Abstract
Purpose: :
Soluble flt-1 (s-flt-1) can act as a trap for VEGF, and levels of s-flt-1 have been shown to be elevated in the plasma of pregnant women with pre-eclampsia. Therefore, we hypothesized that infants born to these mothers may demonstrate a difference in severity of ROP and wished to determine the association of ROP severity and maternal pre-eclamsia.
Methods: :
Hospitalization records from University of North Carolina (UNC) Hospitals Labor and Delivery Unit and Neonatal Critical Care Center were queried retrospectively for the final dilated funduscopic examination in preterm infants between April 1996 and October 2007. Four groups were created: 1) Infants with ROP born to mothers with pre-eclampsia (N = 76), 2) Infants with ROP born to mothers without pre-eclampsia (N = 234), 3) Infants without ROP born to mothers with pre-eclampsia (N = 978), and 4) Infants without ROP born to mothers without pre-eclampsia (N = 10147). Post-gestational ages were calculated as the sum of the gestational age and chronologic age from birth in weeks. Severity of ROP was characterized by zones and stages and recorded for the final fundoscopic examination. Statistical analysis was performed using Chi-square analysis and two-way ANOVA, with p < 0.01 considered significant.
Results: :
A total of 11435 infants were identified. Gestational ages ranged from 23 to 42 weeks and birth weights from 376 to 5844 grams. The mean post-gestational ages at the last examination for infants in groups 1 and 2 were not significantly different (p = 0.99). Infants in group 1 compared to infants in group 2, were 3.45 times more likely to have an ROP stage of > 0 (p = 0.003), 1.79 times more likely to have an ROP stage of > 1 (p = 0.054), and 0.32 times more likely to have an ROP stage of > 2 (p = 0.414). Pre-eclampsia status in mothers was highly associated with ROP stage in infants of gestational ages 27 and 28 weeks (p = 0.004), but not in infants of other gestational ages. However, pre-eclampsia status was not significantly associated with ROP zone or stage observed at different post-gestational ages.
Conclusions: :
At final fundoscopic examination, infants born to mothers who had pre-eclampsia were more likely to have ROP. Pre-elampsia is associated with increased s-flt-1, which sequesters VEGF and disrupts its signaling. Our findings suggest that elevated levels of s-flt-1 in mothers with pre-eclampsia may disrupt normal retinal vascular development in infants. Thus, further investigation of the role of s-flt-1 in ROP is indicated and may yield important molecular targets for the treatment of this condition.
Keywords: retinopathy of prematurity • vascular endothelial growth factor • clinical (human) or epidemiologic studies: risk factor assessment