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Objective: Induction of labor (IOL) is one of the most widely used obstetric interventions. However, one-fifth of IOLs result in Cesarean section (CS). We aimed to assess maternal and fetal characteristics that influence the likelihood of CS following IOL, according to the indication for CS. Methods: This was a secondary analysis of pooled data from four randomized controlled trials, including women undergoing IOL at term who had a singleton pregnancy and an unfavorable cervix, intact membranes and the fetus in cephalic presentation. The main outcomes of this analysis were CS for failure to progress (FTP) and CS for suspected fetal compromise (SFC). Restricted cubic splines were used to determine whether continuous maternal and fetal characteristics had a non-linear relationship with outcome. Optimal cut-offs for those characteristics with a non-linear pattern were determined based on the maximum area under the receiver-operating-characteristics curve. Adjusted odds ratios (aOR) were computed, using multivariable logistic regression analysis, for the associations between optimally categorized characteristics and outcome. Results: Of a total of 2990 women undergoing IOL, 313 (10.5%) had CS for FTP and 227 (7.6%) had CS for SFC. The risk of CS for FTP was increased in women aged 31–35 years compared with younger women (aOR, 1.51 (95% CI, 1.15–1.99)), in nulliparous compared with parous women (aOR, 8.07 (95% CI, 5.34–12.18)) and in Sub-Saharan African compared with Caucasian women (aOR, 2.09 (95% CI, 1.33–3.28)). Higher body mass index (BMI) increased incrementally the risk of CS for FTP (aOR, 1.06 (95% CI, 1.04–1.08)). High birth-weight percentile was also associated with an increased risk of CS due to FTP (aOR, 2.66 (95% CI, 1.74–4.07) for birth weight between the 80.0th and 89.9th percentiles and aOR, 4.08 (95% CI, 2.75–6.05) for birth weight ≥ 90th percentile, as compared with birth weight between the 20.0th and 49.9th percentiles). For CS due to SFC, higher maternal age (aOR, 1.09 (95% CI, 1.05–1.12)) and BMI (aOR, 1.05 (95% CI, 1.03–1.08)) were associated with an incremental increase in risk. The risk of CS for SFC was increased in nulliparous compared with parous women (aOR, 5.91 (95% CI, 3.76–9.28)) and in South Asian compared with Caucasian women (aOR, 2.50 (95% CI, 1.23–5.10)). Birth weight < 10.0th percentile increased significantly the risk of CS due to SFC (aOR, 1.93 (95% CI, 1.22–3.05)), as compared with birth weight between the 20.0th and 49.9th percentiles. Bishop score did not demonstrate a significant association with the risk of CS for FTP or for SFC. Conclusions: In women undergoing IOL, maternal age, BMI, parity, ethnicity and birth-weight percentile are predictors of CS due to FTP and of CS due to SFC, but the direction and magnitude of the associations differ according to the indication for CS. These characteristics should be considered in combination with the Bishop score to stratify the risk of CS for different indications in women undergoing IOL.

The ProTWIN Trial (NTR1858) showed that, in women with a multiple pregnancy and a cervical length 25(th) percentile (38 mm), prophylactic use of a cervical pessary reduced the risk of adverse perinatal outcome. We investigated whether other maternal or pregnancy characteristics collected at baseline can improve identification of women most likely to benefit from pessary placement.ProTWIN is a multicenter randomized trial in which 808 women with a multiple pregnancy were assigned to pessary or control. Using these data we developed a multivariable logistic model comprising treatment, cervical length, chorionicity, pregnancy history and number of fetuses, and the interaction of these variables with treatment as predictors of adverse perinatal outcome.Short cervix, monochorionicity and nulliparity were predictive factors for a benefit from pessary insertion. History of previous preterm birth and triplet pregnancy were predictive factors of possible harm from pessary. The model identified 35% of women as benefiting (95% CI, 32-39%), which is 10% more than using cervical length only (25%) for pessary decisions. The model had acceptable calibration. We estimated that using the model to guide the choice of pessary placement would reduce the risk of adverse perinatal outcome significantly from 13.5% when no pessary is inserted to 8.1% (absolute risk reduction, 5.4% (95% CI, 2.1-8.6%)).We developed and internally validated a multivariable treatment selection model, with cervical length, chorionicity, pregnancy history and number of fetuses. If externally validated, it could be used to identify women with a twin pregnancy who would benefit from a pessary, and lead to a reduction in adverse perinatal outcomes in these women. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section.This was a secondary analysis of two randomized trials conducted in 57 hospitals in The Netherlands. We assessed the univariable association between risk indicators, including second-trimester CL in quartiles, and emergency Cesarean delivery using a logistic regression model. For multivariable analysis, we assessed whether adjustment for other risk indicators altered the associations found in univariable (unadjusted) analysis. Separate analyses were performed for suspected fetal distress and failure to progress in labor as indications for Cesarean section.In total, 311 women with a twin pregnancy attempted vaginal delivery after 34 weeks' gestation. Emergency Cesarean delivery was performed in 111 (36%) women, of which 67 (60%) were performed owing to arrest of labor. There was no relationship between second-trimester CL and Cesarean delivery (adjusted odds ratio (aOR): 0.97 for CL 26(th) -50(th) percentiles; 0.71 for CL 51(st) - 75(th) percentiles; and 0.92 for CL75(th) percentile, using CL ≤ 25(th) percentile as reference). In multivariable analysis, the only variables associated with emergency Cesarean delivery were maternal age (aOR, 1.07 (95% CI, 1.00-1.13)), body mass index (BMI) (aOR, 3.99 (95% CI, 1.07-14.9) for BMI 20-23 kg/m(2) ; 5.04 (95% CI, 1.34-19.03) for BMI 24-28 kg/m(2) ; and 3.1 (95% CI, 0.65-14.78) for BMI28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5)).In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery.

Studies conducted in the first three decades after discovery of a link between venous thromboembolism (VTE) and oral contraceptive (OC) users showed a relative risk of first thrombosis during OC use of 2.9 (95% CI 0.5-17). In recent studies in which the sub-50-mcg ethinyl estradiol-containing pills were investigated comparing current users with non-users the RR is 3.8 for nonfatal deep VTE 2.7 for superficial VTE deep VTE and pulmonary embolism (PE) together and 2.1 for fatal VTE and PE together. The association is attributed to the estrogenic component and not related to duration of pill use. The risk disappears once the pill has been stopped and it is not elevated among past users. Smoking does not appear to be a risk factor for VTE; obesity and varicose veins are at the most weak risk factors. Since a causal relationship between OC use and VTE is tempting clues for unraveling the mechanism were sought in the hemostatic system. Studies of the coagulation system found changes in the activation of coagulation and fibrinolytic compartments but within the normal range. An epidemiologic study showed that the risk of VTE among women using OCs is increased 30-fold by the presence of a mutation of factor V called Factor V Leiden (5% prevalence in the Caucasian population). Selective screening for the mutated factor V should be limited to women with a personal or family history of VTE. Four epidemiologic studies showed a two-fold increase in risk of VTE with the use of OCs containing third-generation progestins (gestodene and desogestrel) relative to second-generation products (levonorgestrel). Biases cannot devaluate the conclusion that the increased risk of VTE in especially first-time and younger users of third-generation OCs is highly likely. The clinical consequence is therefore that second-generation OCs are the first choice in prescription to first-time users. (authors)

Increasingly, maternal administration of 17-α-hydroxyprogesterone caproate (17-OHPC) is utilized to prevent preterm birth, but the fetal safety of 17-OHPC is still a matter of concern. This study aimed to assess whether exposure to 17-OHPC during the second and third trimesters of pregnancy affects fetal biometry in twin gestations.This study included a subset of women with a twin pregnancy who had been previously included in a randomized clinical trial comparing the effectiveness of 17-OHPC and placebo on neonatal outcomes and preterm birth rates in multiple pregnancy. In the present study, the individual growth patterns of femur length, head circumference and abdominal circumference were compared between fetuses of women who had been randomized to receive weekly injections of either 17-OHPC (n = 52) or placebo (n = 58) at between 16-20 and 36 weeks' gestation.The three biometric variables assessed developed similarly in fetuses in both the group exposed to 17-OHPC and the placebo group during the second half of pregnancy. Birth weight adjusted for parity and fetal sex was also comparable between groups.The use of 17-OHPC has no adverse effects on fetal biometry and birth weight in twins.

To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel.Economic evaluation alongside a randomised controlled trial.Obstetric departments of one university and 11 teaching hospitals in the Netherlands.Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section.Cost-effectiveness analysis from a hospital perspective.We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes.Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E₂ gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval -€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction.Foley catheter and prostaglandin E2 labour induction generate comparable costs.

Recent concern about the safety of combined oral contraceptives (OCs) with third-generation progestagens prompted an examination of data from a population-based case-control study (Leiden Thrombophilia Study). We compared the risk of deep-vein thrombosis (DVT) during use of the newest OCs, containing a third-generation progestagen, with the risk of "older" products. We also investigated the influence of family history of thrombosis, previous pregnancy, age, and the thrombogenic factor V Leiden mutation. We selected 126 women with DVT and 159 controls aged 15-49 (mean age 34.9) and premenopausal and found, as compared with non-users, the highest age-adjusted relative risks to be that for an OC containing desogestrel and 30 micrograms ethinyloestradiol (relative risk [RR] 8.7, 95% CI 3.9-19.3). We found lower relative risks for all other types of OC, ranging from 2.2 to 3.8. In a direct comparison, users of the desogestrel-containing oral contraceptive had a 2.5-fold higher risk (95% CI 1.2-5.2) than users of all other OC types combined. The relative risk for the desogestrel-containing OC was similar among women with and without a family history--ie, preferential prescription because of family history cannot explain our findings. Nor could the excess risk be explained by previous pregnancy, and it was highest in the youngest age categories, where we would expect most new users. The age-adjusted RR for the desogestrel-containing contraceptive was 9.2 (3.9-21.4) among non-carriers of the factor V Leiden mutation and 6.0 (1.9-19.0) among carriers of the mutation. This latter risk is superimposed on the 8-fold increased risk of venous thrombosis for carriers of the factor V Leiden mutation. The risk of carriers using the desogestrel-containing OC as compared with noncarrier non-users will therefore be increased almost 50-fold. Use of low-dose OCs with a third-generation progestagen carries a higher risk of DVT than the previous generation of OCs. The absolute risk of DVT associated with these OCs seems to be especially high among carriers of the factor V Leiden mutation and among women with a family history of thrombosis. However, the higher risk associated with OC with a third-generation progestagen compared with previous generations was also present in women without factor V Leiden and with no family history. In the Netherlands, researchers compared data on 126 women with deep-vein thrombosis (DVT) with data on 159 premenopausal women aged 15-49 to examine the risk of DVT during use of oral contraceptives (OCs) containing a third generation progestogen as well as the influence of the thrombogenic factor V Leiden mutation, family history of thrombosis, age, and previous pregnancy. The desogestrel-containing monophasic OC had the highest relative risk for DVT (8.7 vs. 2.2-3.8). There were too few women using OCs containing gestodene or norgestimate to draw substantial conclusions. The OC with 30 mcg ethinyl estradiol (E2) and desogestrel increased the risk of DVT 2.2 times when compared with the levonorgestrel-containing OC with the same amount of E2. When compared with all other OCs, desogestrel-containing OCs had a 2.5 higher risk. When the researchers compared carriers of the factor V Leiden mutation with non-carriers, the risk of DVT increased about 50 times among women using desogestrel-containing OCs. The age-adjusted relative risk of DVT for desogestrel-containing OCs was 7.2. Even though a positive family history of DVT and factor V Leiden mutation enhanced the effect of desogestrel-containing Ocs, neither could account for all the excess risk of the desogestrel-containing OC since the risk of DVT increased in women with and without a family history of DVT and those with and without factor V Leiden. These findings suggest that the OCs containing a third-generation progestogen (i.e., desogestrel) contribute to a reverse of the gains achieved in reducing the thrombotic risk by decreasing the dose of E2

To describe the panel audit process and to identify substandard care in selected women from a nationwide prospective cohort study into severe acute maternal morbidity (SAMM) in the Netherlands.Prospective audit of selected women with SAMM.Eight audit meetings held throughout the Netherlands.All pregnant women in the Netherlands.Before each meeting, SAMM details of selected women were sent to all panel members for individual assessment by completing an audit form. During a subsequent plenary meeting, findings were discussed and substandard care factors as judged by the majority of assessors were scored.Incidence of substandard care and recommendations for improving the quality of care.Substandard care was identified in 53 of 67 women (79%). Specific recommendations were formulated concerning the procedure of audit and concerning local as well as national management guidelines.Our findings reflect SAMM in the Netherlands and substandard care is present in four out of five women. Ongoing audit of women with SAMM is promoted both at local and national level.

To assess incidence of uterine rupture in scarred and unscarred uteri and its maternal and fetal complications in a nationwide design.Population-based cohort study.All 98 maternity units in The Netherlands.All women delivering in The Netherlands between August 2004 and August 2006 (n = 371,021).Women with uterine rupture were prospectively collected using a web-based notification system. Data from all pregnant women in The Netherlands during the study period were obtained from Dutch population-based registers. Results were stratified by uterine scar.Population-based incidences, severe maternal and neonatal morbidity and mortality, relative and absolute risk estimates.There were 210 cases of uterine rupture (5.9 per 10,000 pregnancies). Of these women, 183 (87.1%) had a uterine scar, incidences being 5.1 and 0.8 per 10,000 in women with and without uterine scar. No maternal deaths and 18 cases of perinatal death (8.7%) occurred. The overall absolute risk of uterine rupture was 1 in 1709. In univariate analysis, women with a prior caesarean, epidural anaesthesia, induction of labour (irrespective of agents used), pre- or post-term pregnancy, overweight, non-Western ethnic background and advanced age had an elevated risk of uterine rupture. The overall relative risk of induction of labour was 3.6 (95% confidence interval 2.7-4.8).The population-based incidence of uterine rupture in The Netherlands is comparable with other Western countries. Although much attention is paid to scar rupture associated with uterotonic agents, 13% of ruptures occurred in unscarred uteri and 72% occurred during spontaneous labour.

To compare the actual situation in tertiary perinatal care in the Netherlands with the objectives laid down in the 2001 decree on perinatal care by the Dutch Ministry of Health, Welfare and Sport.Descriptive, retrospective.Data on tertiary perinatal care, the transfer or refusal of women with very endangered pregnancies and the personnel of obstetric high care (OHC) units in 2006 were compared with the targets laid down in the planning decree on perinatal care and in a report by the Dutch Health Council from 2000. Parameters of tertiary perinatal care output were the number of admissions, and the number of beds in OHC units and neonatal intensive care units (NICU).In 2006, 128 of the 250 beds intended for OHC had been obtained. The degree of capacity utilisation was 94%, while the norm is 80%. 312 women were transferred due to lack of capacity of OHC units and NICU. The number of staff, specialised physicians as well as nurses, was considerably lower than the planned capacity. But training for obstetric perinatologists and OHC nurses was given.The targets for the number of beds for tertiary obstetric care and associated medical personnel have not been achieved as yet. As a consequence, the number of transfers is still too high. The funding of OHC units is not attuned to the complexity of tertiary perinatal care. Closer supervision of the execution of the planning decree and an adequate financing system are needed to achieve the objectives of the planning decree in the next 3 years.

The progestogen component of oral contraceptives (OC) has undergone changes since it was first recognised that their chemical structures could influence the spectrum of minor adverse and beneficial effects. The major determinants of OCs are effectiveness, cycle control and common side effects. The rationale of this review is to provide a systematic comparison of OCs containing the progestogens currently in use worldwide.The objective of this review is to compare currently available low-dose OCs containing ethinyl estradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates.The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases have been searched systematically. Relevant pharmaceutical companies and the authors of articles included in this review have been contacted for clarification.Randomised trials reporting clinical outcomes were considered for inclusion. We excluded studies comparing mono- with multiphasic pills, and crossover trials with trials in which the difference in total content of ethinyl estradiol between preparations exceeded 105 micro g.The methodological quality and validity of studies were assessed based on the above-mentioned inclusion criteria. Both application of inclusion criteria and data extraction were performed independently by the reviewers. Results are expressed as relative risk (RR) with 95% confidence interval (CI) using a random-effects model.Twenty-two trials have been included in this review, thus generating 14 comparisons. Eighteen trials were sponsored by pharmaceutical companies and in only 5 cases had a blind trial been attempted. Most comparisons between different interventions included 1-3 trials. There was less discontinuation with second- compared to first-generation progestogens (RR: 0.79, 95% CI: 0.69-0.91). Cycle control appears to be better when using second- compared to first-generation progestogens for both mono- (RR: 0.69; 95% CI: 0.52-0.91) and triphasic (RR: 0.61; 95% CI: 0.43-0.85) preparations.Contraceptive effectiveness, spotting, breakthrough bleeding and the absence of withdrawal bleeding was similar when using GSD compared to LNG, although there was less intermenstrual bleeding in the GSD group (RR: 0.71, 95% CI: 0.55, 0.91). Drospirenone (DRSP) appeared to be similar to DSG.Based on data from one trial, compared to pills containing LNG, those containing GSD may be associated with less intermenstrual bleeding although they show similar patterns of spotting, breakthrough bleeding and the absence of withdrawal bleeds. GSD is also comparable to DSG. Regarding acceptability, all the indices show that third- and second-generation progestogens are preferred over first-generation preparations. Future research should focus on independently conducted, well-designed randomised trials that compare third- and second-generation progestogens in particular.

The authors respond to Carolyn Westhoffs critique of their study on the association between exposure to oral contraceptives and deep vein thrombosis (DVT). They found an apparent multiplication of risks which was more clearly present for oral contraceptives containing a third-generation progestogen than for those containing a second-generation progestogen. The risks seem to multiply but there is no reason why they should. The authors explain that the appearance of independence of such risks is merely the result of the use of multiplicative models that is relative risks or logistic models. These models are a simple result of a mathematical convenience and have no intrinsic biological meaning which becomes clearer when looking at the same data on an additive scale. The authors agree with Westhoff that the biological interpretation of interaction is considerably more difficult. They do not however believe that they overstated misinterpreted or misled by suggesting that the observed difference in risk among factor V Leiden positive individuals may offer a clue to the biological mechanism underlying the increased risk of venous thrombosis of third-generation oral contraceptives.