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Gunnel Hellgren, Chatarina Lofqvist, Anna-Lena Hård, Ingrid Hansen-Pupp, Magnus Gram, David Ley, Lois E H Smith, Ann Hellström; Serum levels of vascular endothelial growth factor - temporal changes in relation to retinopathy of prematurity. . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4324.
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The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, despite that little is known about temporal changes of circulating VEGF levels in the preterm neonate, off-label treatment with anti-VEGF is becoming more commonplace. The aim of this study was therefor to determine longitudinal serum levels of VEGF in relation to ROP.
The study was conducted as a prospective longitudinal cohort study between 2005 and 2007, and consisted of 52 infants born at median (range) 26.5 (23.0 - 30.6) gestational weeks. All infants were screened for ROP according to a routine protocol. Thirty-three infants were classified as non-ROP, 10 as non-proliferative ROP (stages 1 and 2), and 9 as proliferative ROP (stage 3 and treated for ROP). Plasma samples were collected at birth, and then serum samples were collected at 3 days postnatal age followed by weekly collection of serum samples until at least a postmenstrual age (PMA) of 35 weeks. Circulating VEGF levels were analyzed by Luminex multiplex technology. All statistical analyses were performed by non-parametric tests.
VEGF levels did not differ in cord blood between infants with different degrees of ROP. In contrast, longitudinal postnatal VEGF serum levels differed between groups, with significantly increased levels at the time when ROP first was detected (34 - 36 weeks PMA) in infants with proliferative ROP as compared to infants without ROP. Median (range) VEGF levels at PMA 34 weeks were 1768 (538; 6463) in infants with proliferative ROP vs 1076 (17; 3770) pg/ml in infants without ROP, p<0.05. Corresponding levels at PMA 35 weeks were 2139 (1116; 7729) vs 1058 (1; 3767) pg/ml, p<0.001, and at PMA 36 weeks 1835 (700; 3574) vs 817 (117; 2208) pg/ml, p<0.05. Differences remained significant at PMA 34 and 35 weeks after adjustment for gestational age at birth. At the time for laser therapy, median (range) 39 (34 - 40) postmenstrual weeks, VEGF levels did not differ between ROP groups.
Our findings, of elevated circulatory levels of VEGF in infants who later developed severe ROP, at the time when ROP first was detected but not at the time when treatment most often occurred, support the need for studies of the temporal pattern of circulating VEGF in relation to timing and safety of anti-VEGF treatment.
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