brain injury and its consequences in extremely premature babies
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Brain injury and its consequences in extremely premature babies. John Wyatt Perinatal Brain Protection and Repair Group University College London. Survival of babies 23-25 weeks gestation UCLH 1981-2000 (as percentage of admissions to NICU). Riley et al. Acta Paediatrica 2008; 97:159-65. - PowerPoint PPT PresentationTRANSCRIPT
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Brain injury and its consequences in extremely premature babies
John Wyatt
Perinatal Brain Protection and Repair GroupUniversity College London
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Survival of babies 23-25 weeks gestation UCLH 1981-2000
(as percentage of admissions to NICU)
Riley et al. Acta Paediatrica 2008; 97:159-65
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Percentage of surviving extremely preterm infants with neurodevelopmental impairment
at 1 year of age, UCLH 1981-2000
Riley et al. Acta Paediatrica 2008; 97:159-65
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Neurodevelopmental outcome at 8 years of age
< 28 weeks 28 – 32 weeks (n = 137) (n = 445)
Disability 23% 12%
Brain lesion detected 48% 22%by ultrasound
Vollmer et al, Pediatrics 2003, 112, 1108-1114
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EPICURE nationwide study of all babies in UK and Ireland, born 22-25 weeks gestation in 1995.
Assessment at 6 years of age
Out of 241 survivors:• 15 were unable to walk due to cerebral palsy • 27 had severe learning difficulties• 4 blind and 7 severe hearing loss• Total of 32 had any severe disability
Marlow et al. NEJM 2005; 325: 9-19
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Cognitive (IQ) scores for ex-premature infants at 6 years of age compared with class mates
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White matter loss in the ex-preterm brain
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Thinning of corpus callosum
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Rate of cortical development is maximal between 22 weeks and term
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25 wks GA 27 wks GA 32 wks GA
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Rate of synaptic development
• ~ 1011 neurons in CNS• Each neuron develops ~ 103 synapses
• Therefore total of ~ 1014 synapses created – majority are formed between 22 and 40 weeks of gestation
= ~ 5 x 1011 synapses per day
= ~ 3 x 108 synapses per minute!
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Cranial MRI scans at 14 years in a cohort of ex-preterm infants
MRI Ex-preterm Term controls
Normal 23% 71%
Equivocal 21% 24%
Abnormal 56% 5%
Stewart et al, Lancet 1999, 353: 1653-1657
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MRI abnormalities in ex-preterm adolescents at 14 years
• MRI abnormalities correlated with abnormal behaviour scores.
• MRI abnormalities did not correlate with IQ, with
neurological signs or with need for extra educational help.
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Grey matter changes in ex-preterm adolescentsNosarti et al, Brain 2002, 125, 1616-1623
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White matter changes in ex-preterm adolescents
Nosarti et al, Brain 2002, 125, 1616-1623
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Changed brain microstructure following developmental care programme
Als et al. Pediatrics 2004, 113, 846-857
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Possible mechanisms of improved outcome following perinatal brain injury
• Cell differentiation and replacement from neuronal and glial precursor stem cells
• Refinement and selection of dendritic synaptic connections
• Rerouting of white matter connections• Development of alternative cortical
processing strategies
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Conclusions• White matter injury in extremely premature infants is the
most important cause of long term neurodevelopmental disability.
• The developing central nervous system has remarkable potential for repair and compensation following perinatal injury
• New therapeutic approaches are required to translate experimental findings into practical therapies whilst babies are undergoing intensive care and following discharge from hospital
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Acknowledgements
Ann StewartOsmund ReynoldsMatt AllinTopun AustinJenny BaudinAlan ConnollyDavid EdwardsMichelle de HaanAngela Huertas-CeballosDavid GadianRobin MurrayBrian Neville
UCL NHS TrustCentre for Perinatal Brain Protection &
RepairObstetrics & Gynaecology, Paediatrics & Child Health
Medical Physics & Bioengineering
Chiara NosartiFran O'BrienClaire PriceLarry RifkinKate RileyNikki RobertsonMaeve RooneySimon RothTeresa RusheAl SanthouseAlison SkinnerFaraneh Vargha-KhademBrigitte Vollmer