Background: Thyrotropin-releasing hormones (TRH) added to prenatal corticosteroids has 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 strategy: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1965 to July 2003), EMBASE (1988 to July 2003), Current Contents (1997 to July 2003).
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, quality and data extractions were done by at least two authors independently.
Main results: Over 4600 women were recruited into the 13 included trials. Five trials were rated of high quality. 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 (relative risk (RR) 1.16, 95% confidence interval (CI) 1.03 to 1.29, 3 trials, 1969 infants), having a low Apgar score at five minutes (RR 1.48, 95% CI 1.14 to 1.92, 3 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.
Reviewers' conclusions: Prenatal thyrotropin-releasing hormones, in addition to corticosteroids, given to women at risk of very preterm birth do not improve infant outcomes and can cause maternal side-effects.