Study protocol: PoPE-Prediction of Preterm delivery by Electrohysterography.

BACKGROUND: Traditional methods used for prediction of preterm delivery are subjective and inaccurate. The Electrohysterogram (EHG) and in particular the estimation of the EHG conduction velocity, is a relatively new promising method for detecting imminent preterm delivery. To date the analysis of the conduction velocity has relied on visual inspection of the signals. As a next step towards the introduction of EHG analysis as a clinical tool, we propose an automated method for EHG conduction velocity estimation for both the speed and direction of single spike propagation. METHODS/DESIGN: The study design will be an observational cohort study. 100 pregnant women, gestational age between 23 + 5 and 34 weeks, admitted for threatening preterm labor or preterm prelabor rupture of membranes, will be included. The length of the cervical canal will be measured by transvaginal ultrasound. The EHG will be recorded using 4 electrodes in a fixed configuration. Contractions will be detected by analysis of the EHG and using an estimation of the intra uterine pressure. In the selected contractions, the delays between channels will be estimated by cross-correlation, and subsequently, the average EHG conduction velocity will be derived. Patients will be classified as labor group and non-labor group based on the time between measurement and delivery. The average conduction velocity and cervical length will be compared between the groups. The main study endpoints will be sensitivity, specificity, and area under the ROC curve for delivery within 1,2,4,7, and 14 days from the measurement. DISCUSSION: In this study, the diagnostic accuracy of EHG conduction velocity analysis will be evaluated for detecting preterm labor. Visual and automatic detection of contractions will be compared. Planar wave propagation will be assumed for the calculation of the CV vector. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07603227.

Different ways of subcutaneous tissue and skin closure at cesarean section: a randomized clinical trial on the long-term cosmetic outcome.

OBJECTIVE: To study the effect of subcutaneous tissue closing and the effect of two different skin closure methods at cesarean section on long-term cosmetic results. DESIGN: Randomized controlled trial. SETTING: A large teaching hospital in the Netherlands. POPULATION: Women undergoing a cesarean section. METHODS: Women undergoing a cesarean section were assigned to subcutaneous tissue closure or not, and skin closure with staples or intracutaneous sutures. Operating time, postoperative pain and incidence of complications were recorded. Long-term cosmetic result was assessed 1 year postoperatively through the Patient and Observer Scar Assessment Scale (POSAS) and Numeric Rating Scale (NRS). MAIN OUTCOME MEASURES: The POSAS for subjective and objective scar rating and the NRS to provide an overall opinion on appearance of the scar 1 year after surgery. RESULTS: Of the 218 women randomized, data from 145 women could be analysed after 1 year of follow-up. No significant differences were detected in long-term cosmetic outcome between the different closure methods. Except for operating time, no differences in other secondary outcome measures were found. CONCLUSIONS: At cesarean section, closing the subcutaneous tissue or not and using staples or intracutaneous sutures results in an equivalent long-term cosmetic appearance of the scar.

Identification of cases with adverse neonatal outcome monitored by cardiotocography versus ST analysis: secondary analysis of a randomized trial.

OBJECTIVE: To evaluate whether correct adherence to clinical guidelines might have led to prevention of cases with adverse neonatal outcome. DESIGN: Secondary analysis of cases with adverse outcome in a multicenter randomized clinical trial. SETTING: Nine Dutch hospitals. POPULATION: Pregnant women with a term singleton fetus in cephalic position. METHODS: Data were obtained from a randomized trial that compared monitoring by STAN® (index group) with cardiotocography (control group). In both trial arms, three observers independently assessed the fetal surveillance results in all cases with adverse neonatal outcome, to determine whether an indication for intervention was present, based on current clinical guidelines. MAIN OUTCOME MEASURES: Adverse neonatal outcome cases fulfilled one or more of the following criteria: (i) metabolic acidosis in umbilical cord artery (pH < 7.05 and base deficit in extracellular fluid >12 mmol/L); (ii) umbilical cord artery pH < 7.00; (iii) perinatal death; and/or (iv) signs of moderate or severe hypoxic ischemic encephalopathy. RESULTS: We studied 5681 women, of whom 61 (1.1%) had an adverse outcome (26 index; 35 control). In these women, the number of performed operative deliveries for fetal distress was 18 (69.2%) and 16 (45.7%), respectively. Reassessment of all 61 cases showed that there was a fetal indication to intervene in 23 (88.5%) and 19 (57.6%) cases, respectively. In 13 (50.0%) vs. 11 (33.3%) cases, respectively, this indication occurred more than 20 min before the time of delivery, meaning that these adverse outcomes could possibly have been prevented. CONCLUSIONS: In our trial, more strict adherence to clinical guidelines could have led to additional identification and prevention of adverse outcome.

Prediction of neonatal metabolic acidosis in women with a singleton term pregnancy in cephalic presentation.

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.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial.

BACKGROUND: Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. METHODS/DESIGN: Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised. DISCUSSION: This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity. TRIAL REGISTRATION: NTR1792 CLINICAL TRIAL REGISTRATION: http://www.trialregister.nl.

Perinatal mortality in preterm births: an analysis of causes, presence of substandard care and avoiding mortality in three Dutch regions.

OBJECTIVE: To analyze the causes and underlying events in cases of perinatal mortality (PNM) in preterm children. SETTING: Three regions within the Netherlands. STUDY DESIGN: For this study, we combined data of a PNM audit over a 1-year (2003-2004) with the corresponding data of its source population (n=22,189). In the perinatal audit, all cases of perinatal death have been assessed by multi disciplinary teams of professionals in perinatal care in a consensus model for cause of death and the presence of substandard care factors (SSF). In this article, we restricted our analysis to children born between 22+0 and 37+0 weeks of pregnancy (≥154 and <259 days). We also evaluated avoidability of preterm birth and avoidability of preterm perinatal mortality (PPM) in cases with and without SSF. RESULTS: Of 1885 preterm children, 166 died perinatally (8.81%). The two most important determinants were small-for-gestational-age;ib47.6% of all cases with gestational age (GA) ≥25 weeks;ic and previous PNM (21.1%). In addition, PPM was substantially increased in mothers of non-Dutch origin (PPM 12.1% vs. 6.6% in children of Dutch mothers relative risk (RR)=1.88, 95% confidence interval=1.46-2.43) and in mothers in the age group 20-26 years (PPM 13.4% vs. <9% in all other categories, RR=1.69, 95% confidence interval=1.21-2.38). In 22.6% of the cases perinatal death was considered to be avoidable while in 17.0% perinatal death was related to SSF by caregivers. CONCLUSIONS: Immediate and appropriate actions by both caregivers and care receivers in case of early signals of possible preterm labor may reduce PNM in this category in the Netherlands by more than 20%. Improvement in surveillance of fetal growth may reduce mortality significantly in the preterm gestational period.

A comparison of long-term outcome between Manchester Fothergill and vaginal hysterectomy as treatment for uterine descent.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the Manchester Fothergill (MF) procedure with vaginal hysterectomy (VH) as surgical treatment of uterine descent. METHODS: Consecutive patients who underwent MF were matched for prolapse grade, age and parity to consecutive patients treated with VH. Evaluated outcomes included functional outcome, morbidity, recurrence of pelvic organ prolapse (POP) and sexual function. Follow-up was performed using validated questionnaires. RESULTS: We included 196 patients (98 patients per group). The response rate after a follow-up of 4-9 years was 80%. We found no differences in functional outcome and recurrence rates of POP between groups. Blood loss was significantly less and operating time was significantly shorter in the MF group. However, incomplete emptying of the bladder was more common in the MF group. CONCLUSIONS: The MF procedure is equally effective to the VH and should be considered as a surgical option that allows preservation of the uterus.

Cost-effectiveness of cardiotocography plus ST analysis of the fetal electrocardiogram compared with cardiotocography only.

OBJECTIVE: To assess the cost-effectiveness of addition of ST analysis of the fetal electrocardiogram (ECG; STAN) to cardiotocography (CTG) for fetal surveillance during labor compared with CTG only. DESIGN: Cost-effectiveness analysis based on a randomized clinical trial on ST analysis of the fetal ECG. SETTING: Obstetric departments of three academic and six general hospitals in The Netherlands. Population. Laboring women with a singleton high-risk pregnancy, a fetus in cephalic presentation, a gestational age >36 weeks and an indication for internal electronic fetal monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a health-care provider perspective. MAIN OUTCOME MEASURES: Primary health outcome was the incidence of metabolic acidosis measured in the umbilical artery. Direct medical costs were estimated from start of labor to childbirth. Cost-effectiveness was expressed as costs to prevent one case of metabolic acidosis. RESULTS: The incidence of metabolic acidosis was 0.7% in the ST-analysis group and 1.0% in the CTG-only group (relative risk 0.70; 95% confidence interval 0.38-1.28). Per delivery, the mean costs per patient of CTG plus ST analysis (n= 2 827) were €1,345 vs. €1,316 for CTG only (n= 2 840), with a mean difference of €29 (95% confidence interval -€9 to €77) until childbirth. The incremental costs of ST analysis to prevent one case of metabolic acidosis were €9 667. CONCLUSIONS: The additional costs of monitoring by ST analysis of the fetal ECG are very limited when compared with monitoring by CTG only and very low compared with the total costs of delivery.

Cardiotocography plus ST analysis of fetal electrocardiogram compared with cardiotocography only for intrapartum monitoring: a randomized controlled trial.

OBJECTIVE: To estimate the effectiveness of intrapartum fetal monitoring by cardiotocography plus ST analysis using a strict protocol for performance of fetal blood sampling. METHODS: We performed a multicenter randomized trial among laboring women with a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation. Participants were assigned to monitoring by cardiotocography with ST analysis (index) or cardiotocography only (control). Primary outcome was metabolic acidosis, defined as an umbilical cord artery pH below 7.05 combined with a base deficit calculated in the extracellular fluid compartment above 12 mmol/L. Secondary outcomes were metabolic acidosis in blood, operative deliveries, Apgar scores, neonatal admissions, and hypoxic-ischemic encephalopathy. RESULTS: We randomly assigned 5,681 women to the two groups (2,832 index, 2,849 control). The fetal blood sampling rate was 10.6% in the index compared with 20.4% in the control group (relative risk 0.52; 95% [CI] 0.46-0.59). The primary outcome occurred 0.7% in the index compared with 1.1% in the control group (relative risk 0.70; 95% CI 0.38-1.28; number needed to treat 252). Using metabolic acidosis calculated in blood, these rates were 1.6% and 2.6%, respectively (relative risk 0.63; 95% CI 0.42-0.94; number needed to treat 100). The number of operative deliveries, low Apgar scores, neonatal admissions, and newborns with hypoxic-ischemic encephalopathy was comparable in both groups. CONCLUSION: Intrapartum monitoring by cardiotocography combined with ST analysis does not significantly reduce the incidence of metabolic acidosis calculated in the extracellular fluid compartment. It does reduce the incidence of metabolic acidosis calculated in blood and the need for fetal blood sampling without affecting the Apgar score, neonatal admissions, hypoxic-ischemic encephalopathy, or operative deliveries. LEVEL OF EVIDENCE: I.

Avoidable mortality in small-for-gestational-age children in the Netherlands.

OBJECTIVE: To analyze avoidable perinatal mortality in small-for-gestational-age (SGA) children. METHODS: All SGA-children (< or =10(th) percentile) among 22,189 newborns delivered after 24 weeks' gestation (175 days), from three regions of the Netherlands during 2003-2004 were evaluated. Cases of perinatal mortality were identified and assessed in a consensus model by perinatal audit groups for cause of death and the presence of substandard care factors (SSF). We analyzed all singleton SGA-cases with and without SSF for avoidable perinatal mortality. RESULTS: Out of 20,927 singletons, 2396 newborns were SGA. Of those, 59 died perinatally (2.46%), and 55 of which were assessed by perinatal audit groups. SSF by caregivers were found in 22 cases (40%). In 16 of these cases (29%) the relation to the perinatal death was considered possible or (very) probable. Of the cases without SSF by caregivers, 15 cases (25%) could possibly have been avoided: in 13 cases an avoidable condition and in 2 cases avoidable death were identified. Failure in the correct and timely diagnosis of fetal growth restriction appears to be an important issue in all cases of perinatal mortality in SGA-children. Before referral growth restriction was suspected only in 22% of all SGA cases during the third trimester of pregnancy. CONCLUSIONS: More adequate action by caregivers could decrease perinatal mortality in nearly 1/3 among SGA-children. Adjustments in pregnancy monitoring, especially in low-risk pregnancies, such as routine ultrasound biometry examination, may improve the accuracy in detecting growth deviations and decreasing the number of possibly avoidable cases of perinatal mortality in this category.

The Dutch Perinatal Audit Project: a feasibility study for nationwide perinatal audit in the Netherlands.

OBJECTIVE: To investigate the feasibility of nationwide perinatal mortality audits in the Netherlands. STUDY DESIGN: Over a one-year period, data for all cases of perinatal mortality were collected. Six perinatal audit panels of professionals within perinatal care investigated and classified causes of death and identified the presence of substandard care factors (SSF). RESULTS: Out of 22,189 newborns, 228 cases of perinatal mortality were audited. Placental pathology, congenital anomalies and preterm birth were the main causes of perinatal death. SSF by caregivers were identified in 72 cases (32 %). Almost 20% of the cases were not reported. CONCLUSIONS: In the Netherlands, perinatal audit is well supported by all groups of caregivers. It reveals usable facts and findings for the quality assessment of perinatal care. This audit showed that in 9% of the cases perinatal death was related to SSF and potentially avoidable. However, immediate reporting of cases of perinatal death apart from regular registration in the perinatal database proved to be inaccurate. Once a nationwide audit program is realized, in which data from the different caregivers will be collected in a single database instead of collection by linkage afterwards, this problem should be solved. Local audits will start from 2009. These audits will assess mortality cases within their respective areas and may initiate adjustments for perinatal care and optimize the quality of care and inter-professional collaboration. Yearly nationwide audits will focus on specific items (e.g. term or post-term deliveries) and may well offer an opportunity for the development or adjustment of national guidelines.

Gender- and parity-specific reference charts for fetal size in low risk singleton pregnancies at the onset of the third trimester.

OBJECTIVES: To determine fetal growth in low risk pregnancies at the beginning of the third trimester and to assess the relative importance of fetal gender and maternal parity. SETTING: Dutch primary care midwifery practice. STUDY DESIGN: Retrospective cohort study on 3641 singleton pregnancies seen at a primary care midwifery center in the Netherlands. Parameters used for analysis were fetal abdominal circumference (AC), fetal head circumference (HC), gestational age, fetal gender and maternal parity. Regression analysis was applied to describe variation in AC and HC with gestational age. Means and standard deviations in the present population were compared with commonly used reference charts. Multiple regression analysis was applied to examine whether gender and parity should be taken into account. RESULTS: The fetal AC and HC increased significantly between the 27th and the 33rd week of pregnancy (AC r2=0.3652, P<0.0001; HC r2=0.3301, P<0.0001). Compared to some curves, our means and standard deviations were significantly smaller (at 30+0 weeks AC mean=258+/-13 mm; HC mean=281+/-14 mm), but corresponded well with other curves. Fetal gender was a significant determinant for both AC (P<0.0001) and HC (P<0.0001). Parity contributed significantly to AC only but the difference was small (beta=0.00464). CONCLUSION: At the beginning of the third trimester, fetal size is associated with fetal gender and, to a lesser extent, with parity. Some fetal growth charts (e.g., Chitty et al.) are more suitable for the low-risk population in the Netherlands than others.

The incidence of congenital cytomegalovirus infections in The Netherlands.

Cytomegalovirus (CMV) is one of the most common causes of congenital infection without an effective treatment or an effective vaccine available to date. The emphasis has to be on preventive strategies, which rely on the epidemiological situation. The incidence of congenital CMV infections, however, is not known for The Netherlands. Therefore, a prospective virological study was carried out in a population of 7,524 pregnant women and 7,793 newborns. CMV-specific IgG antibodies were determined in cord blood by ELISA. When CMV antibodies were present, a CMV specific PCR was performed on the throat swab. A positive PCR was confirmed by urine culture. In addition, the seroepidemiology for CMV was investigated in the metropolitan region (Amsterdam and Rotterdam) which has a different ethnic composition. Congenital CMV infection was found in 7 infants (0.9 per 1,000). None had symptoms at birth or during 24 month follow-up. Carriage or CMV was 41%, with a variation between 35% and 100% depending on ethnicity. The ethnic composition in the south-eastern region was different from that in large cities, but similar to that in the rest of the country. The incidence of congenital CMV infections in The Netherlands is the lowest described to date, which does not justify special preventive policies.

Role of magnetic resonance imaging in the diagnosis of incarceration of the gravid uterus.

BACKGROUND: Incarcerated uterus is a rare condition with potentially serious complications that is often difficult to diagnose. This series shows the value of magnetic resonance imaging (MRI). CASES: Five pregnant women with incarcerated uterus are presented and the MRI findings compared with MRI in normal pregnancy. CONCLUSION: The use of MRI can be helpful in diagnosing this rare condition.