A new study has demonstrated that a potential new therapy, thyrotropin-releasing hormone (TRH), given in combination with the steroid hormone glucocorticoid to mothers who were threatening to deliver a very preterm infant, was no more effective in improving their newborn infants’ outcome than glucocorticoid treatment alone.
This study, the largest and most comprehensive of its kind to date, will appear in the February 19 issue of the New England Journal of Medicine. The trial was conducted at 13 centers in the North American Thyrotropin Releasing Hormone Study Group and led by Dr. Roberta Ballard of the University of Pennsylvania School of Medicine and the Children’s Hospital of Philadelphia. The double-masked trial randomized 996 women who were between 24 and 30 weeks pregnant and in preterm labor, to either thyrotropin releasing hormone in addition to glucocorticoid or to the current standard treatment, which is glucocorticoid alone.
Overall, TRH had no effect on the outcomes in either infants born at or before the 32nd week (who were at increased risk for premature lung disease/respiratory distress syndrome) or the more mature group, born after the 32nd week. For both groups, the outcomes were the same whether the mothers had received TRH in addition to the standard treatment, or the standard treatment alone. There was no evidence that TRH affected the incidence of other problems associated with prematurity in the infants, but it did cause transient nausea and vomiting, headache, and flushing in a minority of the mothers.
Finding that TRH was not effective in reducing the complications of prematurity was unexpected, since TRH in animal models stimulates lung development and the combination of TRH and glucocorticoid has synergistic effects. Previous smaller, unmasked trials in humans had suggested that pulmonary outcomes were improved in premature infants whose mothers had received TRH in combination with glucocorticoid before delivery.
The study concluded that TRH administration to women who are at risk for delivery of a premature infant is not indicated. The trial was funded by the National Institute of Child Health and Human Development; additional funding was received from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.