Child outcomes after induction of labour or expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks of gestation: study protocol of the PPROMEXIL Follow-up trial. A long-term follow-up study of the randomised controlled trials PPROMEXIL and PPROMEXIL-2.

INTRODUCTION: Late preterm prelabour rupture of membranes (PROM between 34+0 and 36+6 weeks gestational age) is an important clinical dilemma. Previously, two large Dutch randomised controlled trials (RCTs) compared induction of labour (IoL) to expectant management (EM). Both trials showed that early delivery does not reduce the risk of neonatal sepsis as compared with EM, although prematurity-related risks might increase. An extensive, structured long-term follow-up of these children has never been performed. METHODS AND ANALYSIS: The PPROMEXIL Follow-up trial (NL6623 (NTR6953)) aims to assess long-term childhood outcomes of the PPROMEXIL (ISRCTN29313500) and PPROMEXIL-2 trial (ISRCTN05689407), two multicentre RCTs using the same protocol, conducted between 2007 and 2010 evaluating IoL versus EM in women with late preterm PROM. The PPROMEXIL Follow-up will analyse children of mothers with a singleton pregnancy (PPROMEXIL trial n=520, PPROMEXIL-2 trial n=191, total IoL n=359; total EM n=352). At 10-12 years of age all surviving children will be invited for a neurodevelopmental assessment using the Wechsler Intelligence Scale for Children-V, Color-Word Interference Test and the Movement Assessment Battery for Children-2. Parents will be asked to fill out questionnaires assessing behaviour, motor function, sensory processing, respiratory problems, general health and need for healthcare services. Teachers will fill out the Teacher Report Form and answer questions regarding school attainment. For all tests means with SDs will be compared, as well as predefined cut-off scores for abnormal outcome. Sensitivity analyses consisting of different imputation techniques will be used to deal with lost to follow-up. ETHICS AND DISSEMINATION: The study has been granted approval by the Medical Centre Amsterdam (MEC) of the AmsterdamUMC (MEC2016_217). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders. This protocol is published before analysis of the results. TRIAL REGISTRATION NUMBER: NL6623 (NTR6953).

Does vaginal breech delivery have a future despite low volumes for training? Results of a questionnaire.

OBJECTIVE: Since publication of the Term Breech Trial in 2000 only 15% of term breech presentations is delivered vaginally in the Netherlands. This declined exposure to vaginal breech deliveries (VBD) is a problem for those who still need to be trained. The aim of this study was to evaluate the level of training of the Dutch gynecological residents, and their intentions on guiding VBDs during their careers. STUDY DESIGN: Via an online questionnaire Dutch residents and starting gynecologists, were asked about their training, exposure and confidence in guiding VBDs during their residency. MAIN OUTCOME MEASURES: Number of VBDs performed, level of entrustment of independent practice in guiding VBDs, courses in guiding VBDs, confidence in guiding VBDs after finishing their residency. RESULTS: The response rate was 64% (N = 294). Thirteen per cent performed less than three VBDs, 15% more than 15. Of sixth year residents 65% has not yet obtained entrustment for personally guiding VBDs. The residents are trained in VBDs at least once during a national mandatory course. Further training is strongly dependent on local hospital policy: 34% are trained every quarter versus 29% who never receive a local training. CONCLUSION: Our survey showed that more than half of the respondents judge the current residency program to be insufficient for guiding VBDs. This seems to be related to the low overall exposure to VBDs and the lack of quantity and quality of attended courses.

Development and internal validation of a clinical prediction model for external cephalic version.

OBJECTIVE: To develop a prediction model for the chance of successful external cephalic version (ECV). STUDY DESIGN: This is a secondary analysis of a multicenter, open-label randomized controlled trial that assessed the effectiveness of atosiban compared to fenoterol as uterine relaxant during ECV in women with a singleton fetus in breech presentation with a gestational age of 36 weeks or more. Potential predictors included maternal, pregnancy, fetal, and treatment characteristics and were recorded in all participants. Multivariable logistic regression analysis with a stepwise backward selection procedure was used to construct a prediction model for the occurrence of successful ECV. Model performance was assessed using calibration and discrimination. RESULTS: We included a total of 818 women with an overall ECV success rate of 37%. Ten predictive factors were identified with the stepwise selection procedure to be associated with a successful ECV: fenoterol as uterine relaxant, nulliparity, Caucasian ethnicity, gestational age at ECV, Amniotic Fluid Index, type of breech presentation, placental location, breech engagement, possibility to palpate the head and relaxation of the uterus. Our model showed good calibration and a good discriminative ability with a c-statistic of 0.78 (95% CI 0.75 to 0.81). CONCLUSION: Prediction of success of ECV seems feasible with a model showing good performance. This can be used in clinical practice after external validation.

Atosiban versus fenoterol as a uterine relaxant for external cephalic version: randomised controlled trial.

OBJECTIVE:  To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation. DESIGN:  Multicentre, open label, randomised controlled trial. SETTING:  Eight hospitals in the Netherlands, August 2009 to May 2014. PARTICIPANTS:  830 women with a singleton fetus in breech presentation and a gestational age of more than 34 weeks were randomly allocated in a 1:1 ratio to either 6.75 mg atosiban (n=416) or 40 µg fenoterol (n=414) intravenously for uterine relaxation before ECV. MAIN OUTCOME MEASURES:  The primary outcome measures were a fetus in cephalic position 30 minutes after the procedure and cephalic presentation at delivery. Secondary outcome measures were mode of delivery, incidence of fetal and maternal complications, and drug related adverse events. All analyses were done on an intention-to-treat basis. RESULTS:  Cephalic position 30 minutes after ECV occurred significantly less in the atosiban group than in the fenoterol group (34% v 40%, relative risk 0.73, 95% confidence interval 0.55 to 0.93). Presentation at birth was cephalic in 35% (n=139) of the atosiban group and 40% (n=166) of the fenoterol group (0.86, 0.72 to 1.03), and caesarean delivery was performed in 60% (n=240) of women in the atosiban group and 55% (n=218) in the fenoterol group (1.09, 0.96 to 1.20). No significant differences were found in neonatal outcomes or drug related adverse events. CONCLUSIONS:  In women undergoing ECV for breech presentation, uterine relaxation with fenoterol increases the rate of cephalic presentation 30 minutes after the procedure. No statistically significant difference was found for cephalic presentation at delivery. TRIAL REGISTRATION:  Dutch Trial Register, NTR 1877.

Risk factors for cesarean section and instrumental vaginal delivery after successful external cephalic version.

Aim of this article is to examine if we could identify factors that predict cesarean section and instrumental vaginal delivery in women who had a successful external cephalic version. We used data from a previous randomized trial among 25 hospitals and their referring midwife practices in the Netherlands. With the data of this trial, we performed a cohort study among women attempting vaginal delivery after successful ECV. We evaluated whether maternal age, gestational age, parity, time interval between ECV and delivery, birth weight, neonatal gender, and induction of labor were predictive for a vaginal delivery on one hand or a CS or instrumental vaginal delivery on the other hand. Unadjusted and adjusted odds ratios were calculated with univariate and multivariate logistic regression analysis. Among 301 women who attempted vaginal delivery after a successful external cephalic version attempt, the cesarean section rate was 13% and the instrumental vaginal delivery rate 6%, resulting in a combined instrumental delivery rate of 19%. Nulliparity increased the risk of cesarean section (OR 2.7 (95% CI 1.2-6.1)) and instrumental delivery (OR 4.2 (95% CI 2.1-8.6)). Maternal age, gestational age at delivery, time interval between external cephalic version and delivery, birth weight and neonatal gender did not contribute to the prediction of failed spontaneous vaginal delivery. In our cohort of 301 women with a successful external cephalic version, nulliparity was the only one of seven factors that predicted the risk for cesarean section and instrumental vaginal delivery.

Preterm Breech Presentation: A Comparison of Intended Vaginal and Intended Cesarean Delivery.

OBJECTIVE: To study the association of the intended mode of delivery and perinatal morbidity and mortality among breech fetuses who are delivered preterm. METHODS: We conducted a nationwide cohort study of women with a singleton pregnancy in breech presentation who delivered preterm (26 0/7-36 6/7 weeks of gestation) in the years 2000-2011. We compared perinatal outcomes according to the intended and actual mode of delivery using multivariate logistic regression analysis. We performed subgroup analyses of gestational age and parity. RESULTS: We studied 8,356 women with a preterm singleton breech delivery. Intended cesarean delivery (n=1,935) was not associated with a significant reduction in perinatal mortality compared with intended vaginal delivery (n=6,421) (1.3% compared with 1.5%; adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.60-1.57). However, the composite of perinatal mortality and morbidity was significantly reduced in the intended cesarean delivery group (8.7% compared with 10.4%; adjusted OR 0.77, 95% CI 0.63-0.93). In the subgroup of women delivering at 28-32 weeks of gestation, intended cesarean delivery was associated with a 1.7% risk of perinatal mortality compared with 4.1% with intended vaginal delivery (adjusted OR 0.27, 95% CI 0.10-0.77) and significantly reduced composite mortality and severe morbidity, 5.9% compared with 10.1% (adjusted OR 0.37, 95% CI 0.20-0.68). CONCLUSION: In women delivering a preterm breech fetus, cesarean delivery is associated with reduced perinatal mortality and morbidity. LEVEL OF EVIDENCE: II.

Implementation of client versus care-provider strategies to improve external cephalic version rates: a cluster randomized controlled trial.

OBJECTIVE: To determine the effectiveness of a client or care-provider strategy to improve the implementation of external cephalic version. DESIGN: Cluster randomized controlled trial. SETTING: Twenty-five clusters; hospitals and their referring midwifery practices randomly selected in the Netherlands. POPULATION: Singleton breech presentation from 32 weeks of gestation onwards. METHODS: We randomized clusters to a client strategy (written information leaflets and decision aid), a care-provider strategy (1-day counseling course focused on knowledge and counseling skills), a combined client and care-provider strategy and care-as-usual strategy. We performed an intention-to-treat analysis. MAIN OUTCOME MEASURES: Rate of external cephalic version in various strategies. Secondary outcomes were the percentage of women counseled and opting for a version attempt. RESULTS: The overall implementation rate of external cephalic version was 72% (1169 of 1613 eligible clients) with a range between clusters of 8-95%. Neither the client strategy (OR 0.8, 95% CI 0.4-1.5) nor the care-provider strategy (OR 1.2, 95% CI 0.6-2.3) showed significant improvements. Results were comparable when we limited the analysis to those women who were actually offered intervention (OR 0.6, 95% CI 0.3-1.4 and OR 2.0, 95% CI 0.7-4.5). CONCLUSIONS: Neither a client nor a care-provider strategy improved the external cephalic version implementation rate for breech presentation, neither with regard to the number of version attempts offered nor the number of women accepting the procedure.

Implementation of external cephalic version in the Netherlands: a retrospective cohort study.

BACKGROUND: External cephalic version (ECV) reduces the rate of elective cesarean sections as a result of breech presentation. Several studies have shown that not all eligible women undergo an ECV attempt. The aim of this study was to evaluate the implementation of ECV in the Netherlands and to explain variation in implementation rates with hospital characteristics and individual factors. METHODS: We invited 40 hospitals to participate in this retrospective cohort study. We reviewed hospital charts for all singleton breech deliveries from 36 weeks' gestation and onwards between January 2008 and December 2009. We documented whether an ECV attempt was performed, reasons for not performing an attempt, mode of delivery, and hospital characteristics. RESULTS: We included 4,770 women from 36 hospitals. ECV was performed in 2,443 women (62.2% of eligible women, range 8.2-83.6% in different hospitals). Implementation rates were higher in teaching hospitals, hospitals with special office hours for ECV, larger obstetric units, and hospitals located in larger cities. Suboptimal implementation was mainly caused by health care providers who did not offer ECV. CONCLUSION: ECV implementation rates vary widely among hospitals. Suboptimal implementation is mostly caused by the care provider not offering the treatment and secondly due to women not opting for the offered attempt. A prerequisite for designing a proper implementation strategy is a detailed understanding of the exact reasons for not offering and not opting for ECV.

Term breech deliveries in the Netherlands: did the increased cesarean rate affect neonatal outcome? A population-based cohort study.

OBJECTIVE: The aim of this study was to evaluate the effect of the increased cesarean rate for term breech presentation on neonatal outcome. We also investigated whether the clinical case selection for vaginal delivery applied by Dutch obstetricians led to an optimization of neonatal outcome, or whether there is still room for improvement in terms of perinatal outcome. DESIGN: Retrospective cohort. SETTING: The Netherlands. POPULATION: Singleton term breech deliveries from 37+0 to 41+6 weeks, excluding fetuses with congenital malformations or antenatal death. METHOD: We used data from the Dutch national perinatal registry from 1999 up to 2007. MAIN OUTCOME MEASURES: Perinatal mortality and morbidity. RESULTS: We studied 58,320 women with a term breech delivery. There was an increase in the elective cesarean rate (from 24 to 60%). As a consequence, overall perinatal mortality decreased [1.3 0/00 vs. 0.7 0/00;odds ratio 0.51 (95% confidence interval 0.28­0.93)], whereas it remained stable in the planned vaginal birth group [1.7 0/00 vs. 1.6 0/00; odds ratio 0.96(95% confidence interval 0.52­1.76)]. The number of cesareans done to prevent one perinatal death was 338. CONCLUSIONS: Adjustment of the national guidelines after publication of the Term Breech Trial resulted in a shift towards elective cesarean and a decrease of perinatal mortality and morbidity among women delivering a child in breech at term. Still, 40% of these women attempt vaginal birth. The relative safety of an elective cesarean should be weighed against the consequences of a scarred uterus in future pregnancies.

Facilitators and barriers to external cephalic version for breech presentation at term among health care providers in the Netherlands: a quantitative analysis.

OBJECTIVE: guidelines recommend that external cephalic version (ECV) should be offered to all women with a fetus in breech presentation at term. However, only 50-60% of the women receive an ECV attempt. We explored the determinants (barriers and facilitators) affecting the uptake of the guidelines among gynaecologists and midwives in the Netherlands. DESIGN: national online survey. SETTING: the Netherlands. PARTICIPANTS: gynaecologists and midwives. MEASUREMENTS: in the online survey, we identified the determinants that positively or negatively influenced the professionals׳ adherence to three key recommendations in the guidelines: (a) counselling, (b) advising for ECV, (c) arranging an ECV. Determinants were identified in a previously performed qualitative study and were categorised into five underlying constructs; attitude towards ECV, professional obligation, outcome expectations, self-efficacy and preconditions for successful ECV. We performed a multivariate analysis to assess the importance of the different constructs for adherence to the guideline. FINDINGS: 364 professionals responded to the survey. Adherence varied: 84% counselled, 73% advised, and 82% arranged an ECV for (almost) all their clients. Although 90% of respondents considered ECV to be an effective treatment for preventing caesarean childbirths, only 30% agreed that 'every client should undergo ECV'. Self-efficacy (perceived skills) was the most important determinant influencing adherence. KEY CONCLUSIONS: self-efficacy appears to be the most significant determinant for counselling, advising and arranging an ECV. IMPLICATIONS FOR PRACTICE: to improve adherence to the guidelines on ECV we must improve self-efficacy.

Patient's willingness to opt for external cephalic version.

OBJECTIVE: External cephalic version (ECV) is a relatively simple and safe maneuver that reduces the cesarean section (CS) rate for breech presentation. There is professional consensus that ECV should be offered to all women, but only up to 70% of patients opt for this treatment. To improve counseling, we investigated the value patients place on various aspects of ECV. METHODS: We studied patient preferences by means of a vignette study. Varying levels of treatment characteristics were investigated in 16 scenarios, all including the "opt out" alternative of an elective CS. The probability that women preferred ECV was estimated using a logistic regression approach. RESULTS: Forty seven women participated in the study. Pain was the most important factor negatively influencing the willingness to opt for ECV (OR 0.11 (95% confidence interval (CI) 0.05-0.23) for a pain score of 8-10 compared to 1-2 on a visual analog scale of 0-10). Higher success rates of vaginal delivery after successful ECV increased women's willingness (OR 3.42 (95% CI 2.04-5.74), if chance of vaginal delivery after successful ECV increased from 24% to 52%). The risk of an emergency CS during ECV did not influence the willingness to opt for ECV (OR 0.83 (95% CI 0.59-1.18) of chance increased from 0% to 1%). CONCLUSIONS: We conclude that expected pain during treatment and the success rate are the most important factors influencing the willingness to undergo ECV. Taking this information into account when counseling for ECV and reassuring women that unbearable pain is always a reason to stop ECV, and that the vast majority of women reported that the experienced pain is bearable, might improve the uptake of ECV and decrease the number of CS due to breech presentation.

Contraindications for external cephalic version in breech position at term: a systematic review.

OBJECTIVE: External cephalic version (ECV) is a safe and effective intervention that can prevent breech delivery, thus reducing the need for cesarean delivery. It is recommended in national guidelines. These guidelines also mention contraindications for ECV, and thereby restrict the application of ECV. We assessed whether the formulation of these contraindications in guidelines are based on empiric data. DESIGN: Systematic review. POPULATION: Pregnant women with a singleton breech presentation from 34 weeks. METHODS: We searched the National Guideline Clearinghouse, the Cochrane Central Register of Controlled Trials, MEDLINE (1953-2009), EMBASE (1980-2009), TRIP database (until 2011), NHS (National Health Services, until 2011), Diseases database (until 2011) and NICE guidelines (until 2011) for existing guidelines on ECV and studied the reproducibility of the contraindications stated in the guidelines. Furthermore, we systematically reviewed the literature for contraindications and evidence on these contraindications. MAIN OUTCOME MEASURES: Contraindications of ECV. RESULTS: We found five guidelines mentioning 18 contraindications, varying from five to 13 per guideline. The contraindications were not reproducible between the guidelines with oligohydramnios as the only contraindication mentioned in all guidelines. The literature search yielded 60 studies reporting on 39 different contraindications, of which we could only assess evidence of six of them. CONCLUSION: The present study shows that there is no general consensus on the eligibility of patients for ECV. Therefore we propose to limit contraindications for ECV to clear empirical evidence or to those with a clear pathophysiological relevance.

External validation of a prediction model for successful external cephalic version.

We sought external validation of a prediction model for the probability of a successful external cephalic version (ECV). We evaluated the performance of the prediction model with calibration and discrimination. For clinical practice, we developed a score chart to calculate the probability of a successful ECV. We studied 320 women undergoing ECV, of which 117 (37%) were successful. The model underestimated the success rate by 4 to 14%. The area under the receiver operating characteristic curve was moderate (0.66; 95% confidence interval: 0.60 to 0.72), but the model was able to make good distinction between women with a higher predicted probability of a successful ECV (more than 50%) compared with women with a lower predicted probability of a successful ECV (less than 20%). Our model to predict the outcome of ECV holds in external validation. It can be used to support patient counseling and decision making for ECV in singleton term breech presentations.

Implementation of the external cephalic version in breech delivery. Dutch national implementation study of external cephalic version.

BACKGROUND: Breech presentation occurs in 3 to 4% of all term pregnancies. External cephalic version (ECV) is proven effective to prevent vaginal breech deliveries and therefore it is recommended by clinical guidelines of the Royal Dutch Organisation for Midwives (KNOV) and the Dutch Society for Obstetrics and Gynaecology (NVOG). Implementation of ECV does not exceed 50 to 60% and probably less.We aim to improve the implementation of ECV to decrease maternal and neonatal morbidity and mortality due to breech presentations. This will be done by defining barriers and facilitators of implementation of ECV in the Netherlands. An innovative implementation strategy will be developed based on improved patient counselling and thorough instructions of health care providers for counselling. METHOD/DESIGN: The ultimate purpose of this implementation study is to improve counselling of pregnant women and information of clinicians to realize a better implementation of ECV.The first phase of the project is to detect the barriers and facilitators of ECV. The next step is to develop an implementation strategy to inform and counsel pregnant women with a breech presentation, and to inform and educate care providers. In the third phase, the effectiveness of the developed implementation strategy will be evaluated in a randomised trial. The study population is a random selection of midwives and gynaecologists from 60 to 100 hospitals and practices. Primary endpoints are number of counselled women. Secondary endpoints are process indicators, the amount of fetes in cephalic presentation at birth, complications due to ECV, the number of caesarean sections and perinatal condition of mother and child. Cost effectiveness of the implementation strategy will be measured. DISCUSSION: This study will provide evidence for the cost effectiveness of a structural implementation of external cephalic versions to reduce the number of breech presentations at term. TRIAL REGISTRATION: Dutch Trial Register (NTR): 1878.

The cost-effectiveness of drug-eluting stents: a systematic review.

BACKGROUND: Drug-eluting stents have been seen as an attractive alternative to bare-metal stents for percutaneous coronary interventions (PCIs) because of the decreased need for revascularization. However, comparative clinical trials have shown no difference in patient outcomes, and drug-eluting stents are considerably more expensive than their bare-metal counterparts. We conducted a systematic review of all published comparative cost-effectiveness analyses to identify the factors contributing to the heterogeneity of their conclusions. METHODS: We retrieved all articles published between Jan. 1, 2000, and July 31, 2006, in which the cost-effectiveness, from a third-party payer perspective, of drug-eluting stents was compared with that of bare-metal stents for PCI in unrestricted patient populations. Electronic databases, Web sites from health technology assessment groups and references of identified articles were searched. Our outcome variable was whether the study's conclusions favoured widespread use of drug-eluting stents, as assessed by 4 independent reviewers. Study characteristics such as quality, funding source, country and year of publication were extracted. Two-by-2 tables and Fisher's exact test were used to study the association between covariates and the outcome variable. A classification and regression tree (CART) model was used for multivariate analysis. RESULTS: We identified 19 cost-effectiveness analyses. Ten were in favour of widespread use of drug-eluting stents, and 9 favoured more restrained use. Only 1 of 9 high-quality studies supported widespread use, as compared with 9 of 10 lower quality studies (p < 0.001). All of the 7 sponsored studies argued in favour of widespread use, as compared with 3 of the 12 studies without sponsorship (p = 0.003). Studies from the United States were more likely than those from other countries to endorse unlimited use (p = 0.032). A CART model with 2 covariates--study quality and sponsorship--provided the best fit (error rate 10.5%). INTERPRETATION: Conclusions drawn by cost-effectiveness analyses of drug-eluting stents for PCI are associated with the study's quality, funding source and country of origin. Vigilance regarding these study characteristics is required when interpreting findings from cost-effectiveness analyses.