Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity

Abstract

Background: Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP.

Method: This prospective study included 78 Swedish infants, born <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin ≤110 g/L.

Results: During postnatal week 1, infants with severe ROP requiring treatment (28%) more frequently developed anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant.

Conclusions: Among infants born <28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels.

Trial registration: ClinicalTrials.gov NCT02760472.

Figures

Fig. 1

Association between early erythropoietin and severe ROP requiring treatment. a Geometric mean levels of EPO from birth to 40 weeks postmenstrual age, among infants with ROP that did not require treatment (no ROP treatment, dotted line) or did require treatment (ROP treatment, solid line). b Geometric mean levels of EPO during the first 28 days of life; this plot is a magnification of the plot shown in a

Fig. 2

Association between anaemia and EPO levels in infants with ROP. a Probability of developing anaemia during the first 28 days of life, among infants that did not require ROP treatment (no ROP treatment, dotted line) and those that did require ROP treatment (ROP treatment, solid line). b Mean levels of haemoglobin during the first 28 days of life among infants that did not require ROP treatment and infants that require ROP treatment. c Probability for blood transfusion during the first 28 days of life, among infants that did not require ROP treatment and infants that require ROP treatment. d Mean EPO levels on postnatal day 7 for infants with and without anaemia during days 0–7 and with ROP that required ROP treatment (grey boxes) or did not require ROP treatment (white boxes). e The estimated probability and the observed proportion with 95% CI of developing ROP that required treatment, for different EPO levels on day 7