1. Neurodevelopmental Challenges of Premature Infants Nathalie Maitre, MD, PhD

2.  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

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

4. 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

5. In the Beginning

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

7. The NICU environment

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

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

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

11. Positive influences in the NICU

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

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

14. 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.

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

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

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

18. 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.

19. Severe disability

20. Major Disabilities Based Upon Birth Weight

21. 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.

22. Cognitive Impairment: IQ <70  9.54x greater in children who were born < 750 g who were born < 750 g  2.15x greater in those 751-1499 g  10 points < sibling controls

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

24. 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.

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

26. 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

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

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

29. Attention and Behavior Impairments Delobel, EPIPAGE 06

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

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

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

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

34. Evidence-based therapies  Constraint induced movement therapy

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

36. Evidence-based therapies  Body weight supported treadmill training

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

38. Sensory integration therapy

39. Speech Therapy Feeding therapy Therapy for apraxia

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