Background: 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
E4 (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 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.
Design: Prospective, blinded,
Setting: Neonatal ICUs of a
tertiary-care university hospital.
Thirty-seven premature infants (< 33 weeks of gestational age) were
enrolled prospectively at birth. Urinary LTE4 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 LTE4 were compared between the two groups.
Results: 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 LTE4
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.
LTE4 levels at 2 days, 7 days, and 28 days did not
correlate with the subsequent development of BPD. LTE4
levels at day 28 were significantly higher than LTE4 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 LTE4 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.
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 reflect lung injury and/or inflammation in premature infants, not
necessarily related to BPD as it is presently