Haemorrhagia post partum; an implementation study on the evidence-based guideline of the Dutch Society of Obstetrics and Gynaecology (NVOG) and the MOET (Managing Obstetric Emergencies and Trauma-course) instructions; the Fluxim study

Contains fulltext : 88435.pdf (publisher's version ) (Open Access)BACKGROUND: One of the most important causes of maternal mortality and severe morbidity worldwide is post partum haemorrhage (PPH). Factors as substandard care are frequently reported in the international literature and there are similar reports in the Netherlands. The incidence of PPH in the Dutch population is 5% containing 10.000 women a year. The introduction of an evidence-based guideline on PPH by the Dutch society of Obstetrics and Gynaecology (NVOG) and the initiation of the MOET course (Managing Obstetrics Emergencies and Trauma) did not lead to a reduction of PPH. This implies the possibility of an incomplete implementation of both the NVOG guideline and MOET-instructions. Therefore, the aim of this study is to develop and test a tailored strategy to implement both the NVOG guideline and MOET-instructions METHODS/DESIGN: One step in the development procedure is to evaluate the implementation of the guideline and MOET-instructions in the current care. Therefore measurement of the actual care will be performed in a representative sample of 20 hospitals. This will be done by prospective observation of the third stage of labour of 320 women with a high risk of PPH using quality indicators extracted from the NVOG guideline and MOET instructions. In the next step barriers and facilitators for guideline adherence will be analyzed by performance of semi structured interviews with 30 professionals and 10 patients, followed by a questionnaire study among all Dutch gynaecologists and midwives to quantify the barriers mentioned. Based on the outcomes, a tailored strategy to implement the NVOG guideline and MOET-instructions will be developed and tested in a feasibility study in 4 hospitals, including effect-, process- and cost evaluation. DISCUSSION: This study will provide insight into current Dutch practice, in particular to what extent the PPH guidelines of the NVOG and the MOET-instructions have been implemented in the actual care, and into the barriers and facilitators regarding guideline adherence. The knowledge of the feasibility study regarding the effects and costs of the tailored strategy and the experiences of the users can be used in countries with a relatively high incidence of PPH. TRIAL REGISTRATION: ClinicTrials.gov NCT00928863

Treatment of retained placenta with misoprostol: a randomised controlled trial in a low-resource setting (Tanzania)

Background: Retained placenta is one of the common causes of maternal mortality in developing countries where access to appropriate obstetrical care is limited. Current treatment of retained placenta is manual removal of the placenta under anaesthesia, which can only take place in larger health care facilities. Medical treatment of retained placenta with prostaglandins E1 (misoprostol) could be cost-effective and easy-to-use and could be a life-saving option in many low-resource settings. The aim of this study is to assess the efficacy and safety of sublingually administered misoprostol in women with retained placenta in a low resource setting. Methods: Design: Multicentered randomised, double-blind, placebo-controlled trial, to be conducted in 5 hospitals in Tanzania, Africa. Discussion: Inclusion criteria: Women with retained placenta, at a gestational age of 28 weeks or more and blood loss less than 750 ml, 30 minutes after delivery of the newborn despite active management of third stage of labour. Clinical Trial Registration: Trial Entry & Randomisation & Study Medication: After obtaining informed consent, eligible women will be allocated randomly to the treatment groups using numbered envelopes that will be randomized in variable blocks containing identical capsules with either 800 microgram of misoprostol or placebo. The drugs will be given sublingually. The women, maternal care providers and researchers will be blinded to treatment allocation. Sample Size: 117 women, to show a 40% reduction in manual removals of the placenta (p = 0.05, 80% power). The randomization will be misoprostol: placebo = 2:1. Primary Study Outcome: Expulsion of the placenta without manual removal. Secondary outcome is the number of blood transfusions. This is a protocol for a randomized trial in a low resource setting to assess if medical treatment of women with retained placenta with misoprostol reduces the incidence of manual remov

Assessment of perinatal outcome after sustained tocolysis in early labour (APOSTEL-II trial)

Contains fulltext : 80242.pdf (publisher's version ) (Open Access)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, beta 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

Cost-effectiveness of fibronectin testing in a triage in women with threatened preterm labor: alleviation of pregnancy outcome by suspending tocolysis in early labor (APOSTEL-I trial)

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 <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. 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

History of preeclampsia is more predictive of cardiometabolic and cardiovascular risk factors than obesity

OBJECTIVE: To determine to what extent a history of preeclampsia affects traditional cardiometabolic (insulin resistance and dyslipidemia) and cardiovascular (hypertension and micro-albuminuria) risk factors of the metabolic syndrome irrespective of BMI. STUDY DESIGN: In a retrospective case-control study we compared 90 formerly preeclamptic women, divided in 3 BMI-classes (BMI 19.5-24.9, 25.0-29.9, >/=30.0kg/m(2)) to 30 controls, matched for BMI, age and parity. Cardiometabolic and cardiovascular risk factors (WHO-criteria) were tested 6-18 months post partum. Statistical analysis included unpaired t-tests, Mann-Whitney U test, or Chi square test and two-way ANOVA. RESULTS: Constituents of the metabolic syndrome (glucose, insulin, HOMAIR, HDL-cholesterol, triglycerides, blood pressure, micro-albuminuria) were higher in formerly preeclamptic women than in BMI-matched controls. Resultantly, traditional risk factors were more prevalent in formerly preeclamptic women than in controls (insulin resistance 80% vs 30%, dyslipidemia 52% vs 3%, hypertension 24% vs 0%, micro-albuminuria 30% vs 0%). Cardiometabolic risk factors increased with BMI, to the same extent in both groups. Formerly preeclamptic women had metabolic syndrome more often than their BMI-matched controls (38% vs 3%, p<0.001). CONCLUSION: Traditional risk factors of the metabolic syndrome are more prevalent in formerly preeclamptic women than in BMI-matched controls and increase with BMI to the same extent in both groups. A history of preeclampsia seems to be a stronger indicator of cardiovascular risk than obesity per se

Comparison of two point-of-care testing (POCT) devices for fetal lactate during labor

Point-of-care testing (POCT) of fetal scalp blood lactate is used as an alternative for pH analysis. Lactate measurements have not been standardized and values vary with each device used. The aim of this study was to evaluate the performance of two POCT lactate meters for intrapartum use.Analytical performance of StatStrip Lactate (Nova Biomedical) and Lactate Pro (Arkray) was evaluated using CLSI EP10. Both POCT meters were compared with our lactate reference method (RapidLab 860; Siemens Healthcare Diagnostics) using fetal scalp and neonatal cord blood. Deming regression analysis was performed.StatStrip Lactate coefficients of variation (CVs) were 5.1%, 5.0% and 2.6% at 0.9, 7.5 and 14.1 mmol/L lactate, respectively. CVs for Lactate Pro were 10.7%, 5.2% and 5.7% at 1.7, 4.1 and 6.4 mmol/L lactate, respectively. Consecutive lactate measurements in 37 fetal scalp and 122 cord blood samples revealed different test characteristics for the two POCT devices. In fetal scalp blood: StatStrip Lactate=1.13*RapidLab-0.39 (R(2)=0.907) and Lactate Pro=0.95*RapidLab-0.03 (R(2)=0.823). In cord artery blood: StatStrip Lactate=1.08*RapidLab-0.09 (R(2)=0.810) and Lactate Pro=0.72*RapidLab+0.59 (R(2)=0.807).Overall performance of both Lactate Pro and StatStrip Lactate was good, with StatStrip Lactate having smallest CVs and closest correlation to our reference method. Both StatStrip Lactate and Lactate Pro can be used as a lactate POCT device for obstetric use

Co-occurrence of Cardiovascular and Prothrombotic Risk Factors in Women With a History of Preeclampsia

OBJECTIVE: Formerly preeclamptic women are at increased risk for remote cardiovascular and thrombotic diseases. We studied co-occurrence of cardiovascular and prothrombotic risk factors within a cohort of formerly preeclamptic women and tested if prevalence of these risk profiles related to onset of preeclampsia in previous pregnancy. METHODS: We evaluated 1,297 nonpregnant formerly preeclamptic women (6-12 months postpartum) for the presence of four risk profiles: circulatory risk profile (hypertension or latent hypertension [low plasma volume, increased vascular resistance, or both]; metabolic syndrome (World Health Organization criteria); thrombophilia (factor V Leiden, prothrombin mutation, or protein C or S deficiency); and hyperhomocysteinemia. Trends between prevalence of these four profiles and onset of preeclampsia were studied using linear regression analysis. RESULTS: After exclusion of 63 women (4.9%) because of incomplete data, 1,234 women were included. One or more risk profiles were detected in 958 of 1,234 (77.6%) formerly preeclamptic women. Circulatory risk profile was more prevalent (66.1%) than hyperhomocysteinemia (18.7%), metabolic syndrome (15.4%), or thrombophilia (10.8%). Prevalence of circulatory risk profile, metabolic syndrome, and hyperhomocysteinemia decreased significantly with gestational age at delivery, whereas thrombophilia did not (P=.22). There was minimal overlap (less than 2%) between metabolic syndrome, thrombophilic profile, and hyperhomocysteinemia. CONCLUSION: Circulatory risk profile is present in two thirds of formerly preeclamptic women. Metabolic syndrome, thrombophilia, and hyperhomocysteinemia are prevalent in 10-20%. There is considerable overlap between circulatory risk profile and other profiles, but not among the three other profiles. Prevalence of these risk factors, except thrombophilia, decreases with gestational age at delivery in preceding pregnancy. (Obstet Gynecol 2013;121:97-105) DOI: http://10.1097/AOG.0b013e318273764

Impaired vascular responses to relaxin in diet-induced overweight female rats

C1 - Journal Articles RefereedRelaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a reduction in arterial diameter. In this study, we tested the hypothesis that local vascular responses to relaxin are impaired in diet-induced overweight female rats on a high-fat cafeteria-style diet for 9 wk. Rats were chronically infused with either relaxin or placebo for 5 days, and vascular responses were measured in isolated mesenteric arteries and the perfused kidney. Diet-induced overweight significantly increased sensitivity to phenylephrine (by 17%) and vessel wall thickness, and reduced renal perfusion flow (RPFF; by 16%), but did not affect flow-mediated vasodilation, myogenic reactivity, and vascular compliance. In the normal weight rats, relaxin treatment significantly enhanced flow-mediated vasodilation (2.67-fold), decreased myogenic reactivity, and reduced sensitivity to phenylephrine (by 28%), but had no effect on compliance or RPFF. NO blockade by l-NAME diminished most relaxin-mediated effects. In diet-induced overweight rats, the vasodilator effects of relaxin were markedly reduced for flow-mediated vasodilation, sensitivity to phenylephrine, and myogenic response compared with the normal diet rats, mostly persistent under l-NAME. Our data demonstrate that some of the vasodilator responses to in vivo relaxin administration are impaired in isolated mesenteric arteries and the perfused kidney in diet-induced overweight female rats. This does not result from a decrease in Rxfp1 (relaxin family peptide receptor) expression but is likely to result from downstream disruption to endothelial-dependent mechanisms in diet-induced overweight animals

Fetal abdominal wall repair with a collagen biomatrix in an experimental sheep model for gastroschisis.

Contains fulltext : 70287.pdf (publisher's version ) (Open Access)We evaluated the regeneration of the abdominal wall using a dual-layer collagen biomatrix, and the protective effect on the bowel of fetal abdominal wall repair in a fetal sheep model for gastroschisis. In 14 fetal lambs, the abdominal wall was opened at 79 days' gestation, creating a gastroschisis. In group 1, the gastroschisis was left uncovered. In group 2, the bowel was repositioned, and the defect was closed by suturing a collagen biomatrix into the abdominal wall. A cesarean section was performed at 140 days' gestation, and macroscopic and histological evaluation was performed. In the five lambs with a gastroschisis, the eviscerated part of the bowel was coalescent, showed extensive adhesions, and was covered by fibrous peel. In group 2, the abdominal wall had closed, with a firm connection to the native abdominal wall. The biomatrix was largely degraded and replaced by connective tissue with collagen and fibroblasts, neovascularisation, and scattered muscle cells. Minor or no adhesions of the bowel and no peel formation were observed. Abdominal wall tissue replacement using a collagen biomatrix was feasible in fetal lambs, resulting in a closed abdominal wall at birth. Immediate closure of the gastroschisis strongly diminished or prevented bowel adhesions and peel formation