Christine Willekes

Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT)

Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term. Design Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)). Setting Eight academic and 44 non-academic hospitals in the Netherlands between November 2004 and November 2008. Participants Pregnant women who had a singleton pregnancy beyond 36+0 weeks’ gestation with suspected intrauterine growth restriction. Interventions Induction of labour or expectant monitoring. Main outcome measures The primary outcome was a composite measure of adverse neonatal outcome, defined as death before hospital discharge, five minute Apgar score of less than 7, umbilical artery pH of less than 7.05, or admission to the intensive care unit. Operative delivery (vaginal instrumental delivery or caesarean section) was a secondary outcome. Analysis was by intention to treat, with confidence intervals calculated for the differences in percentages or means. Results 321 pregnant women were randomly allocated to induction and 329 to expectant monitoring. Induction group infants were delivered 10 days earlier (mean difference −9.9 days, 95% CI −11.3 to −8.6) and weighed 130 g less (mean difference −130 g, 95% CI −188 g to −71 g) than babies in the expectant monitoring group. A total of 17 (5.3%) infants in the induction group experienced the composite adverse neonatal outcome, compared with 20 (6.1%) in the expectant monitoring group (difference −0.8%, 95% CI −4.3% to 3.2%). Caesarean sections were performed on 45 (14.0%) mothers in the induction group and 45 (13.7%) in the expectant monitoring group (difference 0.3%, 95% CI −5.0% to 5.6%). Conclusions In women with suspected intrauterine growth restriction at term, we found no important differences in adverse outcomes between induction of labour and expectant monitoring. Patients who are keen on non-intervention can safely choose expectant management with intensive maternal and fetal monitoring; however, it is rational to choose induction to prevent possible neonatal morbidity and stillbirth. Trial registration International Standard Randomised Controlled Trial number ISRCTN10363217.

Automated Detection of Local Artery Wall Thickness Based on M-Line Signal Processing

The Youngs 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.

An integrated system for the non-invasive assessment of vessel wall and hemodynamic properties of large arteries by means of ultrasound

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.

17α-hydroxyprogesterone caproate for the prevention of adverse neonatal outcome in multiple pregnancies: a randomized controlled trial.

OBJECTIVE: To estimate whether administration of 17&agr;-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 17&agr;-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 17&agr;-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 17&agr;-hydroxyprogesterone caproate group and 35.7 weeks for the placebo group (P=.32). Treatment with 17&agr;-hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks (6% in the 17&agr;-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: 17&agr;-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies. CLINICAL TRIAL REGISTRATION: ISRCTN Register, www.isrctn.org, ISRCTN40512715. LEVEL OF EVIDENCE: I

Induction of Labor versus Expectant Management in Women with Preterm Prelabor Rupture of Membranes between 34 and 37 Weeks: A Randomized Controlled Trial

In a randomized controlled trial David van der Ham and colleagues investigate induction of labor versus expectant management for women with preterm prelabor rupture of membranes.

Effect of Maintenance Tocolysis With Nifedipine in Threatened Preterm Labor on Perinatal Outcomes A Randomized Controlled Trial

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.

Accuracy of C-reactive protein determination in predicting chorioamnionitis and neonatal infection in pregnant women with premature rupture of membranes: A systematic review

Preterm premature rupture of the fetal membranes (PPROM) is associated with intra-uterine infection. Early detection of intra-uterine infection may help prevent neonatal sepsis. C-reactive protein (CRP) is an acute phase protein often elevated when inflammation is present. The aim of this review was to assess whether CRP accurately predicts chorioamnionitis and/or neonatal sepsis in women with PPROM. We searched Medline and Embase databases for articles reporting on CRP and chorioamnionitis and/or neonatal sepsis. Two reviewers extracted clinical and methodological study characteristics and test accuracy data. Accurate data were used to form 2 x 2 data tables comparing CRP and the occurrence of infection. For the selected studies, sensitivity and specificity of CRP in the prediction of histological chorioamnionitis, clinical chorioamnionitis and neonatal sepsis were calculated separately. A bivariate meta-regression model was used to calculate pooled estimates of sensitivity and specificity. The search revealed 200 articles, of which only five met the inclusion criteria. These five articles reported on 381 patients, of which four articles (227 patients) reported on CRP as a predictor for histological chorioamnionitis and four studies (330 patients) reported on CRP as a predictor for clinical chorioamnionitis. None of the selected articles fulfilled our criteria for the use of CRP as a predictor of neonatal sepsis. CRP was moderately predictive of histological chorioamnionitis. Unfortunately, the studies of clinical chorioamnionitis were too heterogeneous to pool data. Current literature does not support the use of CRP in women with PPROM.

Evaluation of off-line automated intima–media thickness detection of the common carotid artery based on M-line signal processing

Intima-media thickness (IMT) measurements have gained increasing attention, because IMT is assumed to represent the endothelial adaptive response to physiological and pathophysiological processes. The main aim of the present study was to assess the intrasubject intrasession variability of a new off-line automated radio frequency (RF) IMT method in comparison with an already established off-line manual B-mode IMT method. IMT also was assessed by means of an on-line manual B-mode and an on-line manual RF IMT method. We investigated posterior wall IMT 0-1 cm proximal to the bulb in both common carotid arteries of 16 young (20-31 y; mean 25 y) female and male and 13 elderly (51-65 y; mean 56 y) female volunteers. Two commercially available ultrasound devices (Pie Medical Scanner 200 and Ultramark 9) were used to assess the effects of signal processing on the off-line automated RF IMT method. Intrasubject intrasession variability was determined using the standard deviation to evaluate and compare the various methods. Spearman rank correlation coefficients and Bland and Altman bias and limits of agreement were calculated to objectivate the comparability between the various methods. Intrasubject intrasession variation of IMT estimates was not statistically different between any of the methods. We observed a good comparability between the commonly used off-line manual B-mode IMT method and the off-line automated RF IMT method at the level of the common carotid artery.

Effects on (neuro)developmental and behavioral outcome at 2 years of age of induced labor compared with expectant management in intrauterine growth-restricted infants: long-term outcomes of the DIGITAT trial

OBJECTIVE We sought to study long-term (neuro)developmental and behavioral outcome of pregnancies complicated by intrauterine growth restriction at term in relation to induction of labor or an expectant management. STUDY DESIGN Parents of 2-year-old children included in the Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) answered the Ages and Stages Questionnaire (ASQ) and Child Behavior Checklist (CBCL). RESULTS We approached 582 (89.5%) of 650 parents. The response rate was 50%. Of these children, 27% had an abnormal score on the ASQ and 13% on the CBCL. Results of the ASQ and the CBCL for the 2 policies were comparable. Low birthweight, positive Morbidity Assessment Index score, and admission to intermediate care increased the risk of an abnormal outcome of the ASQ. This effect was not seen for the CBCL. CONCLUSION In women with intrauterine growth restriction at term, neither a policy of induction of labor nor expectant management affect developmental and behavioral outcome when compared to expectant management.

Induction of labour versus expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks (the PPROMEXIL-trial)

BackgroundPreterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries.Methods/DesignWe aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring.The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling.DiscussionThis trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis.Controlled clinical trial registerISRCTN29313500