Abstract
Purpose:
It has been reported that anti-vascular endothelial growth factor (VEGF) antibody decreased serum VEGF level in eyes with retinopathy of prematurity (ROP). However, it has not been determined if the decreased level was tolerable for a normal vascularization in developing premature infants. This study was to report consecutive changes in serum VEGF levels in premature infants and to try to determine a normal range of VEGF level in the developing process.
Methods:
Thirty-seven newborns were included in this study and grouped into 4 groups according to their gestational age (GA); 22-26 weeks (n=7), 27-31 weeks (n=10), 32-36 weeks (n=10) and 37 weeks and greater (n=10). The serum VEGF levels were measured at birth, and 1, 2, 3, 4 weeks, and then 2 weeks intervals by Enzyme-linked ImmunoSorbent Assay until their discharge from Neonatal Intensive Care Unit. In group of 22-26 weeks, VEGF levels were compared between infants with and without ROP. In infants who received an intravitreal bevacizumab (IVB) injection, VEGF levels were also measured at 1 day, 3 days, 1, 2, 3, 4 weeks, and 2 weeks interval thereafter. The relationships between serum VEGF levels and leukocyte counts after birth and severity of chorioamnionitis (Blanc classification) determined by histological exam of the placenta were also analyzed.
Results:
The VEGF levels at birth were higher as GA was greater. The VEGF levels after birth increased and peaked at 1 to 3 weeks, then decreased gradually. This pattern was the same as the change in leukocyte counts, and VEGF levels were higher as chorioamnionitis was severer. In group of 22-26 weeks, VEGF levels were higher in infants with ROP than those without ROP, however, the relation was reversed after ROP developed, and the range of VEGF level was between 150-250pg/mL at 36 weeks of postmenstrual age (PMA) or greater when most IVB injections are performed for ROP. Twin infants with a GA of 24 weeks developed stage 4A ROP and received an IVB injection at a PMA of 37 weeks and 48 weeks, respectively. The VEGF levels decreased significantly at 1 to 3 days and the decreased levels continued for at least 3 weeks.
Conclusions:
There might be some relationship between a transient increase of VEGF level and leukocyte counts and the severity of chorioamnionitis. The range of VEGF levels can give us a merkmal on what is the tolerable VEGF level after IVB injection.