RESUMEN
BACKGROUND: Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone. METHODS: We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 µg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH ≤7·05 or 5-min Apgar score <7) or post-partum haemorrhage (≥1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466. FINDINGS: Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12·2%) of 924 participants in the misoprostol group versus 106 (11·5%) of 921 in the Foley catheter group (adjusted relative risk 1·06, 90% CI 0·86-1·31). Caesarean section occurred in 155 (16·8%) women versus 185 (20·1%; relative risk 0·84, 95% CI 0·69-1·02, p=0·067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure. INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness. FUNDING: FondsNutsOhra.
Asunto(s)
Cateterismo/métodos , Trabajo de Parto Inducido/métodos , Misoprostol/administración & dosificación , Oxitócicos/administración & dosificación , Administración Oral , Adulto , Puntaje de Apgar , Asfixia Neonatal/etiología , Cateterismo/efectos adversos , Maduración Cervical/efectos de los fármacos , Parto Obstétrico/métodos , Esquema de Medicación , Femenino , Humanos , Recién Nacido , Trabajo de Parto Inducido/efectos adversos , Misoprostol/efectos adversos , Oxitócicos/efectos adversos , Hemorragia Posparto/etiología , Embarazo , Nacimiento a Término , Cateterismo Urinario/instrumentaciónRESUMEN
BACKGROUND: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. METHODS/DESIGN: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. DISCUSSION: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. TRIAL REGISTRATION: Trial registration number: NTR 4414 . Date of registration January 29th 2014.
Asunto(s)
Cuello del Útero/patología , Pesarios , Nacimiento Prematuro/prevención & control , Progesterona/administración & dosificación , Progestinas/administración & dosificación , Enfermedades del Cuello del Útero/complicaciones , Administración Intravaginal , Adolescente , Adulto , Medición de Longitud Cervical , Protocolos Clínicos , Femenino , Humanos , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/etiología , Resultado del Tratamiento , Enfermedades del Cuello del Útero/diagnóstico por imagen , Enfermedades del Cuello del Útero/patología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the management of imminent preterm delivery with respect to prescription of antenatal corticosteroids (ACS) and referral to a tertiary center. STUDY DESIGN: A retrospective cohort study existing of 1 perinatal center and 9 referring hospitals. All women who received their first dose of ACS in 1 of the 10 hospitals between 24+0 and 32+0 weeks of gestation and/or delivered before 32 weeks of gestation from 2005 until 2010. Patients were identified using the electronic database of hospital pharmacies. Main outcome measures were time interval from administration to delivery for different indications and number of women who were not referred in time to a tertiary center. RESULTS: In total, 1375 women received ACS. Main indications were suspected preterm labor (44.7%), preterm prelabor rupture of membranes (15.9%), maternal indication (12.8%), fetal indication (9.2%) and vaginal blood loss (8.4%). Overall, 467 (34.0%) women delivered ≤7 days after ACS administration; 8.7% of women with vaginal blood loss and 54.5% of women with maternal indication. Among the 931 women who received ACS in the secondary hospitals, 452 (48.5%) women were referred to a tertiary hospital and 89 (6.5%) women delivered in a secondary hospital with a gestational age of less than 32 weeks. CONCLUSION: One-third of all women receiving ACS delivered within 7 days and half of the women who received ACS in a secondary hospital were referred to a tertiary center. There seems to be room for improvement regarding the timing of ACS administration and subsequently referral to a tertiary center.
Asunto(s)
Betametasona/uso terapéutico , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Enfermedades del Prematuro/prevención & control , Trabajo de Parto Prematuro/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Prenatal/métodos , Adulto , Esquema de Medicación , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Estimación de Kaplan-Meier , Masculino , Países Bajos , Embarazo , Nacimiento Prematuro , Atención Prenatal/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Estudios Retrospectivos , Centros de Atención Secundaria , Centros de Atención Terciaria , Factores de TiempoRESUMEN
BACKGROUND: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre with neonatal intensive care unit facilities is the standard treatment for women with threatening preterm delivery in most centres. However, there is controversy as to which tocolytic agent is the drug of first choice. Previous trials have focused on tocolytic efficacy and side effects, and are probably underpowered to detect clinically meaningfull differences in neonatal outcome. Thus, the current evidence is inconclusive to support a balanced recommendation for clinical practice. This multicenter randomised clinical trial aims to compare nifedipine and atosiban in terms of neonatal outcome, duration of pregnancy and maternal side effects. METHODS/DESIGN: The Apostel III trial is a nationwide multicenter randomised controlled study. Women with threatened preterm labour (gestational age 25 - 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a cervical length of ≤ 10 mm or 2) a cervical length of 11-30 mm and a positive Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment with nifedipine or atosiban. Primary outcome is a composite measure of severe neonatal morbidity and mortality. Secondary outcomes will be time to delivery, gestational age at delivery, days on ventilation support, neonatal intensive care (NICU) admittance, length admission in neonatal intensive care, total days in hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven meningitis, pneumothorax, maternal side effects and costs. Furthermore, an economic evaluation of the treatment will be performed. Analysis will be by intention to treat principle. The power calculation is based on an expected 10% difference in the prevalence of adverse neonatal outcome. This implies that 500 women have to be randomised (two sided test, ß 0.2 at alpha 0.05). DISCUSSION: This trial will provide evidence on the optimal drug of choice in acute tocolysis in threatening preterm labour. CLINICAL TRIAL REGISTRATION: NTR2947, date of registration: June 20th 2011.
Asunto(s)
Nifedipino/administración & dosificación , Trabajo de Parto Prematuro/prevención & control , Evaluación de Resultado en la Atención de Salud , Tocólisis/métodos , Vasotocina/análogos & derivados , Administración Oral , Adolescente , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Mortalidad Infantil/tendencias , Recién Nacido , Inyecciones Intravenosas , Mortalidad Materna/tendencias , Países Bajos/epidemiología , Embarazo , Pronóstico , Tocolíticos/administración & dosificación , Vasotocina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Induction of labour is a common obstetric procedure. At present, different methods are used for induction of labour in women with an unfavourable cervix. Recently, we showed that in term women with an unfavorable cervix the use of a Foley catheter in comparison with vaginal Prostaglandin E2 gel, results in a comparable vaginal delivery rate. A meta-analysis on the subject indicated lower rates of hyperstimulation, and probably as a sequel fewer cases of postpartum haemorrhage. Misoprostol (PgE1) is another type of prostaglandin frequently used for labour induction, recommended by the international federation of gynaecology and obstetrics (FIGO). Misoprostol can be administered by vaginal, rectal and oral route. There is evidence that oral administration results in less asphyxia and hyperstimulation than vaginal administration. At present, valid comparisons between oral misoprostol and Foley catheter are lacking. Therefore, we propose a randomised controlled trial comparing Foley catheter to oral misoprostol in order to assess safety and cost-effectiveness. METHODS/DESIGN: We plan a multicentre, randomised, controlled, open-label clinical trial among term pregnant women with a vital singleton in cephalic presentation, unfavorable cervix, intact membranes and an indication for induction of labour. After informed consent, women will be randomly allocated by a webbased randomisation system to transcervical Foley catheter or oral misoprostol (50 mcg every 4 hours). The primary outcome will be a composite of complications of uterine hyperstimulation, i.e. post partum haemorrhage and asphyxia. Secondary outcomes are mode of delivery, maternal and neonatal morbidity, costs and women's preference. Serious adverse events such as severe maternal or neonatal morbitity or mortality will be monitored and reported to an independent data safety monitory board. With a sample size of 1860 women we will be able to demonstrate a 5% non-inferiority of the Foley catheter as compared to misoprostol for the composite outcome. DISCUSSION: Worldwide, various methods are being used for labour induction. Results of the proposed trial will contribute to the answer which method of induction of labour is most safe, cost-effective, and patient friendly and will help to construct evidence based guidelines. TRIAL REGISTRATION: The Netherlands Trial Register NTR3466.
Asunto(s)
Trabajo de Parto Inducido/métodos , Misoprostol/administración & dosificación , Oxitócicos/administración & dosificación , Cateterismo Urinario , Administración Oral , Adolescente , Adulto , Asfixia Neonatal/etiología , Femenino , Humanos , Recién Nacido , Misoprostol/efectos adversos , Misoprostol/economía , Oxitócicos/efectos adversos , Oxitócicos/economía , Prioridad del Paciente , Hemorragia Posparto/etiología , Embarazo , Proyectos de Investigación , Cateterismo Urinario/efectos adversos , Cateterismo Urinario/economía , Adulto JovenRESUMEN
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.
Asunto(s)
Cateterismo , Dinoprostona/administración & dosificación , Trabajo de Parto Inducido/métodos , Oxitócicos/administración & dosificación , Adulto , Cateterismo/efectos adversos , Maduración Cervical , Cesárea , Parto Obstétrico , Dinoprostona/efectos adversos , Femenino , Humanos , Oxitócicos/efectos adversos , Embarazo , Cremas, Espumas y Geles VaginalesRESUMEN
OBJECTIVE: The 2009-2010 A/H1N1 pandemic provided a unique setting to study the safety of MF59-adjuvanted vaccination in pregnancy. STUDY DESIGN: This was an observational cohort study of the safety of an MF59-adjuvanted A/H1N1 vaccine (Focetria) conducted among 4508 pregnant women (2295 vaccinated vs 2213 unvaccinated), with 3 month follow-up of neonates. RESULTS: No maternal deaths or abortions occurred among the vaccinated women. No differences between the vaccinated and unvaccinated cohorts were observed for gestational diabetes, preeclampsia, stillbirth, low birthweight, neonatal deaths, or congenital malformations. The risk of premature birth was significantly decreased among the vaccinated women (adjusted proportional hazard, 0.69; 95% confidence interval, 0.51-0.92). No differences were observed in rates of congenital malformations after vaccination in the first (2.1%), second (2.7%), or third (2.1%) trimesters. CONCLUSION: There was no evidence of a safety risk for MF59-adjuvanted A/H1N1 vaccination in pregnant women; protection was observed against premature birth.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Polisorbatos/efectos adversos , Complicaciones Infecciosas del Embarazo/prevención & control , Escualeno/efectos adversos , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the added value of the baseline T/QRS ratio to other known risk factors in predicting adverse outcome and interventions for suspected fetal distress. DESIGN: Prospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Laboring women with a high-risk cephalic singleton pregnancy beyond 36 weeks of gestation. METHODS: We obtained STAN(®) recordings (ST-analysis, Neoventa, Sweden) from two previous studies. Three patient groups were defined: cases with adverse outcome, cases with emergency delivery because of suspected fetal distress without adverse outcome, and a reference group of uncomplicated cases. Baseline T/QRS ratios among the adverse outcome and intervention for suspected fetal distress cases were compared to those of the uncomplicated cases. The ability of baseline T/QRS to predict adverse outcome and suspected fetal distress was determined using a multivariable logistic model. MAIN OUTCOME MEASURES: The added value of the baseline T/QRS to other known risk factors in the prediction of adverse outcome and interventions for suspected fetal distress. RESULTS: From 3462 recordings, 2459 were available for analysis. Median baseline T/QRS for uncomplicated cases, adverse outcome and interventions for suspected fetal distress were 0.12 (range 0.00-0.52), 0.12 (0.00-0.42) and 0.13 (0.00-0.39), respectively. There was no statistical difference between these groups. Multivariable analysis showed no added value of baseline T/QRS in the prediction of either adverse outcome or interventions for suspected fetal distress. CONCLUSION: Baseline T/QRS has no added value in the prediction of adverse neonatal outcome or interventions for suspected fetal distress.
Asunto(s)
Electrocardiografía , Sufrimiento Fetal/diagnóstico , Monitoreo Fetal/métodos , Adulto , Femenino , Humanos , Recién Nacido , Modelos Logísticos , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND: Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments. METHODS/DESIGN: The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared. DISCUSSION: This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR2551, http://www.trialregister.nl.
Asunto(s)
Analgesia Epidural , Analgesia Obstétrica/métodos , Analgesia Controlada por el Paciente , Analgésicos Opioides/uso terapéutico , Dolor/tratamiento farmacológico , Piperidinas/uso terapéutico , Adolescente , Adulto , Analgesia Epidural/efectos adversos , Analgesia Epidural/economía , Analgesia Obstétrica/efectos adversos , Analgesia Controlada por el Paciente/efectos adversos , Analgesia Controlada por el Paciente/economía , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/economía , Análisis Costo-Beneficio , Femenino , Humanos , Recién Nacido , Trabajo de Parto , Dimensión del Dolor , Satisfacción del Paciente/economía , Piperidinas/efectos adversos , Piperidinas/economía , Embarazo , Remifentanilo , Proyectos de Investigación , Adulto JovenRESUMEN
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.
Asunto(s)
Cardiotocografía , Electrocardiografía , Sufrimiento Fetal/diagnóstico , Monitoreo Fetal/métodos , Adhesión a Directriz , Acidosis/diagnóstico , Adulto , Femenino , Frecuencia Cardíaca Fetal , Humanos , Hipoxia-Isquemia Encefálica/diagnóstico , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Embarazo , Resultado del Embarazo , Arterias UmbilicalesRESUMEN
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.
Asunto(s)
Acidosis/epidemiología , Modelos Estadísticos , Complicaciones del Embarazo/metabolismo , Cesárea , Diabetes Gestacional , Femenino , Predicción , Edad Gestacional , Humanos , Recién Nacido , Trabajo de Parto , Paridad , Embarazo , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
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.
Asunto(s)
Hipertensión Inducida en el Embarazo/terapia , Trabajo de Parto Inducido/métodos , Preeclampsia/terapia , Resultado del Embarazo/epidemiología , Atención Prenatal/métodos , Adulto , Eclampsia/epidemiología , Femenino , Monitoreo Fetal/métodos , Síndrome HELLP/epidemiología , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Bienestar del Lactante , Recién Nacido , Masculino , Bienestar Materno , Estudios Multicéntricos como Asunto , Preeclampsia/epidemiología , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Índice de Severidad de la Enfermedad , Nacimiento a Término , Adulto JovenRESUMEN
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.
Asunto(s)
Cardiotocografía/economía , Electrocardiografía/economía , Monitoreo Fetal/economía , Costos de la Atención en Salud , Resultado del Embarazo , Embarazo de Alto Riesgo , Acidosis/diagnóstico , Acidosis/epidemiología , Adulto , Cardiotocografía/métodos , Ahorro de Costo , Análisis Costo-Beneficio , Parto Obstétrico/economía , Parto Obstétrico/métodos , Electrocardiografía/métodos , Femenino , Sangre Fetal/química , Monitoreo Fetal/métodos , Edad Gestacional , Humanos , Países Bajos , Embarazo , Tercer Trimestre del Embarazo , Adulto JovenRESUMEN
BACKGROUND: Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis. METHODS/DESIGN: We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options. Women in labour with a gestational age > or = 36 weeks and an indication for CTG-monitoring can be included in the trial. Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG. The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bdecf > 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals. The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied. DISCUSSION: This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed. TRIAL REGISTRATION NUMBER: ISRCTN95732366.
Asunto(s)
Hipoxia Fetal/diagnóstico , Monitoreo Fetal/economía , Monitoreo Fetal/métodos , Acidosis/sangre , Acidosis/etiología , Asfixia Neonatal/prevención & control , Análisis de los Gases de la Sangre/economía , Análisis de los Gases de la Sangre/métodos , Cardiotocografía/economía , Cardiotocografía/métodos , Análisis Costo-Beneficio , Electrocardiografía/economía , Electrocardiografía/métodos , Femenino , Sangre Fetal , Hipoxia Fetal/sangre , Humanos , Recién Nacido , EmbarazoRESUMEN
BACKGROUND: Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to 15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates. METHODS/DESIGN: Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%. DISCUSSION: This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications. TRIAL REGISTRATION: The protocol is registered in the clinical trial register number ISRCTN08132825.
Asunto(s)
Hipertensión Inducida en el Embarazo/terapia , Trabajo de Parto Inducido/métodos , Preeclampsia/terapia , Resultado del Embarazo , Proyectos de Investigación , Nacimiento a Término , Adulto , Intervalos de Confianza , Femenino , Humanos , Bienestar del Lactante , Recién Nacido , Bienestar Materno , Estudios Multicéntricos como Asunto , Embarazo , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. DESIGN: Multicentre randomised controlled equivalence trial. SETTING: 15 hospitals in the Netherlands. PARTICIPANTS: Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data. INTERVENTION: Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour. MAIN OUTCOME MEASURES: Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome. RESULTS: 1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference -2.8, 95% confidence interval -6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference -10.4, -13.9 to -7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups. CONCLUSION: In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia. TRIAL REGISTRATION: Netherlands Trial Register NTR2551.
Asunto(s)
Analgesia Epidural , Analgesia Obstétrica/métodos , Analgesia Controlada por el Paciente , Analgésicos Opioides/administración & dosificación , Piperidinas/administración & dosificación , Adulto , Analgésicos Opioides/farmacocinética , Área Bajo la Curva , Estudios Cruzados , Femenino , Humanos , Países Bajos , Manejo del Dolor/métodos , Dimensión del Dolor , Satisfacción del Paciente , Piperidinas/farmacocinética , Embarazo , Remifentanilo , Equivalencia Terapéutica , Adulto JovenRESUMEN
OBJECTIVE: To compare group counselling to individual counselling with respect to the second trimester ultrasound. DESIGN: A prospective cohort study at two hospitals. METHOD: At one hospital, 100 pregnant women were counselled on the risks and benefits of the second trimester ultrasound in groups of up to 15 patients. Shortly before the ultrasound they were asked to fill out a questionnaire. Results were compared to 100 women who were counselled individually at another hospital. The primary outcome was the level of informed choice whether or not to undergo the ultrasound, defined as sufficient knowledge and a value-consistent decision. The secondary outcome measures were level of understanding of the second trimester ultrasound and the degree of satisfaction with the counselling. RESULTS: The resulting level of informed choice was 87.0% after group counselling compared to 79.4% after individual counselling (p = 0.47). The mean knowledge score was 8.8 for the women who attended group counselling; women who were individually counselled had a mean score of 7.4 (p < 0.001). Satisfaction with counselling was 7.0 for group counselling and 6.2 for individual counselling (p < 0.001). CONCLUSION: Although there was no statistically significant difference in the level of informed choice, group counselling was associated with higher post-counselling knowledge and satisfaction scores. Group counselling should therefore be considered as an alternative counselling method.
Asunto(s)
Consejo/métodos , Toma de Decisiones , Conocimientos, Actitudes y Práctica en Salud , Satisfacción del Paciente , Segundo Trimestre del Embarazo , Ultrasonografía Prenatal , Adulto , Factores de Edad , Conducta de Elección , Estudios de Cohortes , Femenino , Humanos , Paridad , Embarazo , Mujeres Embarazadas/psicología , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Ultrasonografía Prenatal/psicología , Ultrasonografía Prenatal/estadística & datos numéricosRESUMEN
OBJECTIVE: Gestational hypertension (GH) and preeclampsia (PE) are major contributors to maternal and neonatal morbidity and mortality. In GH or PE, labor may be either induced or monitored expectantly. We studied maternal health-related quality of life (HR-QoL) after induction of labor versus expectant monitoring in GH or PE at term. We performed the HR-QoL study alongside a multicenter randomized controlled trial comparing induction of labor to expectant monitoring in women with GH or PE after 36 weeks. METHODS: We used written questionnaires, covering background characteristics, condition-specific issues, and validated measures: the Short-Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression Scale (HADS), and Symptom Checklist (SCL-90). Measurements were at the following time points: baseline, 6 weeks postpartum, and 6 months postpartum. A multivariate mixed model with repeated measures was defined to assess the effect of the treatments on the physical component score (PCS) and mental component score (MCS) of the SF-36. Analysis was by intention to treat. RESULTS: We analyzed the data of 491 randomized and 220 nonrandomized women. We did not find treatment effect on long-term HR-QoL (PCS: p = 0.09; MCS: p = 0.82). The PCS improved over time (p < 0.001) and was better in nonrandomized patients (p = 0.02). CONCLUSION: Despite a clinical benefit of induction of labor, long-term HR-QoL is equal after the induction of labor and expectant management in women with GH or PE beyond 36 weeks of gestation.
Asunto(s)
Monitoreo Fetal , Hipertensión Inducida en el Embarazo/terapia , Trabajo de Parto Inducido , Calidad de Vida , Adulto , Femenino , Estado de Salud , Humanos , Preeclampsia/terapia , Embarazo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Acidosis/prevención & control , Cardiotocografía/métodos , Electrocardiografía , Adulto , Femenino , Humanos , Hipoxia-Isquemia Encefálica/prevención & control , Recién Nacido , EmbarazoRESUMEN
OBJECTIVE: Polyethylene glycol (PEG), an osmotic laxative, is a potent inhibitor of colon cancer in rats. In a search for the underling mechanisms, the hypothesis that fecal bulking and moisture decrease colon carcinogenesis was tested. We also investigated the PEG effects on crypt cells in vivo. MATERIAL AND METHODS: Fischer 344 rats (n=272) were injected with the colon carcinogen, azoxymethane. They were then randomized to a standard AIN76 diet containing one of 19 laxative agents (5% w/w in most cases): PEG 8000 and other PEG-like compounds, carboxymethylcellulose, polyvinylpyrrolidone, sodium polyacrylate, calcium polycarbophil, karaya gum, psyllium, mannitol, sorbitol, lactulose, propylene glycol, magnesium hydroxide, sodium phosphate, bisacodyl, docusate, and paraffin oil. Aberrant crypt foci (ACF) and fecal values were measured blindly after a 30-day treatment regimen. Proliferation, apoptosis, and the removal of cells from crypts were studied in control and PEG-fed rats using various methods, including TUNEL and fluorescein dextran labeling. RESULTS: PEG 8000 reduced the number of ACF 9-fold in rats (p<0.001). The other PEGs and magnesium hydroxide modestly suppressed ACF, but not the other laxatives. ACF number did not correlate with fecal weight or moisture. PEG doubled the apoptotic bodies per crypt (p<0.05), increased proliferation by 25-50% (p<0.05) and strikingly increased (>40-fold) a fecal marker of epitheliolysis in the gut (p<0.001). PEG normalized the percentage of fluorescein dextran labeled cells on the top of ACF (p<0.001). CONCLUSIONS: Among laxatives, only PEG afforded potent chemoprevention. PEG protection was not due to increased fecal bulking, but in all likelihood to the elimination of cells from precancerous lesions.