Presentation on theme: "Assessment of Perinatal Outcome by uSe of Tocolysis in Early Labour"— Presentation transcript:
1Assessment of Perinatal Outcome by uSe of Tocolysis in Early Labour APOSTEL IVAssessment of Perinatal Outcome by uSe of Tocolysis in Early LabourNifedipine versus placebo in the treatment of preterm premature rupture of membranesSeptember 2012
2Background Preterm birth 75% of neonatal deaths1 40% of childhood neurological morbiditiesHigh immediate and long-term costs2Neonatal outcome is strongly related to gestational age at delivery31 Ananth et al. Epidemiology of preterm birth and its clinical subtypes. J Matern Fetal Neonatal Med 20062 Gilbert et al. The cost of prematurity: quantification by gestational age and birth weight. Obstet Gynecol 20033 Landelijke Neonatale Registratie Dutch Neonatal Database Prismant 2002
3APOSTEL II StudyAssessment of Perinatal Outcome with Sustained Tocolysis in Early LaborObjective: To evaluate the effectiveness of tocolytic maintenance therapy for postponing delivery after initial 48-hour tocolytic therapy in women with threatened preterm birth from weeks gestational age.
4APOSTEL I StudyAlleviation of Pregnancy Outcome by Suspending of Tocolysis in Early Labour:Costs and effects of fibronectin as a triage in women with threatened preterm labour.Objective: To assess whether testing for fibronectin is a cost-effective strategy that prevents unnecessary treatment in women with threatened preterm labour.
5APOSTEL III StudyAssessment of Perinatal Outcome by use of Specific Tocolytics in Early Labour:Nifedipine versus Atosiban in the treatment of threatened preterm labour.Objective: To compare the effectiveness of the tocolytic agents Nifedipine (a calcium channel blocking agent) versus Atosiban (an oxytocin receptor antagonist) in the improvement of neonatal outcome in women with threatened preterm labour (25-34 weeksgestation).
6Assessment of Perinatal Outcome by uSe of Tocolysis in Early Labour APOSTEL IV StudyAssessment of Perinatal Outcome by uSe of Tocolysis in Early LabourNifedipine versus placebo in the treatment of preterm premature rupture of membranesPreterm Premature Rupture of MembranesIncidence of all pregnancies: 3-5%1Incidence of preterm birth: 25-40%1Lee T, Silver H. Etiology and epidemiology of preterm premature rupture of the membranes. Clinics in Perinatology: Prelabor Rupture of Membranes. 2001;28(4):721–734.
7PPROM Delivery after PPROM Kenyon (2004)1: Partus <48 hours after PPROM (20-37 wk): 39.9% (717/1799)Partus < 7 days after PPROM (20-37 wk): 67.5% (1189/1762)Pasquier (2008)2Partus < 7 days after PPROM (24-34 wk): 60%1Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev 2003; CD2Pasquier JC, Rabilloud M, Picaud JC et al. Modeling the duration of the latency period after preterm premature rupture of the membranes according to maternal and pregnancy characteristics: DOMINOS study. European Journal of Obstetrics, Gynecology, & Reproductive Biology 2008; 139:
8PPROM PPROMEXIL Trial: Induction of labour versus expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks
9PPROM Current situation Effectiveness of tocolysis has not been proven No uniform guidelineNo uniform treatment
10APOSTEL IV StudyMulticenter randomised placebo-controlled clinical trial in all ten perinatal centers in the Netherlands .Intervention: Random allocation to nifedipine (intervention) or placebo (control) during the period until the start of signs of active labour (≥ 3 contractions per 10 minutes) (with a maximum of 18 days).Objective: To assess whether in women with early PPROM tocolytics improve perinatal outcome.N= 120 patients
11Inclusion criteriaWomen with PPROM between 24+0/7 and 33+6/7 weeks gestational ageExclusion criteria≥ 3 contractions per 10 minutesPrevious treatment with tocolysis (Tocolysis for less than 6 hours for transportation is allowed)Ruptured membranes longer than 72 hourSigns of chorioamnionitisPlacenta praeviaSevere maternal disease (hypertension, HELLP syndrome, preeclampsia or other)Women with any contraindication for the use of nifedipineMajor congenital anomalySigns of fetal distress (abnormal CTG, abnormal biophysical profile)Signs of intra uterine infection
12FlowchartAPOSTEL IV Study: Multicenter randomised placebo-controlled clinical trial in all ten perinatal centers in the NetherlandsWomen with a gestational age between 24+0/7 and 33+6/7 weeks with ruptured membranes without other signs of active labour.Inclusion APOSTEL IV≥ 3 contractions per 10 minutesPrevious treatment with tocolysisRuptured membranes longer than 72 hourSigns of chorioamnionitisPlacenta praeviaSevere maternal diseaseWomen with any contraindication for the use of nifedipineMajor congenital anomalySigns of fetal distressSigns of intra uterine infectionRExclusionNifedipine 4dd20 mg orally during the period until the start of signs of active labour (≥ 3 contractions per 10 minutes) with a maximum of 18 days.Placebo 4dd20 mg orallyduring the period until the start of signs of active labour (≥ 3 contractions per 10 minutes) with a maximum of 18 days
13Endpoints Main study parameter/endpoint Neonatal mortalityComposite neonatal morbidityChronic Lung diseasePeriventricular leucomalacia > grade 1Severe intraventricular haemorrhage > grade 2Necrotising enterocolitisProven sepsisSecondary study parameters/endpointsGestational age at deliveryBirth weightNumber of days on additional oxygenNumber of days on supported ventilationNumber of days in intensive careTotal days in hospitalCosts