ALIFE2 study : low-molecular-weight heparin for women with recurrent miscarriage and inherited thrombophilia : study protocol for a randomized controlled trial

Background A large number of studies have shown an association between inherited thrombophilia and recurrent miscarriage. It has been hypothesized that anticoagulant therapy might reduce the number of miscarriages and stillbirth in these women. In the absence of randomized controlled trials evaluating the efficacy of anticoagulant therapy in women with inherited thrombophilia and recurrent miscarriage, a randomized trial with adequate power that addresses this question is needed. The objective of the ALIFE2 study is therefore to evaluate the efficacy of low-molecular-weight heparin (LMWH) in women with inherited thrombophilia and recurrent miscarriage, with live birth as the primary outcome. Methods/Design Randomized study of LMWH plus standard pregnancy surveillance versus standard pregnancy surveillance alone. Study population: pregnant women of less than 7 weeks’ gestation, and confirmed inherited thrombophilia with a history of 2 or more miscarriages or intra-uterine fetal deaths, or both. Setting: multi-center study in centers from the Dutch Consortium of Fertility studies; centers outside the Netherlands are currently preparing to participate. Intervention: LMWH enoxaparin 40 mg subcutaneously once daily started prior to 7 weeks gestational age plus standard pregnancy surveillance or standard pregnancy surveillance alone. Main study parameters/endpoints: the primary efficacy outcome is live birth. Secondary efficacy outcomes include adverse pregnancy outcomes, such as miscarriage, pre-eclampsia, syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP syndrome), fetal growth restriction, placental abruption, premature delivery and congenital malformations. Safety outcomes include bleeding episodes, thrombocytopenia and skin reactions. Discussion After an initial period of slow recruitment, the recruitment rate for the study has increased. Improved awareness of the study and acknowledgement of the need for evidence are thought to be contributing to the improved recruitment rates. We aim to increase the number of recruiting centers in order to increase enrollment into the ALIFE2 study. The study website can be accessed via www.ALIFE2study.org. Trial registration The ALIFE2 study was registered on 19 March 2012 under registration number NTR336

Identification of barriers and facilitators for optimal cesarean section care : Perspective of professionals

Background: The cesarean section (CS) rate has increased over recent decades with poor guideline adherence as a possible cause. The objective of this study was to explore barriers and facilitators for delivering optimal care as described in clinical practice guidelines.  Methods: Key recommendations from evidence-based guidelines were used as a base to explore barriers and facilitators for delivering optimal CS care in The Netherlands. Both focus group and telephone interviews among 29 different obstetrical professionals were performed. Transcripts from the interviews were analysed. Barriers and facilitators were identified and categorised in six domains according to the framework developed by Grol: the guideline recommendations (I), the professional (II), the patient (III), the social context (IV), the organizational context (V) and the financial/legislation context (VI).  Results: Most barriers were found in the professional and organizational domain. Barriers mentioned by healthcare professionals were disagreement with specific guideline recommendations, and hesitation to allow women to be part of the decision making process. Other barriers are lack of adequately trained personal staff, lack of collaboration between professionals, and lack of technical equipment.  Conclusions: Clear facilitators and barriers for guideline adherence were identified in all domains. Several barriers may be addressed by using decision aids on mode of birth or prediction models to individualise care in women in whom both planned vaginal birth and CS are equal options. In women with an intended vaginal birth, adequate staffing and the availability of both fetal blood sampling and epidural analgesia are important

Identification of barriers and facilitators for optimal cesarean section care : Perspective of professionals

Background: The cesarean section (CS) rate has increased over recent decades with poor guideline adherence as a possible cause. The objective of this study was to explore barriers and facilitators for delivering optimal care as described in clinical practice guidelines.  Methods: Key recommendations from evidence-based guidelines were used as a base to explore barriers and facilitators for delivering optimal CS care in The Netherlands. Both focus group and telephone interviews among 29 different obstetrical professionals were performed. Transcripts from the interviews were analysed. Barriers and facilitators were identified and categorised in six domains according to the framework developed by Grol: the guideline recommendations (I), the professional (II), the patient (III), the social context (IV), the organizational context (V) and the financial/legislation context (VI).  Results: Most barriers were found in the professional and organizational domain. Barriers mentioned by healthcare professionals were disagreement with specific guideline recommendations, and hesitation to allow women to be part of the decision making process. Other barriers are lack of adequately trained personal staff, lack of collaboration between professionals, and lack of technical equipment.  Conclusions: Clear facilitators and barriers for guideline adherence were identified in all domains. Several barriers may be addressed by using decision aids on mode of birth or prediction models to individualise care in women in whom both planned vaginal birth and CS are equal options. In women with an intended vaginal birth, adequate staffing and the availability of both fetal blood sampling and epidural analgesia are important

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