Cost-effectiveness analysis of vaginal misoprostol versus dinoprostone pessary: A non-inferiority large randomized controlled trial in France.

OBJECTIVE: To assess the cost-effectiveness of vaginal misoprostol (PGE1; 25 µg) compared with a slow-release dinoprostone (PGE2) pessary (10 µg) for labor induction due to an unfavorable cervix at term. METHODS: We used data from an open-label multicenter, randomized non-inferiority trial that recruited women for whom labor was induced for medical reasons. The incremental cost-effectiveness ratio was assessed from the payer's perspective, with the focus on inpatient care costs and using the cesarean deliveries avoided (CDA) rate as the primary analysis and the rate of vaginal delivery within 24 h (VD24) as the secondary analysis. RESULTS: Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4410 and €4399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol, respectively. Dinoprostone is not cost-effective according to the CDA rate and misoprostol was either a cost-effective or a dominant strategy according to the VD24. CONCLUSION: Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals as the price is lower and it is easier to use. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01765881. URL: https://clinicaltrials.gov/ct2/show/NCT01765881. ClinicalTrialRegistrer.eu: 2011-000933-35. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000933-35/FR.

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.

Planned delivery route and outcomes of cephalic singletons born spontaneously at 24-31 weeks' gestation: The EPIPAGE-2 cohort study.

INTRODUCTION: The objective of this study was to investigate the association between planned mode of delivery and neonatal outcomes with spontaneous very preterm birth among singletons in cephalic presentation. MATERIAL AND METHODS: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national, prospective, population-based cohort study of preterm infants. For this study, we included women with a singleton cephalic pregnancy and spontaneous preterm labor or preterm premature rupture of membranes at 24-31 weeks' gestation. The main exposure was the planned mode of delivery (ie planned vaginal delivery or planned cesarean delivery at the initiation of labor). The primary outcome was survival at discharge and secondary outcome survival at discharge without severe morbidity. Propensity scores were used to minimize indication bias in estimating the association. RESULTS: The study population consisted of 1008 women: 206 (20.4%) had planned cesarean delivery and 802 (79.6%) planned vaginal delivery. In all, 723 (90.2%) finally had a vaginal delivery. Overall, 187 (92.0%) and 681 (87.0%) neonates in the planned cesarean delivery and planned vaginal delivery groups were discharged alive, and 156 (77.6%) and 590 (76.3%) were discharged alive without severe morbidity. After matching on propensity score, planned cesarean delivery was not associated with survival (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 0.48-2.28) or survival without severe morbidity (aOR 0.64, 95% CI 0.36-1.16). CONCLUSIONS: Planned cesarean delivery for cephalic presentation at 24-31 weeks' gestation after preterm labor or preterm premature rupture of membranes does not improve neonatal outcomes.

Risk factors for obstetric anal sphincter injuries (OASIS) and the role of episiotomy: A retrospective series of 496 cases.

OBJECTIVE: The objective of this study was to determine the prevalence and identify risk factors for obstetric anal sphincter injuries (OASIS), and to determine the prevalence of episiotomy and whether it is protective for the posterior perineum. STUDY DESIGN: This is a retrospective case-control study carried out in a level 2 maternity unit and a level 3 maternity unit between 1 January 2006 and 31 December 2015. The sample population included all vaginal deliveries at term of a living singleton foetus in cephalic presentation. The case group comprised patients with an OASIS. The control group comprised patients without OASIS. Statistical analysis was subdivided into descriptive and inferential parts. RESULTS: 42,626 patients were included in the study of whom 496 were cases of OASIS, i.e. a rate of 1.2%. The overall episiotomy rate was 10.0%, which reflects a restrictive practice. Episiotomy doesn't appear to be a statistically significant protective factor for OASIS (OR=0.89-95%CI [0.68-1.16]). The principal independent risk factors for OASIS were nulliparity (ORa=4.19-95%CI [3.03-5.84] - p<0.001), previous caesarean (ORa=5.59-95%CI [3.68-8.44] - p<0.001), uterine fundal height greater than 32cm (ORa=1.35-95%CI [1.03-1.77] - p=0.03), gestational or pre-pregnancy diabetes (ORa=1.76-95%CI [1.22-2.46] - p=0.002), birthweight of more than 3500g (ORa=1.48-95%CI [1.17-1.87] - p=0.001), assisted delivery (ORa=1.81-95%CI [1.18-2.86] - p=0.007), and use of a second instrument or obstetrical manoeuvre (ORa=1.93-95%CI [1.05-3.30] - p=0.02). CONCLUSION: Episiotomy doesn't appear to be a statistically significant protective factor on the perineal prognosis. A deeper understanding of the factors which promote OASIS and greater awareness of them would improve the perineal prognosis of parturient women.

Elective abortion: Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF).

The number of elective abortions has been stable for several decades. Many factors explain women's choice of abortion in cases of unplanned pregnancies. Early initiation of contraceptive use and a choice of contraceptive choices appropriate to the woman's life are associated with lower rates of unplanned pregnancies. Reversible long-acting contraceptives should be favored as first-line methods for adolescents because of their effectiveness (grade C). Ultrasound scan before an elective abortion must be encouraged but should not be obligatory (professional consensus). As soon as the embryo appears on the ultrasound scan, the date of pregnancy is estimated by measuring the crown-rump length (CRL) or, from 11 weeks on, by measuring the biparietal diameter (BPD) (grade A). Because reliability of these parameters is ±5 days, the abortion may be done if measurements are respectively less than 90 mm for CRL and less than 30 mm for BPD (professional consensus). A medically induced abortion, performed with a dose of 200 mg mifepristone combined with misoprostol, is effective at any gestational age (Level of Evidence (LE) 1). Before 7 weeks, mifepristone should be followed 24-48 h later by misoprostol, administered orally, buccally, sublingually, or even vaginally followed if needed by a further dose of 400 µg after 3 h, to be renewed if needed after 3 h (LE 1, grade A). After 7 weeks, administration of misoprostol by the vaginal, sublingual, or buccal routes is more effective and better tolerated than by the oral route (LE 1). Cervical preparation is recommended for systematic use in surgical abortions (professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 µg (grade A). Vacuum aspiration is preferable to curettage (grade B). A uterus perforated during surgical aspiration should not routinely be considered to be scarred (professional consensus). An elective abortion is not associated with a higher risk of subsequent infertility or ectopic pregnancy (LE 2). The medical consultation before an elective abortion generally does not affect the decision to end or continue the pregnancy, and most women are sufficiently certain about their choice at this time. Women appear to find the method used most acceptable and to be most satisfied when they were able to choose the method (grade B). Elective abortions are not associated with an increased rate of psychiatric disorders (LE 2). However, women with psychiatric histories are at a higher risk of psychological disorders after the occurrence of an unplanned pregnancy than women with such a history (LE 2). For surgical abortions, combined hormonal contraceptives - oral or transdermal - should be started on the day of the abortion, while the vaginal ring should be inserted 5 days afterwards (grade B). For medical abortions, the vaginal ring should be inserted in the week after mifepristone administration, while the combined contraceptives should begin the same day as the misoprostol or the day after (grade C). Contraceptive implants should be inserted on the same day as a surgical abortion, and may be inserted the day the mifepristone is administered for medical abortions (grade B and C respectively). In case of medical abortion, the implant can be inserted the same day the mifepristone is administered (grade C). Both the copper IUDs and levonorgestrel intrauterine system should be inserted on the day of the surgical abortion (grade A). After medical abortions, an IUD can be inserted in 10 days after mifepristone administration, after ultrasound scan verification of the absence of an intrauterine pregnancy (grade C).

Usefulness of diffusion-weighted imaging for diagnosis of adrenal ischemia during pregnancy: a preliminary report.

This case report aims to illustrate the clinical usefulness of diffusion-weighted imaging for diagnosis of bilateral adrenal ischemia during pregnancy. We also provide a retrospective analysis of adrenal gland diffusion data in a control group of 12 pregnant women with no adrenal dysfunction, to assess the normal range of apparent diffusion coefficient of adrenal gland during pregnancy.

Pilot randomised controlled trial comparing the risk of neonatal respiratory distress in elective caesarean section at 38 weeks' gestation following a course of corticosteroids versus caesarean at 39 weeks.

INTRODUCTION: The objective of this study was to compare neonatal respiratory morbidity and rate of emergency caesarean section between elective caesarean sections at 38 gestational weeks following a course of corticosteroids and planned caesarean sections at 39 gestational weeks. MATERIAL AND METHODS: This was a multicentre randomised controlled trial. The study was conducted between 2007 and 2013 in level 2 and 3 maternity units in France. A total of 208 women with an indication for elective caesarean section were enrolled and 200 analysed in per-protocol analysis. Women were randomised to either elective caesarean section at 38 gestational weeks after a course of corticosteroids (trial group) or elective caesarean section at 39 weeks (control group). The primary outcome was the rate of admission to the neonatal intensive care unit for respiratory distress. RESULTS: Two (2.1%) newborn in the tested group were admitted because of respiratory distress versus four (3.8%) in the control group. The relative risk was 0.54 in favour of the corticosteroid group (95% CI: 0.10; 2.86). There were fewer emergency caesareans in the trial group than in the control group: 12 (12.69%) versus 28 (26.67%), p=0.01. CONCLUSIONS: Our study suggests that planning caesarean sections at 38 gestational weeks after a course of corticosteroids would enable a significant reduction in the number of emergency caesareans without increasing the risk of neonatal respiratory distress. Limitations of this study include difficulties in patient recruitment and the small number of subjects.

Predicting the difficulty of operative vaginal delivery by ultrasound measurement of fetal head station.

BACKGROUND: Clinical assessment of fetal head station is difficult and subjective; it is mandatory before attempting operative vaginal delivery. OBJECTIVE: The principal objective of our study was to assess whether measurement of the perineum-to-skull ultrasound distance was predictive of a difficult operative vaginal delivery. Secondary objectives included evaluation of the interobserver reproducibility of perineum-to-skull ultrasound distance and comparison of this measurement and digital examination in predicting a difficult operative delivery. STUDY DESIGN: This was a prospective cohort study including all cases of operative vaginal deliveries in singleton pregnancies in cephalic presentation >34 weeks' gestation, from 2012 through 2015. All data were entered prospectively in a medical record system specially devised to meet the requirements of this study. RESULTS: Of the 659 patients in whom perineum-to-skull ultrasound distance was measured prior to operative vaginal delivery, 120 (18%) met the composite criterion for a difficult extraction. Perineum-to-skull ultrasound distance measurement of ≥40 mm was significantly associated with the occurrence of a difficult extraction based on the composite criterion, after adjustment for parity, presentation type, and fetal macrosomia (odds ratio, 2.38; 95% confidence interval, 1.51-3.74; P = .0002). The intraclass correlation coefficient between the perineum-to-skull ultrasound distance measured by the first operator and that measured by the second operator was 0.96 (95% confidence interval, 0.95-0.97; P < .0001). Based on the receiver operating characteristic curve analyses, perineum-to-skull ultrasound distance was a more accurate predictor of difficult operative delivery than digital vaginal examination (P = .036). CONCLUSION: Measurement of the perineum-fetal skull ultrasound distance is a reproducible and predictive index of the difficulty of instrumental extraction. Ultrasound is a useful supplementary tool to the usual clinical findings.

A comparison of vaginal ultrasound and digital examination in predicting preterm delivery in women with threatened preterm labor: a cohort study.

INTRODUCTION: The aim of this study is to evaluate the utility of digital examination in addition to ultrasonic measurement of cervical length for predicting spontaneous preterm delivery in women with threatened preterm labor. MATERIAL AND METHODS: This was a prospective cohort study in Strasbourg University Hospital, France, between January 2013 and January 2015. All women with a singleton pregnancy hospitalized with threatened preterm labor between 23 and 34 weeks of gestation were included. Cases of iatrogenic preterm delivery were excluded. A multivariable logistic regression model to estimate the significant predictive parameters of spontaneous preterm delivery was performed. The primary endpoint of our study was a preterm birth before 34 weeks of gestation. RESULTS: A total of 395 women were included in our study. The rate of preterm delivery before 34 weeks was 13%. In univariate analysis every single cervical parameter assessed by the digital examination and all the ultrasound parameters were significantly associated with preterm delivery. The final model included five variables predicting preterm birth: visualization of the membranes at the speculum examination (OR 15.8, 95% CI 2.43-146), ultrasound cervical length (OR 0.82, 95% CI 0.75-0.89), signs of inflammation (OR 6.23, 95% CI 2.07-22.9), gestational age on admission (OR 0.84, 95% CI 0.71-1.0), and presence of vaginal infection (OR 4.28, 95% CI 1.52-12.7). None of the cervical parameters assessed by the digital examination provided additional predictive value of preterm delivery. CONCLUSION: Our study suggests that digital examination does not add to the information given by vaginal ultrasound evaluation in predicting preterm labor.

Evaluation of long-term neurodevelopment in twin-twin transfusion syndrome after laser therapy.

OBJECTIVE: The primary objective of our study was to evaluate the long-term neurodevelopment outcome after laser surgery for twin-twin transfusion syndrome (TTTS). The secondary objective was to identify perinatal prognostic factors associated with neurodevelopmental impairment. METHOD: This was a single-center cohort prospective study carried out in pregnancies complicated by TTTS and treated by laser. Neurodevleopmental assesment included the administration of Ages and Stages Questionnaires® (ASQ), for the infants between 2 and 5 years of age. RESULTS: A total of 187 patients underwent a laser for TTTS between 2004 and 2013. Significant brain lesions were detected in eight (2.9%) cases by ultrasound and/or magnetic resonance imaging including intraventricular hemorrhage, periventricular leukomalacia, and porencephaly. Questionnaires were administered to 126 children (50.4%) at 24 months or older at the moment of testing. There were 13.5% of those infants who had an abnormal ASQ (established as one area or more scoring < 2 SD) at 3.6 years ±1.3 follow-up. There was a higher rate of abnormal ASQ among the infants with a birth weight below the fifth percentile (p = 0.036). CONCLUSION: Twin-twin transfusion syndrome is associated with a risk of abnormal neurological development, even in case of laser surgery. Further studies are necessary to identify the risk factors for neurological impairment. © 2016 John Wiley & Sons, Ltd.