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469 Expression and localization of iNOS and COX-2 throughout gestation in rat cervical tissue
$210 SMFM Abstracts
December 2001 A m J Obstet Gynecol
468
ELECTIVE I N D U C T I O N OF LABOR IN NULLIPAROUS WOMEN INCREASES THE RISK OF CESAREAN DELIVERY ANTHONY SCISCIONE ~, MATI'HEW HOFFMANn, ~Newark, DE ~Chrisfiana Hospital, Newark, DE OBJECTIVE: The induction rate continues to rise in the U.S., with rates as high as 40% in some hospitals. O n e of the most important contributors to the rising induction rate is the use of elective induction of labor. We sought to assess the impact of elective induction with a n d without preinduction cervical ripening on the m o d e of delivery in primagravid women. STUDY DESIGN: A c o h o r t of all primagravid w o m e n with a vertex presentation between 37 a n d 41 weeks gestation delivering between 7 / 9 6 and 7/01 was identified using a contemporaneously maintained perinatal database. Women with a fetal or maternal indication for induction or primary cesarean section were excluded. Women were divided into groups, those u n d e r , vent elective induction with preinduction cervical ripening (PRE), elective induction without preinduction cervical ripening (IND), a n d spontaneous labor (LABOR). Stepwise logistic regression was used to identify a n d control lot confounders using Cesarean section as the primary outcome. A Pvalue of <.05 was used as criterion to include a variable in the model. RESULTS: A total of 6,218 women were indentified. Four thousand seven h u n d r e d a n d sixty-one presented in spontaneous labor, 1,160 h a d induction of labor without p r e i n d u c t i o n ripening, a n d 297 were electively i n d u c e d with preinduction ripening. Maternal age (odds ratio 1.05/yeai, 95% CI 1.04-1.07), fetal birth weight (odds ratio 1.0005/gin, 95% CI 1.0004-1.0007) a n d a n occiput anterior position (odds ratio 0.1, 95% CI 0.08-0.13) were all predictive of Cesarean section. Atter controlling for potential confounders, women in the PRE g r o u p were 3.7 (95% CI 2.7-4.9) times m o r e likely to be delivered by Cesarean section compared to women in the LABOR group. Women in the IND were 2.8 (95% CI 2.3-3.4! times more likely to be delivered by Cesarean section c o m p a r e d to women in the LABOR group. CONCLUSION: Elective induction of labor independently increases the risk for Cesarean delivery in nulliparous women.
470
REMIFENTANIL: A NEW SYSTEMIC ANALGESIC FOR LABOR PAIN AND AN ALTERNATIVE T O DOLESTINE SHMUEL EVRON t , OSCAR SADAN l, TIBERIU EZRI 2, MONA BOAZ 3, MAREK GLEZERMAN1; ]Edith Wolfson Medical Center, Obstetrics & Gynecology, Holon; 2Edith Wolfson Medical Center, Anasthesiology, H o l o m 3Edith Woltgon Medical Center, Statistic Unit, Holon OBJECTIVE: Remitentauil is a novel short acting potent Ix-opioid agonist with rapid onset of action and clearance to an inactive metabolite. There is only scarce a n d inconsistent data available regarding its use in obstetrics. STUDY DESIGN: We studied the efficacy of remifentanil as patient controlled intravenous analgesia (PCIA) d u r i n g labor a n d delivery a n d its maternal a n d neonatal effects as compared to dolestine. Seventy-seven healthy, term parturients, cephalic presentation, who requested systemic analgesia for labor were enrolled a n d randomly assigned to either remit;entanil (n ~ 42) or dolestine (n = 35). RESULTS: Administration of intermittent increasing doses of renrifentanil (starting dose 20 p.g) was significantly more reliable with lower visual analogue scores (VAS) for pain ( P < .0001), higher patient satisl~tction (P < .0001), less sedative effects (P< .000l), lower respiratory depression (P< .007) a n d lower failure rate (conversion to epidural analgesia) 9.8% vs 35.3% as c o m p a r e d to systemic dolestine. T h e r e were n o significant differences in the m o d e of delivery or neonatal outcome between the study groups. Fetal heart rate was significantly m o r e olden reassuring a n d reactive, a n d h a d better variability a n d fewer decelerations u n d e r rentifentanil as compared to dolestine (P = .001). CONCLUSION: Increasing PCIA boluses of rernilentanil provided an effective a n d reliable analgesic during the whole labor a n d delivel~' process as compared to dolestine. The technique was shown to be safe for m o t h e r a n d baby even with high doses. Due to these positive findings, remifentanil may have the potential to replace dolestine as the systemic opioid of choice in labor a n d in cases when regional analgesia is contraindicated.
469
EXPRESSION AND LOCALIZATION OF INOS AND COX-2 THROUGHO U T GESTATION IN RAT CERVICAL TISSUE STEPHEN MARX 1, HOLGER MAUL'-', MELISSA WENTZ 1, CORDULA FITTKOW 2, RANDALL GIVEN 3, YURI VEDERNIKOV 4, GEORGE SAADE 2, ROBERT GARFIELD2; l University of Texas Medical Branch at Galveston, Obstetrics a n d (~ynecology, Galveston, TX; 2University of Texas Medical Branch, Obstetrics a n d Gynecology, Galveston, TX; 3University of Texas Medical Branch, Anatomy and Neurosciences, Galveston, TX; 4University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX OBJECTIVE: To determine if there is a temporal relationship between gestational c h a n g e s in inducible nitric oxide syntbase (iNOS) a n d cyclooxyg.enase-2 (COX-2) mRNA expression a n d protein localization in the rat
471
SALIVARY ESTRIOL/PROGESTERONE RATIO AND THE SUCCESS OF LABOR I N D U C T I O N MICHAEL J. FASSETT l, DEBORAH A. WING t, lUniversity of Southern Calitbrnia Keck School of Medicine, Department of Obstetrics a n d Gynecology, Los Angeles, CA OBJECTIVE: The salivary estriol/progesterone (E3/P) ratio rises before the onset of spontaneous term labor. A ratio of 1.65 has been reported 24 hours before the onset of labor. This normal rise in the E 3 / P ratio is absent in postterm pregnancies. We sought to evaluate the relationship of salivary E 3 / P ratio to the outcome of induced labor in the postterm pregnancy. STUDY DESIGN: 180 women with well
cervix.
STUDY DESIGN: Cervices were obtained fi-om non-pregnant estrous (NP) and timed-pregnant Sprague-Dawley rats days 14, 18, 22 non-laboring and 22 laboring, as well as postpartum (PP) days 1 a n d 3 (n = 4-10/group). iNOS and COX-2 mRNA levels were d e t e r m i n e d using quantitative real-time RT-PCR (Tagman, PE Biosystems). Data were normalized against the internal control (18srRNA). hnmunohistochemistry (IHS) was p e r f o r m e d on paraformaldehyde fixed, paraffin e m b e d d e d cervical sections using specific polyclonal antibodies a n d a c h r o m a g e n reaction. Quantitative data were analyzed using a 1-way ANOVA followed by a Tukey test, S p e a r m a n correlation, or a 2-way ANOVA as appropriate (significance: P < .05). RESULTS: Cervical iNOS mRNA levels were highest in NP a n d PP animals. Differences did not reach significance. COX-2 mRNA levels peaked in labor, a n d were significantly higher compared to all other time points. Changes in mRNA levels over gestation were significantly different between iNOS a n d COX-2 (Spearman r for iNOS: 0.55 a n d COX-2: -0.15; P - .01, a n d 2oway ANOVA P = .02). iNOS a n d COX-2 proteins were detected by IHS at all time points, being primarily expressed within cervical smooth muscle cells. Transient epithelial staining was observed a r o u n d labor tor both enzymes. iNOS, but not COX-2 was expressed in large leukocyte/monocyte like cells t h r o u g h o u t gestation. CONCLUSION: iNOS a n d COX-2 mRNA a n d their proteins are present in the rat cervix t h r o u g h o u t gestation. Although no temporal relationship between iNOS a n d COX-2 is apparent at the transcriptional level, it may still exist at the translational level resulting in sintilar patterns of protein expression. iNOS a n d COX-2 may take part in separate mechanisms to ripen the cervix during pregnancy. (Supported by NIH grant F31HD0873901.)
December 2001 A m J Obstet Gynecol
468
ELECTIVE I N D U C T I O N OF LABOR IN NULLIPAROUS WOMEN INCREASES THE RISK OF CESAREAN DELIVERY ANTHONY SCISCIONE ~, MATI'HEW HOFFMANn, ~Newark, DE ~Chrisfiana Hospital, Newark, DE OBJECTIVE: The induction rate continues to rise in the U.S., with rates as high as 40% in some hospitals. O n e of the most important contributors to the rising induction rate is the use of elective induction of labor. We sought to assess the impact of elective induction with a n d without preinduction cervical ripening on the m o d e of delivery in primagravid women. STUDY DESIGN: A c o h o r t of all primagravid w o m e n with a vertex presentation between 37 a n d 41 weeks gestation delivering between 7 / 9 6 and 7/01 was identified using a contemporaneously maintained perinatal database. Women with a fetal or maternal indication for induction or primary cesarean section were excluded. Women were divided into groups, those u n d e r , vent elective induction with preinduction cervical ripening (PRE), elective induction without preinduction cervical ripening (IND), a n d spontaneous labor (LABOR). Stepwise logistic regression was used to identify a n d control lot confounders using Cesarean section as the primary outcome. A Pvalue of <.05 was used as criterion to include a variable in the model. RESULTS: A total of 6,218 women were indentified. Four thousand seven h u n d r e d a n d sixty-one presented in spontaneous labor, 1,160 h a d induction of labor without p r e i n d u c t i o n ripening, a n d 297 were electively i n d u c e d with preinduction ripening. Maternal age (odds ratio 1.05/yeai, 95% CI 1.04-1.07), fetal birth weight (odds ratio 1.0005/gin, 95% CI 1.0004-1.0007) a n d a n occiput anterior position (odds ratio 0.1, 95% CI 0.08-0.13) were all predictive of Cesarean section. Atter controlling for potential confounders, women in the PRE g r o u p were 3.7 (95% CI 2.7-4.9) times m o r e likely to be delivered by Cesarean section compared to women in the LABOR group. Women in the IND were 2.8 (95% CI 2.3-3.4! times more likely to be delivered by Cesarean section c o m p a r e d to women in the LABOR group. CONCLUSION: Elective induction of labor independently increases the risk for Cesarean delivery in nulliparous women.
470
REMIFENTANIL: A NEW SYSTEMIC ANALGESIC FOR LABOR PAIN AND AN ALTERNATIVE T O DOLESTINE SHMUEL EVRON t , OSCAR SADAN l, TIBERIU EZRI 2, MONA BOAZ 3, MAREK GLEZERMAN1; ]Edith Wolfson Medical Center, Obstetrics & Gynecology, Holon; 2Edith Wolfson Medical Center, Anasthesiology, H o l o m 3Edith Woltgon Medical Center, Statistic Unit, Holon OBJECTIVE: Remitentauil is a novel short acting potent Ix-opioid agonist with rapid onset of action and clearance to an inactive metabolite. There is only scarce a n d inconsistent data available regarding its use in obstetrics. STUDY DESIGN: We studied the efficacy of remifentanil as patient controlled intravenous analgesia (PCIA) d u r i n g labor a n d delivery a n d its maternal a n d neonatal effects as compared to dolestine. Seventy-seven healthy, term parturients, cephalic presentation, who requested systemic analgesia for labor were enrolled a n d randomly assigned to either remit;entanil (n ~ 42) or dolestine (n = 35). RESULTS: Administration of intermittent increasing doses of renrifentanil (starting dose 20 p.g) was significantly more reliable with lower visual analogue scores (VAS) for pain ( P < .0001), higher patient satisl~tction (P < .0001), less sedative effects (P< .000l), lower respiratory depression (P< .007) a n d lower failure rate (conversion to epidural analgesia) 9.8% vs 35.3% as c o m p a r e d to systemic dolestine. T h e r e were n o significant differences in the m o d e of delivery or neonatal outcome between the study groups. Fetal heart rate was significantly m o r e olden reassuring a n d reactive, a n d h a d better variability a n d fewer decelerations u n d e r rentifentanil as compared to dolestine (P = .001). CONCLUSION: Increasing PCIA boluses of rernilentanil provided an effective a n d reliable analgesic during the whole labor a n d delivel~' process as compared to dolestine. The technique was shown to be safe for m o t h e r a n d baby even with high doses. Due to these positive findings, remifentanil may have the potential to replace dolestine as the systemic opioid of choice in labor a n d in cases when regional analgesia is contraindicated.
469
EXPRESSION AND LOCALIZATION OF INOS AND COX-2 THROUGHO U T GESTATION IN RAT CERVICAL TISSUE STEPHEN MARX 1, HOLGER MAUL'-', MELISSA WENTZ 1, CORDULA FITTKOW 2, RANDALL GIVEN 3, YURI VEDERNIKOV 4, GEORGE SAADE 2, ROBERT GARFIELD2; l University of Texas Medical Branch at Galveston, Obstetrics a n d (~ynecology, Galveston, TX; 2University of Texas Medical Branch, Obstetrics a n d Gynecology, Galveston, TX; 3University of Texas Medical Branch, Anatomy and Neurosciences, Galveston, TX; 4University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX OBJECTIVE: To determine if there is a temporal relationship between gestational c h a n g e s in inducible nitric oxide syntbase (iNOS) a n d cyclooxyg.enase-2 (COX-2) mRNA expression a n d protein localization in the rat
471
SALIVARY ESTRIOL/PROGESTERONE RATIO AND THE SUCCESS OF LABOR I N D U C T I O N MICHAEL J. FASSETT l, DEBORAH A. WING t, lUniversity of Southern Calitbrnia Keck School of Medicine, Department of Obstetrics a n d Gynecology, Los Angeles, CA OBJECTIVE: The salivary estriol/progesterone (E3/P) ratio rises before the onset of spontaneous term labor. A ratio of 1.65 has been reported 24 hours before the onset of labor. This normal rise in the E 3 / P ratio is absent in postterm pregnancies. We sought to evaluate the relationship of salivary E 3 / P ratio to the outcome of induced labor in the postterm pregnancy. STUDY DESIGN: 180 women with well
cervix.
STUDY DESIGN: Cervices were obtained fi-om non-pregnant estrous (NP) and timed-pregnant Sprague-Dawley rats days 14, 18, 22 non-laboring and 22 laboring, as well as postpartum (PP) days 1 a n d 3 (n = 4-10/group). iNOS and COX-2 mRNA levels were d e t e r m i n e d using quantitative real-time RT-PCR (Tagman, PE Biosystems). Data were normalized against the internal control (18srRNA). hnmunohistochemistry (IHS) was p e r f o r m e d on paraformaldehyde fixed, paraffin e m b e d d e d cervical sections using specific polyclonal antibodies a n d a c h r o m a g e n reaction. Quantitative data were analyzed using a 1-way ANOVA followed by a Tukey test, S p e a r m a n correlation, or a 2-way ANOVA as appropriate (significance: P < .05). RESULTS: Cervical iNOS mRNA levels were highest in NP a n d PP animals. Differences did not reach significance. COX-2 mRNA levels peaked in labor, a n d were significantly higher compared to all other time points. Changes in mRNA levels over gestation were significantly different between iNOS a n d COX-2 (Spearman r for iNOS: 0.55 a n d COX-2: -0.15; P - .01, a n d 2oway ANOVA P = .02). iNOS a n d COX-2 proteins were detected by IHS at all time points, being primarily expressed within cervical smooth muscle cells. Transient epithelial staining was observed a r o u n d labor tor both enzymes. iNOS, but not COX-2 was expressed in large leukocyte/monocyte like cells t h r o u g h o u t gestation. CONCLUSION: iNOS a n d COX-2 mRNA a n d their proteins are present in the rat cervix t h r o u g h o u t gestation. Although no temporal relationship between iNOS a n d COX-2 is apparent at the transcriptional level, it may still exist at the translational level resulting in sintilar patterns of protein expression. iNOS a n d COX-2 may take part in separate mechanisms to ripen the cervix during pregnancy. (Supported by NIH grant F31HD0873901.)