Published online May 26, 2009
PEDIATRICS Vol. 123 No. 6 June 2009, pp. 1541-1547 (doi:10.1542/peds.2008-1670)
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ARTICLE

Soluble Vascular Endothelial Growth Factor Receptor 1 in Tracheal Aspirate Fluid of Preterm Neonates at Birth May Be Predictive of Bronchopulmonary Dysplasia/Chronic Lung Disease

Jamal Hasan, MDa,b, Kay D. Beharry, BSa, Arwin M. Valencia, MDb, Arthur Strauss, MDb and Houchang D. Modanlou, MDa

a Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of California, Irvine, California
b Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Miller Children's Hospital, Long Beach, California

OBJECTIVE. We tested the hypothesis that soluble vascular endothelial growth factor receptors are involved in the development of bronchopulmonary dysplasia/chronic lung disease.

PATIENTS AND METHODS. Neonates with a birth weight of ≤1500 g and/or ≤30 weeks’ gestation, with respiratory failure, requiring O2 and mechanical ventilation within 24 hours, were eligible. Tracheal aspirate fluid samples were collected from 65 neonates before surfactant and/or assisted mechanical ventilation (baseline), at 3 and 7 days after birth, and weekly thereafter until extubation. Samples were analyzed for total vascular endothelial growth factor, soluble vascular endothelial growth factor receptor 1 and 2 levels and compared in infants with bronchopulmonary dysplasia/chronic lung disease (n = 31) versus those with no bronchopulmonary dysplasia/chronic lung disease (n = 34).

RESULTS. Mean gestational age and birth weight were lower in infants with bronchopulmonary dysplasia/chronic lung disease. At baseline, vascular endothelial growth factor levels in the tracheal aspirate fluid were significantly lower, whereas soluble vascular endothelial growth factor receptor 1 levels were higher in the bronchopulmonary dysplasia/chronic lung disease infants compared with infants with no bronchopulmonary dysplasia/chronic lung disease. Vascular endothelial growth factor levels progressively increased from baseline to 4 weeks in all of the infants developing bronchopulmonary dysplasia/chronic lung disease. Conversely, soluble vascular endothelial growth factor receptor 1 declined in both groups from baseline to 5 weeks of age. Similarly, soluble vascular endothelial growth factor receptor 2 declined from baseline to 5 weeks in the control infants, but there were significant increases at 3 and 4 weeks in infants developing bronchopulmonary dysplasia/chronic lung disease.

CONCLUSIONS. We speculate that low vascular endothelial growth factor levels in tracheal aspirate fluid, concurrent with elevated soluble vascular endothelial growth factor receptor 1 levels on the first day of life, are biological markers for the development of bronchopulmonary dysplasia/chronic lung disease in very low birth weight infants requiring O2 and assisted mechanical ventilation.

Key Words: bronchopulmonary dysplasia • chronic lung disease • preterm infants • vascular endothelial growth factor

Abbreviations: VLBW—very low birth weight • BPD—bronchopulmonary dysplasia • CLD—chronic lung disease • VEGF—vascular endothelial growth factor • VEGFR—vascular endothelial growth factor receptor • sVEGFR—soluble vascular endothelial growth factor receptor • TAF—tracheal aspirate fluid • IUGR—intrauterine growth restriction • HIF—hypoxia-inducible factor

Accepted Oct 24, 2008.


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