Ohls RK, et al. Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin. Pediatrics. 2016;137(3):1-9.
Robin Ohls has been working on Erythropoietin, and its longer acting analogue darbepoietin, for many years now. As well as demonstrating that it stimulates the bone marrow in preterm babies, it now is clear that erythropoietin in some models is neuro-protective. In 2014 she reported the developmental follow up of a randomized trial in infants of 500 to 1250 g birthweight, about 100 infants were randomized to either placebo, erythropoietin or darbepoietin and then followed to discharge and again at 18 months of age with a Bayley assessment of development. During the initial hospitalization the infants in the 2 intervention groups received half as many blood transfusions, and there were no significant complications (in particular no effect on retinopathy). At follow up the 2 “poietin” groups had better scores on the Bayley 3 cognitive composite and on the language composite. It must be said, though, that there are only 24 placebo babies in the follow up, and they had relatively poor scores on the Bayleys, 83 mean for language and 88 for cognitive. Although the differences were significant, these are lower scores than you would normally expect from an unselected group of babies under 1250 g, so it may be that by chance the outcomes of the followed-up babies in the placebo group were worse, the “poietin” groups results were in contrast 91 and 97 on those two scales.
The new data published in the last few weeks are from continued follow-up of the babies to 3.5 to 4 years of age. Unfortunately there has been a lot of drop off, so only 14 placebo and 39 “poietin” babies were examined with IQ tests, and tests of executive function. The previously shown differences persisted, but again it has to be noted that the 14 placebo babies had extremely adverse results, with a full-scale IQ mean of 79, and a performance IQ of 79 whereas the active treatment groups, taken together had means of 93 and 91.
If you were to compare this, for example, to the 5 year follow up of the babies in the caffeine trial, the mean IQ of the control group of babies, who were also of birth weight between 500 and 1250 g, was 97 for the full-scale IQ and 99 for the performance score. The CAP babies may have been lower risk (to be eligible, they had to be considered for caffeine treatment at less than 10 days of age, whereas Ohls’ study took any baby expected to survive for at least 48 hours) but those differences are enormous. The babies in Robin Ohls study were not all that sick either, judging from a mortality of 7% in the group after enrollment (it was just over 5% for the infants in the CAP trial). So the very poor scores in the controls can’t be easily understood.
Although these data for erythro- or darbe- poietin are hopeful, I think we definitely need to get more data from a much larger trial with high rates of long term follow up before we can be sure that this difference is really an effect of the medications. As darbepoietin seems effective, and there is no evidence of a differential benefit of one bone-marrow stimulator over another, then darbepoietin, which can be given once a week instead of 3 injections a week would probably be the most appropriate to study in a trial.
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