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PGE2-induced cervical ripening is mediated by the PTGER-EP4 receptor
S202 SMFM Abstracts 523
DIFFERENCES IN WOMEN PRESENTING IN LATENT AND ACTIVE PHASE OF LABOR JENNIFER BAILIT1, LEROY DIERKER1, BRIAN MERCER1, 1MetroHealth Medical Center, Case Western Reserve University, Obstetrics/Gynecology, Cleveland, OH OBJECTIVE: Women presenting in latent phase are at increased risk for Cesarean (CD) than those presenting in active phase. We sought to evaluate patient, labor, management and outcome differences between those presenting in latent phase and active phase. STUDY DESIGN: We evaluated all low-risk singleton, term women with vertex presentations, presenting in active phase (AP: contractions with or without ROM > = 4 cm) or latent phase (LP: contractions with or without ROM < 4 cm or ROM only) delivering at MetroHealth Medical Center between January 1993 and June 2001. Women with a prior CD, or contraindication to labor or vaginal delivery were excluded, as were those with medical/obstetric complications or substance abuse. AP and LP gravidas were compared for baseline characteristics. Labor outcomes were assessed by logistic regression, controlling for parity. P < 0.01 considered significant. OR = Odds ratio. RESULTS: 11,176 of 25,998 singleton gestations (43%) met our strict inclusion criteria: 6,744 AP and 4,432 LP gravidas. LP women were more likely nulliparous (57 vs. 33%), had smaller infants (3316 vs 3365 g), had more private insurance (26 vs 23%), p < 0.0001 for each. Maternal race, age, weight, gestation at delivery were not different. LP women were at increased risk for CD (nulliparas: 15.7 vs 7.8%, multiparas; 3.7 vs 1.7, p < 0.0001 for each). LP women had more prolonged latent phase (OR = 5.6), active phase arrest (OR = 2.2), and had more oxytocin use (OR = 3.1) scalp pH (OR = 2.0), IUPC (OR = 2.5) and ECG (OR = 1.8) monitoring performed, p < 0.001 for each, but not more CDs for arrest of descent. LP women had more amnionitis (OR 2.6) and postpartum infection (OR = 2.0) but not operative vaginal delivery, postpartum hemorrhage or need for neonatal intubation. CONCLUSION: Arriving in latent phase may be a marker for labor abnormalities in active phase unrelated to maternal or fetal characteristics. Whether these labor abnormalities cause or result from early presentation or subsequent physician intervention remains unresolved.
December 2003 Am J Obstet Gynecol 525
EFFECTS OF EARLY EPIDURAL ANALGESIA VS IV ANALGESIA ON LABOR PROGRESSION: A NATURAL EXPERIMENT ANJEL VAHRATIAN1, JUN ZHANG1, JILL HASLING2, JAMES TROENDLE1, MARK KLEBANOFF1, JOHN THORP, JR.3, 1National Institutes of Health, Department of Health and Human Services, Division of Epidemiology, Statistics, and Prevention Research, Bethesda, MD 2Tripler Army Medical Center, Obstetrics and Gynecology, Tripler, HI 3University of North Carolina at Chapel Hill, Obstetrics and Gynecology, Chapel Hill, NC OBJECTIVE: To examine the effect of an early placement of epidural analgesia (on or before 4 cm) on labor progression, in comparison to IV analgesia. STUDY DESIGN: This is a retrospective analysis of data from a military medical center where the rate of epidural analgesia in labor increased from 1% to 84% in a one-year period after on-demand epidural analgesia became available (a natural experiment). For this analysis, we systematically selected singleton, nulliparous, term pregnancies with a spontaneous onset of labor and admission and analgesia placement at or before 4 cm. Baseline characteristics were compared between group I (n = 223; 98% IV and 2% epidural analgesia) and group II (n = 278; 93% epidural and 7% IV analgesia). ‘‘Intent-to-treat’’ analysis was used. The median duration of labor by each cm of dilation was computed as a measurement of labor progression. RESULTS: There was no statistically significant difference between groups I and II in oxytocin use (75% vs 70%), infant birth weight (3394 vs 3391 g), or rate of cesarean delivery (18% for both). After adjusting for age, pre-pregnancy body mass index, and gravidity, early epidural analgesia use was associated with a slower labor progression only from 4 to 5 cm (Table). As many women were admitted to labor around 3 cm and analgesia was placed around 4 cm, slow labor at 4-5 cm may reflect both the time of admission and the epidural analgesia placement procedure. CONCLUSION: In comparison to IV analgesia, the early use of epidural analgesia is associated with a slower labor progression from 4 to 5 cm but has no significant effect on most of the active phase. Our study suggests that epidural analgesia before 4 cm should not be restrained. Table: Median duration of labor progression (in minutes) (*P < 0.01)
3-4 cm 4-5 cm 5-6 cm 6-7 cm 7-8 cm 8-9 cm 9-10 cm
524
PGE2-INDUCED CERVICAL RIPENING IS MEDIATED BY THE PTGER-EP4 RECEPTOR HELEN FELTOVICH1, HUILING LI1, EDWARD CHIEN1, 1 University of Vermont, Obstetrics and Gynecology, Burlington, VT OBJECTIVE: Cervical remodeling (ripening) precedes preterm and term labor by days to weeks. Structural changes that accompany ripening suggest a biochemical process involving MMP expression. MMP expression is mediated by cAMP. Of four known PGE2 receptors, two (Ep2 and 4) signal through cAMP. Marked upregulation of only Ep4 occurs near term. We hypothesize that PGE2induced cervical ripening is mediated through Ep4, but not Ep2, activation. STUDY DESIGN: We measured cervical creep (an assessment of tensile strength) in timed pregnant Sprague-Dawley rats during normal gestation and after PGE2 (non-selective agonist) or butaprost (Ep2 agonist) administration. Animals were pretreated with indomethacin to inhibit endogenous prostaglandin production. Cervical creep was determined using the Hollingsworth technique. The agonist or vehicle was applied intravaginally to the cervix on days 15, 19, or 20 and assayed 24 hours later. Creep rates were compared by oneway ANOVA with multiple comparisons and t-tests where appropriate. RESULTS: Cervical creep progressively increased throughout gestation and peaked on days 21 and 22 (animals deliver on evening day 22 or morning day 23). The increase in cervical creep (decreased tensile strength) was significant (ANOVA, P = 0.005). Animals treated with PGE2 on day 20 showed significantly higher creep rates than controls (ANOVA, P = 0.005). No statistically significant differences in cervical creep were detected in animals treated on day 15 or 19 with PGE2. The Ep2-specific agonist Butaprost produced no statistically significant differences in cervical creep when administered on day 20. CONCLUSION: The non-specific agonist PGE2 did induce cervical ripening, while the Ep2-specific agonist had no effect when applied on day 20. Earlier administration of PGE2 failed to induce cervical ripening. This difference in PGE2 responsiveness corresponds to the gestationally regulated expression of Ep4 receptors previously described. Supported by PHS HDO1232-01.
526
Group I
Group II
118 77 38 36 26 24 26
135 128* 40 34 31 31 29
MATERNAL OBESITY AND LABOR PROGRESSION IN NULLIPAROUS WOMEN ANJEL VAHRATIAN1, JUN ZHANG1, JAMES TROENDLE1, ANNA MARIA SIEGA-RIZ2, DAVID SAVITZ3, JOHN THORP, JR.4, 1National Institutes of Health, Department of Health and Human Services, Division of Epidemiology, Statistics, and Prevention Research, Bethesda, MD 2 University of North Carolina at Chapel Hill, Nutrition and Maternal and Child Health, Chapel Hill, NC 3University of North Carolina at Chapel Hill, Epidemiology, Chapel Hill, NC 4University of North Carolina at Chapel Hill, Obstetrics and Gynecology, Chapel Hill, NC OBJECTIVE: Maternal obesity is associated with an increased risk for a cesarean delivery, but it is unclear what factors may contribute to this risk. Thus, we examined the effect of maternal obesity on labor progression. STUDY DESIGN: We analyzed data on 542 nulliparous women with a prepregnancy BMI greater than 19.8 kg/m2 and a singleton, term pregnancy that participated in the Pregnancy, Infection, and Nutrition Study (1995-2000). Women with an elective cesarean delivery and those with only one cervical exam were excluded. Baseline characteristics were compared among obese (BMI > 29.0 kg/m2; n = 272), overweight (BMI 26.1-29.0 kg/m2; n = 103), and normal weight (BMI 19.8-26.0 kg/m2; n = 167) women; and the median duration of time elapsed for each cm of dilation was computed as a measurement of labor progression using interval censored regression. RESULTS: After adjusting for labor induction, epidural analgesia, payer status, and infant birth weight, obese women had a significantly slower labor prior to 6 cm, compared to normal women (Table). In contrast, the duration of the active phase was similar among the groups. Overweight and obese women were more likely to deliver by cesarean section, compared to normal women. Over 50% of cesareans among obese women occurred prior to 6 cm. CONCLUSION: The pattern of labor progression in obese women differs significantly from that of normal weight women prior to 6 cm. These differences must be considered before further interventions are considered. Table: Median duration of labor (in minutes) by BMI (*P < 0.05; §P = 0.07)
3-4 cm 4-5 5-6 6-7 7-8 8-9 9-10 Cesarean (%) Cesarean < 6 cm (%)
Normal Weight
Overweight
Obese
86 69 49 37 31 29 25 18.0 40.8
89 103 * 57 42 33 34 31 29.1 * 26.7
125 * 92 § 68 * 46 27 25 26 27.5 * 52.2
DIFFERENCES IN WOMEN PRESENTING IN LATENT AND ACTIVE PHASE OF LABOR JENNIFER BAILIT1, LEROY DIERKER1, BRIAN MERCER1, 1MetroHealth Medical Center, Case Western Reserve University, Obstetrics/Gynecology, Cleveland, OH OBJECTIVE: Women presenting in latent phase are at increased risk for Cesarean (CD) than those presenting in active phase. We sought to evaluate patient, labor, management and outcome differences between those presenting in latent phase and active phase. STUDY DESIGN: We evaluated all low-risk singleton, term women with vertex presentations, presenting in active phase (AP: contractions with or without ROM > = 4 cm) or latent phase (LP: contractions with or without ROM < 4 cm or ROM only) delivering at MetroHealth Medical Center between January 1993 and June 2001. Women with a prior CD, or contraindication to labor or vaginal delivery were excluded, as were those with medical/obstetric complications or substance abuse. AP and LP gravidas were compared for baseline characteristics. Labor outcomes were assessed by logistic regression, controlling for parity. P < 0.01 considered significant. OR = Odds ratio. RESULTS: 11,176 of 25,998 singleton gestations (43%) met our strict inclusion criteria: 6,744 AP and 4,432 LP gravidas. LP women were more likely nulliparous (57 vs. 33%), had smaller infants (3316 vs 3365 g), had more private insurance (26 vs 23%), p < 0.0001 for each. Maternal race, age, weight, gestation at delivery were not different. LP women were at increased risk for CD (nulliparas: 15.7 vs 7.8%, multiparas; 3.7 vs 1.7, p < 0.0001 for each). LP women had more prolonged latent phase (OR = 5.6), active phase arrest (OR = 2.2), and had more oxytocin use (OR = 3.1) scalp pH (OR = 2.0), IUPC (OR = 2.5) and ECG (OR = 1.8) monitoring performed, p < 0.001 for each, but not more CDs for arrest of descent. LP women had more amnionitis (OR 2.6) and postpartum infection (OR = 2.0) but not operative vaginal delivery, postpartum hemorrhage or need for neonatal intubation. CONCLUSION: Arriving in latent phase may be a marker for labor abnormalities in active phase unrelated to maternal or fetal characteristics. Whether these labor abnormalities cause or result from early presentation or subsequent physician intervention remains unresolved.
December 2003 Am J Obstet Gynecol 525
EFFECTS OF EARLY EPIDURAL ANALGESIA VS IV ANALGESIA ON LABOR PROGRESSION: A NATURAL EXPERIMENT ANJEL VAHRATIAN1, JUN ZHANG1, JILL HASLING2, JAMES TROENDLE1, MARK KLEBANOFF1, JOHN THORP, JR.3, 1National Institutes of Health, Department of Health and Human Services, Division of Epidemiology, Statistics, and Prevention Research, Bethesda, MD 2Tripler Army Medical Center, Obstetrics and Gynecology, Tripler, HI 3University of North Carolina at Chapel Hill, Obstetrics and Gynecology, Chapel Hill, NC OBJECTIVE: To examine the effect of an early placement of epidural analgesia (on or before 4 cm) on labor progression, in comparison to IV analgesia. STUDY DESIGN: This is a retrospective analysis of data from a military medical center where the rate of epidural analgesia in labor increased from 1% to 84% in a one-year period after on-demand epidural analgesia became available (a natural experiment). For this analysis, we systematically selected singleton, nulliparous, term pregnancies with a spontaneous onset of labor and admission and analgesia placement at or before 4 cm. Baseline characteristics were compared between group I (n = 223; 98% IV and 2% epidural analgesia) and group II (n = 278; 93% epidural and 7% IV analgesia). ‘‘Intent-to-treat’’ analysis was used. The median duration of labor by each cm of dilation was computed as a measurement of labor progression. RESULTS: There was no statistically significant difference between groups I and II in oxytocin use (75% vs 70%), infant birth weight (3394 vs 3391 g), or rate of cesarean delivery (18% for both). After adjusting for age, pre-pregnancy body mass index, and gravidity, early epidural analgesia use was associated with a slower labor progression only from 4 to 5 cm (Table). As many women were admitted to labor around 3 cm and analgesia was placed around 4 cm, slow labor at 4-5 cm may reflect both the time of admission and the epidural analgesia placement procedure. CONCLUSION: In comparison to IV analgesia, the early use of epidural analgesia is associated with a slower labor progression from 4 to 5 cm but has no significant effect on most of the active phase. Our study suggests that epidural analgesia before 4 cm should not be restrained. Table: Median duration of labor progression (in minutes) (*P < 0.01)
3-4 cm 4-5 cm 5-6 cm 6-7 cm 7-8 cm 8-9 cm 9-10 cm
524
PGE2-INDUCED CERVICAL RIPENING IS MEDIATED BY THE PTGER-EP4 RECEPTOR HELEN FELTOVICH1, HUILING LI1, EDWARD CHIEN1, 1 University of Vermont, Obstetrics and Gynecology, Burlington, VT OBJECTIVE: Cervical remodeling (ripening) precedes preterm and term labor by days to weeks. Structural changes that accompany ripening suggest a biochemical process involving MMP expression. MMP expression is mediated by cAMP. Of four known PGE2 receptors, two (Ep2 and 4) signal through cAMP. Marked upregulation of only Ep4 occurs near term. We hypothesize that PGE2induced cervical ripening is mediated through Ep4, but not Ep2, activation. STUDY DESIGN: We measured cervical creep (an assessment of tensile strength) in timed pregnant Sprague-Dawley rats during normal gestation and after PGE2 (non-selective agonist) or butaprost (Ep2 agonist) administration. Animals were pretreated with indomethacin to inhibit endogenous prostaglandin production. Cervical creep was determined using the Hollingsworth technique. The agonist or vehicle was applied intravaginally to the cervix on days 15, 19, or 20 and assayed 24 hours later. Creep rates were compared by oneway ANOVA with multiple comparisons and t-tests where appropriate. RESULTS: Cervical creep progressively increased throughout gestation and peaked on days 21 and 22 (animals deliver on evening day 22 or morning day 23). The increase in cervical creep (decreased tensile strength) was significant (ANOVA, P = 0.005). Animals treated with PGE2 on day 20 showed significantly higher creep rates than controls (ANOVA, P = 0.005). No statistically significant differences in cervical creep were detected in animals treated on day 15 or 19 with PGE2. The Ep2-specific agonist Butaprost produced no statistically significant differences in cervical creep when administered on day 20. CONCLUSION: The non-specific agonist PGE2 did induce cervical ripening, while the Ep2-specific agonist had no effect when applied on day 20. Earlier administration of PGE2 failed to induce cervical ripening. This difference in PGE2 responsiveness corresponds to the gestationally regulated expression of Ep4 receptors previously described. Supported by PHS HDO1232-01.
526
Group I
Group II
118 77 38 36 26 24 26
135 128* 40 34 31 31 29
MATERNAL OBESITY AND LABOR PROGRESSION IN NULLIPAROUS WOMEN ANJEL VAHRATIAN1, JUN ZHANG1, JAMES TROENDLE1, ANNA MARIA SIEGA-RIZ2, DAVID SAVITZ3, JOHN THORP, JR.4, 1National Institutes of Health, Department of Health and Human Services, Division of Epidemiology, Statistics, and Prevention Research, Bethesda, MD 2 University of North Carolina at Chapel Hill, Nutrition and Maternal and Child Health, Chapel Hill, NC 3University of North Carolina at Chapel Hill, Epidemiology, Chapel Hill, NC 4University of North Carolina at Chapel Hill, Obstetrics and Gynecology, Chapel Hill, NC OBJECTIVE: Maternal obesity is associated with an increased risk for a cesarean delivery, but it is unclear what factors may contribute to this risk. Thus, we examined the effect of maternal obesity on labor progression. STUDY DESIGN: We analyzed data on 542 nulliparous women with a prepregnancy BMI greater than 19.8 kg/m2 and a singleton, term pregnancy that participated in the Pregnancy, Infection, and Nutrition Study (1995-2000). Women with an elective cesarean delivery and those with only one cervical exam were excluded. Baseline characteristics were compared among obese (BMI > 29.0 kg/m2; n = 272), overweight (BMI 26.1-29.0 kg/m2; n = 103), and normal weight (BMI 19.8-26.0 kg/m2; n = 167) women; and the median duration of time elapsed for each cm of dilation was computed as a measurement of labor progression using interval censored regression. RESULTS: After adjusting for labor induction, epidural analgesia, payer status, and infant birth weight, obese women had a significantly slower labor prior to 6 cm, compared to normal women (Table). In contrast, the duration of the active phase was similar among the groups. Overweight and obese women were more likely to deliver by cesarean section, compared to normal women. Over 50% of cesareans among obese women occurred prior to 6 cm. CONCLUSION: The pattern of labor progression in obese women differs significantly from that of normal weight women prior to 6 cm. These differences must be considered before further interventions are considered. Table: Median duration of labor (in minutes) by BMI (*P < 0.05; §P = 0.07)
3-4 cm 4-5 5-6 6-7 7-8 8-9 9-10 Cesarean (%) Cesarean < 6 cm (%)
Normal Weight
Overweight
Obese
86 69 49 37 31 29 25 18.0 40.8
89 103 * 57 42 33 34 31 29.1 * 26.7
125 * 92 § 68 * 46 27 25 26 27.5 * 52.2