Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial.

BACKGROUND: 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies. METHODS/DESIGN: We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length. DISCUSSION: This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40512715.

Cervical incompetence prevention randomized cerclage trial: emergency cerclage with bed rest versus bed rest alone.

OBJECTIVE: The purpose of this study was to compare preterm delivery rates and neonatal morbidity/mortality rates for women with cervical incompetence with membranes at or beyond a dilated external cervical os that was treated with emergency cerclage, bed rest plus indomethacin, versus just bed rest. STUDY DESIGN: Women with cervical incompetence with membranes at or beyond a dilated external cervical os, before 27 weeks of gestation, were treated with antibiotics and bed rest and randomly assigned for emergency cerclage and indomethacin or bed rest only. RESULTS: Twenty-three women were included; 13 women were allocated randomly to the emergency cerclage and indomethacin group, and 10 women were allocated randomly to the bed rest-only group. Gestational age at time of randomization was 22.2 weeks in the emergency cerclage and indomethacin group and 23.0 weeks in the bed rest-only group. Mean interval from randomization until delivery was 54 days in the emergency cerclage and indomethacin group and 20 days in the bed rest-only group (P=.046). Mean gestational age at delivery was 29.9 weeks in the emergency cerclage and indomethacin group and 25.9 weeks in the bed rest-only group. Preterm delivery before 34 weeks of gestation was significantly lower in the emergency cerclage and indomethacin group, with 7 of 13 deliveries versus all 10 deliveries in the bed rest-only group (P=.02). CONCLUSIONS: Emergency cerclage, indomethacin, antibiotics, and bed rest reduce preterm delivery before 34 weeks compared with bed rest and antibiotics alone.