Brain injury and its consequences in extremely premature babies John Wyatt Perinatal Brain Protection and Repair Group University College London
Survival of babies weeks gestation UCLH (as percentage of admissions to NICU) Riley et al. Acta Paediatrica 2008; 97:159-65
Percentage of surviving extremely preterm infants with neurodevelopmental impairment at 1 year of age, UCLH Riley et al. Acta Paediatrica 2008; 97:159-65
Neurodevelopmental outcome at 8 years of age < 28 weeks 28 – 32 weeks (n = 137) (n = 445) Disability23%12% Brain lesion detected48%22% by ultrasound Vollmer et al, Pediatrics 2003, 112,
EPICURE nationwide study of all babies in UK and Ireland, born weeks gestation in 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
Cognitive (IQ) scores for ex-premature infants at 6 years of age compared with class mates
White matter loss in the ex-preterm brain
Thinning of corpus callosum
Rate of cortical development is maximal between 22 weeks and term
25 wks GA 27 wks GA 32 wks GA
Rate of synaptic development ~ neurons in CNS Each neuron develops ~ 10 3 synapses Therefore total of ~ synapses created – majority are formed between 22 and 40 weeks of gestation = ~ 5 x synapses per day = ~ 3 x 10 8 synapses per minute!
Cranial MRI scans at 14 years in a cohort of ex-preterm infants MRI Ex-pretermTerm controls Normal23%71% Equivocal21%24% Abnormal56%5% Stewart et al, Lancet 1999, 353:
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.
Grey matter changes in ex-preterm adolescents Nosarti et al, Brain 2002, 125,
White matter changes in ex-preterm adolescents Nosarti et al, Brain 2002, 125,
Changed brain microstructure following developmental care programme Als et al. Pediatrics 2004, 113,
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
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
Acknowledgements Ann Stewart Osmund Reynolds Matt Allin Topun Austin Jenny Baudin Alan Connolly David Edwards Michelle de Haan Angela Huertas- Ceballos David Gadian Robin Murray Brian Neville UCL NHS Trust Centre for Perinatal Brain Protection & Repair Obstetrics & Gynaecology, Paediatrics & Child Health Medical Physics & Bioengineering Chiara Nosarti Fran O'Brien Claire Price Larry Rifkin Kate Riley Nikki Robertson Maeve Rooney Simon Roth Teresa Rushe Al Santhouse Alison Skinner Faraneh Vargha-Khadem Brigitte Vollmer