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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 degrees 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Contains fulltext : 118346.pdf (Publisher’s version ) (Open Access) IMPORTANCE: In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome. OBJECTIVE: To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth. DESIGN, SETTING, AND PARTICIPANTS: APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in The Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010). INTERVENTION: Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n = 201) or placebo (n = 205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses. MAIN OUTCOME MEASURES: Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis. RESULTS: Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45). CONCLUSIONS AND RELEVANCE: In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1336.

Background Preterm prelabour rupture of membranes (PPROM) before 26 weeks can delay lung development and can cause pulmonary hypoplasia, as a result of oligohydramnios. Restoring the amniotic fluid volume by transabdominal amnioinfusion might prevent abnormal lung development and might have a protective effect for neurological complications, fetal deformities and neonatal sepsis. Objectives To assess the effectiveness of transabdominal amnioinfusion in improving perinatal outcome in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). Selection criteria All randomised controlled trials comparing transabdominal amnioinfusion with no transabdominal amnioinfusion. Cluster- or quasi-randomised trials were not eligible for inclusion. In cases where only an abstract was available, we attempted to find the full articles. Data collection and analysis Two review authors assessed trials for inclusion. No eligible trials were identified. Main results There are no included studies. Authors' conclusions There is currently no evidence to evaluate the use of transabdominal amnioinfusion in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks for improving perinatal outcome. Further research examining the effects of this intervention is needed. Two randomised controlled trials are ongoing but final data have not yet been published.

Contains fulltext : 172293.PDF (Publisher’s version ) (Open Access) BACKGROUND: There is an ongoing discussion on the rising CS rate worldwide. Suboptimal guideline adherence may be an important contributor to this rise. Before improvement of care can be established, optimal CS care in different settings has to be defined. This study aimed to develop and measure quality indicators to determine guideline adherence and identify target groups for improvement of care with direct effect on caesarean section (CS) rates. METHOD: Eighteen obstetricians and midwives participated in an expert panel for systematic CS quality indicator development according to the RAND-modified Delphi method. A multi-center study was performed and medical charts of 1024 women with a CS and a stratified and weighted randomly selected group of 1036 women with a vaginal delivery were analysed. Quality indicator frequency and adherence were scored in 2060 women with a CS or vaginal delivery. RESULTS: The expert panel developed 16 indicators on planned CS and 11 indicators on unplanned CS. Indicator adherence was calculated, defined as the number of women in a specific obstetrical situation in which care was performed as recommended in both planned and unplanned CS settings. The most frequently occurring obstetrical situations with low indicator adherence were: 1) suspected fetal distress (frequency 17%, adherence 46%), 2) non-progressive labour (frequency 12%, CS performed too early in over 75%), 3) continuous support during labour (frequency 88%, adherence 37%) and 4) previous CS (frequency 12%), with adequate counselling in 15%. CONCLUSIONS: We identified four concrete target groups for improvement of obstetrical care, which can be used as a starting point to reduce CS rates worldwide.

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

We sought to predict neonatal metabolic acidosis at birth using antepartum obstetric characteristics (model 1) and additional characteristics available during labor (model 2). In 5667 laboring women from a multicenter randomized trial that had a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation, we predicted neonatal metabolic acidosis. Based on literature and clinical reasoning, we selected both antepartum characteristics and characteristics that became available during labor. After univariable analyses, the predictors of the multivariable models were identified by backward stepwise selection in a logistic regression analysis. Model performance was assessed by discrimination and calibration. To correct for potential overfitting, we (internally) validated the models with bootstrapping techniques. Of 5667 neonates born alive, 107 (1.9%) had metabolic acidosis. Antepartum predictors of metabolic acidosis were gestational age, nulliparity, previous cesarean delivery, and maternal diabetes. Additional intrapartum predictors were spontaneous onset of labor and meconium-stained amniotic fluid. Calibration and discrimination were acceptable for both models (c-statistic 0.64 and 0.66, respectively). In women with a high-risk singleton term pregnancy in cephalic presentation, we identified antepartum and intrapartum factors that predict neonatal metabolic acidosis at birth.

To evaluate the added value of the baseline T/QRS ratio to other known risk factors in predicting adverse outcome and interventions for suspected fetal distress.Prospective cohort study.Three academic and six non-academic teaching hospitals in the Netherlands.Laboring women with a high-risk cephalic singleton pregnancy beyond 36 weeks of gestation.We obtained STAN(®) recordings (ST-analysis, Neoventa, Sweden) from two previous studies. Three patient groups were defined: cases with adverse outcome, cases with emergency delivery because of suspected fetal distress without adverse outcome, and a reference group of uncomplicated cases. Baseline T/QRS ratios among the adverse outcome and intervention for suspected fetal distress cases were compared to those of the uncomplicated cases. The ability of baseline T/QRS to predict adverse outcome and suspected fetal distress was determined using a multivariable logistic model.The added value of the baseline T/QRS to other known risk factors in the prediction of adverse outcome and interventions for suspected fetal distress.From 3462 recordings, 2459 were available for analysis. Median baseline T/QRS for uncomplicated cases, adverse outcome and interventions for suspected fetal distress were 0.12 (range 0.00-0.52), 0.12 (0.00-0.42) and 0.13 (0.00-0.39), respectively. There was no statistical difference between these groups. Multivariable analysis showed no added value of baseline T/QRS in the prediction of either adverse outcome or interventions for suspected fetal distress.Baseline T/QRS has no added value in the prediction of adverse neonatal outcome or interventions for suspected fetal distress.

Purpose. To evaluate reproducibility of fetal renal pelvis volume as assessed by the Virtual Organ Computer Aided AnaLysis (VOCAL) imaging program and by Automatic Volume Calculation (SonoAVC). In addition, the intra- and interobserver reliability of fetal renal pelvis volume measurements with SonoAVC were established. Methods. In this study, the fetal renal pelvis volume was measured using 3D ultrasonography in 76 kid- neys of 66 fetuses with renal pelvis dilatation in the second or third trimester of pregnancy. After volume acquisition by one observer, the reproducibility of volume calculation was assessed using VOCAL imag- ing program and SonoAVC by two observers. Intra- and interobserver reproducibility was evaluated by calculating intraclass correlation coefficients (ICC), coefficient of variation (CV) and repeatability coeffi- cient (r). Bland-Altman plots were generated to explore agreement. Results. A high degree of reproducibility was observed between VOCAL and SonoAVC, ICC of 0.989; 95% CI 0.983-0.993, respectively. Intraobserver reproducibility of volume measure- ments performed by SonoAVC demonstrated a high degree of reliability with ICC of 0.995 (95% CI 0.993- 0.997), CV 6.05% and r of 0.75. The interobserver reproducibility with ICC of 0.995 (95% CI 0.992-0.997), CV 10.14% and r 1.21 was also indicative of good reliability. Conclusion. Volume measurements of fetal renal pelvis performed by SonoAVC renders reproducible measurements in comparison with the VOCAL imag- ing program. There is no significant difference between VOCAL imaging program and SonoAVC. The intra- and interobserver reliability of the fetal renal pel- vis measurements made by SonoAVC were consid- ered to be very good. SonoAVC, however, needs post processing in the majority of cases but is less time consuming than VOCAL. V C 2013 Wiley Periodicals, Inc. J Clin Ultrasound 00:000-000, 2013; Published online in Wiley Online Library (wileyonlinelibrary. com). DOI: 10.1002/jcu.22039

Contains fulltext : 108337.pdf (Publisher’s version ) (Open Access) BACKGROUND: At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term. METHODS AND FINDINGS: We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34(+0) and 37(+0) wk of gestation. Participants were randomly allocated in a 1:1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate. From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported. Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM. CONCLUSIONS: In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29313500

Item does not contain fulltext OBJECTIVE: Gestational hypertension (GH) and preeclampsia (PE) are major contributors to maternal and neonatal morbidity and mortality. In GH or PE, labor may be either induced or monitored expectantly. We studied maternal health-related quality of life (HR-QoL) after induction of labor versus expectant monitoring in GH or PE at term. We performed the HR-QoL study alongside a multicenter randomized controlled trial comparing induction of labor to expectant monitoring in women with GH or PE after 36 weeks. METHODS: We used written questionnaires, covering background characteristics, condition-specific issues, and validated measures: the Short-Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression Scale (HADS), and Symptom Checklist (SCL-90). Measurements were at the following time points: baseline, 6 weeks postpartum, and 6 months postpartum. A multivariate mixed model with repeated measures was defined to assess the effect of the treatments on the physical component score (PCS) and mental component score (MCS) of the SF-36. Analysis was by intention to treat. RESULTS: We analyzed the data of 491 randomized and 220 nonrandomized women. We did not find treatment effect on long-term HR-QoL (PCS: p = 0.09; MCS: p = 0.82). The PCS improved over time (p < 0.001) and was better in nonrandomized patients (p = 0.02). CONCLUSION: Despite a clinical benefit of induction of labor, long-term HR-QoL is equal after the induction of labor and expectant management in women with GH or PE beyond 36 weeks of gestation.

Contains fulltext : 96560.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To estimate whether administration of 17alpha-hydroxyprogesterone caproate can prevent neonatal morbidity in multiple pregnancies by reducing the preterm birth rate. METHODS: We conducted a multicenter, double-blind, placebo-controlled randomized trial in 55 obstetric clinics in the Netherlands. Women with a multiple pregnancy were randomized to weekly injections of either 250 mg 17alpha-hydroxyprogesterone caproate or placebo, starting between 16 and 20 weeks of gestation and continuing until 36 weeks of gestation. The main outcome measure was adverse neonatal outcome. Secondary outcome measures were gestational age at delivery and delivery before 28, 32, and 37 weeks of gestation. RESULTS: We randomized 671 women. A composite measure of adverse neonatal outcome was present in 110 children (16%) born to mothers in the 17alpha-hydroxyprogesterone caproate group, and in 80 children (12%) of mothers in the placebo group (relative risk [RR] 1.34; 95% confidence interval [CI] 0.95-1.89). The mean gestational age at delivery was 35.4 weeks for the 17alpha-hydroxyprogesterone caproate group and 35.7 weeks for the placebo group (P=.32). Treatment with 17alpha-hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks (6% in the 17alpha-hydroxyprogesterone caproate group compared with 5% in the placebo group, RR 1.04; 95% CI 0.56-1.94), 32 weeks (14% compared with 10%, RR 1.37; 95% CI 0.91-2.05), or 37 weeks of gestation (55% compared with 50%, RR 1.11; 95% CI 0.97-1.28). CONCLUSION: 17alpha-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies. CLINICAL TRIAL REGISTRATION: ISRCTN Register, www.isrctn.org, ISRCTN40512715.

Background One of the most commonly reported problems of randomised trials is that recruitment is usually slower than expected. Trials will cost more and take longer, thus delaying the use of the results in clinical practice, and incomplete samples imply decreased statistical power and usefulness of its results. We aim to identify barriers and facilitators for successful patient recruitment at the level of the patient, the doctor and the hospital organization as well as the organization and design of trials over a broad range of studies. Methods/design We will perform two cohort studies and a case-control study in the Netherlands. The first cohort study will report on a series of multicenter trials performed in a nationwide network of clinical trials in obstetrics and gynaecology. A questionnaire will be sent to all clinicians recruiting for these trials to identify determinants - aggregated at centre level - for the recruitment rate. In a case control-study nested in this cohort we will interview patients who refused or consented participation to identify factors associated with patients' consent or refusal. In a second cohort study, we will study trials that were prospectively registered in the Netherlands Trial Register. Using a questionnaire survey we will assess whether issues on hospital organization, trial organization, planning and trial design were associated with successful recruitment, i.e. 80% of the predefined number of patients recruited within the planned time. Discussion This study will provide insight in barriers and facilitators for successful patient recruitment in trials. The results will be used to provide recommendations and a checklist for individual trialists to identify potential pitfalls for recruitment and judge the feasibility prior to the start of the study. Identified barriers and motivators coupled to evidence-based interventions can improve recruitment of patients in clinical trials.

Background Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy. Methods/Design The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia. Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20). Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated. We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis. Discussion In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia. Trial registration number Clinical Trials, protocol registration system: NCT00189007

Contains fulltext : 79491.pdf (Publisher’s version ) (Open Access) BACKGROUND: Multiple pregnancies are at high risk for preterm birth, and therefore an important cause of infant mortality and morbidity. A pessary is a simple and potentially effective measure for the prevention of preterm birth. Small studies have indicated its effectiveness, but large studies with sufficient power on the subject are lacking. Despite this lack of evidence, the treatment is at present applied by some gynaecologists in The Netherlands. METHODS/DESIGN: We aim to investigate the hypothesis that prophylactic use of a cervical pessary will be effective in the prevention of preterm delivery and the neonatal mortality and morbidity resulting from preterm delivery in multiple pregnancy. We will evaluate the costs and effects of this intervention. At study entry, cervical length will be measured. Eligible women will be randomly allocated to receive either a cervical pessary or no intervention. The cervical pessary will be placed in situ at 16 to 20 weeks, and will stay in situ up to 36 weeks gestation or until delivery, whatever comes first.The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 7.2% without to 3.9% with a cervical pessary, using a two-sided test with an alpha of 0.05 and a power of 0.80. DISCUSSION: This trial will provide evidence on whether a cervical pessary will decrease the incidence of early preterm birth and its concomitant bad neonatal outcome in multiple pregnancies. TRIAL REGISTRATION: Current Controlled Trials: NTR 1858.

Contains fulltext : 79641.pdf (Publisher’s version ) (Open Access) BACKGROUND: At present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective. METHODS/DESIGN: We will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, beta 0.2, alpha 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin. DISCUSSION: This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor. TRIAL REGISTRATION: Nederlands Trial Register (NTR) number 1857, http://www.trialregister.nl.

Background Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours. Methods/Design The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first. Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, β 0.2 at alpha 0.05). Discussion This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks. Trial Registration Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3rd 2008.

Objective To assess the reproducibility of fetal renal pelvis volume measurement in hydronephrotic kidneys using transabdominal three-dimensional (3D) ultrasound. Methods The fetal renal pelvis volume was measured using 3D ultrasound in one kidney in each of 15 fetuses with hydronephrosis in the second or third trimester of pregnancy. Hydronephrosis was diagnosed when the fetus had an anteroposterior renal pelvis diameter ≥ 5 mm. After volume acquisition by one of the observers, the repeatability of volume calculation with manual delineation of the fetal renal pelvis was assessed by six different observers using the Virtual Organ Computer-aided AnaLysis (VOCAL™) imaging program. The intraclass correlation coefficients (ICC), coefficient of variation (CV) and within- and between-observer repeatability coefficient (r) were calculated and Bland–Altman plots were constructed. Results Both intra- and interobserver reliability of the fetal renal pelvis volume measurements were considered to be very good. For intraobserver reliability, the ICC was 0.996 and the CV was 10.8%. For the overall interobserver reliability, the ICC was 0.998 and the CV was 15.7%; the interobserver reliability between pairs of observers had ICCs between 0.994 and 0.999, and CVs between 19.5% and 7.6% for inexperienced and experienced observers, respectively. Conclusion With 3D ultrasound using the VOCAL imaging program, it is technically feasible to reproduce fetal renal pelvis volume measurements. Further research to establish the clinical applications of this technology is warranted. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

In this article, the effects of pregnancy and delivery on the development of stress urinary incontinence are described with special emphasis on the obstetrical management in women who wish to become pregnant or are pregnant after a preceding mid-urethral sling procedure. Three case histories and a review of literature are presented. Pregnancy after a preceding incontinence operation is rare and makes it quite difficult to formulate guidelines about delivery when a pregnancy occurs. The best advice is to postpone incontinence surgery until after the last pregnancy. There is evidence that an elective caesarean delivery protects against stress urinary incontinence in case of pregnancy after bladder neck suspension. For mid-urethral sling procedures, this evidence is not available. The presented case reports do not clearly demonstrate that caesarean delivery is necessary in case of pregnancy and delivery after a mid-urethral sling procedure. Furthermore, a second mid-urethral sling operation is a minor procedure compared to a caesarean section, and there is evidence that a second mid-urethral sling operation has the same success rate as the first procedure.

Contains fulltext : 65628.pdf ( ) (Open Access) BACKGROUND: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. METHODS/DESIGN: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm. DISCUSSION: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. TRIAL REGISTRATION: Dutch Trial Register and ISRCTN-Register: ISRCTN10363217.

Background Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates. Methods/Design Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%. Discussion This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications. Trial Registration The protocol is registered in the clinical trial register number ISRCTN08132825.

To test the hypothesis that in pregnancies with a clinically suspected growth restricted foetus at term, induction of labour is as safe as expectant management, and does not lead to increased obstetrical interventions or perinatal morbidity.In one obstetric centre, 33 women with a clinically suspected growth restricted foetus at term were randomly allocated after stratification for parity to either induction or to expectant management. Obstetric and neonatal outcome variables were compared.There was a lower gestational age at labour (median 38(0) weeks versus 40(1) weeks) with a corresponding tendency to lower birth weight (mean 2428 g versus 2651 g), and a reduced need for ante partum medical surveillance, in the induction group. No significant differences in obstetrical interventions (25% versus 24%) and neonatal morbidity rates (50% versus 35%) were found.A larger multicenter study with a sufficient power and long-term follow-up to decide the best policy for the term growth restricted foetus is feasible.

Objective: Early pregnancy is characterized by a fall in total peripheral vascular resistance. In this study we tested the hypothesis that this phenomenon is accompanied by rising compliances of the large arteries and veins. Study Design: In 42 women with a history of preeclampsia and 10 healthy parous control subjects we measured the following variables in the midfollicular phase and the midluteal phase during the menstrual cycle and again at 5 and at 7 weeks of amenorrhea: cardiac output, mean arterial pressure, carotid and femoral artery compliances, and venous compliance. The total peripheral vascular resistance was determined as the ratio of mean arterial pressure and cardiac output. After screening for thrombophilia and hypertension, women with a history of preeclampsia were divided into subgroups with hypertension, thrombophilic disorders, and no underlying abnormalities. Results: In parallel with the fall in total peripheral vascular resistance during early pregnancy, femoral artery compliance and venous compliance increased in the control group. Except for venous compliance, these changes were also observed in the women with thrombophilia and a history of preeclampsia. In the subgroups of the women with a history of preeclampsia with hypertension and with no underlying disorder both arterial and venous compliance failed to increase despite a drop in total peripheral vascular resistance. Conclusion: These data support the concept that during normal pregnancy the fall in total peripheral vascular resistance is paralleled by improved macrovascular compliance. The latter adaptive change did not occur in women with a history of preeclampsia with hypertension or without an underlying disorder. (Am J Obstet Gynecol 2000;183:1278-86.)

Objectives: To integrate methods for non-invasive assessment of vessel wall properties (diastolic diameter, distension waveform and intima-media thickness) and hemodynamic properties (blood flow velocity and shear rate distribution) of large arteries by means of dedicated ultrasound signal processing. Methods: we have developed an arterial laboratory (ART-lab) system. ART-lab consists of software running on a standard personal computer, equipped with a data acquisition card for the acquisition of radio frequency (RF) ultrasound signals obtained with a conventional echo scanner. It operates either (1) off-line or (2) in real-time. Real-time operation is restricted to the assessment of vessel wall properties because of limitations in computational power. Results: This paper provides an overview of ART-lab ultrasound radio frequency data acquisition and dedicated RF-signal processing methods. The capabilities of the system are illustrated with some typical applications. Conclusions: ART-lab in real-time mode is a useful tool for monitoring arterial vessel wall dynamics, while off-line it can be employed to investigate the elastic vessel wall properties in combination with hemodynamics, such as blood flow velocity and shear rate distribution.

Intimal thickening may be focal in nature and is especially found in areas with low shear rate. To be able to study the relation between intima-media thickness (IMT) and wall shear rate appropriately, a method to assess IMT locally is required. It was the aim of the present study to investigate the ability of a recently developed automated method to assess local differences in IMT, if any, in relatively short arterial segments. Therefore, intrasession interlocation differences in IMT were assessed at the posterior wall of the common carotid artery close to the bulb (0 mm) and 10 and 20 mm more upstream in terms of mean difference ± 2 standard deviations. Prior to this study we investigated the ability of the system to reproducibly assess IMT locally (intersession intralocation) in terms of repeatability coefficient (= 2 standard deviations). The measurements were performed in the common carotid artery 20 mm proximal to the bulb. The study was performed on young and older subjects presumed to be healthy. The intersession intralocation repeatability coefficient was 0.07 mm in the young group and 0.11 mm in the older group. The IMT close to the bulb (0 mm) was significantly larger (±0.050–0.065 mm) than that at the other locations in both age groups. We conclude that local IMT can be assessed reproducibly and local differences in wall morphology in short arterial segments can be studied reliably.

The Young's modulus of an arterial segment, a measure of the elastic properties of the arterial wall, requires the simultaneous and local assessment of pulse pressure, wall thickness, diameter, and distensibility (relative increase in cross-sectional area per change in blood pressure). The diameter and relative increase in cross-sectional area can be obtained with a wall track system, processing the radiofrequency (r.f.) ultrasound signals received along a single line of observation (M-line processing). It will be demonstrated that it is feasible to combine, in a single measurement, the assessment of wall thickness and the (relative change in) diameter involving a minimum of user interaction. Phantom tests show a standard error of the estimate for intima-media thickness measurements of less than 20 microns; in vivo registrations exhibit a variation on the order of 45 microns. It is concluded that processing of the radiofrequency ultrasound signal, acquired along an M-line, provides an accurate and time-efficient alternative for videoprocessing of 2-dimensional B-mode ultrasound images to estimate artery wall thickness.

1. The objective of this study was to investigate whether the luteal phase of the menstrual cycle differs from the follicular phase by the development of a state of general vascular relaxation. 2. Once in the follicular and once in the luteal phase of the menstrual cycle, we measured by non-invasive techniques: arterial blood pressure (by finger blood pressure measurements), vascular tone (by pulse-wave velocity and plethysmography), blood flow to skin (by laser-Doppler), blood flow to forearm (by plethysmography) and blood flow to kidneys (by para-aminohippurate clearance), and the glomerular filtration rate (by inulin clearance). The data points obtained in the luteal phase were compared with those in the follicular phase by non-parametric tests. 3. Arterial blood pressure, vascular tone and the blood flows to the forearm and kidneys were comparable in the two phases of the menstrual cycle. In contrast, the blood flow to the skin was consistently lower, and the glomerular filtration rate higher in the luteal phase of the menstrual cycle. 4. The results of the present study do not support our hypothesis of a general vascular relaxation in the luteal phase of the menstrual cycle. The lower skin flow in the luteal phase may be an adaptation needed to ensure the higher core temperature of 0.3–0.5°C in the luteal phase. The higher glomerular filtration rate was in most cases paralleled by a higher renal blood flow in the luteal phase. This suggests that the higher glomerular filtration rate is secondary to a selective vasorelaxation of the afferent renal arterioles.

The initial sample size calculation in our protocol (Hegeman et al, BMC Pregnancy Childbirth, 2009, 9:44) was based on the expected proportion of 'bad neonatal outcome' in the intervention group (3.9%) and control group (7.2%) and accounts for the fact that the outcomes in children form multiple pregnancies are non-independent using an intra class correlation of 0.6. As the intervention is performed on the mother, analysis should be done on the maternal level. This adjustment was made during recruitment and approved by the medical ethics committee of the Academic Medical Centre in Amsterdam (ref. No. MEC 09/107). The sample size is calculated based on the primary outcome 'bad neonatal outcome'.

and perinatal outcome in patients with preterm delivery Jantien van der Heyden, Stijn van Teeffelen, David van der Ham, Jelle Schaaf, Anita Ravelli, Christine Willekes, Jan Nijhuis, Ben Mol VieCuri Medical Center, Department of Obstetrics and Gynaecology, Venlo, Netherlands, Maastricht University Medical Center, Obstetrics and Gynecology, Maastricht, Netherlands, Maastricht University Medical Center, Obstetrics & Gynecology, GROW School for Oncology and Developmental Biology, Maastricht, Netherlands, Academic Medical Center, Obstetrics and Gynecology, Amsterdam, Netherlands, Academic Medical Center, Medical Informatics, Amsterdam, Netherlands, Academic Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, Netherlands OBJECTIVE: To assess the association between duration of rupture of membranes on perinatal outcome in patients with preterm delivery. STUDY DESIGN: We used data from the nationwide perinatal registry (PRN) from 1999 to 2007. We selected singleton pregnancies with preterm delivery between 26 0/7 and 36 6/7 weeks. We studied the association between duration of rupture of membranes (ROM) and perinatal outcome for different gestational ages. Perinatal outcome was defined as perinatal mortality, neonatal sepsis, Apgar score 7 after 5 minutes and composite morbidity (respiratory distress syndrome, necrotizing enterocolitis and intraventricular hemorrhage). RESULTS: During the study period, 166,118 births were complicated by preterm delivery between 26 0/7 and 36 6/7 weeks. The perinatal mortality rate in this group was 2.5%. For a gestational age between 26-30 weeks, the mortality rates for women delivering before and after 24 hours of ROM were 30% and 3.9% respectively (OR .34 (.22 to .55)). For gestational age groups at 30-33, 34, 35 and 36 weeks, these rates were 6.9% versus 0.9%, 2.6% versus 0.5%, 1.5% versus 0.4%, and 0.8% versus 0.4%, respectively (OR .21, .33, .32 and .36, all P .05). Sepsis rates were comparable with short and prolonged PPROM when PPROM occurred before 34 weeks (OR 1.1), but higher after prolonged PPROM when PPROM occurred after 34 weeks (OR 1.6, 1.9 and 2.6 for 34, 35 and 36 weeks, all P .05). The patterns of low Apgar score and composite morbidity resembled that of perinatal mortality. CONCLUSION: In women with a preterm delivery, prolonged duration of ROM is not associated with an increased risk of perinatal mortality, morbidity or low Apgar score at any gestational age. The risk of neonatal sepsis increases with longer duration of ROM in pregnancies over 34 weeks. These data do not support a policy of induction of labor in case of PPROM. 484 Ethnic disparities in spontaneouspreterm-birth-related perinatal mortality Jelle M. Schaaf, Ben Mol, Ameen Abu Hanna, Anita C.J. Ravelli Academic Medical Center, Medical Informatics, Amsterdam, Netherlands, Academic Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, Netherlands OBJECTIVE: Although preterm birth has been defined as delivery before 37 weeks of gestation, ethnic disparities both in the risk of preterm birth as well as in the risk of perinatal mortality after preterm birth have been identified. We hypothesize that the definition of preterm birth should incorporate ethnicity, as normality could be different between women of different ethnic origins. To test this hypothesis, we studied ethnic disparities in spontaneous preterm birth and its subsequent mortality. STUDY DESIGN: We used data of the nationwide perinatal registry (PRN) of The Netherlands. For this study all singleton births between 1 January 1999 and 31 December 2007 were selected. We defined preterm birth as birth before 37 weeks. First, we studied the risk of preterm birth for Caucasians, Mediterraneans, Black women, SouthAsians and other Asian women. We then analysed mortality, defined as intrapartum or neonatal mortality within 28 days, in case of preterm birth in these ethnic groups. We chose 26 weeks as lower limit as there were active management differences between hospitals below this gestational age during the study period. We used multivariate logistic regression methods. RESULTS: We analyzed data of 969,491 women. Risk of delivery before 37 weeks was 5.3% in Caucasians, 4.7% in Mediterranean, 7.5% in Black women, 8.5% in South-Asians and 5.8% in other Asian women (Table 1). For the 50,823 women who experienced preterm birth between 26 and 37 weeks, the risks of perinatal mortality were 73, 65, 67, 67 and 67 respectively. The risk of mortality after preterm birth seems to be lower for all ethnic groups (when compared to Caucasians) and was significantly lower for Mediterranean women (odds 0.67). CONCLUSION: When preterm birth was defined as delivery before 37 weeks, both Black and South-Asian women had a significantly increased risk to deliver preterm. Since the subsequent risk of perinatal mortality after delivery before 37 weeks seems to be decreased in all ethnic groups as compared to Caucasian women, we plead for ethnic specific definitions for preterm delivery. Poster Session III Doppler Assessment, Fetus, Prematurity www.AJOG.org

In a case of hydrops fetalis, serological examination showed a recent maternal human parvovirus B19 infection. Amniocentesis revealed a unique unbalanced translocation between chromosomes 3 and 11 of the fetus. The mother proved to have a balanced reciprocal translocation between chromosomes 3 and 11. A grossly macerated hydropic male fetus was delivered with a flat nose and low implanted deformed ears. Histopathological examination revealed nuclear inclusion bodies in fetal erythroid cells, confirming human parvovirus B19 infection. Parvovirus B19 DNA was demonstrated by in situ hybridization in the nuclei of heart muscle cells. Our finding of two different disorders in one case illustrates the importance of a complete evaluation of every case of hydrops fetalis, especially concerning counselling on the outcome of future pregnancies. The human parvovirus B19 infection will not recur due to the acquired immunity of the mother, whereas the balanced reciprocal translocation will endanger future pregnancies.