Martina Porath

Foley catheter versus vaginal prostaglandin E2 gel for induction of labour at term (PROBAAT trial): an open-label, randomised controlled trial

BACKGROUND Induction of labour is a common obstetric procedure. Both mechanical (eg, Foley catheters) and pharmacological methods (eg, prostaglandins) are used for induction of labour in women with an unfavourable cervix. We aimed to compare the effectiveness and safety of induction of labour with a Foley catheter with induction with vaginal prostaglandin E2 gel. METHODS We did an open-label, randomised controlled trial in 12 hospitals in the Netherlands between Feb 10, 2009, and May 17, 2010. We enrolled women with a term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix, an indication for induction of labour, and no prior caesarean section. Participants were randomly allocated by an online randomisation system to induction of labour with a 30 mL Foley catheter or vaginal prostaglandin E2 gel (1:1 ratio). Because of the nature of the intervention this study was not blinded. The primary outcome was caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from intervention to birth. All analyses were done on an intention-to-treat basis. We also did a meta-analysis that included our trial. The trial was registered with the Dutch trial registry, number NTR 1646. FINDINGS 824 women were allocated to induction of labour with a Foley catheter (n=412) or vaginal prostaglandin E2 gel (n=412). Caesarean section rates were much the same between the two groups (23%vs 20%, risk ratio [RR] 1·13, 95% CI 0·87-1·47). A meta-analysis including our trial data confirmed that a Foley catheter did not reduce caesarean section rates. We recorded two serious maternal adverse events, both in the prostaglandin group: one uterine perforation and one uterine rupture. INTERPRETATION In women with an unfavourable cervix at term, induction of labour with a Foley catheter is similar to induction of labour with prostaglandin E2 gel, with fewer maternal and neonatal side-effects. FUNDING None.

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.

Cardiovascular risk factors in women who had hypertensive disorders late in pregnancy: a cohort study

OBJECTIVE The purpose of this study was to determine cardiovascular risk factors in women with a history of hypertensive pregnancy disorders at term (HTP) 2.5 years after pregnancy. STUDY DESIGN In a multicenter cohort study in The Netherlands from June 2008 through November 2010, cardiovascular risk factors were compared between women with a history of HTP (HTP cohort, n = 306) and women with a history of normotensive pregnancies at term (NTP cohort, n = 99). HTP women had participated in a randomized, longitudinal trial assessing the effectiveness of induction of labor in women with hypertensive pregnancy disorders at term. All women were assessed 2.5 years after pregnancy for blood pressure, anthropometrics, glucose, glycosylated hemoglobin, insulin, homeostatic model assessment score, total cholesterol, high-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and microalbumin and metabolic syndrome. RESULTS After a mean follow-up period of 2.5 years, hypertension (HTP, 34%; NTP, 1%; P < .001) and metabolic syndrome (HTP, 25%; NTP, 5%; P < .001) were more prevalent in HTP women compared with NTP women. HTP women had significantly higher systolic and diastolic blood pressure, higher body mass index, and higher waist circumference. Glucose, glycosylated hemoglobin, insulin, homeostatic model assessment score, total cholesterol, triglycerides, and high-sensitivity C-reactive protein levels were significantly higher and high-density lipoprotein cholesterol was significantly lower in HTP women. CONCLUSION In women with a history of HTP, hypertension and metabolic syndrome are more common, and they have higher levels of biochemical cardiovascular risk factors 2.5 years after pregnancy.

Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor

OBJECTIVE: To estimate the performance of combining cervical length measurement with fetal fibronectin testing in predicting delivery in women with symptoms of preterm labor. METHODS: We conducted a prospective nationwide cohort study in all 10 perinatal centers in The Netherlands. Women with symptoms of preterm labor between 24 and 34 weeks of gestation with intact membranes were included. In all women, qualitative fibronectin testing (0.050-microgram/mL cutoff) and cervical length measurement were performed. Logistic regression was used to predict spontaneous preterm delivery within 7 days after testing. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk. RESULTS: Between December 2009 and August 2012, 714 women were enrolled. Fibronectin results and cervical length were available for 665 women, of whom 80 (12%) delivered within 7 days. Women with a cervical length of at least 30 mm or with a cervical length between 15 and 30 mm with a negative fibronectin result were at low risk (less than 5%) of spontaneous delivery within 7 days. Fibronectin testing in case of a cervical length between 15 and 30 mm additionally classified 103 women (15% of the cohort) as low risk and 36 women (5% of the cohort) as high risk. CONCLUSION: Cervical length measurement, combined with fetal fibronectin testing in case of a cervical length between 15 and 30 mm, improves identification of women with a low risk to deliver spontaneously within 7 days. LEVEL OF EVIDENCE: II

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

To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage.

Peri-partum reference ranges for ROTEM® thromboelastometry

BACKGROUND Post-partum haemorrhage (PPH) causes rapidly developing deficiencies in clotting factors and contributes to substantial maternal morbidity and mortality. Rotational thromboelastometry (ROTEM(®)) is increasingly used as a point of care coagulation monitoring device in patients with massive haemorrhage; however, there are limited data on reference ranges in the peri-partum period. These are required due to the haemostatic changes in pregnancy. METHODS In a Dutch multi-centre trial, 161 subjects were included; blood samples were obtained during labour (T1) and within 1 h of delivery (T2). Reference ranges of ROTEM(®) INTEM, EXTEM, FIBTEM, and APTEM were set and correlation with laboratory results was investigated using the guidelines of the International Federation of Clinical Chemistry. RESULTS Reference ranges were obtained for clotting time (CT), clot formation time (CFT), α-angle, clot firmness at 10 and 20 min (A10, A20), maximum clot firmness (MCF), and maximum lysis (ML). These were comparable from centre to centre, and between T1 and T2. Reference ranges T1: EXTEM: CT 31-63 s, CFT 41-120 s, and MCF 42-78 mm. INTEM CT 109-225 s, CFT 40-103, and MCF 63-78 mm. FIBTEM CT 31-79 s and MCF 13-45 mm. APTEM CT 33-62 s, CFT 42-118, and MCF 61-79 mm. CONCLUSIONS Reference values for ROTEM(®) parameters are reported. The previously published correlation between FIBTEM parameters and plasma fibrinogen levels by the Clauss method is confirmed. Further research is needed to define threshold values for haemostatic therapy in the course of PPH. Clinical trial registration NTR 2515 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2515).

Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial

BACKGROUND There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women. METHODS We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792). FINDINGS Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12-1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4-8·2; p=0·005). No maternal or perinatal deaths occurred. INTERPRETATION For women with non-severe hypertensive disorders at 34-37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered. FUNDING ZonMw.

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