Urinary leukotriene E-4 excretion during the first month of life and subsequent bronchopulmonary dysplasia in premature infants

Background: Inflammation plays an important role in the pathogenesis of bro nchopulmonary dysplasia (BPD), but the exact nature of this inflammatory pr ocess is incompletely understood, Older infants with established BPD have h igher levels of urinary leukotriene E-4 (LTE4) compared to healthy infants of the same age. This suggests that cysteinyl leukotrienes may play a role in the abnormalities seen in BPD. Objectives: To measure urinary LTE4 levels during the first month of life i n premature infants, and to determine whether there are significant differe nces in premature infants who develop BPD, as compared to those who do not develop BPD, Design: Prospective, blinded, controlled study. Setting: Neonatal ICUs of a tertiary-care university hospital. Methods: Thirty-seven premature infants (< 33 weeks of gestational age) wer e enrolled prospectively at birth. Urinary LTE4 levels were measured blinde d, using a standard radioimmunoassay technique at 2 days, 7 days, and 28 da ys of life. ht 1 month of age, infants were classified as with or without B PD, based on need for supplemental oxygen, and characteristic chest radiogr aphs. Clinical features and urinary LTE, were compared between the two grou ps. Results: Mean +/- SD gestational age was 29 +/- 2.6 weeks, None of the infa nts 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 d eveloped BPD was 27 +/- 2.4 weeks, compared to 30 +/- 2 weeks in infants wh o did not develop BPD (p < 0.05), In infants with BPD, mean urinary LTE4 le vels 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. LTE4 levels at 2 days, 7 days, and 28 days did not cor relate with the subsequent development of BPD. LTE4 levels at day 28 were s ignificantly higher than LTE4 levels at day 2 and day 7 in both groups, eve n after correcting for gestational age or birth weight (p < 0.05). There wa s significant inverse correlation between LTE, levels at day 2 with gestati onal age and birth weight (p < 0.05). All 13 infants with BPD received ster oid pulses, compared to 3 of 26 infants without BPD. Gestational age and us e of postnatal steroid purses, diuretics, and theophylline (for apnea of pr ematurity) were significantly associated with each other and with the subse quent development of BPD, Conclusion: Urinary LTE4 levels measured on the second day of life in very- low-birth-weight infants inversely correlate with gestational age and birth weight. Urinary LTE4 levels may relied lung injury and/or inflammation in premature infants, not necessarily related to BPD as it is presently define d.