Respiratory disease in very-low-birthweight infants after prenatal thyrotropin-releasing hormone and glucocorticoid

Abstract

Although prenatal glucocorticoid treatment reduces neonatal respiratory morbidity, respiratory distress syndrome and chronic lung disease (CLD) develop in many very-low-birthweight infants despite therapy. To investigate the effect of additional prenatal treatment with thyrotropin-releasing hormone (TRH), we did a multicentre, blinded, randomised trial. 404 women with threatened preterm delivery at less than 32 weeks' gestation received betamethasone plus TRH (4 doses of 400 μg 8-hourly) or betamethasone plus placebo. 103 infants who were fully treated and of less than 1 500 g birthweight were evaluated during the neonatal period. TRH treatment (55 infants) did not affect the total incidence of respiratory distress syndrome (47% vs 58% in controls) or of severe respiratory distress syndrome (13% vs 25% in controls, p=0·11). CLD (defined as requirement for supplemental oxygen at 28 days after birth) developed in significantly fewer TRH-treated infants (18% vs 44% of controls, p<0·01). The unadjusted relative risk of CLD with TRH therapy was 0·40 (95% Cl 0·26-0·80, p<0·05), and this was not materially changed after adjustment for potentially modifying variables. There were significantly fewer adverse outcomes, defined as death or continuing oxygen requirement, in the TRH group than in the steroid-alone group both at 28 days and when infants reached 36 weeks' postconceptional age. The incidence of other complications of prematurity was similar in the two groups. Prenatal TRH reduces the incidence of chronic lung disease among betamethasone-treated infants.