AN INCREASE IN FETAL PLASMA-CORTISOL BUT NOT DEHYDROEPIANDROSTERONE-SULFATE IS FOLLOWED BY THE ONSET OF PRETERM LABOR IN PATIENTS WITH PRETERM PREMATURE RUPTURE OF THE MEMBRANES

OBJECTIVE: The role of steroid hormones in the control of human partur ition has been a subject of debate. Activation of the fetal hypothalam ic-pituitary-adrenal axis leading to an increase in plasma cortisol is followed by the onset of parturition in sheep. In contrast, androgens , specifically dehydroepiandrosterone sulfate, have been implicated in the control of parturition in nonhuman primates. The purpose of this study was to determine the relationship between human fetal plasma cor tisol and dehydroepiandrosterone sulfate and the onset of preterm labo r in patients with preterm premature rupture of the membranes. STUDY D ESIGN: Fetal blood sampling was performed in 51 patients with preterm premature rupture of membranes who were not in labor on admission. Amn iotic fluid was cultured for aerobic and anaerobic bacteria and mycopl asmas. Corticosteroids had not been administered before fetal blood sa mpling. Cortisol and dehydroepiandrosterone sulfate were measured with sensitive and specific immunoassays. Analysis was conducted with nonp arametric statistics and survival analysis. RESULTS: (1) Patients who went into spontaneous labor and delivered within 7 days of cordocentes is had a significantly higher median level of fetal plasma cortisol bu t not of dehydroepiandrosterone sulfate than those delivered after 7 d ays (for fetal plasma cortisol: median 8.35 [4.7 to 12.4] mu g/dL vs m edian 4.75 [3.0 to 10.4] mu g/dL, P<.0001; for fetal plasma dehydroepi androsterone sulfate. median 154.4 [8.6 to 333.8] mu g/dL vs median 19 4.6 [96.7 to 402.5] mu g/dL, P = .09). (2) The cordocentesis-to-delive ry interval was significantly shorter in patients with a fetal plasma cortisol value of greater than or equal to 7 mu g/dL (derived by recei ver-operating characteristic curve analysis) than in those with fetal cortisol <7 mu g/dL (median 49 [4 to 1849] hours vs median 325 [11 to 2590] hours, P<.001). (3) Fetal plasma cortisol, but not maternal cort isol, was an independent predictor of the duration of pregnancy after we adjusted for gestational age and the results of amniotic fluid cult ure (hazards ratio 2.9, P<.05). (4) There was a significant correlatio n between fetal plasma cortisol and fetal plasma interleukin-6 (r = 0. 3, P<.05). (5) A strong relationship was found between the fetal plasm a cortisol/dehydroepiandrosterone sulfate ratio and the interval to de livery (P<.005). CONCLUSION: An elevation in fetal plasma cortisol but not dehydroepiandrosterone sulfate was followed by the onset of spont aneous preterm labor in patients with preterm premature rupture of the membranes.