Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease (Review)

Abstract

Background Thyrotropin-releasing hormones (TRH) added to prenatal corticosteroids had been suggested as a way to further reduce breathing problems and neonatal lung disease in infants born preterm. Objectives To assess the effect of giving prenatal TRH in addition to corticosteroids to women at risk of very preterm birth for the prevention of neonatal respiratory disease. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 2), MEDLINE (1965 to July 2009), EMBASE (1988 to July 2009) and reference lists. We also contacted trial authors. Selection criteria Randomised controlled trials in women at sufficient risk of preterm birth to warrant the use of prenatal corticosteroids to promote lung maturity. TRH and corticosteroids were compared with corticosteroids with or without placebo. The main outcomes considered were fetal and infant mortality, infant morbidity, childhood development and maternal morbidity. Data collection and analysis All assessments of trial eligibility, risk of bias and data extractions were done by at least two review authors independently. Main results Over 4600 women were recruited into the 13 included trials. The five trials had a low risk of bias in the five risk of bias domains. Overall, prenatal TRH, in addition to corticosteroids, did not reduce the risk of neonatal respiratory disease or chronic oxygen dependence, and did not improve any of the fetal, neonatal or childhood outcomes assessed by intention-to-treat analyses. Indeed, the data showed prenatal TRH to have adverse effects for women and their infants. All side-effects monitored were more likely to occur in women receiving TRH. In the infants, prenatal TRH increased the risk of needing ventilation (risk ratio (RR) 1.16, 95% confidence interval (CI) 1.03 to 1.29, three trials, 1969 infants), having a low Apgar score at five minutes (RR 1.48, 95% CI 1.14 to 1.92, three trials, 1969 infants) and, for the two trials providing data, was associated with poorer outcomes at childhood follow up. Sensitivity analyses by trial quality, or subgroups with differing times from entry to birth, or different dose regimens of TRH, did not change these findings. Authors' conclusions Prenatal TRH, in addition to corticosteroids, given to women at risk of very preterm birth do not improve infant outcomes and can cause maternal side-effects.