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

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.

Conflict of interest statement

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.

Figures

Fig 1 Distribution of index of multiple deprivation 10ths, based on English population, for EPICure 2 cohort showing excess of children with low values (more disadvantage) in those not evaluated face to face

Fig 2 Functional outcomes graded according to Gross Motor Function Classification System for babies born before 27 weeks’ gestation in 2006, England

Fig 3 Developmental scores for babies born before 27 weeks’ gestation in 2006, England, by completed week of gestation (mean and 95% confidence interval of mean also shown). Children scoring <50 were allocated a nominal score of 49. Predicted mental development index (MDI) scores are shown instead of Bayley III scores

Fig 4 Changes in outcome for babies born at 22-25 weeks’ gestation or less in England in 1995 (EPICure) and 2006 (EPICure 2) cohorts