OBJECTIVES: To determine whether the addition of antenatal thyrotrophin-releasing hormone (TRH) to corticosteroids, given to women at risk of preterm delivery, would decrease the risk of death and severe morbidity associated with prematurity. DESIGN: Two concurrent multicentre, double blind, randomised, placebo-controlled trials were designed with a common core dataset to be analysed as a single large pragmatic trial. SETTING:Hospital maternity units. POPULATIONS: Pregnant women at risk of preterm delivery who had been prescribed a course of corticosteroids to enhance fetal maturation. INTERVENTIONS: Antenatal administration of TRH 400 microg every eight hours for four doses versus matching placebo. MAIN OUTCOME MEASURES: Primary: death of the baby or chronic lung disease (defined as oxygen dependency at 28 days after birth). Secondary: other measures of respiratory morbidity, in particular respiratory distress syndrome. Other measures of short term neonatal morbidity including intraventricular haemorrhage and necrotising enterocolitis. Measures of maternal side effects. RESULTS: The antenatal TRH trial was halted early on the basis of external evidence. Overall a total of 225 women were recruited who delivered 275 babies. The primary outcome of death or chronic lung disease occurred in 33 babies in the TRH group and 43 babies in the placebo group (RR 0.8, 95% CI 0.5-1.2). There were no other differences between the two groups. Stratified analysis did not reveal any differences between the two groups depending on how long before the time of delivery the mother had received the TRH or placebo. CONCLUSIONS: These trials are too small to provide convincing evidence of the effect of antenatal TRH on neonatal outcome. When added to the existing systematic review and meta-analysis, however, these data should provide evidence on which subsequent practice can be based. The process by which the trials were monitored and stopped is of relevance to future trials.
RCT Entities:
OBJECTIVES: To determine whether the addition of antenatal thyrotrophin-releasing hormone (TRH) to corticosteroids, given to women at risk of preterm delivery, would decrease the risk of death and severe morbidity associated with prematurity. DESIGN: Two concurrent multicentre, double blind, randomised, placebo-controlled trials were designed with a common core dataset to be analysed as a single large pragmatic trial. SETTING: Hospital maternity units. POPULATIONS: Pregnant women at risk of preterm delivery who had been prescribed a course of corticosteroids to enhance fetal maturation. INTERVENTIONS: Antenatal administration of TRH 400 microg every eight hours for four doses versus matching placebo. MAIN OUTCOME MEASURES: Primary: death of the baby or chronic lung disease (defined as oxygen dependency at 28 days after birth). Secondary: other measures of respiratory morbidity, in particular respiratory distress syndrome. Other measures of short term neonatal morbidity including intraventricular haemorrhage and necrotising enterocolitis. Measures of maternal side effects. RESULTS: The antenatal TRH trial was halted early on the basis of external evidence. Overall a total of 225 women were recruited who delivered 275 babies. The primary outcome of death or chronic lung disease occurred in 33 babies in the TRH group and 43 babies in the placebo group (RR 0.8, 95% CI 0.5-1.2). There were no other differences between the two groups. Stratified analysis did not reveal any differences between the two groups depending on how long before the time of delivery the mother had received the TRH or placebo. CONCLUSIONS: These trials are too small to provide convincing evidence of the effect of antenatal TRH on neonatal outcome. When added to the existing systematic review and meta-analysis, however, these data should provide evidence on which subsequent practice can be based. The process by which the trials were monitored and stopped is of relevance to future trials.