Psychosis Studies /

General Psychiatry
Follow-Up Study of Infants Born Prematurely

This study examines the effects of being born prematurely and low birth weight on subsequent health, development and brain stucture. The study began in 1979 when a team of specialist paediatricians and psychologists followed up all premature and high-risk babies admitted to the neonatal unit at University College Hospital in London. Since then, more than 1,500 children have taken part, and it is now arguably the most detailed long term study of premature babies to be carried out anywhere in the world.

The UK has the highest number of premature births in Europe, with one out of every 13 babies born prematurely. In 2005, 37,620 (six per cent) of a total of 627,000 live single births in England and Wales were premature. These numbers are on the increase.

Around 25 per cent of babies born early will need intensive care, but thanks to advances in medicine, care and technology, the survival rate of those born prematurely has increased dramatically. Those born at 25 weeks gestation now have a 50 per cent chance of survival. 80 per cent of babies born weighing less than 1,000 grams (2lb 2oz) now survive, while 20 years ago they had only a 20 per cent chance.

Despite the increase in the survival rate and the increase in the occurrence of premature births, little is known about the effect of prematurity on the child’s development throughout childhood, adolescence and into adulthood.

Our research team is carrying out assessments of participants at different stages in their development to try to understand more about the lasting effects of prematurity.

Neuropsychological development

A group of people born prematurely have carried out a number of different neuropsychological tasks from ages one through to 20 to allow us to assess neurological development such as memory, IQ, language skills, response initiation/inhibition, and attention.

The most surprising finding from these studies is that with a few exceptions, preterm-born adolescents perform as well as those born full-term. For example in a study by Dr Elena Giouroukou, preterm-born adolescents scored as highly as the full-term adolescents in tests of memory function, and had no problem performing efficiently on attention tasks. However, Dr Giouroukou did find small differences between those born preterm and those born full-term in the language assessment. Particularly, preterm participants produced fewer words in the test that required them to produce words that started with certain letters, although no differences were found in the production of words that belonged to certain categories (either objects or animals).

Social and behavioural development

We have been interested to look at the emotional and behavioural development of individuals born preterm. To do this, we used questionnaires and carried out interviews with a group of those born prematurely and their parents/carers. Our study, by Dr Elaine Healy, reported that preterm-born adolescents saw themselves as equally competent in extracurricular activities and in social relationships as their full-term born peers, but did acknowledge a slight difference in academic difficulties.

Structural brain development

A lot of participants in the study had an MRI scan when they were aged both 14-16 and 18-20 to allow us to take a picture of the structure of their brains. What we found was that those born preterm had delayed white matter development, which may be a consequence of damage to the white matter around the time of birth. We are still at an early stage of this research and it will be important to follow-up individuals born early into their 20s and 30s, as we would particularly like to know if the delayed development of white matter will ‘catch up’.

Functional brain development

Some participants have also had an fMRI scan which allows us to see which areas of the brain are active when an individual is completing a certain task. This allows us to discover which parts of the brain are used for each cognitive process – memory and verbal fluency (the ease at which some can recall words), for example. We want to discover which functional strategies the brain may use to overcome any changes in the structure due to premature birth.

A recent study by our group found differences between preterm individuals and a full-term comparison group on tests of cognitive functioning. The main findings were that the premature group performed as well as the full-term comparison group on the memory and verbal fluency tasks, but brain activation differences were observed. During the memory tasks, the premature group did not seem to use an area of the brain which is considered to be important for the performance of this type of task. Instead, the preterm group tended to use an adjacent area. During the verbal fluency task, the preterm group did not use areas of the brain that are ordinarily considered important for this kind of task but again they showed intact performance. This suggests the brain has the ability to rewire and allow nearby regions to take over ’functions’ typically performed by other areas. To conclude, this study suggests that the human brain is remarkably resilient and can rewire to allow different regions to those typically used to underpin skills such as memory and verbal fluency.

A new fMRI study

A new fMRI study started in April 2007 and is due to completed by March 2010. This new study will involve fMRI tasks for cognitive functions which have been found to be affected in those born preterm – memory for everyday events and the ability to generate as many words as possible beginning with a given letter (verbal fluency). This new study will improve the understanding of the long-term consequences of preterm birth, especially in the subgroup of preterm individuals who sustained brain damage during the neonatal period, and clarify some of the ‘healing’ processes following various degrees of early brain injury.

Follow-Up Study of Infants Born Prematurely newsletter

To find out more about some of the work undertaken as part of the Follow up Study of Infants Born Prematurely, download our newsletter.
Follow-Up Study of Infants Born Prematurely newsletter

Funders of the Study

Our research has been funded by the following organisations:

The Wellcome Trust
March of Dimes
The Sir Jules Thorn Charitable Trust
The Health Foundation (previously PPP Medical Trust)
BDF Newlife

Who’s who in Follow-Up Study of Infants Born Prematurely

Dr Matthew Allin, Honorary Consultant Psychiatrist and Clinical Lecturer
Dr Elaine Healy, Visiting Research Associate
Anastasia Kalpakidou, PhD Student
Dr Dimitris Kontis, Visiting Research Associate
Dr Emma Lawrence, Lecturer in Cognition and Neuroimaging
Dr Nadia Micali, Clinical Lecturer
Professor Robin Murray, Lead Researcher and Professor of Psychiatric Research
Dr Chiara Nosarti, Senior Lecturer in Mental Health Studies and Neuroimaging
Dr Jennifer Parker, Visiting Research Associate
Dr Larry Rifkin, Lead Researcher
Dr Muriel Walshe, Lecturer and Study Co-ordinator

Publications 1999 - 2010

BOOKS

Nosarti C, Murray RM, Hack M (Eds) (2010). Neurodevelopmental Outcomes of Preterm Birth: From Childhood to Adult Life. Cambridge University Press: Cambridge, UK.

NEUROPSYCHOLOGY

Parker J, Mitchell A, Kalpakidou A, Walshe M, Nosarti C, Rifkin L, Wyatt J, Murray R, Allin M. (2008) Cerebellar Growth and Behavioural & Neuropsychological Outcome in Preterm Adolescents. Brain. 131:1344-51.

Allin M, Walshe M, Fern A, Nosarti C, Cuddy M, Wyatt, Rifkin L, Murray RM. (2008) Cognitive maturation in preterm and term born adolescents. Journal of Neurology, Neurosurgery & Psychiatry. 79: 381-386.

Nosarti C, Giouroukou E, Micali N et al (in press-a). Impaired executive functioning in young adults born very preterm. Journal of the International Neuropsychological Society.

Rushe TM, Temple CM, Rifkin L et al (2004). Lateralisation of language function in young adults born very preterm. Arch. Dis. Child. Fetal Neonatal Ed., 89, F112-118.

Rushe TM, Rifkin L, Stewart AL et al (2001). Neuropsychological outcome at adolescence of very preterm birth and its relation to brain structure. Developmental Medicine & Child Neurology, 43, 226-233.

Stewart AL, Rifkin L, Amess PN et al (1999). Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm. The Lancet, 353, 1653-1657.

NEUROLOGY

Allin M, Rooney M, Griffiths T et al (2006b). Neurological abnormalities in young adults born preterm. J Neurol Neurosurg Psychiatry, 77, 495-499.

MAGNETIC RESONANCE IMAGING

Lawrence, E, Allen E, Walshe, M, Allin, M Murray RM,  Rifkin L, McGuire P, Nosarti, C. The Corpus Callosum and Empathy in Adults with a History of Preterm Birth. Accepted Journal of the International Neuropsychological Society.

Lawrence E, McGuire PK, Allin M, Walshe M, Giampietro V, Murray RM, Rifkin L, Nosarti C. The Very Preterm Brain in Young Adulthood: The Neural Correlates of Verbal Paired Associate Learning. Journal of Pediatrics. In press.

Kontis D, Catani M, Cuddy M, Walshe M, Nosarti C, Jones D, Wyatt J, Rifkin L, Murray R, Allin M. 2009. Diffusion tensor MRI of the corpus callosum and cognitive function in adults born preterm. Neuroimage Mar 4;20(4):424-8.

Nosarti C, Shergill S, Allin MP, Walshe M, Rifkin L, Murray RM, McGuire PK. 2009. Neural substrates of letter fluency processing in young adults who were born very preterm: Alterations in frontal and striatal regions. Neuroimage 47:1904-13

Narberhaus A, Lawrence E, Allin M, Walshe M, Maguire P, Rifkin L, Murray RM, Nosarti C. (2009) Neural substrates of visual paired associates in young adults with a history of very preterm birth: alterations in fronto-parieto-occipital networks and caudate nucleus. Neuroimage. 47:1884-93.

Lawrence E, Rubia K, Murray RM, McGuire P, Walshe M, Allin M, Giampietro V, Rifkin L, Williams S, Nosarti C. (2009) The neural basis of response inhibition and attention allocation as mediated by gestational age. Human Brain Mapping. 30:1038-50.

Parker J, Mitchell A, Kalpakidou A, Walshe M, Nosarti C, Rifkin L, Wyatt J, Murray R, Allin M. (2008) Cerebellar Growth and Behavioural & Neuropsychological Outcome in Preterm Adolescents. Brain. 131:1344-51.

Nosarti C, Giouroukou E, Healy E, Rifkin L, Walshe M, Chitnis X, Williams S, Murray RM. (2008) Abnormalities Of Grey And White Matter Distribution In Adolescents Who Were Born Very preterm. Brain. 131: 205-17.

Allin M, Nosarti C, Narberhaus A, Walshe M, Frearson S, Kalpakidou A, Wyatt J, Rifkin L, Murray RM. (2007) Growth of the corpus callosum in adolescents born preterm.  Archives of Pediatrics and Adolescent Medicine. 161:1183-1189.

Lancefield K, Nosarti C, Rifkin L et al (2006). Cerebral asymmetry in 14 year olds born very preterm. Brain Research, 1093, 33-40.

Nosarti C, Rubia K, Smith AB et al (2006). Altered functional neuroanatomy of response inhibition in adolescent males who were born very preterm. Developmental Medicine & Child Neurology, 48, 265-271.

Allin M & Nosarti C (2005a). Premature birth and the adult brain. Italian Journal of Psychiatry, 31, 38-43.

Allin M, Salaria S, Nosarti C et al (2005b). Vermis and lateral lobes of the cerebellum in adolescents born very preterm. Neuroreport, 16, 1821-1824.

Nosarti C, Allin M, Frangou S et al (2005a). Decreased caudate volume is associated with hyperactivity in adolescents born very preterm. Biological Psychiatry, 57, 661-666.

Nosarti C, Allin MP, Frangou S et al (2005b). Hyperactivity in adolescents born very preterm is associated with decreased caudate volume. Biological Psychiatry, 57, 661-666.

Allin M, Henderson M, Suckling J et al (2004a). Effects of very low birthweight on brain structure in adulthood. Developmental Medicine & Child Neurology, 46, 46-53.

Allin M, Nosarti C, Rifkin L et al (2004b). Brain Plasticity and Long Term Function after Early Cerebral Insult: the Example of Very Preterm Birth. In Neurodevelopment and Schizophrenia (eds M. Keshavan, J. Kennedy & R. Murray). Cambridge: Cambridge University Press.

Fearon P, O’Connell P, Frangou S et al (2004). Brain Volumes in Adult Survivors of Very Low Birth Weight: A Sibling-Controlled Study. Pediatrics, 114, 367-371.

Nosarti C, Rifkin L & Murray R (2003). The neurodevelopmental consequences of very preterm birth: brain plasticity and its limits. In Neurodevelopmental Mechanisms in Psychopathology (eds C. Cicchetti & E. Walker). Cambridge: Cambridge University Press.

Nosarti C, Rushe TM, Woodruff PWR et al (2004). Corpus callosum size and very preterm birth: relationship to neuropsychological outcome. Brain, 127, 2080-2089.

Nosarti C, Al-Asady MHS, Frangou S et al (2002). Adolescents who were born very preterm have decreased brain volumes. Brain, 125, 1616-1623.

Santhouse AM, Ffytche DH, Howard RJ et al (2002a). Functional Imaging of the Mechanisms Underlying the Bilateral Field Advantage. NeuroImage, 17, 680-687.

---- (2002b). The functional significance of perinatal corpus callosum damage: an fMRI study in young adults. Brain, 125, 1782-1792.

Allin M, Matsumoto H, Santhouse AM et al (2001). Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term. Brain, 124, 60-66.

PSYCHOLOGICAL WELLBEING AND GENERAL OUTCOMES

Allin MPG. Preterm babies grown up: understanding a hidden public health problem. Preterm babies grown up: understanding a hidden public health problem. 2010;40:5-7.

Walshe M, Rifkin L, Rooney M, Healy E, Stahl D, Nosarti C,Wyatt J, Murray RM, Allin M. (2008) Psychiatric Disorder in young adults born very preterm: role of family history. European Journal of Psychiatry. 23:527-531.

Allin M, Rooney M, Cuddy M, Wyatt J, Walshe M, Rifkin L, Murray RM. (2006) Personality dimensions in young adults born preterm. Pediatrics. 117: 309-316.

 

More information about the Study

Muriel Walshe, Study Co-ordinator
Follow-Up Study of Infants Born Prematurely
Section of General Psychiatry
Division of Psychological Medicine and Psychiatry, PO63
Institute of Psychiatry
De Crespigny Park
London, SE5 8AF.

Email: m.walshe@iop.kcl.ac.uk
Phone: 020 7848 0057

More information about prematurity

BLISS, the UK charity that works for special care babies and their families. The website contains general information and statistics on premature birth.
www.bliss.org.uk/

March of Dimes, a birth charity that supports research into prematurity. The website contains information and news about prematurity.
www.marchofdimes.com/prematurity/

Nuffield Council on Bioethics
Critical care decisions in fetal and neonatal medicine: ethical issues
www.nuffieldbioethics.org/go/ourwork/neonatal/introduction