention– ADHD/ADDADHD/ADD

– Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS. Cognitive and Behavioral Outcomes of Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS. Cognitive and Behavioral Outcomes of School-Aged Children Who Were Born Preterm: A Meta-Analysis. JAMA. 2002; 288: 728-737.School-Aged Children Who Were Born Preterm: A Meta-Analysis. JAMA. 2002; 288: 728-737.

– Anderson PJ, Doyle LW, and Victorian Infant Collaborative Study Group. Executive Functioning in School-Anderson PJ, Doyle LW, and Victorian Infant Collaborative Study Group. Executive Functioning in School-Aged Children Who Were Born Very Preterm or With Extremely Low Birth Weight in the 1990’s. Pediatrics Aged Children Who Were Born Very Preterm or With Extremely Low Birth Weight in the 1990’s. Pediatrics 2004; 114: 50-57.2004; 114: 50-57.

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• Generally average abilities in:Generally average abilities in:– Receptive Receptive – ExpressiveExpressive

• Subtle difficulties common with:Subtle difficulties common with:– SyntaxSyntax– Complexity of language used & understoodComplexity of language used & understood

Foster-Cohen S, Edgin JO, Champion PR, Woodward LJ. Early delayed language in very preterm infants: Foster-Cohen S, Edgin JO, Champion PR, Woodward LJ. Early delayed language in very preterm infants: Evidence from the MacArthur-Bates CDI. J Child Lang 2007; 34: 655-675.Evidence from the MacArthur-Bates CDI. J Child Lang 2007; 34: 655-675.

Foster-Cohen SH, Friesen MD, Champion PR, Woodward LJ. High Prevalence/Low Severity Language Delay in Foster-Cohen SH, Friesen MD, Champion PR, Woodward LJ. High Prevalence/Low Severity Language Delay in Preschool Children Born Very Preterm. J Dev Behav Pediatr 2010; 31: 658-667.Preschool Children Born Very Preterm. J Dev Behav Pediatr 2010; 31: 658-667.

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• Cognitive skills historically regarded as best Cognitive skills historically regarded as best marker of school successmarker of school success– Actually only a piece of puzzleActually only a piece of puzzle

• Preterm at particular risk with:Preterm at particular risk with:– Lower IQ than termLower IQ than term– More likely to have borderline IQMore likely to have borderline IQ

Marlowe NM, Wolke DM, Bracewell MA et al. Neurologic and Developmental Disability at Six Marlowe NM, Wolke DM, Bracewell MA et al. Neurologic and Developmental Disability at Six Years of Age after Extremely Preterm Birth. NEJM 2005; 353: 9-19.Years of Age after Extremely Preterm Birth. NEJM 2005; 353: 9-19.

Whitfield MF, Grunau RV, Holsti L. Extremely premature (Whitfield MF, Grunau RV, Holsti L. Extremely premature (<< 800g) schoolchildren: multiple areas 800g) schoolchildren: multiple areas of hidden disability. Arch Dis Child 1997; 77: F85-90.of hidden disability. Arch Dis Child 1997; 77: F85-90.

Saigal S, den Ouden L, Wolke D, Saigal S, den Ouden L, Wolke D, et alet al. School Age Outcomes in Children Who Were Extremely . School Age Outcomes in Children Who Were Extremely Low Birth Weight From Four International Population-Based Cohorts. Pediatrics 2003; 112: Low Birth Weight From Four International Population-Based Cohorts. Pediatrics 2003; 112: 943-950.943-950.

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• Challenges with:– Language comprehension and expression

• (Verbal and nonverbal communication) – Spatial relationships– Eye contact– Impulse control– Organizational abilities – Physical attributes– Motor coordination– Anxiety (separation anxiety)– Emotional lability

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NeurodevelopmentNeurodevelopment

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NeurodevelopmentNeurodevelopment

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Neurodevelopment• Interplay between intrinsic brain development and Interplay between intrinsic brain development and

experienceexperience

• Intrinsic: driven by genetic code with proliferation and Intrinsic: driven by genetic code with proliferation and migrationmigration

• Critical cells Critical cells – Subplate neuronsSubplate neurons– Pre-oligodendrocytesPre-oligodendrocytes– External granule cellsExternal granule cells

• Kolb B, Gibb R. Brain Plasticity and Behaviour in the Developing Brain. J Can Acad Child Adolesc Psychiatry 2011; 20: 265-276.Kolb B, Gibb R. Brain Plasticity and Behaviour in the Developing Brain. J Can Acad Child Adolesc Psychiatry 2011; 20: 265-276.• Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental disturbances. J Lancet 2009; 8: 110-124.Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental disturbances. J Lancet 2009; 8: 110-124.• Volpe JJ. Subplate Neurons—Missing Link in Brain Injury in the Premature Infant? Pediatrics 1996; 97: 112-113.Volpe JJ. Subplate Neurons—Missing Link in Brain Injury in the Premature Infant? Pediatrics 1996; 97: 112-113.• Volpe JJ. Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important. J Child Neurol 2009; 24: 1085-1104.Volpe JJ. Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important. J Child Neurol 2009; 24: 1085-1104.

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Neurodevelopment

• Extrinsic element=Neuronal plasticity

• Experience expectant development– Experience leads to pruning

– Critical period with early synapse development

• Experience dependent development– Sensitive period with synapse formation/pruning

– Specific regions of brain

• Kolb B, Gibb R. Brain Plasticity and Behaviour in the Developing Brain. J Can Acad Child Adolesc Psychiatry 2011; 20: 265-276.Kolb B, Gibb R. Brain Plasticity and Behaviour in the Developing Brain. J Can Acad Child Adolesc Psychiatry 2011; 20: 265-276.

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Neurosensory developmentNeurosensory development

• Specific sequence – TactileVestibularChemicalAuditoryVisual

• Interrelated and redundant nature of sensory perception– Contributes to later perceptual organization

• Impact of stimulation mediated by:– Timing – Developmental trajectory

• Lickliter R. The Integrated Development of Sensory Development. Clin Perinatol 2011;38:591-603.

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NeurodevelopmentAttachment

• Begins in utero through sensory input– Sounds & smells

• Wired to provide rapid learning

• Early purpose=survival– Keep infant close to mother– Guide brain development

• Provides secure base for future exploration

• Sullivan R, Perry R, Sloan A, Kleinhaus K, Burtchen N. Infant Bonding and Attachment to the Caregiver: Insights from Basic and Clinical Science. Clin Perinatol 2011;38:643-55.

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NeurodevelopmentImpact of Prematurity

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• Interruption of normal neurosensory developmentInterruption of normal neurosensory development

• Developmental susceptibilityDevelopmental susceptibility– Plastic system at critical pointPlastic system at critical point

• Injury or atypical inputInjury or atypical input

• Epigenetic changesEpigenetic changes

• Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental disturbances. J Lancet 2009; 8: 110-124.Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental disturbances. J Lancet 2009; 8: 110-124.• Lickliter R. The Integrated Development of Sensory Development. Clin Perinatol 2011;38:591-603.

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• ““Normal” head ultrasound NOT guarantee of Normal” head ultrasound NOT guarantee of normal outcomenormal outcome– 9% with CP9% with CP– 25% with MDI less than 7025% with MDI less than 70

• Laptook AR, O’Shea TM, Shankaran S, Bhaskar B. Adverse Neurodevelopmental outcomes among extremely Laptook AR, O’Shea TM, Shankaran S, Bhaskar B. Adverse Neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: prevalence and antecedents. Pediatrics. 2005; 115: 673-low birth weight infants with a normal head ultrasound: prevalence and antecedents. Pediatrics. 2005; 115: 673-680.680.

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•3-4% with abnormality on HUS3-4% with abnormality on HUS•20-65% with abnormality on MRI20-65% with abnormality on MRI

Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ. Defining the Nature of the Cerebral Abnormalities in the Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ. Defining the Nature of the Cerebral Abnormalities in the Premature Infant: A Qualitative Magnetic Resonance Imaging Study. J Pediatr 2003; 143: 171-179.Premature Infant: A Qualitative Magnetic Resonance Imaging Study. J Pediatr 2003; 143: 171-179.

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• Developmental vulnerability with preterm birthDevelopmental vulnerability with preterm birth

• Critical cells in preterm brain lack protection Critical cells in preterm brain lack protection from injuryfrom injury– Subplate neuronsSubplate neurons– InterneuronsInterneurons– Pre-oligodendrocytesPre-oligodendrocytes– External granule cellsExternal granule cells

• Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental disturbances. J Lancet 2009; 8: 110-124.Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental disturbances. J Lancet 2009; 8: 110-124.• Volpe JJ. Subplate Neurons—Missing Link in Brain Injury in the Premature Infant? Pediatrics 1996; 97: 112-113.Volpe JJ. Subplate Neurons—Missing Link in Brain Injury in the Premature Infant? Pediatrics 1996; 97: 112-113.• Volpe JJ. Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important. J Child Neurol 2009; 24: 1085-1104.Volpe JJ. Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important. J Child Neurol 2009; 24: 1085-1104.

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• Cell death via:Cell death via:– NecrosisNecrosis– ApoptosisApoptosis

• Can occur on:Can occur on:– Macroscopic (IVH, Macroscopic (IVH,

PVL, PVHI) PVL, PVHI) – Microscopic level Microscopic level

(diffuse injury)(diffuse injury)

• Volpe JJ. Brain injury in preterm infants: a Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and complex amalgam of destructive and developmental disturbances. J Lancet 2009; developmental disturbances. J Lancet 2009; 8: 110-124.8: 110-124.

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NeurodevelopmentNeurodevelopmentImpact of PrematurityImpact of Prematurity

• Altered synaptogenesisAltered synaptogenesis– Experience expectant versus experience Experience expectant versus experience

dependent dependent

– Similar experience with different effects Similar experience with different effects

• Plasticity can be good or badPlasticity can be good or bad

• Neuronal Group Selection TheoryNeuronal Group Selection Theory

• Kolb B, Gibb R. Brain Plasticity and Behaviour in the Developing Brain. J Can Acad Child Adolesc Psychiatry 2011; 20: 265-276.Kolb B, Gibb R. Brain Plasticity and Behaviour in the Developing Brain. J Can Acad Child Adolesc Psychiatry 2011; 20: 265-276.

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• Loss of controlled sensory exposure

• Alterations to timing (too much too soon, too little too late)– Impact perceptual organization

• Loss of redundancy– Impacts selective attention, perceptual organization, learning

• Lickliter R. The Integrated Development of Sensory Development. Clin Perinatol 2011;38:591-603.

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Neuro-DevelopmentNeuro-Development

• End result is:End result is:– Gray matter architecture distortedGray matter architecture distorted– White matter connectivity alteredWhite matter connectivity altered– Cerebellum under-developedCerebellum under-developed

• Leads to Leads to secondary cortical dysplasiasecondary cortical dysplasia

• Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental Volpe JJ. Brain injury in preterm infants: a complex amalgam of destructive and developmental disturbances. J Lancet 2009; 8: 110-124.disturbances. J Lancet 2009; 8: 110-124.

• Alyward GP. Neurodevelopmental Outcomes of Infants Born Prematurely. J Dev Behav Pediatr Alyward GP. Neurodevelopmental Outcomes of Infants Born Prematurely. J Dev Behav Pediatr 2005; 26: 427-440.2005; 26: 427-440.



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Targets for InterventionTargets for InterventionLuciana M. Cognitive development in children born preterm: Implications for theories of brain plasticity following early injury. Devel Luciana M. Cognitive development in children born preterm: Implications for theories of brain plasticity following early injury. Devel

Psychopathol 2003;15:1017-47Psychopathol 2003;15:1017-47

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Targets for InterventionTargets for Intervention

Hadders-Algra M. The Neuronal Group Selection Theory: a framework to explain variation in normal Hadders-Algra M. The Neuronal Group Selection Theory: a framework to explain variation in normal development. Dev Med Child Neurol 2000;42:566-72.development. Dev Med Child Neurol 2000;42:566-72.

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Targets for InterventionTargets for Intervention

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Targets for Intervention: NICU

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Targets for Intervention: NICU“Kangaroo care is crucial for babies to grow and develop and is

also medicine for the souls of parents”

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Targets for Intervention: NICUTargets for Intervention: NICU

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Targets for Intervention: NICUHack MB. Commentary: Care of Preterm Infants in the Neonatal Intensive Care Unit. Pediatrics 2009;123:1246.

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• Randomized controlled trial with standard care and family care rooms (2 units)

• Family care resulted in:– Decreased length of stay– No effect on mortality

– Trend toward decreased BPD

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• Neuronal Group Selection Theory– Nesting versus containment

• Skin to skin

• Cluster non-emergent care

• Pain management (non-pharmacological if possible)

• Family integrated care

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• Non-nutritive sucking

• Breast milk• Holding with feeds (NG or PO)

• Environment– Fosters family presence– Sensory protection (ambient light exposure, sounds, smells)

• Primary nursing– Infants can have up to 120 care providers in hospitalization

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Targets for InterventionNeonatal Follow Up

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• Follow up not only surveillance for outcomesFollow up not only surveillance for outcomes– Need assessment, diagnosis and interventionNeed assessment, diagnosis and intervention

• Homework critical—small stepsHomework critical—small steps

• Reports with clear languageReports with clear language

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• Awareness of statistics not equivalent to child Awareness of statistics not equivalent to child becoming statisticbecoming statistic

• Should provide heightened surveillance and Should provide heightened surveillance and attention to ‘small’ problemsattention to ‘small’ problems

• Constant contextualization Constant contextualization

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• Collaboration with schools criticalCollaboration with schools critical

• Parents need to be educated in positive Parents need to be educated in positive advocacyadvocacy– Education on transition to schoolsEducation on transition to schools– Special education resourcesSpecial education resources– Major morbidities and minor morbidities not mutually Major morbidities and minor morbidities not mutually

exclusiveexclusive

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Future DirectionsFuture Directions

• Emphasis shift in NICU Emphasis shift in NICU – Minimize stressMinimize stress

– Normalize environmental exposure-Parents ideal Normalize environmental exposure-Parents ideal environmentenvironment

• Extended follow up ideal model with Extended follow up ideal model with collaboration with emphasis on interventioncollaboration with emphasis on intervention

• SpecializedSpecialized training essential training essential

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Future DirectionsFuture Directions

• Ongoing research neededOngoing research needed– Correlation to neuroimaging patternsCorrelation to neuroimaging patterns– Neonatal care & impacts on outcomeNeonatal care & impacts on outcome

– Outcomes Outcomes

• Particularly School based and school interventions!Particularly School based and school interventions!– Functional outcome measurements neededFunctional outcome measurements needed

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Thank You!Thank You!

• Sunnybrook Health Sciences CentreSunnybrook Health Sciences Centre• Neonatal Follow Up Clinic Neonatal Follow Up Clinic

– Marion DeLand, RNMarion DeLand, RN– Maureen Luther, PTMaureen Luther, PT– Pat Maddalena, PNPPat Maddalena, PNP– Laura Cooper, OTLaura Cooper, OT– Rudaina Banihani, MD and Jessie VanDyk, MD (neonatal Rudaina Banihani, MD and Jessie VanDyk, MD (neonatal

fellows)fellows)– Vanessa Warsh, administratorVanessa Warsh, administrator– Carol Grenade, administratorCarol Grenade, administrator

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SourcesSources

• Anderson PJ et al. Executive Functioning in School Aged Children Who Were Born Very Preterm or With Extremely Low Birth Weight in the 1990’s. Anderson PJ et al. Executive Functioning in School Aged Children Who Were Born Very Preterm or With Extremely Low Birth Weight in the 1990’s. Pediatrics. 2004;114:50-57Pediatrics. 2004;114:50-57

• Anderson P, Doyle L. Neurobehavioral Outcomes of School Age Children Born Extremely Low Birth Weight or Very Preterm in the 1990’s. JAMA. Anderson P, Doyle L. Neurobehavioral Outcomes of School Age Children Born Extremely Low Birth Weight or Very Preterm in the 1990’s. JAMA. 2003;289:3264-3272.2003;289:3264-3272.

• Aylward GP. ADHD in Children with Disabilities: Etiologic, Diagnostic, and Psychopharmacologic Issues. Lecture, AACPDM, September 2005.Aylward GP. ADHD in Children with Disabilities: Etiologic, Diagnostic, and Psychopharmacologic Issues. Lecture, AACPDM, September 2005.• Aylward GP. Cognitive and Neuropsychological Outcomes: More than IQ Scores. Mental Retardation and Developmental Disabilities Research Aylward GP. Cognitive and Neuropsychological Outcomes: More than IQ Scores. Mental Retardation and Developmental Disabilities Research

Reviews. 2002;8:234-240.Reviews. 2002;8:234-240.• Aylward GP. Neurodevelopmental Outcomes of Infants Born Prematurely. JDBP. 2005;26:427-440.Aylward GP. Neurodevelopmental Outcomes of Infants Born Prematurely. JDBP. 2005;26:427-440.• Aylward GP. Presidential Address. Prediction of Function from Infancy to Early Childhood: Implications for Pediatric Psychology. Journal of Pediatric Aylward GP. Presidential Address. Prediction of Function from Infancy to Early Childhood: Implications for Pediatric Psychology. Journal of Pediatric

Psychology. 2004;29:555-564Psychology. 2004;29:555-564• Berlin CI et al. Auditory neuropathy/dyssynchrony: Its diagnosis and management. Pediatric Clinics of North America. 2003;50:331-340.Berlin CI et al. Auditory neuropathy/dyssynchrony: Its diagnosis and management. Pediatric Clinics of North America. 2003;50:331-340.• Bracewell M et al. Patterns of Motor Disability in Very Preterm Children. Mental Retardation and Developmental Disabilities Research Reviews. Bracewell M et al. Patterns of Motor Disability in Very Preterm Children. Mental Retardation and Developmental Disabilities Research Reviews.

2002;8:241-248.2002;8:241-248.• Brandt I et al. Transient abnormal neurologic signs (TANS) in a longitudinal study of very low birth weight preterm infants. Early Human Development. Brandt I et al. Transient abnormal neurologic signs (TANS) in a longitudinal study of very low birth weight preterm infants. Early Human Development.

2000;59:107-126.2000;59:107-126.• Breslau N et al. Neurologic Soft Signs and Low Birth Weight: Their Association and Neuropsychiatric Implications. Biol Psychiatry. 2000;47:71-79Breslau N et al. Neurologic Soft Signs and Low Birth Weight: Their Association and Neuropsychiatric Implications. Biol Psychiatry. 2000;47:71-79• deGraaf-Peters VB, Hadders-Algra M. Ontogeny of the human central nervous system: What is happening when? Early Human Development 2006; deGraaf-Peters VB, Hadders-Algra M. Ontogeny of the human central nervous system: What is happening when? Early Human Development 2006;

82:257-266.82:257-266.• Delobel-Ayoub M et al. Behavioral Problems and Cognitive Performance at 5 Years of Age After Very Preterm Birth: The EPIPAGE Study. Pediatrics. Delobel-Ayoub M et al. Behavioral Problems and Cognitive Performance at 5 Years of Age After Very Preterm Birth: The EPIPAGE Study. Pediatrics.

2009;6:1485-1492.2009;6:1485-1492.• Goyen T-A. Developmental Coordination Disorder in ‘Apparently Normal’ School Children Born Extremely Preterm. Goyen T-A. Developmental Coordination Disorder in ‘Apparently Normal’ School Children Born Extremely Preterm. • Hack M et al. Poor Predictive Validity of BSID for Cognitive Function of Extemely Low Birth Weight Children at School Age. Pediatrics. 2005;116:333-Hack M et al. Poor Predictive Validity of BSID for Cognitive Function of Extemely Low Birth Weight Children at School Age. Pediatrics. 2005;116:333-

341.341.• Hack M. School Age Outcomes in Children with Birth Weights Under 750 g. NEJM. 1994;331:753-759.Hack M. School Age Outcomes in Children with Birth Weights Under 750 g. NEJM. 1994;331:753-759.• Harris LL et al. School Readiness. Up to Date. 2010. Harris LL et al. School Readiness. Up to Date. 2010. • High PC et al. School Readiness. Pediatrics 2008;121:e1008-e1015.High PC et al. School Readiness. Pediatrics 2008;121:e1008-e1015.• Inder TE et al. Defining the Nature of the Cerebral Abnormalities in the Premature Infant: A Qualitative Magnetic Resonance Imaging Study. Journal of Inder TE et al. Defining the Nature of the Cerebral Abnormalities in the Premature Infant: A Qualitative Magnetic Resonance Imaging Study. Journal of

Pediatrics. 2003;171-179. Pediatrics. 2003;171-179. • Klein N, Hack M, Gallagher J, Fanaroff AA. Preschool Performance of Childrein with Normal Intelligence Who Were very Low-Birth-Weight Infants. Klein N, Hack M, Gallagher J, Fanaroff AA. Preschool Performance of Childrein with Normal Intelligence Who Were very Low-Birth-Weight Infants.

Pediatrics 1985;75:513-37.Pediatrics 1985;75:513-37.• Kuban KCK et al. Positive Screening on the Modified Checklist for Autism in Toddlers (M-CHAT) in Extremely Low Birth Gestational Age Newborns. Kuban KCK et al. Positive Screening on the Modified Checklist for Autism in Toddlers (M-CHAT) in Extremely Low Birth Gestational Age Newborns.

Journal of Pediatrics. In press.Journal of Pediatrics. In press.

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SourcesSources

• Laptook AR et al. Adverse Neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: Laptook AR et al. Adverse Neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: prevalence and antecedents. Pediatrics. 2005;115:673-680. prevalence and antecedents. Pediatrics. 2005;115:673-680.

• Lian WB, Ying SHK et al. Preschool Teachars’ Knowledge, attitudes, and practices on childhood developmental and behavioural Lian WB, Ying SHK et al. Preschool Teachars’ Knowledge, attitudes, and practices on childhood developmental and behavioural disorders in Singapore. J. of Paediatrics and Child Health. 2008;44:187-194.disorders in Singapore. J. of Paediatrics and Child Health. 2008;44:187-194.

• Limperopoulos C et al. Positive Screening for Autism in Ex-Preterm Infants: Prevalence and Risk Factors. Pediatrics. 2008;121:758-765.Limperopoulos C et al. Positive Screening for Autism in Ex-Preterm Infants: Prevalence and Risk Factors. Pediatrics. 2008;121:758-765.• Lowe J et al. Emotional Regulation and Its Impact on Development in the Extremely Low Birth Weight Infants. Developmental and Lowe J et al. Emotional Regulation and Its Impact on Development in the Extremely Low Birth Weight Infants. Developmental and

Behavioral Pediatrics. 2005;26:209-213.Behavioral Pediatrics. 2005;26:209-213.• Marlow N et al. Motor and Executive Function at 6 Years of Age After Extremely Preterm Birth. Pediatrics. 2007;120:793-804.Marlow N et al. Motor and Executive Function at 6 Years of Age After Extremely Preterm Birth. Pediatrics. 2007;120:793-804.• Marlow N et al. Neurologic and Developmental Disability at 6 Years After Extremely Preterm Birth. NEJM. 2005;352:9-19.Marlow N et al. Neurologic and Developmental Disability at 6 Years After Extremely Preterm Birth. NEJM. 2005;352:9-19.• McCormick MC. The Outcomes of Very Low Birth Weight Infants: Are We Asking the Right Questions? Pediatrics. 1997;99:869-876.McCormick MC. The Outcomes of Very Low Birth Weight Infants: Are We Asking the Right Questions? Pediatrics. 1997;99:869-876.• Ment LR et al. Longitudinal Brain Volume Changes in Preterm and Term Control Subjects During Late Childhood and Adolescence. Ment LR et al. Longitudinal Brain Volume Changes in Preterm and Term Control Subjects During Late Childhood and Adolescence.

Pediatrics. 2009;123:503-511.Pediatrics. 2009;123:503-511.• Miller KJ. Executive Functions. Pediatric Annals. 2005;34:311-317.Miller KJ. Executive Functions. Pediatric Annals. 2005;34:311-317.• Mulder H, Pitchford N et al. Processing Speed and Working Memory underlie academic attainment in very preterm children. Archives of Mulder H, Pitchford N et al. Processing Speed and Working Memory underlie academic attainment in very preterm children. Archives of

Disease in Childhood, Fetal Neonatal Edition. 2010.Disease in Childhood, Fetal Neonatal Edition. 2010.• Patrianakos-Hoobler A, Msall ME et al. Predicting school readiness from neurodevelopmental assessments at age 2 years after Patrianakos-Hoobler A, Msall ME et al. Predicting school readiness from neurodevelopmental assessments at age 2 years after

respiratory distress syndrome in infants born preterm. Developmental Medicine & Child Neurology. 2010;52:379-385.respiratory distress syndrome in infants born preterm. Developmental Medicine & Child Neurology. 2010;52:379-385.• Roberts G, Bellinger D et al. A Cumulative Risk Factor Model for Early Identification of Academic Difficulties in Premature and Low Birth Roberts G, Bellinger D et al. A Cumulative Risk Factor Model for Early Identification of Academic Difficulties in Premature and Low Birth

Weight Infants. Maternal Child Health Journal. 2007;11:161-172.Weight Infants. Maternal Child Health Journal. 2007;11:161-172.• Saigal S. School-Age Outcomes in Children Who Were Extremely Low Birth Weight From Four International Population-Based Cohorts. Saigal S. School-Age Outcomes in Children Who Were Extremely Low Birth Weight From Four International Population-Based Cohorts.

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Health & Medicine