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

Induction of labor with Foley catheter and risk of subsequent preterm birth: follow-up study of two randomized controlled trials (PROBAAT-1 and -2)

Objective: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins. Methods: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks’ gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38–2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30–3.51). Conclusion: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins

The influence of tocolytic drugs on cardiac function, large arteries, and resistance vessels

Purpose Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs, but are associated with cardiovascular side-effects. Atosiban, a newer drug, is a competitive antagonist of oxytocin and has been claimed to have fewer cardiovascular side effects. Until now, there has mainly been a subjective reporting of adverse reactions and few objective cardiovascular data. Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban compared with placebo on cardiac function, large artery properties, blood pressure, and resistance vessels. Methods A double-blind, randomized trial was carried out in 20 non-pregnant female volunteers. Hemodynamic measurements were made under standardized conditions during kinetic steady state. Cardiac output was measured with echocardiography, large artery properties with an echo-tracking device. The effect on the microcirculation was estimated using the total peripheral resistance index (TPRI). Results Atosiban did not differ from placebo. With ritodrine, cardiac function increased by 79% compared with placebo because of a rise in heart rate (91%). TPRI decreased by 48%. Ritodrine increased the distensibility of the common carotid artery by 62% and the compliance by 83%, independent of blood pressure. Compliance of the common femoral artery increased independently of pressure by 33% and the distensibility by 59%. Aortic pulse wave velocity was not influenced by either medication. Conclusions The present study shows potential beneficial vascular effects of ritodrine that are counterbalanced by the cardiac effects. Atosiban has no clinically relevant cardiovascular effects and may be a good alternative for ritodrine in pregnant women at risk of cardiovascular complications