Is there a role for antenatal TRH therapy for the prevention of neonatal lung disease?

Unfortunately, surfactant therapy is not routinely available to infants in some parts of the world because of its cost. It is the hypothesis of this article that in situations where surfactant is not available, there may be a role for antenatal thyrotropin-releasing hormone (TRH) plus glucocorticoid therapy. Data from randomized clinical trials, which compared therapy with antenatal glucocorticoid plus TRH to that with glucocorticoid alone were extracted and subjected to meta-analysis. The trials that incorporated surfactant therapy were analyzed separately from those in which surfactant was not used. In addition, because surfactant therapy was only available to some patients in the Australian ACTOBAT trial, each group analysis was performed with and without the ACTOBAT data. A characteristic of the earlier presurfactant trials is that few were designed for "intention to treat" analysis. In most of these studies, it was decided a priori to include babies who delivered within a specified time period after hormone therapy. The addition of TRH did not decrease respiratory distress syndrome in those trials in which surfactant therapy was used. In the presurfactant trials, respiratory distress syndrome was significantly decreased when "intention to treat" data were examined, as well as in those infants who delivered between 1 and 10 days after maternal therapy. There was also a significant decrease in oxygen dependency at 28 days after birth, and in oxygen dependency or death at this time, in those infants who delivered 1 to 10 days after treatment. Antenatal TRH had no significant effect of on neonatal complications such as air leak, intraventricular hemmorhage, patent ductus arteriosus, retinopathy of prematurity, or necrotizing enterocolitis. However, TRH did produce transient suppression of the pituitary thyroid axis. There were also a variety of transient complications in the mothers, including nausea, vomiting or flushing, light-headed feeling, and increased blood pressure. The authors conclude that the implementation of appropriate antenatal glucocorticoid treatment is the first priority. Once this has been established, the data presented here suggest that addition of antenatal TRH should be considered in those situations where surfactant is not available.