Two trials of antenatal thyrotrophin-releasing hormone for fetal maturation: stopping before the due date. Antenatal TRH Trial and the Thyroneth Trial Groups.
OBJECTIVE
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.


METHODS
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.


METHODS
Hospital maternity units.


METHODS
Pregnant women at risk of preterm delivery who had been prescribed a course of corticosteroids to enhance fetal maturation.


METHODS
Antenatal administration of TRH 400 microg every eight hours for four doses versus matching placebo.


METHODS
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.
Alfirevic
Z
Z
University of Liverpool.
Boer
K
K
Borcklehurst
P
P
Buimer
M
M
Elbourne
D
D
Kok
J
J
Tansey
S
S
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005313:Fetal Death / Q000517:prevention & control*; D005865:Gestational Age; D006340:Heart Rate, Fetal / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011295:Prenatal Care / Q000379:methods; D012307:Risk Factors; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D013973:Thyrotropin-Releasing Hormone