Two publications have just appeared from the EPICURE 2 study. The first (Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES: Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 2012, 345:e7976) describes the survival and serious complications among all the babies born in the UK and Ireland during 2006. It also compares the figures with EPICURE 1, which ran for 10 months in 1995.
One of the issues with the first EPICURE cohort was the large number of infants who were born outside of tertiary care centers and never transferred for intensive care, or who remained in tiny units that only looked after one or two such babies a year. Of course their outcomes are not as good as centers who do it all the time. Part of the UK response to the EPICURE results was to improve regionalisation, and there is a higher proportion of extremely preterm babies born in centers with a tertiary NICU this time. But, it is still an inadequate percentage: At 22, 23, 24 and 25 weeks the percentages are 45%, 48%, 58%, 66% even at 26 weeks more than a third of babies are born in the wrong place (40%).
This means that substantial proportions of babies had to be transported during the first day of life to a tertiary unit, a process which we know increases all sorts of complications.
What can be done to improve these outcomes further?
The latest CNN annual report is now available on-line. The data are in many ways not comparable. They do not include babies never admitted to a participating hospital, so a baby born elsewhere and not referred for intensive care is nowhere to be found in the CNN report. However, I just wanted to point out that, of babies admitted to NICU in Canada at 25 weeks there was 78% survival, at 24 weeks there was 54% survival, and at 23 weeks there was 42% survival, all of these figures are around 10% better than the EPICURE data. So I think one thing that needs to be done in the UK is to get more of these babies born in tertiary care centers. Plus in Canada we still have more to do, survival rates seem to be substantially better in Japan than in Canada, what can we all do to improve survival and outcomes?
There are some pointers in the report of other things that can be done, in 2006 99% of the 26 weekers, 98% of the 25 weekers and 99% of the 24 week infants received surfactant. Which means that almost none of them were kept extubated during the first few days of life. I find that a little surprising, things were starting to change in terms of trying to use CPAP from birth in many places, but that obviously wasn’t the case in the British Isles in 2006. Early CPAP rather than routine intubation for surfactant appears to reduce severe BPD; BPD was very common in this cohort, but we don’t have any indication of severity.
We also now have probiotics which can reduce Necrotising Enterocolitis and mortality, and the incidence of late onset sepsis can be reduced with aggressive quality control and perhaps also with lactoferrin.
One thing that the investigators note is the older age of death in this cohort compared to the previous one, with half of the deaths occurring after the first week of life. Others have noted the same thing, these deaths are often due to NEC, Sepsis and sometimes to end-stage respiratory failure, EPICURE 2 showed a very high proportion of their late deaths were due to sepsis and NEC. If we can get reductions in those complications and also find ways to treat them better when they occur, we can really make a difference to survival, and to long term disability also, as BPD, NEC and Sepsis are major determinants of poorer long term outcomes.
Onto the second instalment; (Moore T, Hennessy EM, Myles J, Johnson SJ, Draper ES, Costeloe KL, Marlow N: Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies. BMJ 2012, 345:e7961.) The EPICURE investigators have followed up to 3 years of age a good proportion of the survivors. Much fewer than they would have liked however. Changes in certain regulations in the UK inhibited, and continue to inhibit, good follow up studies. So they had to estimate what the outcomes of the non-followed babies would have been, using the perinatal characteristics of the babies who were seen, and assuming that the influence of being a boy with sepsis (for example) was the same between babies who were examined and the others. This is called multiple imputation, and is the best you can do if you don’t have the children in front of you. Anyway the increase in survivors compared to the previous cohort was not associated with more impaired survivors, or indeed with a reduction in impairment. The proportions were almost identical. The proportions of severely impaired survivors are higher than in other regional cohorts such as from Victoria in Australia, which again I think shows that there are more improvements to be found.