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In Masanga, Sierra Leone, a multigravid woman presented with a urine pregnancy test negative molar pregnancy. This can be explained by the 'hook-effect'. In resource-poor settings where quantitative serum hCG cannot be determined, it is of paramount importance to remain vigilant of the diagnosis of molar pregnancy. Clinical judgement and sonography remain key in diagnosing molar pregnancy in district hospitals in low- and middle-income countries (LMICs), especially since their occurrence is much more common in these countries. [ABSTRACT FROM AUTHOR]

Objective: To assess the economic consequences of immediate delivery compared with expectant monitoring in women with preterm non-severe hypertensive disorders of pregnancy.Design: A cost-effectiveness analysis alongside a randomised controlled trial (HYPITAT-II).Setting: Obstetric departments of seven academic hospitals and 44 non-academic hospitals in the Netherlands.Population: Women diagnosed with non-severe hypertensive disorders of pregnancy between 340/7 and 370/7  weeks of gestation, randomly allocated to either immediate delivery or expectant monitoring.Methods: A trial-based cost-effectiveness analysis was performed from a healthcare perspective until final maternal and neonatal discharge.Main Outcome Measures: Health outcomes were expressed as the prevalence of respiratory distress syndrome, defined as the need for supplemental oxygen for >24 hours combined with radiographic findings typical for respiratory distress syndrome. Costs were estimated from a healthcare perspective until maternal and neonatal discharge.Results: The average costs of immediate delivery (n = 352) were €10 245 versus €9563 for expectant monitoring (n = 351), with an average difference of €682 (95% confidence interval, 95% CI -€618 to €2126). This 7% difference predominantly originated from the neonatal admissions, which were €5672 in the immediate delivery arm and €3929 in the expectant monitoring arm.Conclusion: In women with mild hypertensive disorders between 340/7 and 370/7  weeks of gestation, immediate delivery is more costly than expectant monitoring as a result of differences in neonatal admissions. These findings support expectant monitoring, as the clinical outcomes of the trial demonstrated that expectant monitoring reduced respiratory distress syndrome for a slightly increased risk of maternal complications.Tweetable Abstract: Expectant management in preterm hypertensive disorders is less costly compared with immediate delivery. [ABSTRACT FROM AUTHOR]

Objective To investigate whether vaginal Group B Streptococcus ( GBS) colonisation or other baseline characteristics of women with preterm premature rupture of membranes ( PPROM) can help in identifying subgroups of women who would benefit from immediate delivery. Design Secondary analysis of the PPROMEXIL trials. Setting Sixty hospitals in the Netherlands. Population Women with PPROM between 34 and 37 weeks of gestation. Methods Random assignment of 723 women to immediate delivery or expectant management. Main outcome measures Early onset neonatal sepsis. Results Vaginal GBS colonisation status was the only marker which was significantly associated with the benefit of immediate delivery ( P for interaction: 0.04). GBS colonisation was observed in 14% of women. The risk of early onset neonatal sepsis in GBS-positive women was high (15.2%) when they were managed expectantly but this risk was reduced to 1.8% with immediate delivery. The early onset neonatal sepsis risk was much lower in neonates of GBS-negative women: 2.6% after expectant management and 2.9% with immediate delivery. We estimated that by inducing labour only in GBS-positive women, there would be a 10.4% increase in term delivery rate, while keeping neonatal sepsis and caesarean delivery rates comparable to a strategy of labour induction for all. Conclusions Our post hoc findings suggest that women with PROM between 34 and 37 weeks might benefit from immediate delivery if they have GBS vaginal colonisation, while in GBS-negative women labour induction could be delayed until 37 weeks. [ABSTRACT FROM AUTHOR]

Objective To develop and internally validate a model that predicts the outcome of an intended vaginal birth after caesarean ( VBAC) for a Western European population that can be used to personalise counselling for deliveries at term. Design Registration-based retrospective cohort study. Setting Five university teaching hospitals, seven non-university teaching hospitals, and five non-university non-teaching hospitals in the Netherlands. Population A cohort of 515 women with a history of one caesarean section and a viable singleton pregnancy, without a contraindication for intended VBAC, who delivered at term. Methods Potential predictors for a vaginal delivery after caesarean section were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. Main outcome measures Predictors for VBAC. For model validation, the area under the receiver operating characteristic curve (AUC) for discriminative capacity and calibration-per-risk-quantile for accuracy were calculated. Results A total of 371 out of 515 women had a VBAC (72%). Variables included in the model were: estimated fetal weight greater than the 90th percentile in the third trimester; previous non-progressive labour; previous vaginal delivery; induction of labour; pre-pregnancy body mass index; and ethnicity. The AUC was 71% (95% confidence interval, 95% CI = 69-73%), indicating a good discriminative ability. The calibration plot shows that the predicted probabilities are well calibrated, especially from 65% up, which accounts for 77% of the total study population. Conclusion We developed an appropriate Western European population-based prediction model that is aimed to personalise counselling for term deliveries. [ABSTRACT FROM AUTHOR]

Background: Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function., Methods: The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18-42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or β2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0·5-1·0 μg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39., Results: Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1·03 [95% CI 0·77 to 1·38]; absolute risk difference 1·6% [95% CI -12·7 to 15·9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure., Interpretation: Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function., Funding: Dutch Organization for Health Research and Development, Fonds NutsOhra, Dutch Patient Organization of Thyroid Disorders, the Jan Dekkerstichting and Dr Ludgardine Bouwmanstichting, and a personal donation through the Dutch Patient Organization of Thyroid Disorders., Competing Interests: Declaration of interests MG received research and educational grants from Guerbet, Merck, and Ferring, not related to the presented work, paid to their institution. AH reports an unrestricted educational grant from Ferring, not related to the presented work, paid to their institution. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth., Methods and Findings: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates., Conclusions: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth., Trial Registration: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BM reported an Investigator grant from the National Health and Medical Research Council (NHMRC; grant no. GNT1176437); receipt of research funding from Guerbet; and is a former advisory board member at ObsEva. All other authors do not report any relevant financial activities outside the submitted work.

Background: A rare, but potentially life-threatening complication of a Cesarean section is a so-called Cesarean scar pregnancy (CSP). This concerns an ectopic pregnancy, where the implantation takes place in a niche of the Cesarean section scar., Case Description: We describe the case of a 29-year-old pregnant woman (G5P3), who after a amenorrhoea period of 6 weeks was referred to us by a midwife because the sonography showed an empty uterus. She had previously undergone two Cesarean sections. During transvaginal sonography we observed a small amiotic sac in the Cesarean section scar, lacking a clear heart rhythm., Conclusion: Since there are no general guidelines for the treatment of CSP, a patient-specific approach should be taken to determine optimal management. There is, however, a clear preference to terminate the pregnancy as soon as possible.

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial., Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo., Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth., Trial Registration: Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

Objective: 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., Methods: 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., Results: 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%))., Conclusions: 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 Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking., Methods: We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization., Results: We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99)., Conclusions: In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.).

Objective: To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section., Methods: 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., Results: 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 CL > 75(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 BMI > 28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5))., Conclusion: In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL)., Study Design: Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat., Results: Between 2009 and 2013, 20,234 women were screened. A CL of 30 mm or less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5)., Conclusion: In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women., Methods: We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792)., Findings: Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12-1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4-8·2; p=0·005). No maternal or perinatal deaths occurred., Interpretation: For women with non-severe hypertensive disorders at 34-37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered., Funding: ZonMw., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour., Design: Multicentre randomised controlled equivalence trial., Setting: 15 hospitals in the Netherlands., Participants: Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data., Intervention: Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour., Main Outcome Measures: Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome., Results: 1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference -2.8, 95% confidence interval -6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference -10.4, -13.9 to -7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups., Conclusion: In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia., Trial Registration: Netherlands Trial Register NTR2551., (© Freeman et al 2015.)

Objective: To assess the cost-effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy., Methods: The study design comprised an economic analysis of data from a randomized clinical trial evaluating cervical pessaries (ProTWIN). Women with a multiple pregnancy were included and an economic evaluation was performed from a societal perspective. Costs were estimated between the time of randomization and 6 weeks postpartum. The prespecified subgroup of women with a cervical length (CL) < 25(th) centile (< 38 mm) was analyzed separately. The primary endpoint was poor perinatal outcome occurring up to 6 weeks postpartum. Direct medical costs and health outcomes were estimated and incremental cost-effectiveness ratios for costs to prevent one poor outcome were calculated., Results: Mean costs in the pessary group (n = 401) were € 21,783 vs € 21,877 in the group in which no pessary was used (n = 407) (difference, -€ 94; 95% CI, -€ 5975 to € 5609). In the prespecified subgroup of women with a CL < 38 mm we demonstrated a significant reduction in poor perinatal outcome (12% vs 29%; RR, 0.40; 95% CI, 0.19-0.83). Mean costs in the pessary group (n = 78) were € 25,141 vs € 30,577 in the no-pessary group (n = 55) (difference, -€ 5436 (95% CI, -€ 11,001 to € 1456). In women with a CL < 38 mm, pessary treatment was the dominant strategy (more effective and less costly) with a probability of 94%., Conclusion: Cervical pessaries in women with a multiple pregnancy involve costs comparable to those in women without pessary treatment. However, in women with a CL < 38 mm, treatment with a cervical pessary appears to be highly cost-effective., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM)., Design: Economic analysis based on a randomized clinical trial., Setting: Obstetric departments of eight academic and 52 non-academic hospitals in the Netherlands., Population: Women with PPROM near term who were not in labor 24 h after PPROM., Methods: A cost-minimization analysis was done from a health care provider perspective, using a bottom-up approach to estimate resource utilization, valued with unit-costs reflecting actual costs., Main Outcome Measures: Primary health outcome was the incidence of neonatal sepsis. Direct medical costs were estimated from start of randomization to hospital discharge of mother and child., Results: Induction of labor did not significantly reduce the probability of neonatal sepsis [2.6% vs. 4.1%, relative risk 0.64 (95% confidence interval 0.25-1.6)]. Mean costs per woman were €8094 for induction and €7340 for expectant management (difference €754; 95% confidence interval -335 to 1802). This difference predominantly originated in the postpartum period, where the mean costs were €5669 for induction vs. €4801 for expectant management. Delivery costs were higher in women allocated to induction than in women allocated to expectant management (€1777 vs. €1153 per woman). Antepartum costs in the expectant management group were higher because of longer antepartum maternal stays in hospital., Conclusions: In women with pregnancies complicated by PPROM near term, induction of labor does not reduce neonatal sepsis, whereas costs associated with this strategy are probably higher., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: The evidence for the management of near term prelabor rupture of membranes is poor. From January 2007 until September 2009, we performed the PPROM Expectant Management versus Induction of Labor (PPROMEXIL) trial. In this trial, we showed that in women with preterm prelabor rupture of membranes (PPROM), the incidence of neonatal sepsis was low, and the induction of labor (IoL) did not reduce this risk. Because the PPROMEXIL trial was underpowered and because of a lower-than-expected incidence of neonatal sepsis, we performed a second trial (PPROMEXIL-2), aiming to randomize 200 patients to improve the evidence in near-term PPROM., Study Design: In a nationwide multicenter study, nonlaboring women with PPROM between 34 and 37 weeks' gestational age were eligible for inclusion. Patients were randomized to IoL or expectant management (EM). The primary outcome measure was neonatal sepsis., Results: From December 2009 until January 2011, we randomized 100 women to IoL and 95 to EM. Neonatal sepsis was seen in 3 neonates (3.0%) in the IoL-group versus 4 neonates (4.1%) in the EM group (relative risk, 0.74; 95% confidence interval, 0.17-3.2). One of the sepsis cases in the IoL group resulted in neonatal death because of asphyxia. There were no significant differences in secondary outcomes., Conclusion: The risk of neonatal sepsis after PPROM near term is low. Induction of labor does not reduce this risk., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: Ischemia-modified albumin (IMA) has emerged as a new biomarker of myocardial ischemia. Currently, no information is available on maternal IMA levels during normal and complicated pregnancy. Preeclampsia is associated with ischemia and increased formation of free radicals in the placenta. We therefore hypothesized that production of IMA may occur in women with preeclampsia., Methods: Serum IMA and albumin concentrations were assessed in 12 patients with preeclampsia, 12 normal pregnant controls, and 12 nonpregnant controls. IMA levels were compared between groups and corrected for albumin by multivariate regression analysis., Results: Mean IMA levels were elevated in normal pregnant controls (107.3 U/mL; 95% CI, 102.5 to 112.01), compared with nonpregnant controls (94.5 U/mL; CI, 89.4 to 99.6; p = 0.015). In patients with preeclampsia, IMA levels were similar to those in normal pregnant controls (109.7 U/mL; CI, 102.2 to 117.2; p = 0.65). Also, no difference in IMA levels was observed between women with preeclampsia who delivered small-for-gestational-age (SGA) infants (99.0 U/mL; CI, 87.9 to 110.1; p = 0.13) and women with preeclampsia but without SGA., Conclusion: Serum IMA, which has been advocated as a clinical marker of cardiac ischemia, appears to be elevated during normal pregnancy. We found no significant relationship between IMA levels and preeclampsia, in women with or without SGA infants.

In recent years several large epidemiological studies have been published that demonstrate that women who experience gestational diabetes, pregnancy-induced hypertension or pre-eclampsia have an increased risk of developing type-2 diabetes mellitus and cardiovascular disease. 15-50% of women who experience gestational diabetes develop type-2 diabetes mellitus; the risk is particularly high in those who require insulin therapy during pregnancy. - Chronic hypertension frequently develops years after a pregnancy complicated by pregnancy-induced hypertension, especially in women who have had pregnancy-induced hypertension in multiple pregnancies. Women who experience pre-eclampsia in the first 36 weeks of pregnancy or in multiple pregnancies have an increased risk of cardiovascular morbidity and mortality in later life. Therefore gestational diabetes, pregnancy-induced hypertension and pre-eclampsia provide an opportunity to identify individuals with an increased risk of type-2 diabetes mellitus and cardiovascular disease at an early age. This may create new perspectives on prevention.

Introduction: Pregnancy has recently been described as a generalized intravascular inflammatory response to the conceptus. Total fibrinogen concentrations increase during pregnancy. The percentage high molecular weight fibrinogen (HMW-Fg) of the concentration total fibrinogen is known to increase during acute-phase conditions like inflammation. Therefore, we investigated whether the percentage high molecular weight fibrinogen increases during normal pregnancy., Materials and Methods: Eighteen healthy nulliparous women with uncomplicated pregnancies with normal course and outcome participated in this study. Five blood samples were drawn from every woman in the gestational age periods 9 to 16, 17 to 24, 25 to 33 and 34 to 42 weeks and at 12 to 20 weeks after delivery. Total fibrinogen concentrations were determined according to Clauss and the percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. One-way analysis of variance (ANOVA) was used to evaluate differences between gestational age periods and correlation coefficients were calculated by Pearson's method., Results: Total fibrinogen concentrations increased with advancing gestational age and decreased after delivery. The percentage high molecular weight fibrinogen of the total fibrinogen remained unaltered during and after pregnancy., Conclusions: During normal pregnancy, there is an increase of total fibrinogen concentrations with advancing gestational age, without a rise in percentage high molecular weight fibrinogen. After delivery, the total fibrinogen returns to baseline concentrations.

Unexplained intra-uterine fetal death is still a problem in diabetic pregnancies, especially in those with an LGA-infant. We hypothesized that in these pregnancies impaired placental function, in terms of abnormal placental weight and/or abnormal placental histology, may account for this phenomenon. To test this hypothesis, we assessed the relative placental weight and scored several histological abnormalities in 34 AGA- and 24 LGA-placentae of type 1 diabetic women and in 22 AGA- and 16 LGA-placentae of control women. Relative placental weight was comparable in the LGA-diabetic cases and in the control groups, but was significantly higher in the AGA-diabetic subgroup. Histological abnormalities such as the presence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity and chorangiosis were observed more often in the diabetic placentae compared with the control placentae. These differences in histology were particularly observed when we compared both AGA-groups. LGA-control placentae showed a high incidence of histological abnormalities, almost comparable to the diabetic placentae. Only fibrinoid necrosis was significantly more common in the LGA-diabetic placentae. Three of the four cases of perinatal death/asphyxia in the diabetic group concerned an LGA-infant with a relative low placental weight. In conclusion, placentae of women with type 1 diabetes showed several abnormalities that can be associated with impaired functioning. The difference between AGA- and LGA-diabetic placentae was related to relative placental weight and our data suggest that an increase in relative weight may protect the fetus from asphyxia. Placentae from LGA-non-diabetic women showed several similarities to those of women with diabetes.

Introduction: The major coagulation protein fibrinogen (Fg) is a heterogeneous protein with three main fractions: high molecular weight fibrinogen (HMW-Fg), low molecular weight fibrinogen (LMW-Fg) and low molecular weight' fibrinogen. The clottability of high molecular weight fibrinogen is highest as compared to the other fractions. Pre-eclampsia is associated with a state of hypercoagulability, and with an increase of fibrinogen concentration. The aim of the present study was to examine if the increased total fibrinogen plasma concentration in patients with pre-eclampsia is associated with a change in distribution of the main fibrinogen fractions., Material and Methods: Plasma was collected from 14 patients with pre-eclampsia and from 14 healthy pregnant matched controls. Total fibrinogen concentrations were determined according to Clauss. The percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. The study groups were compared by the Mann-Whitney U-test., Results: The median (range) total fibrinogen concentration in the pre-eclampsia group was 5.04 (3.25-6.51) g/l and in the control group 4.19 (3.61-5.38) g/l (p<0.05). The median (range) percentage high molecular weight fibrinogen was 76.5 (69.6-84.0)% and 73.0 (69.0-78.9)% in the pre-eclampsia and control group, respectively (p<0.05)., Conclusions: In pre-eclampsia, the concentration of total fibrinogen is increased and the percentage high molecular weight fibrinogen is also slightly higher than in normal pregnancy. These results may be a reflection of the exaggerated inflammatory response, and subsequent endothelial activation, which are currently believed to be the key pathophysiological mechanisms in pre-eclampsia.

Background: Semicarbazide sensitive amine-oxidase (SSAO) is an adhesion molecule and thought to play a role in endothelial cell dysfunction (ECD). SSAO has never been associated with markers of ECD. Pre-eclampsia (PE) is, like the early stages of atherosclerosis, characterised by ECD. SSAO could contribute to ECD in PE., Methods: Plasma samples were obtained in 14 pre-eclamptic patients and 14 matched controls. In these SSAO-activity, von Willebrand factor (vWF) levels and ED1 fibronectin levels were determined. Placental tissue was collected of 12 pre-eclamptic pregnancies, 8 preterm deliveries and 12 term controls. In these samples, SSAO activity was assessed. In a subset of these placentas, immunohistochemical staining was performed for SSAO, ICAM-1 and VCAM-1., Results: Plasma SSAO activity was not significantly different between pre-eclamptic subjects and controls. VWF and ED1 fibronectin were both significantly increased in the pre-eclamptic subjects. There was no correlation between SSAO activity and vWF or ED1 fibronectin levels. Placental SSAO activity was not different between pre-eclamptic pregnancies, preterm deliveries and term controls. There was strong staining of SSAO in vascular smooth muscle cells (VSM) and moderate staining of trophoblast in all three groups. Endothelial cell expression of SSAO was only seen in term controls and the placentas of pre-eclamptic patients. There was no association between the expression of SSAO, ICAM-1 or VCAM-1 in the placentas of pre-eclamptic patients., Conclusion: SSAO expression and activity are not related to markers of ECD., (Copyright 2002 Elsevier Science B.V.)

Objective: The incidence of placental thrombotic lesions in early onset preeclampsia (PE) and/or intrauterine growth restriction (IUGR) were compared between women with and without thrombophilia or hyperhomocysteinemia., Study Design: Matched case-control study. 183 women with a history of early onset PE and/or IUGR were tested for thrombophilia and hyperhomocysteinemia. From the 66 women with a thrombophilic factor the placental histological slides were available in 47 women. These were matched for maternal condition (PE and/or IUGR), gestational age at delivery, parity and maternal age, to 47 women with no thrombophilic factor. All slides were revised for lymphohistiocytic villitis, fetal thrombosis and fibrin depositions., Results: There were no significant differences between the placentas of the matched groups with and without a thrombophilic factor., Conclusion: Placental thrombotic and inflammatory lesions associated with early onset PE and/or IUGR do not occur more often in women with compared to women without thrombophilia or hyperhomocysteinemia., (Copyright 2002 Elsevier Science Ltd.)

One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states that the placenta secretes one or more cytotoxic factors resulting in maternal endothelial dysfunction. Among the candidate factors are the products of increased oxidative stress. Although there is circumstantial evidence of such an increase, direct evidence is still lacking. Electron paramagnetic spin trap resonance (EPR), the most direct method to detect free radicals in tissues, was used to measure superoxide levels in placentae from normal pregnancies (n=13) and pregnancies complicated by PE (n=10). The superoxide level was significantly increased in the placental tissue of pre-eclamptic women. Moreover, upon inhibition of Cu-Zn superoxide dismutase (SOD) activity the relative increase of the superoxide levels was significantly smaller in the placentae from the PE patients, implying decreased basal Cu-Zn SOD activity. These findings lend direct support to the hypothesis that oxidative stress in placental tissue is increased in PE., (Copyright 2001 Harcourt Publishers Ltd.)

Objective: To compare salivary cortisol levels and maternal anxiety (general and pregnancy-specific) in the early and late second trimester of pregnancy between women who developed preeclampsia (PE) and women who remained normotensive., Design: Nested case-referent study. In a prospectively studied cohort of 250 pregnant women, nine women developed PE in late pregnancy. These nine patients were matched and compared with nine controls. Diurnal cortisol levels were obtained by collecting saliva samples at 17-18 and 27-28 weeks gestation. Salivary cortisol levels were determined by radioimmunoassay. Maternal anxiety was determined by Spielberger's State-Trait Anxiety Inventory (STAI) and a pregnancy-specific stress questionnaire., Results: For both patients and controls, a similar pattern of salivary cortisol excretion was observed. Salivary cortisol levels and anxiety scores (general and pregnancy-specific) did not differ significantly between patients and controls., Conclusions: Our findings do not lend support to a role for maternal anxiety or second trimester increases in circulating stress hormones in the pathogenesis of PE.