Two trials of antenatal thyrotrophin-releasing hormone for fetal maturation: stopping before the due date

Objectives To determine whether the addition of antenatal thyrotrophin-rele asing hormone (TRH) to corticosteroids, given to women at risk of preterm d elivery, would decrease the risk of death and severe morbidity associated w ith prematurity. Design Two concurrent multicentre, double blind, randomised, placebo-contro lled trials were designed with a common core dataset to be analysed as a si ngle large pragmatic trial. Setting Hospital maternity units. Populations Pregnant women at risk of preterm delivery who had been prescri bed a course of corticosteroids to enhance fetal maturation. Interventions Antenatal administration of TRH 400 mu g every eight hours fo r four doses versus matching placebo. Main outcome measures Primary: death of the baby or chronic lung disease (d efined as oxygen dependency at 28 days after birth). Secondary: other measu res 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 effect s. Results The antenatal TRH trial was halted early on the basis of external e vidence. Overall a total of 225 women were recruited who delivered 275 babi es. The primary outcome of death or chronic lung disease occurred in 33 bab ies 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 a nalysis 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 pla cebo. Conclusions These trials are too small to provide convincing evidence of th e effect of antenatal TRW on neonatal outcome. When added to the existing s ystematic review and meta-analysis, however, these data should provide evid ence on which subsequent practice can be based. The process by which the tr ials were monitored and stopped is of relevance to future trials.