Induction of labor at term with vaginal misoprostol or a prostaglandin E2 pessary: a noninferiority randomized controlled trial.

BACKGROUND: Induction of labor is among the most common procedures for pregnant women. Only a few randomized clinical trials with relatively small samples have compared misoprostol with dinoprostone. Although their efficacy seems similar, their safety profiles have not been adequately evaluated, and economic data are sparse. OBJECTIVE: This study aimed to test the noninferiority of vaginal misoprostol (prostaglandin E1) (25 µg) to a slow-release dinoprostone (prostaglandin E2) pessary (10 µg) for induction of labor with an unfavorable cervix at term. STUDY DESIGN: This was an open-label multicenter randomized noninferiority trial at 4 university hospitals of the Research Group in Obstetrics and Gynecology between 2012 and 2015. We recruited women who underwent induction of labor for medical reasons, those with a Bishop score of ≤5 at ≥36 weeks' gestation, and those with a cephalic-presenting singleton pregnancy with no previous cesarean delivery. Women were randomly allocated to receive either vaginal misoprostol at 4-hour intervals (25 µg) or a 10-mg slow-release dinoprostone pessary. The primary outcome was the total cesarean delivery rate. Noninferiority was defined as a difference in the cesarean delivery rates between the groups of no more than 5%. Secondary outcomes included neonatal and maternal morbidity, vaginal delivery at <24 hours after starting the induction of labor process, and maternal satisfaction. RESULTS: The study included 1674 randomized women. The per-protocol analysis included 790 women in each group. The total cesarean delivery rates were 22.1% (n=175) in the misoprostol group and 19.9% (n=157) in the dinoprostone group, a difference of 2.2% (with an upper-bound 95% confidence limit of 5.6%) (P=.092). Results in the intention-to-treat analysis were similar. Neonatal and maternal morbidity rates were similar between groups. Vaginal delivery within 24 hours was significantly higher in the misoprostol group (59.3% vs 45.7%; P<.001) as was maternal satisfaction, assessed in the postpartum period by a visual analog scale (mean score, 7.1±2.4 vs 5.8±3.1; P<.001). CONCLUSION: The noninferiority of a 25-µg dose of vaginal misoprostol every 4 hours to the dinoprostone pessary for cesarean delivery rates after induction of labor at term could not be demonstrated, although the confidence limit of the difference barely exceeded the noninferiority margin. Nonetheless, given the small difference between these cesarean delivery rates and the similarity of neonatal and maternal morbidity rates in this large study, the clinical risk-to-benefit ratio justifies the use of both drugs.

Perineal ultrasound for the measurement of urethral mobility: a study of inter- and intra-observer reliability.

INTRODUCTION AND HYPOTHESIS: Ultrasound measurement of urethral mobility is an attractive approach to directly visualize bladder neck descent (BND) during stress. BND assessed by transperineal ultrasound appears to be associated with stress urinary incontinence (SUI) severity. This study evaluated the inter- and intra-observer reliability of ultrasound BND measurement and its correlation with clinical examination. METHODS: We included 50 women from the multicenter randomized 3PN study ("Prenatal Perineal Prevention"). BND was measured by two operators either during pregnancy (at 20 weeks of gestation) or 2 months after delivery. Two measurements were taken by each operator. Intra-class coefficient correlations were used for analysis. Urethral mobility was clinically assessed by measuring the point Aa of the POP-Q classification during maximum strain (Valsalva maneuver) with an empty bladder. RESULTS: Ultrasound analysis showed high intra-observer reliability in the overall population: intraclass correlation coefficients (ICC) = 0.75 (0.59-0.85) and 0.73 (0.55-0.84) for each operator. Intra-observer agreements were considered moderate to high in the post- and antepartum groups. Inter-observer agreements were moderate in the antepartum period [ICC = 0.58 (0.26-0.78) for the first measurement and 0.68 (0.42-0.84) for the second] but low in the postpartum period [ICC = 0.15 (0.10-0.41) and 0.21 (0.10-0.58)]. Correlations between ultrasound and clinical measurements were considered low to moderate (Spearman coefficient, rho = 0.34 and 0.50 for post- and antepartum periods, respectively). CONCLUSIONS: Inter-observer reliability of ultrasound urethral mobility measurements by the transperineal route is moderate antepartum and low postpartum. The correlation with point Aa is low to moderate.

Active Management of the Third Stage of Labor With a Combination of Oxytocin and Misoprostol to Prevent Postpartum Hemorrhage: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of misoprostol administered simultaneously with oxytocin as part of the active management of the third stage of labor. METHODS: This multicenter, double-blind, randomized, placebo-controlled trial recruited women in the first stage of labor with expected vaginal deliveries at 36-42 weeks of gestation. Exclusion criteria were multiple pregnancies, hypersensitivity to misoprostol, and cesarean delivery. Participants received routine intravenous oxytocin and were randomly allocated to receive 400 micrograms misoprostol or placebo orally immediately after delivery of the newborn. The primary outcome was postpartum hemorrhage (500 mL or greater within 2 hours of birth). Secondary outcomes included severe postpartum hemorrhage (1,000 mL or greater) and adverse maternal events such as fever, shivering, and nausea. Two groups of 1,550 women were required to demonstrate a 33% decrease of postpartum hemorrhage according to a two-tailed α at 0.05 with 80% power. An interim analysis was planned after 50% enrollment. RESULTS: Participant enrollment occurred from April 2010 to September 2013. Baseline characteristics were similar in the two groups. The study was discontinued after the planned interim analysis including 1,721 patients showed that misoprostol was not effective and was associated with significantly more adverse effects. The rate of postpartum hemorrhage was 8.4% (68/806) in the misoprostol and 8.3% (66/797) in the placebo group (P=.98), and rates of severe postpartum hemorrhage were 1.8% and 2.4%, respectively (P=.57). Maternal adverse events occurred significantly more frequently in the misoprostol group (for fever 30.4% in the misoprostol group compared with 6.3% in the placebo group, P<.001; for shivering 10.8% in the misoprostol group compared with 0.6% in the placebo group, P<.001). CONCLUSION: Misoprostol administered with prophylactic routine oxytocin did not reduce the rate of postpartum hemorrhage risk and increased the rate of adverse events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01113229.

Is prenatal urethral descent a risk factor for urinary incontinence during pregnancy and the postpartum period?

INTRODUCTION AND HYPOTHESIS: Obstetric trauma during childbirth is considered a major risk factor for postpartum urinary incontinence (UI), particularly stress urinary incontinence. Our aim was to investigate the relation between postpartum UI, mode of delivery, and urethral descent, and to define a group of women who are particularly at risk of postnatal UI. METHODS: A total of 186 women were included their first pregnancy. Validated questionnaires about urinary symptoms during pregnancy, 2 and 12 months after delivery, were administered. Urethral descent was assessed clinically and by ultrasound at inclusion. Multivariate logistic regression analysis was used to determine the risk factors for UI during pregnancy, at 2 months and 1 year after first delivery. RESULTS: The prevalence of UI was 38.6, 46.5, 35.6, and 34.4 % at inclusion, late pregnancy, 2 months postpartum, and 1 year postpartum respectively. No significant association was found between UI at late pregnancy and urethral descent assessed clinically or by ultrasound. The only risk factor for UI at 2 months postpartum was UI at inclusion (OR 6.27 [95 % CI 2.70-14.6]). The risk factors for UI at 1 year postpartum were UI at inclusion (6.14 [2.22-16.9]), body mass index (BMI), and urethral descent at inclusion, assessed clinically (7.21 [2.20-23.7]) or by ultrasound. The mode of delivery was not associated with urethral descent. CONCLUSIONS: Prenatal urethral descent and UI during pregnancy are risk factors for UI at 1 year postpartum. These results indicate that postnatal UI is more strongly influenced by susceptibility factors existing before first delivery than by the mode of delivery.

Steroid profiling in preeclamptic women: evidence for aromatase deficiency.

OBJECTIVE: Experimental data have revealed the critical role played by 2-methoxy-estradiol, a metabolite of 17ß-estradiol, in the pathophysiology of preeclampsia. We used gas chromatography/mass spectrometry to measure a whole panel of hormonal steroids in the plasma from women during the third trimester of their pregnancy. STUDY DESIGN: The population study consists of 24 pregnant patients with different outcomes: normal, or complicated by isolated preeclampsia or by severe preeclampsia with Hemolysis Enzyme Liver Low Platelets (HELLP) syndrome. RESULTS: 17ß-estradiol was reduced by 50% in isolated preeclampsia, and by 70% in severe preeclampsia with HELLP syndrome (normal: 8.54 ± 0.9 ng/mL; isolated preeclampsia: 4.65 ± 1.0 ng/mL; severe preeclampsia with HELLP syndrome: 2.64 ± 0.4 ng/mL), as is estrone. Downstream, 2-methoxy-estradiol was decreased only in severe preeclampsia with HELLP syndrome. The concentrations of estrone and 17ß-estradiol precursors were comparable between groups, suggesting that placental aromatase is deficient in preeclampsia. CONCLUSION: The gradual decrease of estrogen levels with increasing severity of preeclampsia suggests an impairment of placental steroidogenesis.

Soluble endoglin in preeclamptic patients with or without HELLP syndrome.

OBJECTIVE: The pathogenesis of the HELLP (hemolysis, enzyme liver, low platelets) syndrome is unknown. Recently soluble endoglin (sEng) was identified as a cause of the appearance of schistocytes and liver pathology in an animal model of preeclampsia (PE). STUDY DESIGN: We explored the value of sEng in 82 women who delivered in a context of normal pregnancy (NP, n = 10), PE (n = 49), or HELLP (n = 23). RESULTS: sEng was elevated in pathological pregnancies (66.7 +/- 62 and 75.7 +/- 48 pg/mL in PE and HELLP, respectively, vs 5.29 +/- 1.25 in NP, P < .001 for both comparisons) and was correlated with an increase in transaminases (r(2) = 0.17; P = .05), but it was not statistically different between PE and HELLP. CONCLUSION: Although recent literature findings demonstrated a role of sEng in the pathophysiology of HELLP syndrome in animal models, we found that, at the time of delivery, sEng was not specifically elevated in preeclamptic patients with HELLP.