Combined antenatal thyrotropin-releasing hormone and low-dose glucocorticoid therapy improves the pulmonary biochemical immaturity in congenital diaphragmatic hernia

Abstract

The lungs of patients born with severe congenital diaphragmatic hernia (CDH) are biochemically and morphologically immature. Because antenatal glucocorticoid therapy can accelerate pulmonary maturation in premature neonates who have respiratory distress syndrome, we hypothesized that it may correct the pulmonary biochemical and morphological immaturity associated with CDH. We showed in previous experimental studies that antenatal low-dose dexamethasone improved the biochemical and morphological parameters of pulmonary immaturity in rats that had severe CDH. Somatic and pulmonary growth were inhibited with high doses of dexamethasone. In the present study, we examined the effects of antenatal low-dose dexamethasone and thyrotropin-releasing hormone (TRH), alone or in combination, on the pulmonary maturation in CDH. Combined antenatal low-dose dexamethasone and TRH significantly reduced mean lung glycogen concentration ( P = .001), and increased mean disaturated phosphatidylcholine content ( P < .005) to better than that observed with either therapy alone, without changing mean body or lung weight. Combined TRH and low-dose glucocorticoid as an antenatal therapy may reduce the morbidity and mortality of CDH.