Preterm infants with respiratory distress syndrome are at increased risk of adverse neonatal and developmental outcomes. In animal research, thyroid hormones stimulate surfactant production and reduce the incidence and severity of respiratory distress when given antenatally.
To determine whether thyroid hormone therapy used postnatally in preterm infants with suspected respiratory distress syndrome results in clinically important improvements in respiratory morbidity and subsequent improvements in neonatal and long term outcomes.
Searches were performed of The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), PREMEDLINE (March 2006), EMBASE (1980 - March 2006), previous reviews including cross references, abstracts and conference proceedings, supplemented by requests to expert informants.
Trials that enrolled preterm infants with suspected respiratory distress syndrome and allocated infants thyroid hormone treatment compared to control commenced in the first 48 hours after birth.
Data collection and analysis
Independent assessment of trial quality and data extraction by each author. Synthesis of data using relative risk (RR) and weighted mean difference (WMD) using standard methods of the Cochrane Collaboration and its Neonatal Review Group.
Two studies enrolled preterm infants with respiratory distress. Amato (1988) allocated infants to L-thyroxine 50 μg/dose at 1 and at 24 hours or no treatment. Amato (1989) allocated infants to L-triiodothyronine 50 μg/day in two divided doses for two days or no treatment. Both studies had methodological concerns including quasi-random methods of patient allocation, no blinding of treatment or measurement and substantial post allocation losses. Neither study reported any significant benefits in neonatal morbidity or mortality from use of thyroid hormones. Meta-analysis of two studies (80 infants) found no significant difference in mortality to discharge (typical RR 1.00, 95% CI 0.47, 2.14). Amato 1988 reported no significant difference in use of mechanical ventilation (RR 0.64, 95% CI 0.38, 1.09). No significant effects were found in use of mechanical ventilation, duration of mechanical ventilation, air leak, CLD at 28 days in survivors, patent ductus arteriosus, intraventricular haemorrhage or necrotising enterocolitis. Neurodevelopment was not reported.
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.