[Cesarean scar pregnancy]. / Ectopische zwangerschap in litteken van keizersnede.

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.

Urine pregnancy test (UPT) hCG negative molar pregnancy: a short report from Masanga/Sierra Leone.

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.

An economic analysis of immediate delivery and expectant monitoring in women with hypertensive disorders of pregnancy, between 34 and 37 weeks of gestation (HYPITAT-II).

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.

A multivariable model to guide the decision for pessary placement to prevent preterm birth in women with a multiple pregnancy: a secondary analysis of the ProTWIN trial.

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.

Second-trimester cervical length as risk indicator for Cesarean delivery in women with twin pregnancy.

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.

Economic analysis of use of pessary to prevent preterm birth in women with multiple pregnancy (ProTWIN trial).

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.

Using vaginal Group B Streptococcus colonisation in women with preterm premature rupture of membranes to guide the decision for immediate delivery: a secondary analysis of the PPROMEXIL trials.

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.

Predicting successful intended vaginal delivery after previous caesarean section: external validation of two predictive models in a Dutch nationwide registration-based cohort with a high intended vaginal delivery rate.

OBJECTIVE: To externally validate two models from the USA (entry-to-care [ETC] and close-to-delivery [CTD]) that predict successful intended vaginal birth after caesarean (VBAC) for the Dutch population. DESIGN: A nationwide registration-based cohort study. SETTING: Seventeen hospitals in the Netherlands. POPULATION: Seven hundred and sixty-three pregnant women, each with one previous caesarean section and a viable singleton cephalic pregnancy without a contraindication for an intended VBAC. METHODS: The ETC model comprises the variables maternal age, prepregnancy body mass index (BMI), ethnicity, previous vaginal delivery, previous VBAC and previous nonprogressive labour. The CTD model replaces prepregnancy BMI with third-trimester BMI and adds estimated gestational age at delivery, hypertensive disease of pregnancy, cervical examination and induction of labour. We included consecutive medical records of eligible women who delivered in 2010. For validation, individual probabilities of women who had an intended VBAC were calculated. MAIN OUTCOME MEASURES: Discriminative performance was assessed with the area under the curve (AUC) of the receiver operating characteristic and predictive performance was assessed with calibration plots and the Hosmer-Lemeshow (H-L) statistic. RESULTS: Five hundred and fifteen (67%) of the 763 women had an intended VBAC; 72% of these (371) had an actual VBAC. The AUCs of the ETC and CTD models were 68% (95% CI 63-72%) and 72% (95% CI 67-76%), respectively. The H-L statistic showed a P-value of 0.167 for the ETC model and P = 0.356 for the CTD model, indicating no lack of fit. CONCLUSION: External validation of two predictive models developed in the USA revealed an adequate performance within the Dutch population.

Vaginal birth after a caesarean section: the development of a Western European population-based prediction model for deliveries at term.

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 90(th) 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.

[Pregnancy complications as a risk factor for metabolic and cardiovascular disease in later life]. / Zwangerschapscomplicaties als risicofactor voor metabole en cardiovasculaire aandoeningen op latere leeftijd.

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.

Fibrinogen and high molecular weight fibrinogen during and after normal pregnancy.

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.

Increased high molecular weight fibrinogen in pre-eclampsia.

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.

Placental pathology in women with type 1 diabetes and in a control group with normal and large-for-gestational-age infants.

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.

Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia.

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.

Placental superoxide is increased in pre-eclampsia.

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.

Salivary cortisol levels and anxiety are not increased in women destined to develop preeclampsia.

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.