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Chris Stutchfield, Anoo Jain, David Odd, Cathy Williams, Richard Markham; Does the Replacement of Foetal Haemoglobin by Adult Haemoglobin After Blood Transfusion in Very Preterm Infants Contribute to the Development of Retinopathy of Prematurity? A Prospective Cohort Study. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5904.
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Increasing numbers of blood transfusions and higher mean arterial oxygen saturation have both been associated with increased risk of retinopathy of prematurity (ROP). Blood transfusion with adult haemoglobin (HbA) replaces foetal haemoglobin (HbF). HbA has a lower affinity for oxygen than HbF and therefore leads to increased oxygen availability to the tissues including the retina. We hypothesize that the sudden increase in oxygen availability after blood transfusion could be a cause of the capillary obliteration phase of ROP via downregulation of VEGF and associated angiogenic factors and contribute to the development of ROP. We aimed to identify a link between a decrease in the HbF/HbA ratio and the development of ROP.
All infants born at <32 weeks gestation or <1501g birth weight and admitted to the two neonatal intensive care units in Bristol, UK were eligible for inclusion. HbF/HbA ratios were calculated using high pressure liquid chromatography before any blood transfusion and at regular intervals thereafter. Timing and amount of blood transfusion, gestational age at birth and birthweight, were recorded. All infants were screened for ROP according to established national protocols. Student t tests and ordinal logistic regression were performed to quantify the relationship between HbF/HbA ratio and ROP development.
We recruited 31 infants. Mean gestation was 27.8 weeks. Mean birthweight was 1026g. 6 infants died before screening. Of surviving infants, ROP did not develop in 16 infants (64%) and ROP developed in 9 infants (36%). Those who developed ROP had similar initial (first sample after birth and before any transfusion) percentage HbF (85.7% vs. 91.8%, p=0.229), but had lower mean percentage HbF while inpatients (49.9% vs. 92.7%,p=<0.001) than those who did not develop ROP. Odds ratios (OR, 95%CI) for developing ROP, adjusted for birthweight, gestation and number of transfusions, were 1.13 (0.96-1.33) for initial percentage HbF and 0.86 (0.75-0.98) for mean percentage HbF while inpatients.
These data suggest that higher percentage HbA after transfusion may contribute to the development of ROP. Further studies are needed to confirm whether this is a causal and potentially modifiable association.
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