Urinary Leukotriene E4 Excretion During the First Month of Life and Subsequent Bronchopulmonary Dysplasia in Premature Infants

Abstract

Inflammation plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact nature of this inflammatory process is incompletely understood. Older infants with established BPD have higher levels of urinary leukotriene E(4) (LTE(4)) compared to healthy infants of the same age. This suggests that cysteinyl leukotrienes may play a role in the abnormalities seen in BPD. To measure urinary LTE(4) levels during the first month of life in premature infants, and to determine whether there are significant differences in premature infants who develop BPD, as compared to those who do not develop BPD. Prospective, blinded, controlled study. Neonatal ICUs of a tertiary-care university hospital. Thirty-seven premature infants (< 33 weeks of gestational age) were enrolled prospectively at birth. Urinary LTE(4) levels were measured blinded, using a standard radioimmunoassay technique at 2 days, 7 days, and 28 days of life. At 1 month of age, infants were classified as with or without BPD, based on need for supplemental oxygen, and characteristic chest radiographs. Clinical features and urinary LTE(4) were compared between the two groups. Mean +/- SD gestational age was 29 +/- 2.6 weeks. None of the infants had a family history of asthma. Thirteen of 37 infants were classified as having BPD at 28 days after birth. Mean gestational age in infants who developed BPD was 27 +/- 2.4 weeks, compared to 30 +/- 2 weeks in infants who did not develop BPD (p < 0.05). In infants with BPD, mean urinary LTE(4) levels of urinary creatinine were 1,762 +/- 2,003 pg/mg, 1,236 +/- 992 pg/mg, and 5,541 +/- 5,146 pg/mg at days 2, 7, and 28, respectively, compared to 1,304 +/- 1,195 pg/mg, 1,158 +/- 1,133 pg/mg, and 2,800 +/- 2,080 pg/mg in infants without BPD. LTE(4) levels at 2 days, 7 days, and 28 days did not correlate with the subsequent development of BPD. LTE(4) levels at day 28 were significantly higher than LTE(4) levels at day 2 and day 7 in both groups, even after correcting for gestational age or birth weight (p < 0.05). There was significant inverse correlation between LTE(4) levels at day 2 with gestational age and birth weight (p < 0.05). All 13 infants with BPD received steroid pulses, compared to 3 of 26 infants without BPD. Gestational age and use of postnatal steroid pulses, diuretics, and theophylline (for apnea of prematurity) were significantly associated with each other and with the subsequent development of BPD. Urinary LTE(4) levels measured on the second day of life in very-low-birth-weight infants inversely correlate with gestational age and birth weight. Urinary LTE(4) levels may reflect lung injury and/or inflammation in premature infants, not necessarily related to BPD as it is presently defined.