AUSTRALIAN COLLABORATIVE TRIAL OF ANTENATAL THYROTROPIN-RELEASING-HORMONE (ACTOBAT) FOR PREVENTION OF NEONATAL RESPIRATORY-DISEASE

The addition of thyrotropin-releasing hormone (TRH) to antenatal gluco corticoid treatment of women at risk of preterm delivery has been repo rted to lower the risk of respiratory distress syndrome (RDS) in the i nfant, We have assessed the efficacy of 200 mu g TRH in a multicentre randomised trial. 1234 women at 24 weeks to 31 weeks 6 days of gestati on with a singleton or twin pregnancy and at risk of preterm delivery were randomly allocated to groups receiving 200 mu g TRH or placebo in travenously every 12 h up to a maximum of four doses. Randomisation wa s stratified by duration of gestation and centre. All women received g lucocorticoids. Clinical outcome is known for 1231 women and their 139 7 infants. The frequencies of the main prespecified study outcomes RDS (relative risk 1.17 [95% CI 1.00-1.36], p=0.05) and need for ventilat ion (1.15 [1.01-1.31], p=0.04) were higher in TRH-group infants than i n control infants. The excess risk in the TRH group was greater in inf ants who were born more than 10 days after treatment. Multivariate ana lysis adjusting for duration of gestation at randomisation, time from randomisation to delivery, parity, history of perinatal death, and inf ant's sex did not affect the risk estimates. TRH administration was as sociated with increased risks of maternal nausea, vomiting, lightheade dness, and a rise in blood pressure to 140/90 mm Hg or higher. Antenat al TRH given with glucocorticoids to women at high risk of preterm del ivery is associated with maternal and perinatal risks and cannot be re commended for widespread clinical use.