MISOPROSTOL CONTROLLED-RELEASE VAGINAL INSERT FOR CERVICAL RIPENING
AND INDUCTION OF LABOR IN NULLIPAROUS WOMEN CARLOS SANTANACASTENEDA1, JUAN CARLOS IZQUIERDO-PUENTE2, RAUL ANTONIO LEON-OCHOA3, TERRY PLASSE4, WILLIAM RAYBURN5, 1Clinical Materno Infantil Alfredo del Mazo ISSEMYM, Toluca, Edo de Mexico, Mexico, 2Hospital de GinecoObstetricia, Luis Castelazo Ayala #4 IMSS, Mexico DF, Mexico, 3Hospital Regional 1 * de Octubre ISSSTE, Mexico DF, Mexico, 4Cytokine PharmaSciences, Inc, King of Prussia, Pennsylvania, 5University of New Mexico, Obstetrics and Gynecology, Albuquerque, New Mexico OBJECTIVE: To assess the maximum tolerated dose, ecacy and safety of misoprostol incorporated into a controlled release hydrogel polymer. STUDY DESIGN: Nulliparous women at or postterm were treated with misoprostol administered intravaginally in a retrievable hydrogel polymer designed to deliver drug in a controlled manner for 24 hours. The product was similar to controlled release dinoprostone (Cervidil) but contained misoprostol rather than dinoprostone. The insert was removed at 24 hours, upon the onset of active labor, or if treatment-related adverse events occurred. Sequential cohorts were treated with reservoir doses from 25 through 300 mcg. RESULTS: Treatment with increasing doses of misoprostol in the reservoir resulted in a shorter time to delivery as well as a more rapid increase in modied Bishop scores. Adverse uterine and fetal heart rate eects from misoprostol were noted only at 200 or 300 mg. Two women at 300 mg, but none at lower doses, developed hyperstimulation syndrome. Delivery outcomes are outlined below. All cesarean deliveries using 25-100 mg doses and two at 200 mg doses were for events unrelated to misoprostol; while two cesareans using the 200 mg and those at 300 mg doses were for events related to misoprostol. CONCLUSION: Misoprostol administered as a 100 mg dose in a sustained release hydrogel with a retrieval system resulted in rapid cervical ripening and vaginal delivery with a good safety prole.
OBSTETRIC RISK FACTORS AND OUTCOME OF PREGNANCIES COMPLICATED WITH
POSTPARTUM HEMORRHAGE EYAL SHEINER1, LIAT SARID2, AMALIA LEVY3, DANIEL S. SEIDMAN4, MORDECHAI HALLAK5, 1Soroka University Medical Center, BeerSheva, Israel, 2Soroka Medical Center, Beer-Sheva, Israel, 3Ben Gurion University of the Negev, Epidemiology and Health Services Evaluation, BeerSheva, Israel, 4Tel Hashomer and Sackler Faculty of Medicine, Tel-Aviv, Israel, 5 Ben Gurion University Soroka Medical Center, Beer Sheva, Israel OBJECTIVE: The study aimed to identify obstetric risk factors for post partum hemorrhage (PPH), and to determine pregnancy outcome. STUDY DESIGN: A comparison between consecutive singleton deliveries with and without PPH was performed. Deliveries occurred during the years 19882002 in a tertiary medical center. A multiple logistic regression model was constructed in order to dene independent risk factors for PPH. RESULTS: Postpartum hemorrhage complicated 0.4% (n = 666) of all deliveries enrolled in the study (n = 154,312). Signicant risk factors for PPH, using a multivariable analysis, were failure to progress during the second stage of labor (OR = 3.4, 95% CI = 2.4-4.7), instrumental delivery (OR = 2.3, 95% CI 1.6-3.4), large for gestational age (LGA) newborn (OR = 1.9, 95% CI 1.6-2.4), hypertensive disorders (OR = 1.7, 95% CI 1.2-2.1), induction of labor (OR = 1.4 95% CI = 1.1-1.7) and augmentation of labor with oxytocin (OR = 1.4 95% CI = 1.2-1.7). A signicant linear association was found, using the Mantel-Haenszel technique, between the severity of bleeding and the following risk factors: vacuum extraction, oxytocin augmentation of labor and hypertensive disorders (P ! .001 for all variables). CONCLUSION: Hypertensive disorder, failure of progress during the second stage of labor, oxytocin augmentation, vacuum extraction and LGA were found to be major risk factors for severe PPH. Special attention should be given after birth to hypertensive patients, to patients who underwent induction of labor or instrumental delivery, as well as to those delivering a LGA newborn.
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ALTERATIONS IN UTERINE SODIUM PUMP ABUNDANCE MAY CONTRIBUTE TO THE
ONSET OF MOUSE LABOR CARLOS VANCE II1, STEVEN HAMBLIN2, MICHAEL ESPLIN2, STEVEN GRAVES1, 1Brigham Young University, Chemistry and Biochemistry, Provo, Utah, 2University of Utah, Obstetrics and Gynecology, Salt Lake City, Utah OBJECTIVE: Reductions in sodium pump (SP) abundance increase uterine contractile activity. We described a reduction in uterine SPa3 isoform in pregnant women in active labor, however those studies could not determine whether the change occurred before or resulted from labor. To determine whether the mouse might serve as a model for human pregnancy in terms of the SP and to determine whether changes in SP anticipate (and hence potentially increase uterine contractility) or follow labor, we studied pregnant mice over their nal trimester. STUDY DESIGN: Pregnant C57Bl6 mice were sacriced (n = 4) at 14, 16 and 18 days gestation, during birth (wday 19) and 1 day post partum, uterus harvested and RNA isolated for rtPCR. cDNA was obtained by reverse transcriptase. Samples were amplied and quantied using an ABI 7900HT instrument using mouse SPa3 primers. Western Blot analysis using a SPa3 isoform specic monoclonal antibody was also done. Data were analyzed by ANOVA with post hoc Newman-Keuls pair-wise comparisons. RESULTS: SPa3 isoform mRNA was most abundant on day 14 (9.4 G 0.3 ! 10-7 units), was lower day 16 (8.0 G 1.1 ! 10-7 units) and signicantly lower day 18 (4.5 G 0.6 ! 10-7 units) and at birth (wday 19, 3.7 G 0.1 ! 10-7 units). SPa3 rose signicantly post delivery (7.5 G 1.7 ! 10-7 units). The overall trend was signicant (P = .004). Western blot analysis demonstrated a similar but delayed pattern. CONCLUSION: Mouse uterine SPa3 isoform protein expression fell prior to labor and appeared to be mediated by reductions in mRNA. These reductions parallel changes observed in term pregnant women. Such reductions increase uterine contractile activity and may be a fundamental mechanism in mouse and human labor.
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GLYCEMIC PROFILE CHARACTERISTICS DURING ACTIVE LABOR AND DELIVERY IN
NON DIABETIC SUBJECTS YARIV YOGEV1, ODED LANGER1, AVI BEN HAROUSH2, ORLI MOST1, RONY CHEN2, MOSHE HOD2, 1St. Lukes-Roosevelt Hospital Center, University Hospital of Columbia University, Obstetrics and Gynecology, NY, New York, 2Rabin Medical Center, Perinatal Division, Department of Obstetrics and Gynecology, Petach-Tikva, Israel, Israel OBJECTIVE: There is scarcity of data regarding the physiology of glycemic prole during labor. We studied the characteristics of the glycemic prole during labor and early post-partum period in non-diabetic subjects using a novel approach with the use of the Continuous Glucose Monitoring System (CGMS). STUDY DESIGN: In an on-going prospective study, 32 non-diabetic gravid subjects were evaluated using Continuous Glucose Monitoring System-CGMS. CGMS measures glucose levels every 5 minutes for a total of 288 measurements daily. The evaluation timeframe was from the latent phase until 24-h post partum. Eligibility was limited to healthy non-diabetic women >37 weeks gestation with a singleton pregnancy, with no chronic diseases, who did not receive drugs known to have an eect on carbohydrate metabolism (ie, steroids and b-sympathomimetics). All participants did not receive uids containing glucose during labor and had spontaneous vaginal d. RESULTS: (1) Mean maternal age was 27.3 G 3.1 years; gestational age at delivery was 39.2 G 1.1 weeks and BMI of 24.4 G 2.6. (2) Overall, 14,586 glucose determinations were obtained during the study period; the mean time of evaluation was 38 G 11 hours and the mean blood glucose determinations for each subject were 452 G 64. (3) No signicant dierence was found in mean blood glucose (MBG) during latent and active phase (82 G 19 and 79 G 21 mg/ dL, respectively P = .23). (4) During the second stage of labor, signicant lower MBG was recorded (71 G 14 mg/dL) P = .001, and 9/32 of the women had hypoglycemic events (blood glucose !40 mg/dL for more than 10 consecutive minutes) with no alteration in fetal heart rate. (5) MBG during the 24-h postprandial was signicantly higher in comparison to labor and delivery (89 G 17 mg/dL, P = .02). CONCLUSION: During normal labor, there is a gradual physiological decrease in glucose levels which is pronounced during the second stage.