Fetal fibronectin as a predictor of vaginal birth in nulliparas undergoing preinduction cervical ripening.

OBJECTIVE: We sought to evaluate whether the presence of a positive fetal fibronectin (> or = 50 ng/mL) in nulliparous women undergoing preinduction cervical ripening with the intracervical Foley catheter predicted vaginal birth. METHODS: This was a prospective blinded observational trial of nulliparous women undergoing preinduction cervical ripening. We excluded women who had a contraindication to vaginal birth. Cervical and vaginal fetal fibronectin specimens were obtained before preinduction cervical ripening with an intracervical Foley catheter. The managing obstetrician was blinded to these results. RESULTS: A total of 241 women met the inclusion criteria, of which 54.4% delivered vaginally. There was no difference in the rate of vaginal delivery among women with either a positive cervical fetal fibronectin (positive fetal fibronectin 55.8% compared with negative fetal fibronectin 53.3%, P = .70) or positive vaginal fetal fibronectin (positive fetal fibronectin 57.6% compared with negative fetal fibronectin 53.3%, P = .56). Women with a positive cervical fetal fibronectin did have a shorter duration of cervical ripening (fetal fibronectin-positive 229 +/- 220 minutes compared with fetal fibronectin-negative 379 +/- 193 minutes, P < .05), duration of oxytocin (fetal fibronectin-positive 655 +/- 555 minutes compared with fetal fibronectin-negative 731.5 +/- 342 minutes, P < .025) and required lower maximal doses of oxytocin (fetal fibronectin-positive 18.4 mIU/min compared with fetal fibronectin-negative 21.8 mIU/min, P = .005). Women with a positive vaginal fetal fibronectin demonstrated only a shorter duration of cervical ripening compared with their fetal fibronectin negative counterparts (fetal fibronectin-positive 300 +/- 216 minutes compared with fetal fibronectin-negative 345 +/- 201 minutes, P < .05). CONCLUSION: Fetal fibronectin does not predict vaginal delivery in nulliparous women requiring preinduction cervical ripening. LEVEL OF EVIDENCE: II-2.

5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide (RWJ-51204), a new nonbenzodiazepine anxiolytic.

5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5] imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide) (RWJ-51204) binds selectively and with high affinity (K(i) = 0.2-2 nM) to the benzodiazepine site on GABA(A) receptors. Considering the GABA shift, the intrinsic modulatory activity of RWJ-51204 is lower than that of full agonist anxiolytics (lorazepam, diazepam, alprazolam, and clonazepam) but similar to partial agonists (bretazenil, abecarnil, panadiplon, and imidazenil). RWJ-51204 was orally active in anxiolytic efficacy tests; pentylenetetrazole induced seizure inhibition in mice (ED(50) = 0.04 mg/kg), Vogel conflict in rats (ED(50) = 0.36 mg/kg), elevated plus-maze in rats (minimal effective dose = 0.1 mg/kg), and conflict in squirrel monkeys (ED(50) = 0.49 mg/kg). RWJ-51204 attenuated chlordiazepoxide-induced motor impairment in mice. Usually, RWJ-51204 was more potent than reference anxiolytics in rodent efficacy tests but less potent in monkey conflict. Usually, the slope of the dose-response lines for RWJ-51204 was more shallow than the full agonist anxiolytics but steeper than partial agonists in efficacy tests but typically shallow in tests for central nervous system side effects. In monkeys only mild or moderate sedation was observed at doses equivalent to 20 or 40 times the anxiolytic ED(50). RWJ-51204 fits into the partial agonist class of GABA(A) receptor modulators. In conclusion, RWJ-51204 exhibits a profile in in vitro experiments and in animal models, in mice and monkeys (but not in rats), suggesting that it has a profile of anxiolytic activity associated with less sedation, motor impairment, or muscle relaxation than currently available GABA(A) receptor modulators, i.e., the benzodiazepines.