Does Insulin-Like Growth Factor 1 Contribute in Red Blood Cell Transfusions to the Pathogenesis of Retinopathy of Prematurity during Retinal Neovascularization?

Abstract

Background: Red blood cell (RBC) transfusions are associated with the development of retinopathy of prematurity (ROP). During the period of retinal neovascularization a rise of insulin-like growth factor 1 (IGF-1) may trigger rapid growth of new blood vessels. Objectives: To study endocrine factors in RBC transfusions that might be of importance for ROP. Methods: IGF-1, IGF-2 and their binding proteins 1–3 (IGFBP-1–3) were determined by radioimmunoassays in 7 very-low-birthweight (VLBW) infants with ROP ≧ stage 2 receiving a RBC transfusion, in 10 controls (VLBW infants with ROP ≤ stage 1, no transfusion), in supernatants of 7 RBCs and of 5 washed RBCs (WRBC). Results: IGF-1 (mean ± SD) in infants with ROP was 20.0 ± 4.2 µg/l, in controls 35.9 ± 15.2 µg/l (Mann-Whitney U test, p = 0.030). IGF-1 in RBC was 12.88 ± 5.03 µg/l and in WRBC 0.45 ± 0.74 µg/l (average of the three-course washing procedure). IGF-2 in infants with ROP was 485.67 ± 158.73 µg/l, in controls 389.9 ± 102.8 µg/l (not significant), in RBC 109.50 ± 117.89 µg/l, in WRBC 61.07 ± 30.0 µg/l. Except for IGFBP-3 other IGFBPs were barely or not detectable in RBC or WRBC. Conclusions: Considering lower IGF-1 concentrations in preterm infants than in adults (factor 20), the IGF-1 in RBC transfusions is equivalent to a single dose of 1 µg/kg IGF-1 (5–10% of the adult dose with proved metabolic responses). Endocrinological relationships between the donor’s load and the acceptor’s individual features are a new aspect of potential side effects of RBC transfusions. Further research is necessary to clarify the share of the described IGF administration on the development of ROP.

Longitudinal Postnatal Weight and Insulin-like Growth Factor I Measurements in the Prediction of Retinopathy of Prematurity

“…Our previous studies have demonstrated that a prolonged period of a low level of serum IGF-I in children born preterm is strongly associated with ROP. 4 Hubler et al 14 and Villegas Becerril et al 15,16 have confirmed this association. Poor postnatal weight gain has also been suggested as a risk factor for the development of severe (Նstage 3) ROP.…”

Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

“…Only oxygen administration and the number of hemotransfusions were significantly correlated with both free IGF-I and PAPP-A molecules and their ratio. The biological and clinical implications of a red blood cell transfusion given to premature infants in terms of IGF-I load have recently been underlined (21). Of course, ELF IGF-I levels measured in our patients during the first 4 days of life are not dependent on hemotransfusions, since these were only administered after this period.…”

Serum levels of IGF1 are a useful predictor of retinopathy of prematurity

“…A large number of risk factors have been implicated in the aetiology of ROP (10–21): prematurity, birthweight, ethnic background, oxygen levels, hypercapnia, concomitant illness or disease (sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage), acidosis, indication for blood transfusion, ambient light levels, erythropoietin treatment, vaginal birth, etc.…”