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Objective: To compare the accuracy of the Actim Partus test and fetal fibronectin (fFN) test in the prediction of spontaneous preterm delivery within seven days in symptomatic women undergoing cervical length measurement., Study Design: We performed a post-hoc analysis on frozen samples of a nationwide cohort study in all 10 perinatal centres in the Netherlands. We selected samples from women with signs of preterm labour between 24 and 34 weeks of gestational age and a cervical length below 30mm. Delivery within seven days after initial assessment was the primary endpoint. We calculated sensitivity, specificity, and positive and negative predictive values for the combination of both the Actim Partus test and fFN test with cervical length. A test was considered positive in case of a cervical length between 15 and 30mm with a positive Actim Partus or fFN test, and a cervical length below 15mm regardless the test result., Results: In total, samples of 350 women were tested, of whom 69 (20%) delivered within seven days. Eighty-four women had a positive Actim Partus test and 162 women a positive fFN test, of whom 54 (64%) and 63 (39%) delivered within seven days, respectively. Ninety-seven women had a cervical length below 15mm, of whom 50 (52%) delivered within seven days. Sensitivity, specificity, positive and negative predictive values of combining cervical length with the Actim Partus test or the fFN test were 91%, 75%, 47% and 97%, and 96%, 58%, 36% and 98%, respectively., Conclusion: According to this post-hoc study, in combination with cervical length, the Actim Partus test could be used as an alternative for the fFN test to identify women who will not deliver within seven days after presentation. Further evidence should be collected in a prospective comparative study., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with postmenopausal bleeding, the sensitivity of endometrial sampling to detect endometrial cancer and especially atypical hyperplasia and endometrial disease, including endometrial polyps, is lower than previously thought. Therefore, further diagnostic work-up for focal pathology is warranted, after a benign result of endometrial sampling., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Objective: To assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians' decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor., Study Design: This is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks' gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10 mm, group 2 CL 10-30 mm and positive fFN, group 3 CL 10-30 mm and negative fFN, group 4 CL>30 mm., Results: ACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3-61 days), 44 days (IQR 17-69 days), 53 days (IQR 37-77 days) and 66 days (IQR 43-78 days) in group 1, 2, 3 and 4 respectively., Conclusion: ACS were prescribed frequently to women with a CL of 10-30 mm and a negative fFN test or a CL>30 mm. There is room for improvement in the prescription of ACS in these low risk women., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess whether patient characteristics add to the fetal fibronectin test and cervical length measurement in the prediction of preterm delivery in symptomatic women., Study Design: A nationwide prospective cohort study was conducted in all ten perinatal centres in the Netherlands. Women with symptoms of preterm labour between 24 and 34 weeks gestation with intact membranes were invited. In all women qualitative fibronectin testing (0.050 μg/mL cut-off) and cervical length measurement were performed. Only singleton pregnancies were included in this analysis. Logistic regression was used to construct two multivariable models to predict spontaneously delivery within 7 days: a model including cervical length and fetal fibronectin as predictors, and an extended model including all potential predictors. The models were internally validated using bootstrapping techniques. Predictive performances were assessed as the area under the receiver operator characteristic curve (AUC) and calibration plots. We compared the models' capability to identify women with a low risk to deliver within 7 days. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk., Results: Seventy-three of 600 included women (12%) had delivered spontaneously within 7 days. The extended model included maternal age, parity, previous preterm delivery, vaginal bleeding, C-reactive protein, cervical length, dilatation and fibronectin status. Both models had high discriminative performances (AUC of 0.92 (95% CI 0.88-0.95) and 0.95 (95% CI 0.92-0.97) respectively). Compared to the model with fibronectin and cervical length, our extended model reclassified 38 women (6%) from low risk to high risk and 21 women (4%) from high risk to low risk. Preterm delivery within 7 days occurred once in both the reclassification groups., Conclusion: In women with symptoms of preterm labour before 34 weeks gestation, a model that integrates maternal characteristics, clinical signs and laboratory tests, did not predict delivery within 7 days better than a model with only fibronectin and cervical length., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women., Study Design: We used multivariable logistic regression to develop a prediction model. Data were obtained from two recent randomized controlled trials on induction of labor versus expectant management in late preterm PROM (PPROMEXIL trials, (ISRCTN29313500 and ISRCTN05689407). Data from randomized as well as non-randomized women, who consented to the use of their medical data, were used. We evaluated 13 potential antepartum predictors for neonatal sepsis. Missing data were imputed. Discriminative ability of the model was expressed as the area under the receiver operating characteristic (ROC) curve and a calibration with both a calibration plot and the Hosmer and Lemeshow goodness-of-fit test. Overall performance of the prediction model was quantified as the scaled Brier score., Results: We studied 970 women. Thirty-three (3.4%) neonates suffered neonatal sepsis. Maternal age (OR 1.09 per year), maternal CRP level (OR 1.01 per mmol/l), maternal temperature (OR 1.80 per °C) and positive GBS culture (OR 2.20) were associated with an increased risk of neonatal sepsis. The model had an area under the ROC-curve of 0.71. The model had both a good calibration and accuracy., Conclusions: Antepartum parameters aid in the more precise prediction of the risk of neonatal sepsis in women with late preterm PPROM., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Pregnancies complicated by intrauterine growth restriction (IUGR) are at increased risk for neonatal morbidity and mortality. The Dutch nationwide disproportionate intrauterine growth intervention trial at term (DIGITAT trial) showed that induction of labour and expectant monitoring were comparable with respect to composite adverse neonatal outcome and operative delivery. In this study we compare the costs of both strategies., Study Design: A cost analysis was performed alongside the DIGITAT trial, which was a randomized controlled trial in which 650 women with a singleton pregnancy with suspected IUGR beyond 36 weeks of pregnancy were allocated to induction or expectant management. Resource utilization was documented by specific items in the case report forms. Unit costs for clinical resources were calculated from the financial reports of participating hospitals. For primary care costs Dutch standardized prices were used. All costs are presented in Euros converted to the year 2009., Results: Antepartum expectant monitoring generated more costs, mainly due to longer antepartum maternal stays in hospital. During delivery and the postpartum stage, induction generated more direct medical costs, due to longer stay in the labour room and longer duration of neonatal high care/medium care admissions. From a health care perspective, both strategies generated comparable costs: on average €7106 per patient for the induction group (N=321) and €6995 for the expectant management group (N=329) with a cost difference of €111 (95%CI: €-1296 to 1641)., Conclusion: Induction of labour and expectant monitoring in IUGR at term have comparable outcomes immediately after birth in terms of obstetrical outcomes, maternal quality of life and costs. Costs are lower, however, in the expectant monitoring group before 38 weeks of gestation and costs are lower in the induction of labour group after 38 weeks of gestation. So if induction of labour is considered to pre-empt possible stillbirth in suspected IUGR, it is reasonable to delay until 38 weeks, with watchful monitoring., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine and compare the diagnostic accuracy of the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) in the prediction of neonatal respiratory distress syndrome (RDS)., Study Design: A systematic review was performed to identify studies comparing either the L/S ratio or the LBC with the occurrence of RDS published between January 1999 and February 2009. Two independent reviewers performed study selection and data extraction. For each study sensitivity and specificity were calculated. Summary receiver-operating characteristics (ROC) curves, assessing the diagnostic performance of both tests, were constructed. A subgroup analysis was performed to estimate the sensitivity and specificity of the various cut-off values., Results: 13 studies were included. The ROC curves of the collected data illustrate that the LBC and L/S ratio perform equally well in the prediction of RDS. Comparison of the two summary ROC curves of each test indicates that the diagnostic performance of LBC might even have a slight advantage over L/S ratio. Due to the wide cut-off range it was not possible to define specific cut-off values with the best accuracy., Conclusion: We recommend replacing the L/S ratio as gold standard with the lamellar body count since the LBC is easy to perform, rapid, inexpensive, and available to all hospitals 24h per day., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To develop prediction models for long-term respiratory morbidity. To explore if respiratory distress syndrome (RDS) is a risk-indicator for long-term respiratory morbidity and to identify other perinatal risk-indicators for long-term respiratory morbidity., Study Design: In the Dutch POPS cohort 1338 live born infants delivered in The Netherlands in 1983, either before 32 completed weeks gestation and/or with a birth weight below 1500 g, were followed prospectively. We used multivariable logistic regression analyses to construct three prediction models for respiratory morbidity at 2, 5 and 19 years of age., Results: At 2 years of age, maternal smoking (adjusted OR 1.5, 95% CI 1.0-2.4), prolonged rupture of membranes (adjusted OR 2.3, 95% CI 1.3-4.1), pre-eclampsia (adjusted OR 1.9, 95% CI 1.1-4.1), male gender (adjusted OR 1.5, 95% CI 1.1-2.0) and BPD (adjusted OR 1.9, 95% CI 1.1-3.2) were significantly associated with respiratory morbidity. Prolonged rupture of membranes (adjusted OR 3.7, 95% CI 1.6-8.5), family history of asthma (adjusted OR 5.9, 95% CI 2.7-13.0) and BPD (adjusted OR 1.8, 95% CI 1.1-3.0) were significantly associated with respiratory morbidity at 5 years of age. At 19 years of age only higher social class was associated with decreased respiratory morbidity (adjusted OR 0.64, 95% CI 0.41-0.99). The areas under the curves (AUC) were 0.65, 0.71 and 0.61 respectively. The prediction models for respiratory morbidity at 2 and 5 years of age showed a good calibration, while the calibration plot for respiratory morbidity at 19 year was less optimal., Conclusions: RDS is not a risk-indicator for long-term respiratory morbidity at 2, 5 and 19 years in this cohort (OR 1.2, 95% 0.88-1.7; 1.3, 95% 0.88-2.0; OR 0.91, 95% 0.56-1.5 respectively). Future obstetric studies interested in the effect of a specific perinatal intervention on long-term respiratory morbidity, should consider taking bronchopulmonary dysplasia (BPD) as primary outcome instead of RDS., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the cost-effectiveness of diagnostic strategies incorporating the diagnostic value of patient characteristics for endometrial carcinoma using prediction models., Study Design: A decision analytic model was created to compare four diagnostic strategies for women with postmenopausal bleeding: the main outcome measures were 5 year survival, costs, and cost-effectiveness of three model based strategies compared to the strategy reflecting current practice., Results: A strategy selecting women for endometrial biopsy based on their history only, dominated all other strategies (more effective, less cost). In a clinical scenario where transvaginal sonography (TVS) was assumed to be an integral part of the consultation without additional costs, a strategy selecting high-risk women for TVS became the most cost-effective strategy., Conclusions: Strategies taking into account the individual probability based on a prognostic model are less costly than the currently applied strategy for a similar effectiveness. The most cost-effective strategy depends on the clinical setting: in areas where TVS is performed by the consulting gynecologist without extra costs, selective TVS based on history is the most cost-effective strategy. When TVS is not readily available and therefore incurs extra costs, a risk selection based on patient characteristics is most cost-effective., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Although not formally supported by guidelines, random glucose testing (RGT) is frequently used to screen for gestational diabetes mellitus (GDM). Results on test accuracy are inconclusive. The aim of this study was to systematically review the literature and calculate summary estimates of accuracy measures of RGT as screening test for GDM., Study Design: Systematic review to identify studies comparing RGT to oral glucose tolerance testing before 32 weeks of pregnancy. A systematic search without language restrictions was performed in MEDLINE (1950 till April 2008) and EMBASE (1980 to April 2008). Study selection and data extraction were performed by two independent reviewers. Outcome measures were summary estimates of test accuracy of RGT., Results: Six studies were included, reporting on 3537 women. Due to the small number of studies and heterogeneity, no summary estimates of test accuracy were calculated. Reported sensitivities and specificities of individual studies varied. For 100% sensitivity, specificity was around 40%. For sensitivity of 60% specificity was at most 80%. When specificity approached 100%, sensitivity dropped to 20-30%., Conclusion: Available evidence on the accuracy of RGT to test for GDM is limited. Based on studies in our systematic review, we consider single random glucose measurement inadequate to screen for GDM., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)