Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia,☆☆,,★★,

Presented at the Seventeenth Annual Meeting of the Society of Perinatal Obstetricians, Anaheim, California, January 20-25, 1997.
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Abstract

OBJECTIVE: Our purpose was to test the hypothesis that neonates who develop bronchopulmonary dysplasia have higher amniotic fluid concentrations of proinflammatory cytokines than those who do not develop bronchopulmonary dysplasia.

STUDY DESIGN: The relationship between amniotic fluid concentrations of interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8 and the occurrence of bronchopulmonary dysplasia in the neonate was examined in 69 patients who were delivered of preterm neonates (≤33 weeks) within 5 days of amniocentesis. Cytokines were measured by specific immunoassays.

RESULTS: Bronchopulmonary dysplasia was diagnosed in 19% (13/69) of newborns. Median amniotic fluid concentrations of interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8 concentrations were significantly higher in mothers whose infants had bronchopulmonary dysplasia than in mothers whose infants did not have bronchopulmonary dysplasia (p < 0.05 for each). Neonates who had bronchopulmonary dysplasia were delivered at earlier gestational ages and had lower birth weights than those without bronchopulmonary dysplasia. The differences in median amniotic fluid interleukin-6, interleukin-1β, and interleukin-8 between these two groups remained significant after we adjusted for the effect of gestational age at birth (p < 0.05 for each).

CONCLUSIONS: (1) Antenatal exposure to proinflammatory cytokines is a risk factor for the development of bronchopulmonary dysplasia; (2) the injury responsible for bronchopulmonary dysplasia in a subset of neonates may begin before birth. (Am J Obstet Gynecol 1997;177:825-30.)

Section snippets

Study design

A retrospective cohort study was conducted to examine the relationship between amniotic fluid concentrations of interleukin-6 (IL-6), TNF-α, IL-1β, and IL-8 and the occurrence of BPD in the neonate. The cohort consisted of women who were admitted to the Seoul National University Hospital with preterm labor, preterm premature rupture of membranes, or pregnancy-induced hypertension and who met the following criteria: (1) preterm singleton gestation (gestational age at birth ≤33 weeks); (2)

Results

Sixty-nine patients met the entry criteria of this study. BPD was diagnosed in 19% (13/69) of newborns. Table I compares the clinical characteristics of the study population according to the presence or absence of BPD. Neonates who developed BPD were delivered at lower gestational ages and had lower birth weights than those without this complication. However, no significant differences were found between these two groups in the prevalence of positive amniotic fluid cultures and significant

Comment

Our data clearly demonstrate that amniotic fluid concentrations of specific cytokines (IL-6, TNF-α, IL-1β, and IL-8) are significantly higher in fetuses who subsequently develop BPD than in those who do not develop BPD. For IL-6, IL-1β, and IL-8, this association remained significant after we adjusted for the effect of gestational age at birth. These results suggest that exposure to a prenatal inflammatory process, detectable by an elevated concentration of proinflammatory cytokines in amniotic

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    From the Departments of Obstetrics and Gynecology and Pediatrics, College of Medicine, Seoul National University.

    ☆☆

    Supported by grant No. 94-0403-11-3 from the Korea Science and Engineering Foundation (KOSEF) and grant No. 03-97-030 from the Seoul National University Hospital Research Fund.

    Dr. Romero and Dr. Ghezzi have participated as private citizens, not as agents of the U.S. government or any of the universities to which they hold appointments.

    ★★

    Reprint requests: Bo Hyun Yoon, MD, PhD, Department of Obstetrics and, Gynecology, Seoul National University Hospital, Seoul, 110-744, Korea.

    0002-9378/97 $5.00 + 0 6/6/84418

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