Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment

Abstract

IntroductionIbuprofen is one of the most common non-steroidal anti-inflammatory drugs used to close patent ductus arteriosus (PDA) in preterm infants. PDA is associated with bronchopulmonary dysplasia (BPD), while PDA closure by ibuprofen did not reduce the incidence of BPD or death. Previous studies have indicated an anti-angiogenesis effect of ibuprofen. This study investigated the change of angiogenic factors after ibuprofen treatment in preterm infants.MethodsPreterm infants with hemodynamically significant PDA (hsPDA) were included. After confirmed hsPDA by color doppler ultrasonography within 1 week after birth, infants received oral ibuprofen for three continuous days. Paired plasma before and after the ibuprofen treatment was collected and measured by ELISA to determine the concentrations of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A), and hypoxia-inducible factor-2α (HIF-2α).Results17 paired plasma from infants with hsPDA were collected. The concentration of PDGF-BB and VEGF-A significantly decreased after ibuprofen treatment (1,908 vs. 442 pg/mL for PDGF-BB, 379 vs. 174 pg/mL for VEGF-A). HIF-2α level showed a tendency to decrease after ibuprofen treatment, although the reduction was not statistically significant (p = 0.077).ConclusionThis study demonstrated decreased vascular growth factors after ibuprofen exposure in hsPDA infants.

Bronchopulmonary Dysplasia: Pathogenesis and Pathophysiology

“…The absolute risk difference between the two groups was −17.6 percentage points, with a 95% confidence interval ranging from −30.2 to −5.0 [ 85 ]. This higher risk of moderate-to-severe BPD in the intervention group may be related to a decrease in vascular growth factors in preterm infants after exposure to ibuprofen [ 86 ].…”

Vascular and pulmonary effects of ibuprofen on neonatal lung development

“…Similarly, the anti-angiogenic effect of ibuprofen might be absent if given at a later stage when vascular growth is less vulnerable. We have recently demonstrated that ibuprofen reduces vascular growth factors, such as PDGF-BB, VEGF-A and HIF-2ɑ, in infants with PDA [ 59 ], confirming that the anti-angiogenic effect of ibuprofen is already present in human infants exposed for 3 days. Although this adverse effect on vascular growth might be absent when ibuprofen is given at a later stage, it may compromise its positive effect on PDA closure.…”

Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus

“…26,27 A recent prospective study showed decreased vascular growth factors in preterm infants with PDA after exposure to ibuprofen. 28 Of note, previous randomized trials have not shown an increase in the risk of bronchopulmonary dysplasia with ibuprofen treatment. It is possible that this discrepancy can be explained by the high percentage of infants who received open-label treatment in the expectant-management group in these trials.…”