A randomized, controlled trial of antepartum thyrotropin-releasing hormone and betamethasone in the prevention of respiratory disease in preterm infants. Collaborative trial of prenatal thyrotropin-releasing hormone and corticosteroids for prevention of respiratory distress syndrome. Collaborative Santiago Surfactant Group.
The objective was to investigate whether the addition of thyrotropin-releasing hormone to antepartum betamethasone further reduces the incidence of respiratory disease in preterm infants.
                A randomized, placebo-controlled, double-blind trial of antepartum thyrotropin-releasing hormone (400 micrograms given intravenously four times) and betamethasone (5 mg given intramuscularly four times) was conducted in 378 mothers likely to be delivered between 24 and 32.6 weeks' gestation. Statistical analysis was by relative risk, chi 2, t tests, and multiple logistic regression analysis.
                Four hundred five live-born infants were delivered. In infants without lethal abnormalities delivered between 24 hours and 10 days from entry (n = 175) the incidence of respiratory distress syndrome was reduced from 52% to 31% (relative risk 0.61, 95% confidence interval 0.41 to 0.89) and that of severe respiratory distress syndrome from 42% to 20% (relative risk 0.48, 95% confidence interval 0.29 to 0.78) in the placebo and thyrotropin-releasing hormone groups, respectively. The number of deaths fell from 14 to one (relative risk 0.08, 95% confidence interval 0.01 to 0.63). The incidence of chronic lung disease was not significantly different, but that of an adverse outcome (chronic lung disease or death by 36 weeks' gestation) fell from 29% in the placebo group to 16% with thyrotropin-releasing hormone (relative risk 0.55, 95% confidence interval 0.31 to 0.99).
                The addition of thyrotropin-releasing hormone to antepartum glucocorticoid treatment reduces the incidence of respiratory distress syndrome and improves survival in preterm infants. Our purpose was to determine whether adding antenatal thyrotropin-releasing hormone to prenatal corticosteroids reduces the frequency of respiratory distress syndrome.
                A randomized, multicenter, double-blind, placebo-controlled trial was conducted of thyrotropin-releasing hormone (400 micrograms intravenously every 8 hours four times) in women with singleton pregnancies < 33 weeks of gestation who received antenatal betamethasone (12 mg intramuscularly every 24 hours two times). Neonates weighing < 1.0 kg received prophylactic surfactant and those above that weight received rescue therapy.
                One hundred ninety women received thyrotropin-releasing hormone and 180 were given placebo. There were no differences in the frequency of respiratory distress syndrome (relative risk 1.17 [95% confidence interval 0.93 to 1.48]), use of oxygen at age 28 days (1.14 [0.80 to 1.62]), or neonatal mortality (1.05 [0.79 to 1.38]). Air leaks were more frequent in the thyrotropin-releasing hormone group (1.57 [1.23 to 2.01]).
                The combination of antenatal thyrotropin-releasing hormone and corticosteroids does not reduce the frequency of respiratory distress syndrome or improve the outcome of preterm neonates compared with the use of corticosteroids alone.
There is no evidence from controlled clinical trials that postnatal thyroid hormone treatment reduces the severity of respiratory distress syndrome, neonatal morbidity or mortality in preterm infants with respiratory distress syndrome.