Validation of Reference Charts for Mid-Trimester Fetal Biometry.

OBJECTIVE: The aim of our study was to assess charts proposed for international use in the Intergrowth-21st Project. METHODS: Ultrasound data were collected from 43,923 healthy singleton pregnancies examined at 18-23 weeks of gestation in the Netherlands. Fetal measurements were converted into Z-scores using previous and current Dutch reference charts and Intergrowth charts. The distributions of the Z-scores were compared with the expected standard normal distribution. RESULTS: In the Dutch population, Intergrowth curves perform well for head circumference and biparietal diameter, but not for abdominal circumference (AC, Z- score = 0.43) and femur length (FL, Z-score = 0.26). Similar findings have been reported in other European countries. Compared with the population in the Intergrowth study, Dutch women are relatively tall (170 vs. 162 cm) and sturdy (67 vs. 61 kg) with a moderately high BMI. Maternal size, in particular maternal height, is positively correlated with birthweight. CONCLUSIONS: Whilst the establishment of the Intergrowth charts is an important step towards worldwide uniformity, for now locally derived charts still perform better, especially for AC and FL. Results from our validation study indicate that distinction between normal and pathologically small babies may be improved by taking maternal size into account.

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.

A novel immuno-gold labeling protocol for nanobody-based detection of HER2 in breast cancer cells using immuno-electron microscopy.

Immuno-electron microscopy is commonly performed with the use of antibodies. In the last decade the antibody fragment indicated as nanobody (VHH or single domain antibody) has found its way to different applications previously done with conventional antibodies. Nanobodies can be selected to bind with high affinity and specificity to different antigens. They are small (molecular weight ca. 15kDa) and are usually easy to produce in microorganisms. Here we have evaluated the feasibility of a nanobody binding to HER2 for application in immuno-electron microscopy. To obtain highest labeling efficiency combined with optimal specificity, different labeling conditions were analysed, which included nanobody concentration, fixation and blocking conditions. The obtained optimal protocol was applied for post-embedment labeling of Tokuyasu cryosections and for pre-embedment labeling of HER2 for fluorescence microscopy and both transmission and scanning electron microscopy. We show that formaldehyde fixation after incubation with the anti-HER2 nanobody, improves labeling intensity. Among all tested blocking agents the best results were obtained with a mixture of cold water fish gelatine and acetylated bovine serum albumin, which prevented a-specific interactions causing background labeling while preserving specific interactions at the same time. In conclusion, we have developed a nanobody-based protocol for immuno-gold labeling of HER2 for Tokuyasu cryosections in TEM as well as for pre-embedment gold labeling of cells for both TEM and SEM.

Complications of pregnancy and labour in women with Klippel-Trénaunay syndrome: a nationwide cross-sectional study.

OBJECTIVE: To evaluate complications of pregnancy, including thromboembolism, in women with extensive vascular malformations associated with Klippel-Trénaunay syndrome (KTS). DESIGN: Nationwide cross-sectional study. SETTING: Two tertiary expert centres and the Dutch Klippel-Trénaunay patient organisation. SAMPLE: Adult women with KTS. METHODS: Patients with KTS were invited to participate in a comprehensive online survey about their obstetric history. Reference data on pregnancy outcomes and complications of non-diseased women were collected from population-based cohorts from the literature. MAIN OUTCOME MEASURES: Prevalence of complications, specifically venous thromboembolism and postpartum haemorrhage. RESULTS: Sixty women completed the survey. Seventeen patients did not conceive, of whom three refrained from pregnancy because of KTS. A total of 97 pregnancies and 86 deliveries were reported in 43 patients. KTS-related symptoms were aggravated during pregnancy in 43% of patients. Deep vein thrombosis was present in 5.8% and pulmonary embolism was present in 2.3% of pregnancies, which was extremely high compared with the reference population (P < 0.0001), with a relative risk of 108.9 (95% confidence interval, 95% CI 46.48-255.03) and 106.2 (95% CI 26.97-418.10), respectively. Severe postpartum haemorrhage (PPH) occurred in 11% of KTS pregnancies, compared with 5.8% of pregnancies in the reference population (relative risk, RR 1.81, 95% CI 0.97-3.37, P = 0.06). CONCLUSIONS: Our data suggest that women with KTS have a significant risk of venous thromboembolic events, severe postpartum haemorrhage, and aggravation of KTS symptoms during pregnancy, and in early postpartum period. Obstetricians should counsel patients about these risks in the preconception phase. Antithrombotic prophylaxis should be considered in the obstetric management of patients with KTS. TWEETABLE ABSTRACT: High risk of complications during pregnancy and labour in women with Klippel-Trénaunay syndrome.

Labour pain with remifentanil patient-controlled analgesia versus epidural analgesia: a randomised equivalence trial.

OBJECTIVE: To distinguish satisfaction with pain relief using remifentanil patient-controlled analgesia (RPCA) compared with epidural analgesia (EA) in low-risk labouring women. DESIGN: Randomised controlled equivalence trial. SETTING: Eighteen midwifery practices and six hospitals in the Netherlands. POPULATION: A total of 408 pregnant women at low risk for obstetric complications initially under the care of primary-care midwives. METHODS: Women randomised before active labour to receive analgesia with RPCA or EA, if requested. MAIN OUTCOME MEASURES: Primary outcome was satisfaction with pain relief measured hourly using a visual analogue scale and summed as area under the curve (AUC). Secondary outcomes were overall satisfaction with pain relief, pain intensity scores during labour, mode of delivery, and maternal and neonatal outcomes. RESULTS: We randomised 418 women, of whom 409 could be followed for the primary endpoint. Analgesia was received by 46% (94/203) in the remifentanil group and 37% (76/206) in the epidural group. The AUC for satisfaction with pain relief was 32 in the remifentanil group and 31 in the epidural group (mean difference -0.50; 95% CI -6.8 to 5.9). Among women who actually received analgesia, these values were 23 and 35, respectively (mean difference -12; 95% CI -22 to -1.5). Secondary outcomes were comparable. CONCLUSIONS: In low-risk labouring women, we could not demonstrate equivalence between a strategy with RPCA to EA with respect to satisfaction with pain relief assessed during the total duration of labour. However, once applied satisfaction was higher in women who received epidural analgesia. TWEETABLE ABSTRACT: Satisfaction with pain relief is higher in women receiving epidural analgesia compared with Remifentanil PCA.

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.

D-CAT: Density and Clustering Annotation Tool for three dimensional electron microscopic volumes.

Three dimensional (3D) electron microscopy techniques have become valuable tools for investigating cellular architecture and the processes that govern it. A vast amount of information is available in every 3D tomogram but the options for presenting this information in a clear and visually appealing way are limited. To address this, we developed D-CAT; a MatLab-application to accurately visualize the distribution of membrane proteins and/or membrane-bound structures. Presence (density) and distribution (clustering, depletion) are presented as color-coded areas on membranes. By using IMOD models both as input and output format, we ensure that the application fits within workflows common in the field of 3D electron microscopy.

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.

Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial.

OBJECTIVE: To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians' decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term. DESIGN: A post hoc analysis of 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: A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management. METHODS: Data were analysed using logistic regression modelling. MAIN OUTCOME MEASURES: The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes. RESULTS: The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix. CONCLUSION: Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women. TRIAL REGISTRATION: The trial has been registered in the clinical trial register as ISRCTN08132825.

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.

FIB-SEM cathodoluminescence tomography: practical and theoretical considerations.

Focused ion beam-scanning electron microscope (FIB-SEM) tomography is a powerful application in obtaining three-dimensional (3D) information. The FIB creates a cross section and subsequently removes thin slices. The SEM takes images using secondary or backscattered electrons, or maps every slice using X-rays and/or electron backscatter diffraction patterns. The objective of this study is to assess the possibilities of combining FIB-SEM tomography with cathodoluminescence (CL) imaging. The intensity of CL emission is related to variations in defect or impurity concentrations. A potential problem with FIB-SEM CL tomography is that ion milling may change the defect state of the material and the CL emission. In addition the conventional tilted sample geometry used in FIB-SEM tomography is not compatible with conventional CL detectors. Here we examine the influence of the FIB on CL emission in natural diamond and the feasibility of FIB-SEM CL tomography. A systematic investigation establishes that the ion beam influences CL emission of diamond, with a dependency on both the ion beam and electron beam acceleration voltage. CL emission in natural diamond is enhanced particularly at low ion beam and electron beam voltages. This enhancement of the CL emission can be partly explained by an increase in surface defects induced by ion milling. CL emission enhancement could be used to improve the CL image quality. To conduct FIB-SEM CL tomography, a recently developed novel specimen geometry is adopted to enable sequential ion milling and CL imaging on an untilted sample. We show that CL imaging can be manually combined with FIB-SEM tomography with a modified protocol for 3D microstructure reconstruction. In principle, automated FIB-SEM CL tomography should be feasible, provided that dedicated CL detectors are developed that allow subsequent milling and CL imaging without manual intervention, as the current CL detector needs to be manually retracted before a slice can be milled. Due to the required high electron beam acceleration voltage for CL emission, the resolution for FIB-SEM CL tomography is currently limited to several hundreds of nm in XY and up to 650 nm in Z for diamonds. Opaque materials are likely to have an improved Z resolution, as CL emission generated deeper in the material is not able to escape from it.

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.