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Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7961 (Published 04 December 2012) Cite this as: BMJ 2012;345:e7961
  1. Tamanna Moore, research associate1,
  2. Enid M Hennessy, senior lecturer in statistics2,
  3. Jonathan Myles, research fellow in statistics2,
  4. Samantha J Johnson, lecturer (psychologist)1,
  5. Elizabeth S Draper, professor of perinatal and paediatric epidemiology3,
  6. Kate L Costeloe, professor of paediatrics45,
  7. Neil Marlow, professor of neonatal medicine1
  1. 1Academic Neonatology, UCL Institute for Women’s Health, London WC1E 6AU, UK
  2. 2Wolfson Institute of Preventive Medicine, Queen Mary University of London, London
  3. 3Department of Health Sciences, University of Leicester, Leicester, UK
  4. 4Centre For Paediatrics, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London
  5. 5Homerton University Hospital NHS Foundation Trust, Homerton Row, London
  1. Correspondence to: N Marlow n.marlow{at}ucl.ac.uk
  • Accepted 9 November 2012

Abstract

Objective To determine outcomes at age 3 years in babies born before 27 completed weeks’ gestation in 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks’ gestation.

Design Prospective national cohort studies, EPICure and EPICure 2.

Setting Hospital and home based evaluations, England.

Participants 1031 surviving babies born in 2006 before 27 completed weeks’ gestation. Outcomes for 584 babies born at 22-25 weeks’ gestation were compared with those of 260 surviving babies of the same gestational age born in 1995.

Main outcome measures Survival to age 3 years, impairment (2008 consensus definitions), and developmental scores. Multiple imputation was used to account for the high proportion of missing data in the 2006 cohort.

Results Of the 576 babies evaluated after birth in 2006, 13.4% (n=77) were categorised as having severe impairment and 11.8% (n=68) moderate impairment. The prevalence of neurodevelopmental impairment was significantly associated with length of gestation, with greater impairment as gestational age decreased: 45% at 22-23 weeks, 30% at 24 weeks, 25% at 25 weeks, and 20% at 26 weeks (P<0.001). Cerebral palsy was present in 83 (14%) survivors. Mean developmental quotients were lower than those of the general population (normal values 100 (SD 15)) and showed a direct relation with gestational age: 80 (SD 21) at 22-23 weeks, 87 (19) at 24 weeks, 88 (19) at 25 weeks, and 91 (18) at 26 weeks. These results did not differ significantly after imputation. Comparing imputed outcomes between the 2006 and 1995 cohorts, the proportion of survivors born between 22 and 25 weeks’ gestation with severe disability, using 1995 definitions, was 18% (95% confidence interval 14% to 24%) in 1995 and 19% (14% to 23%) in 2006. Fewer survivors had shunted hydrocephalus or seizures. Survival of babies admitted for neonatal care increased from 39% (35% to 43%) in 1995 to 52% (49% to 55%) in 2006, an increase of 13% (8% to 18%), and survival without disability increased from 23% (20% to 26%) in 1995 to 34% (31% to 37%) in 2006, an increase of 11% (6% to 16%).

Conclusion Survival and impairment in early childhood are both closely related to gestational age for babies born at less than 27 weeks’ gestation. Using multiple imputation to account for the high proportion of missing values, a higher proportion of babies admitted for neonatal care now survive without disability, particularly those born at gestational ages 24 and 25 weeks.

Footnotes

  • We thank Heather Palmer for her contribution to the management and coordination of the study and contact tracing. The EPICure outcome studies were sponsored by the University of Nottingham (until September 2008) and subsequently by University College London.

  • Assessors: Tamanna Moore, Philippa Chisholm (EPICure research fellows), Haytham Ali, Katie Banerjee, Jackie Birch, Richard Cooke, Pat Dulson, Sandeep Dharmaraj, Tony Hart, Charlotte Huddy, Angela Huertas, Anoo Jain, Sam Johnson, Julia Lilley, Caroline McFerran, Katherine Martin, Robin Miralles, Vijay Palanivel, Sarah Skinner, Aung Soe, and Nick Wood.

  • Independent members of the EPICure studies steering committee providing oversight: Peter Brocklehurst (chairperson), Jane Abbott, Andrew Bush, Richard Cooke, Noreen Maconochie, Alison Matthews, David Matthews, Richard Morton, Maggie Redshaw, David Taylor, Nigel Turner, Diane Turner, and Patrick Walsh.

  • Contributors: NM and KLC formulated the hypothesis. NM, SJJ, and TM designed the outcome evaluation. TM carried out outcome assessments, led the assessment team, was responsible for data entry and validation, and analysed the data under supervision by EMH and NM. KLC, ESD. EMH collated the perinatal data. NM wrote the first draft of and coordinated the manuscript. All authors were involved in interpretation of the data and writing the report. All have seen and approved the final version. NM is the guarantor, had full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: This study was funded by the Medical Research Council (G0401525). The funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

  • Competing interests: All authors have completed ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that NM receives part funding from the Department of Health’s NIHR Biomedical Research Centre’s funding scheme at UCLH/UCL; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years.

  • Ethical approval: This follow-up study was approved by the Northern and Yorkshire research ethics committee (08/H0903/51).

  • Data sharing: The EPICure studies are subject to a data sharing policy that may be downloaded from www.epicure.ac.uk.

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