Neurodevelopmental Challenges of Premature Infants Nathalie Maitre, MD, PhD

 Identify factors in the intensive care nursery which influence the development of premature infants.  Understand the prevalence of various neurodevelopmental impairments of premature infants.  Review selected therapies with evidence for effect in premature infants. Goals

Goal 1  Identify factors in the intensive care nursery which influence the development of premature infants.

Pathogenesis of Impairment in Premature Infants Immature Neural Development NICU environment Perinatal Injury Remodeling of Neural Pathways MICU Course Interventions Complications Cognitive Impairment Motor Impairment Executive Dysfunction Neurosensory Impairment

In the Beginning

Insults to CNS development  Maternal infections  IVH/PVL  Hypoxic ischemic encephalopathy  Reperfusion  Excitotoxicity, oxidative stress, inflammation  Inherited deficits  Medications

The NICU environment

Ventilators  Neurodevelopmental outcomes worsen the longer an infant is on a ventilator  Oral/sensory consequences  Physical consequences  CLD and long-term function

Touch  Effect of immature system on perception of touch  Perception of pain  Efficacy of pain management  Lasting effects

Sound  Average sound background in NICUs  Sound toxicity Light  Circadian rhythms affect the HPA axis  Darkness vs. cycled light  Phototherapy

Positive influences in the NICU

Developmental Care NIDCAP Stimulation interventions decrease hospitalization duration some studies of long-term effects many show positive short term effects

Kangaroo Care Positive effects on growth, sleep, feeding and stress levels

Summary  Premature infants are at high risk for perinatal insults to the CNS.  The intensive care environment contributes to the altered development of the premature brain.  Few interventions in the intensive care nursery are positive input to the developing nervous system.

 Understand the prevalence of various neurodevelopmental impairments of premature infants Goal 2

The more premature the infant, the more likely there will be an adverse outcome.

Adverse outcomes: Low incidence - High severity Low incidence - High severity High incidence – Low severity High incidence – Low severity

What is a severe disability?  Extreme variation in definitions  Severe: combinations of MDI<70 or 50, PDI <70 or 50, IQ <70, CP, neurosensory deficit.  Can’t run, wash hands or make a 3 word sentence at the age of 3 years.

Severe disability

Major Disabilities Based Upon Birth Weight

Cognitive Abilities “ The mental faculty of knowing, which includes perceiving, recognizing, conceiving, judging, reasoning, and imagining.” The American Heritage ® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company.

Cognitive Impairment: IQ <70  9.54x greater in children who were born < 750 g who were born < 750 g  2.15x greater in those g  10 points < sibling controls

Motor Difficulties Cerebral palsy The Definition and Classification of Cerebral Palsy (2007)Developmental Medicine & Child Neurology

Cerebral Palsy  Overall 40-50% of children with CP were born prematurely.  The more premature the higher risk of CP.  Periventricular leukomalacia and severe grades of IVH increases the risk of CP.

High prevalence / low severity dysfunction  Learning disabilities (30-60%)  Low average or borderline IQ (15-40%)  ADHD (9-10%)  Neuro-psychological deficits  Behavioral disorders

Executive function  Processes responsible for purposeful, goal directed behavior which impact on cognitive, emotional, behavioral and social functions  Normal IQ does not exclude executive dysfunction

Executive function in ELBW  significant dysfunction in metacognition and in behavioral regulation compared to NBW  NOT more impulsive Anderson, Doyle 04

Speech Impairments  Apraxia of speech  Speech delay  Feeding disorders  Stuttering  Language delay (receptive/expressive)  Articulation impairment

Attention and Behavior Impairments Delobel, EPIPAGE 06

Sensory function  Visual Blindness Blindness Refractive errors Refractive errors Strabismus Strabismus Nystagmus Nystagmus  Hearing  Sensory integration

Summary  Premature infants are at high risk for major and minor impairments.  The frequency and severity of impairments increases as gestational age decreases

 Review selected therapies with evidence for effect in premature infants Goal 3

Interventions Modalities  Programs  Therapists  Equipment  Medications  Surgery  Educational support

Evidence-based therapies  Constraint induced movement therapy

Evidence-based therapies  Functional electrical stimulation or neuromuscular electrical stimulation

Evidence-based therapies  Body weight supported treadmill training

Interventions and assistive devices  Botox injections  Surgery  Orthotics, splints, walkers

Sensory integration therapy

Speech Therapy Feeding therapy Therapy for apraxia

Acknowledgements  At UNC Hospitals: Janice Wereszczak, Diane Marshall and the entire SICC team  At Duke University: Ricki Goldstein, Lylie Bonzani, Kara Lardinois