Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Weight loss in pregnancy and cardiometabolic profile in childhood: findings from a longitudinal birth cohort.

OBJECTIVE: To investigate the consequences of weight loss in pregnancy on pregnancy outcomes and cardiometabolic profile in childhood. DESIGN: Prospective birth cohort (ABCD study). SETTING: Between 2003 and 2004, all pregnant women in Amsterdam were approached for study participation. POPULATION: 7818 pregnant women were included, of which 3165 consented to having their children examined at 5-6 years of age. In 1956 children fasting capillary blood samples were also taken. METHODS: At antenatal booking, women answered questions about their pregnancy and whether they suffered from severe weight loss (SWL; >5 kg). Pregnancy details and outcomes were available through the obstetric caregiver. MAIN OUTCOME MEASURES: At birth main outcome measures were prematurity (<37 weeks) and birthweight. At follow-up, body mass index (BMI), blood pressure, glucose and lipids were assessed. RESULTS: SWL occurred in 6.8% of cases. Women with SWL had similar preterm birth rates compared with women without these complaints (adjusted OR 1.1, 95%CI 0.7, 1.7). Birthweight (adjusted difference - 31 g, 95%CI -76, 15) and BMI at 5-6 years of age (adjusted difference 0.2 kg/m(2) , 95%CI 0.0, 0.5) were similar in children born to mothers with SWL and without SWL, but blood pressure was increased. For diastolic blood pressure this association was independent of confounders (adjusted difference 1.4 mmHg, 95%CI 0.4, 2.4). Lipid and glucose levels were not significantly different between these groups. CONCLUSION: Early pregnancy weight loss, usually occurring as a manifestation of hyperemesis gravidarum, could have long-term consequences for offspring health.

Time to conception and time to live birth in women with unexplained recurrent miscarriage.

STUDY QUESTION: What is the time to conception in a cohort of women with unexplained recurrent miscarriage (RM). SUMMARY ANSWER: Median time to conception in women diagnosed with unexplained RM was 21 weeks (interquartile range (IQR) 8-55 weeks), with a cumulative incidence of conception of 74% after 12 months of trying to conceive. WHAT IS KNOWN ALREADY: There is no effective treatment in couples with unexplained RM. Adequate counselling about their prognosis, for example time to conception and time to a live birth, is therefore very important. So far, there are no studies that give insight on these issues. STUDY DESIGN, SIZE, DURATION: A nested prospective cohort study was performed from February 2004 through July 2009 within a multicentre randomized placebo-controlled trial (ALIFE trial) on anticoagulant treatment in 364 women with unexplained RM. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 251 women who were not pregnant at the time of diagnosis of unexplained RM were included in this study. Of these, 13% became pregnant with ART, and all other women conceived naturally. The primary outcome was time to conception in weeks, calculated from the moment of diagnosis until conception measured by a urinary HCG. Secondary outcome was time to a live birth in the subsequent pregnancy. The relative prognostic significance of female age, the number of preceding miscarriages, interventions within the trial and the presence or absence of a preceding late miscarriage, a previous live birth and factor V Leiden mutation, was evaluated by Cox regression for time to conception and by competing risk modelling for time to live birth, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative incidence of conception was 56% after 6 months, 74% after 12 months and 86% after 24 months of which 65% resulted in a live birth. The median time to conception was 21 weeks (IQR 8-55 weeks). Of potential prognostic factors, the presence of the factor V Leiden mutation resulted in a significantly shorter median time to conception of 11 weeks for carriers versus 23 weeks for non-carriers (hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.03-3.65). The cumulative incidence of a live birth of the subsequent pregnancy was 0% after 6 months, 23% after 12 months and 50% after 24 months. The median time to a live birth of the subsequent pregnancy was 102 weeks (IQR 82-115 weeks). The number of previous miscarriages was the only prognostic factor (HR 0.83, 95% CI 0.74-0.94) significantly associated with time to a live birth of the subsequent pregnancy. LIMITATIONS, REASONS FOR CAUTION: In our study only the subsequent pregnancy after diagnosing unexplained RM was included. A future collection of cumulative follow-up data of all the women included in this cohort may provide outcomes of all pregnancies following the diagnosis of unexplained RM. WIDER IMPLICATIONS OF THE FINDINGS: Time to conception in women diagnosed with unexplained RM appears to be comparable with time to conception in healthy fertile women, as reported in the literature. The interesting finding that women with Factor V Leiden mutation have a significant shorter time to conception may suggest a favourable embryo implantation process. Future research is needed to confirm these findings and unravel the biology of early implantation. STUDY FUNDING/COMPETING INTEREST(S): The RCT used for this nested cohort study was funded by a grant (945-27-003) from the Netherlands Organization for Health Research and Development and a grant from GlaxoSmithKline. Study drugs (aspirin and placebo) were packaged and donated by Meda Pharma. This analysis was supported by a VIDI innovative research grant from the Netherlands Organisation for Scientific Research (NWO) 016.126.364. There are no potential conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This cohort study was nested in the randomized controlled trial; ALIFE study (Current Controlled Trials number, ISRCTN 58496168).

Transfusion policy after severe postpartum haemorrhage: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage. DESIGN: Randomised non-inferiority trial. SETTING: Thirty-seven Dutch university and general hospitals. POPULATION: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities. METHODS: Women were allocated to RBC transfusion or non-intervention. MAIN OUTCOME MEASURES: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum. RESULTS: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable. CONCLUSIONS: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified.

Postpartum urinary retention: a systematic review of adverse effects and management.

INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention (PUR) is a well-known condition after childbirth. Often clinicians assume that this condition is transient, either through belief or by not being aware that its occurrence as measurement of post-void residual volume (PVRV) is often not routine. However, long lasting urinary retention is a serious condition that needs management in order to prevent urogenital tract morbidity. By performing a systematic review of the adverse effects of PUR and management of this condition, we aimed to identify the necessity of diagnosing this condition in the puerperium and to evaluate whether treatment is required. METHODS: We searched for all studies on PUR in OVID MEDLINE, OVID EMBASE, and ongoing Trial registers. Two reviewers independently screened and extracted the data. RESULTS: Twenty-four papers were included in this review. Limited data on adverse effects demonstrate potential morbidities, like micturition symptoms and sporadically spontaneous bladder ruptures, related to PUR. CONCLUSIONS: Based on current literature, evidence stating that PUR is harmless is lacking. Future research should focus on management strategies for overt PUR and the long-term consequences of covert PUR. Until these results are available, clinicians should be aware of the potential consequences and therefore keep trying to identify patients at risk of PUR and patients with the actual condition.

Transgenerational effects of prenatal exposure to the 1944-45 Dutch famine.

OBJECTIVE: We previously showed that maternal under-nutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. Also, we found increased neonatal adiposity among the grandchildren of women who had been undernourished during pregnancy. In the present study we investigated whether these transgenerational effects have led to altered body composition and poorer health in adulthood in the grandchildren. DESIGN: Historical cohort study. SETTING: Web-based questionnaire. POPULATION: The adult offspring (F2) of a cohort of men and women (F1) born around the time of the 1944-45 Dutch famine. METHODS: We approached the F2 adults through their parents. Participating F2 adults (n = 360, mean age 37 years) completed an online questionnaire. MAIN OUTCOME MEASURES: Weight, body mass index (BMI), and health in F2 adults, according to F1 prenatal famine exposure. RESULTS: Adult offspring (F2) of prenatally exposed F1 fathers had higher weights and BMIs than offspring of prenatally unexposed F1 fathers (+4.9 kg, P = 0.03; +1.6 kg/m(2), P = 0.006). No such effect was found for the F2 offspring of prenatally exposed F1 mothers. We observed no differences in adult health between the F2 generation groups. CONCLUSIONS: Offspring of prenatally undernourished fathers, but not mothers, were heavier and more obese than offspring of fathers and mothers who had not been undernourished prenatally. We found no evidence of transgenerational effects of grandmaternal under-nutrition during gestation on the health of this relatively young group, but the increased adiposity in the offspring of prenatally undernourished fathers may lead to increased chronic disease rates in the future.

Cost-effectiveness of induction of labour at term with a Foley catheter compared to vaginal prostaglandin E2 gel (PROBAAT trial).

OBJECTIVE: To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Obstetric departments of one university and 11 teaching hospitals in the Netherlands. POPULATION: 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. METHODS: Cost-effectiveness analysis from a hospital perspective. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: Foley catheter and prostaglandin E2 labour induction generate comparable costs.

Transvaginal sonographic assessment of cervical length and wedging for predicting outcome of labor induction at term: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to assess the predictive capacity of transvaginal sonographic assessment of the cervix for the outcome of induction of labor. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library, and manually searched reference lists of review articles and eligible primary articles. Studies in all languages were eligible if published in full. Two reviewers independently selected studies and extracted data on study characteristics, quality and test accuracy. We then calculated pooled sensitivities and specificities (with 95% CIs) and summary receiver-operating characteristics (sROC) curves. Outcome measures were test accuracy of sonographically measured cervical length and cervical wedging for Cesarean section, not achieving vaginal delivery within 24 h and not achieving active labor. RESULTS: We included 31 studies reporting on both cervical length and outcome of delivery. The quality of the included studies was mediocre. Sensitivity of cervical length in the prediction of Cesarean delivery ranged from 0.14 to 0.92 and specificity ranged from 0.35 to 1.00. The estimated sROC curve for cervical length indicated a limited predictive capacity in the prediction of Cesarean delivery. Summary estimates of sensitivity/specificity combinations of cervical length at different cut-offs for Cesarean delivery were 0.82/0.34, 0.64/0.74 and 0.13/0.95 for 20, 30 and 40 mm, respectively. For cervical wedging in the prediction of failed induction of labor summary point estimates of sensitivity/specificity were 0.37/0.80. CONCLUSIONS: Cervical length and cervical wedging as measured sonographically at or near term have moderate capacity to predict the outcome of delivery after induction of labor.

Value of adding second-trimester uterine artery Doppler to patient characteristics in identification of nulliparous women at increased risk for pre-eclampsia: an individual patient data meta-analysis.

OBJECTIVE: To investigate the value of adding second-trimester uterine artery Doppler ultrasound to patient characteristics in the identification of nulliparous women at risk for pre-eclampsia. METHODS: For this individual patient data meta-analysis, studies published between January 1995 and December 2009 were identified in MEDLINE and EMBASE. Studies were eligible in which Doppler assessment of the uterine arteries had been performed among pregnant women and in which gestational age at ultrasound, Doppler ultrasound findings and data on the occurrence of pre-eclampsia were available. We invited corresponding authors to share their original datasets. Data were included of nulliparous women who had had a second-trimester uterine artery Doppler ultrasound examination. Shared data were checked for consistency, recoded to acquire uniformity and merged into a single dataset. We constructed random intercept logistic regression models for each of the patient and Doppler characteristics in isolation and for combinations. We compared goodness of fit, discrimination and calibration. RESULTS: We analyzed eight datasets, reporting on 6708 nulliparous women, of whom 302 (4.5%) developed pre-eclampsia. Doppler findings included higher, lower and mean pulsatility index (PI) and resistance index (RI) and any or bilateral notching. Of these, the best predictors were combinations of mean PI or RI and bilateral notching, with areas under the receiver-operating characteristics curve (AUC) of 0.75 (95% confidence interval (CI), 0.56-0.95) and 0.70 (95% CI, 0.66-0.74), respectively. Addition of Doppler findings to the patient characteristics blood pressure or body mass index (BMI) significantly improved discrimination. A model with blood pressure, PI and bilateral notching had an AUC of 0.85 (95% CI, 0.67-1.00). CONCLUSIONS: The addition of Doppler characteristics of mean PI or RI and bilateral notching to patient characteristics of blood pressure or BMI improves the identification of nulliparous women at risk for pre-eclampsia.

Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND: Biomarkers have been proposed for identification of women at increased risk of developing pre-eclampsia. OBJECTIVES: To investigate the capacity of circulating placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG) to predict pre-eclampsia. SEARCH STRATEGY: Medline and Embase through October 2010 and reference lists of reviews, without constraints. SELECTION CRITERIA: We included original publications on testing of PlGF, VEGF, sFLT1 and sENG in serum or plasma of pregnant women at <30 weeks of gestation and before clinical onset of pre-eclampsia. DATA COLLECTION AND ANALYSIS: Two reviewers independently identified eligible studies, extracted descriptive and test accuracy data and assessed methodological quality. Summary estimates of discriminatory performance were obtained. MAIN RESULTS: We included 34 studies. Concentrations of PlGF (27 studies) and VEGF (three studies) were lower in women who developed pre-eclampsia: standardised mean differences (SMD) -0.56 (95% CI -0.77 to -0.35) and -1.25 (95% CI -2.73 to 0.23). Concentrations of sFLT1 (19 studies) and sENG (ten studies) were higher: SMD 0.48 (95% CI 0.21-0.75) and SMD 0.54 (95% CI 0.24-0.84). The summary diagnostic odds ratios were: PlGF 9.0 (95% CI 5.6-14.5), sFLT1 6.6 (95% CI 3.1-13.7), sENG 4.2 (95% CI 2.4-7.2), which correspond to sensitivities of 32%, 26% and 18%, respectively, for a 5% false-positive rate. AUTHOR'S CONCLUSIONS: PlGF, sFLT1 and sENG showed modest but significantly different concentrations before 30 weeks of gestation in women who developed pre-eclampsia. Test accuracies of all four markers, however, are too poor for accurate prediction of pre-eclampsia in clinical practice.

Risk factors for postpartum urinary retention: a systematic review and meta-analysis.

BACKGROUND: Postpartum urinary retention (PUR) is a common condition with varying prevalence. Measurement of the post-void residual volume (PVRV) is not regularly performed. Various studies have been published on overt (the inability to void after giving birth, requiring catheterisation) and covert (an increased PVRV after spontaneous micturition) PUR. To evaluate which clinical prognostic factors are related to PUR, the identification of independent risk factors for covert and overt PUR is needed. OBJECTIVES: We performed a systematic review and meta-analysis of observational studies reporting on risk factors for PUR. SEARCH STRATEGY: Systematic search of MEDLINE and EMBASE to September 2011. SELECTION CRITERIA: Articles that reported on women diagnosed with PUR or with an abnormal PVRV. DATA COLLECTION AND ANALYSIS: The included articles were selected by two authors. We constructed two-by-two tables for potential risk factors of overt and covert PUR and calculated pooled odds ratios (ORs) with 95% confidence intervals. MAIN RESULTS: Twenty-three observational studies with original data were eligible for data extraction, of which 13 could be used for meta-analysis. Statistically significant risk factors for overt PUR were epidural analgesia (OR 7.7), instrumental delivery (OR 4.5), episiotomy (OR 4.8) and primiparity (OR 2.4). For covert PUR, variety in the definitions used resulted in heterogeneity; no significant prognostic factors were found. CONCLUSIONS: Instrumental delivery, epidural analgesia, episiotomy and nulliparity are statistically significantly associated with a higher incidence of overt PUR. The same factors were identified for covert PUR, but without statistical significance. Uniformity in definitions in future research is essential to create a prognostic model.

Is short first-trimester crown-rump length associated with spontaneous preterm birth?

OBJECTIVE: To assess the association between first-trimester crown-rump length (CRL) and the risk of spontaneous preterm birth before 32 weeks' gestation. METHODS: We performed a matched case-control study of 129 women with spontaneous preterm birth at < 32 weeks' gestation (cases) and 129 women with term deliveries (controls) using data stored in the ultrasound and obstetric databases of our tertiary referral center. Cases and controls were individually matched based on maternal age, parity, history of preterm birth and medical indication for antenatal care. Fetal CRL measured between 8 + 0 and 13 + 6 weeks was expressed as multiples of the median (MoM) expected CRL, based on last menstrual period. We investigated the association between CRL-MoM and spontaneous preterm birth using logistic regression analysis. RESULTS: CRL-MoM was not associated with spontaneous preterm birth: odds ratio (OR) 1.10 (95% CI, 0.89-1.36) per 0.10 MoM increase in CRL. Timing of measurement did not influence the model (P = 0.59). This was confirmed when restricting the analysis to the 93 pairs with CRL measurements made between 10 + 0 and 13 + 6 weeks: OR for preterm birth 1.07 (95% CI, 0.83-1.37) per 0.10 MoM increase in CRL. CONCLUSION: A short CRL in the first trimester is not associated with spontaneous preterm birth before 32 weeks' gestation, thus short CRL cannot be used to identify women at increased risk of preterm birth.

Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis.

BACKGROUND: There is evidence that hyperemesis gravidarum (HG) is associated with a predominance of female fetuses, lower birthweights and shorter gestational ages at birth. As the adverse effects of prematurity and low birthweight on disease risk in later life have become increasingly clear, the repercussions of HG might not be limited to adverse perinatal outcomes. OBJECTIVES: To summarise the evidence on short- and long-term outcomes of pregnancies with HG. SEARCH STRATEGY: A literature search was conducted in the electronic databases Medline and Embase. SELECTION CRITERIA: Studies were included that reported on the fetal, neonatal and long-term outcome of pregnancies complicated by HG. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. Meta-analysis was performed using review manager. MAIN RESULTS: Women with HG during pregnancy were more likely to have a female child (OR 1.27; 95% CI 1.21-1.34). They were also more likely to have a baby with low birthweight (LBW, <2500 kg; OR 1.42; 95% CI 1.27-1.58) that was small for gestational age (SGA; OR 1.28; 95% CI 1.02-1.60), and to deliver prematurely (OR 1.32; 95% CI 1.04-1.68). There was no association with Apgar scores, congenital anomalies or perinatal death. One study described an association between HG and testicular cancer in the offspring. AUTHOR'S CONCLUSIONS: There is evidence that HG is associated with a higher female/male ratio of offspring and a higher incidence of LBW, SGA and premature babies. Little is known about the long-term health effects of babies born to mothers whose pregnancies were complicated by HG.

Ethical review of COVID-19 research in the Netherlands; a mixed-method evaluation among medical research ethics committees and investigators.

BACKGROUND: During the beginning of the COVID-19 pandemic there was an urgent need for accelerated review of COVID-19 research by Medical Research Ethics Committees (MRECs). In the Netherlands this led to the implementation of so-called 'fast-track-review-procedures' (FTRPs) to enable a swift start of urgent and relevant research. The objective of this study is to evaluate FTRPs of MRECs in the Netherlands during the COVID-19 pandemic and to compare them with the regular review procedures (RRPs). METHODS AND FINDINGS: An explanatory sequential mixed method study was conducted. Online questionnaires and four group interviews were conducted among MREC representatives and investigators of COVID-19 research. In addition, data from a national research registration system was requested. Main outcome measures are differences in timelines, quality of the review and satisfaction between FTRPs and RRPs. The total number of review days was shorter in FTRP (median 10.5) compared to RRPs (median 98.0). Review days attributable to the MRECs also declined in FTRPs (median 8.0 versus 50.0). This shortening can be explained by installing ad hoc (sub)committees, full priority given to COVID-19 research, regular research put on hold, online review meetings and administrative leniency. The shorter timelines did not affect the perceived quality of the review and ethical and legal aspects were not weighted differently. Both MREC representatives and investigators were generally satisfied with the review of COVID-19 research. Weaknesses identified were the lack of overview of COVID-19 research and central collaboration and coordination, the delay of review of regular research, and limited reachability of secretariats. CONCLUSIONS: This study shows that accelerated review is feasible during emergency situations. We did not find evidence that review quality was compromised and both investigators and MRECs were content with the FTRP. To improve future medical ethical review during pandemic situations and beyond, distinguishing main and side issues, working digitally, and (inter)national collaboration and coordination are important.

What women want and why. Women's preferences for induction of labour or expectant management in late-term pregnancy.

BACKGROUND: Both induction of labour at 41 weeks and expectant management until 42 weeks are common management strategies in low-risk pregnancy since there is no consensus on the optimal timing of induction in late-term pregnancy for the prevention of adverse outcomes. Our aim was to explore maternal preference for either strategy and the influence on quality of life and maternal anxiety on this preference. METHODS: Obstetrical low-risk women with an uncomplicated pregnancy were eligible when they reached a gestational age of 41 weeks. They were asked to fill in questionnaires on quality of life (EQ6D) and anxiety (STAI-state). Reasons of women's preferences for either induction or expectant management were explored in a semi-structured questionnaire containing open ended questions. RESULTS: Of 782 invited women 604 (77.2%) responded. Induction at 41 weeks was preferred by 44.7% (270/604) women, 42.1% (254/604) preferred expectant management until 42 weeks, while 12.2% (74/604) of women did not have a preference. Women preferring induction reported significantly more problems regarding quality of life and were more anxious than women preferring expectant management (p<0.001). Main reasons for preferring induction of labour were: "safe feeling" (41.2%), "pregnancy taking too long" (35.4%) and "knowing what to expect" (18.6%). For women preferring expectant management, the main reason was "wish to give birth as natural as possible" (80.3%). CONCLUSION: Women's preference for induction of labour or a policy of expectant management in late-term pregnancy is influenced by anxiety, quality of life problems (induction), the presence of a wish for natural birth (expectant management), and a variety of additional reasons. This variation in preferences and motivations suggests that there is room for shared decision making in the management of late-term pregnancy.

An economic analysis of induction of labour and expectant monitoring in women with gestational hypertension or pre-eclampsia at term (HYPITAT trial).

OBJECTIVE: To assess the economic consequences of labour induction compared with expectant monitoring in women with gestational hypertension or pre-eclampsia at term. DESIGN: An economic analysis alongside the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT). SETTING: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. POPULATION: Women diagnosed with gestational hypertension or pre-eclampsia between 36(+0) and 41(+0) weeks of gestation, randomly allocated to either induction of labour or expectant monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a societal perspective during a 1-year time horizon. MAIN OUTCOME MEASURES: One-year costs were estimated and health outcomes were expressed as the prevalence of poor maternal outcome defined as either maternal complications or progression to severe disease. RESULTS: The average costs of induction of labour (n = 377) were €7077 versus €7908 for expectant monitoring (n = 379), with an average difference of -€831 (95% CI -€1561 to -€144). This 11% difference predominantly originated from the antepartum period: per woman costs were €1259 for induction versus €2700 for expectant monitoring. During delivery, more costs were generated following induction (€2190) compared with expectant monitoring (€1210). No substantial differences were found in the postpartum, follow-up and for non-medical costs. CONCLUSION: In women with gestational hypertension or mild pre-eclampsia at term, induction of labour is less costly than expectant monitoring because of differences in resource use in the antepartum period. As the trial already demonstrated that induction of labour results in less progression to severe disease without resulting in a higher caesarean section rate, both clinical and economic consequences are in favour of induction of labour in these women. TRIAL REGISTRATION: The trial has been registered in the clinical trial register as ISRCTN08132825.

Ductus venosus pulsatility index measurement reduces the false-positive rate in first-trimester screening.

OBJECTIVE: To investigate if ductus venosus (DV) pulsatility index for veins (PIV) and a-wave measurements can increase the accuracy of first-trimester Down syndrome screening in a high-risk population. METHODS: The database of our fetal medicine unit was searched for all cases at increased first-trimester Down syndrome risk. Multivariable logistic regression was used to construct a prediction rule for chromosomal anomalies at any given maternal age, nuchal translucency multiples of the median (NT-MoM) and DV-PIV MoM. The discriminative ability of the model was assessed by using receiver-operating characteristics (ROC) analysis. RESULTS: The study population included 445 fetuses. DV-PIV was increased (≥ 95(th) percentile) in 239 (54%) and DV a-wave was abnormal in 187 fetuses (42%). In this cohort, 80% of all chromosomal anomalies were identified by an increased DV-PIV and 68% by an abnormal a-wave. The odds of chromosomal anomalies increased by a factor of 4.2 per MoM increase in DV-PIV, adjusted for NT and maternal age. The area under the ROC curve for the prediction of chromosomal anomalies was 0.79. After correction for DV-PIV, DV a-wave did not significantly add to the prediction of chromosomal anomalies. CONCLUSION: In a population of fetuses at increased first-trimester risk for Down syndrome, the combination in a logistic regression model of NT, DV-PIV and maternal age can improve the accuracy of screening for trisomy 21 and other chromosomal anomalies. This is the first study that models the additional value of DV-PIV as a continuous variable to NT measurement alone in a high-risk first-trimester population.

Indicators for intervention during the expulsive second-stage arrest of labour.

OBJECTIVE: To identify antepartum and intrapartum indicators of obstetric interventions during the expulsive second-stage arrest of labour. DESIGN: Retrospective cohort study. SETTING: The Netherlands. POPULATION: A cohort of 389,086 women with singleton, cephalic, term, live-birth deliveries from 2002 to 2004 who had entered the expulsive second stage of labour. Of all these deliveries, 37,899 (9.7%) were complicated by expulsive second-stage arrest of labour. Women with a prior Caesarean section or women undergoing an elective Caesarean section were excluded. METHODS: All deliveries in the Netherlands from 2002 to 2004 were registered in the Netherlands Perinatal Registry, which contains the linked and validated data of three databases. Uni- and multivariable logistic regression analyses were performed. MAIN OUTCOME MEASURES: Ante- and intrapartum indicators for interventions during expulsive second-stage arrest of labour. RESULTS: Primiparous delivery was the most important antepartum indicator for intervention during expulsive second-stage arrest. Using multivariable analysis the following antepartum indicators were associated with intervention for expulsive second-stage arrest of primiparous labour: maternal age, gestational age, diabetes, hypertension and labour induction. Prominent intrapartum indicators for primiparous deliveries were fetal head position and oxytocin augmentation. CONCLUSION: Multiple significant antepartum and intrapartum indicators associated with intervention for expulsive second-stage arrest of labour were identified in this large retrospective study. Prominent were the associations of parity, maternal age and fetal head position with expulsive second-stage arrest. The identified factors should be further evaluated in prospective studies that aim to develop prediction models.

Seven placental transcripts characterize HELLP-syndrome.

The human placenta is prerequisite for the development of gestational hypertensive diseases like early-onset preeclampsia (PE) and Hemolysis, Elevated Liver enzymes and Low platelets (HELLP) syndrome. Both syndromes are associated with extensive maternal and perinatal mortality, and morbidity with life long consequences. We aimed to investigate differences in gene expression between placental tissue obtained from normotensive pregnant women and women with PE and HELLP syndrome. Firstly, comparison of Serial Analysis of Gene Expression profiles of 28 weeks' control placenta (available after idiopathic premature delivery) to a HELLP/PE placenta matched for gestational age identified 404 differentially expressed transcripts. Secondly, using sqPCR, the expression levels of 37 of these transcripts were analyzed in placentas of 36 pregnant women, 22 with preeclampsia and HELLP syndrome. Thirdly, nearest centroid classification determined the HELLP specific molecular signature consisting of the upregulated expression of genes encoding the vascular endothelial growth factor receptor (FLT1), leptin (LEP), pappalysin 2 (PAPPA2), and WW domain containing transcription regulator 1 (WWTR1) combined with down regulated expression of the genes encoding cadherin-associated protein (CTNNAL), glutathione S-transferase pi (GSTP1) and calgranulin A (S100A8). This set discriminates HELLP placenta from control and PE placenta with a 24% misclassification rate (95% CI 8.3-41.9%), independent from known risk factors like parity and ethnicity. The transcripts involved correspond to diverse molecular pathways, exemplifying the multigenic molecular basis of the disorder. This distinct placental molecular signature suggests that HELLP is not a PE variant but a separate disease entity. Our data may prove fundamental for the further molecular analysis of PE and HELLP syndrome.

Cell-derived microparticles and complement activation in preeclampsia versus normal pregnancy.

BACKGROUND: Inflammation plays a major role in the vascular dysfunction seen in preeclampsia, and several studies suggest involvement of the complement system. OBJECTIVES: To investigate whether complement activation on the surface of microparticles is increased in plasma of preeclamptic patients versus healthy pregnant controls. METHODS: Microparticles from plasma of preeclamptic (n=10), healthy pregnant (n=10) and healthy nonpregnant (n=10) women were analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C-reactive protein [CRP], serum amyloid P component [SAP], immunoglobulin [Ig]M, IgG). Fluid phase complement activation products and activator molecules were also determined. RESULTS: Levels of microparticles with bound complement components showed no increase in complement activation on the microparticle surface in preeclamptic women, in line with levels of fluid phase complement activation products. In healthy nonpregnant and pregnant women, bound CRP was associated with classical pathway activation on the microparticle surface, and in healthy pregnant women IgM and IgG molecules also contributed. In preeclamptic women, microparticles with bound SAP and those with IgG seemed to contribute to C1q binding without a clear association to further classical pathway activation. Furthermore, significantly increased levels of microparticles with bound CRP were present in preeclamptic compared with healthy pregnant women (median 178x10(6)/L versus 47x10(6)/L, P<0.01), but without concomitant increases in complement activation. CONCLUSIONS: We found no evidence of increased complement activation on the microparticle surface in preeclamptic women. Microparticles with bound CRP were significantly increased, but in contrast to healthy pregnant and nonpregnant women, this was not associated with increased classical pathway activation on the surface of the microparticles.