Intrauterine infection and preterm delivery: Evidence for activation of the fetal hypothalamic-pituitary-adrenal axis

OBJECTIVE: We studied pregnant women in preterm labor with and without intr auterine infection to determine whether fetal hypothalamic-pituitary-adrena l axis activation occurs in the setting of infection-induced preterm partur ition. STUDY DESIGN: Amniotic fluid collected by amniocentesis and maternal blood from patients in preterm labor with intact membranes at 24 to 34 weeks' ges tation were analyzed by radioimmunoassay for the steroid hormones estrone, estradiol, progesterone, androstenedione, dehydroepiandrosterone, dehydroep iandrosterone sulfate, and cortisol. Amniotic fluid was also obtained for m icrobial culture and for interleukin 6 measurements by enzyme immunoassay. RESULTS: Patients with intrauterine infection (n = 11) had significantly hi gher amniotic fluid concentrations of dehydroepiandrosterone (539 +/- 79 pg /mL) and of cortisol (5.28 +/- 1.0 mu g/dL) than did patients with preterm labor and preterm delivery without infection (n = 11;273 +/- 82 pg/mL and 1 .61 +/- 1.05 mu g/dL, respectively) or patients with preterm labor and subs equent term delivery (n = 11;202 +/- 79 pg/mL and 1.82 +/- 1.0 mu g/dL, res pectively). Furthermore those patients who were delivered within 7 days aft er enrollment (who were also more likely to have intrauterine infection) ha d higher amniotic fluid concentrations than did those who were not delivere d within 7 days of both estrone (586 +/- 101 pg/mL vs 314 +/- 98 pg/mL) and estradiol (238 +/- 44 pg/mL vs 91 +/- 43 pg/mL). CONCLUSION: Intrauterine infection was associated with increased fetal adre nal androgen and cortisol biosynthesis, and delivery within 7 days after th e onset of preterm labor was associated with increased placental estrogen s ynthesis. These data are consistent with fetal hypothalamic-pituitary-adren al axis activation in the setting of infection-associated preterm delivery.