Prenatal thyrotropin-releasing hormone for preterm birth

Adding thyrotropin-releasing hormones (TRH) to corticosteroids has been suggested as a way of improving fetal lung development.

The objective of this review was 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.

We searched the Cochrane Pregnancy and Childbirth Group trials register, Cochrane Controlled Trials Register, and bibliographies. Date of last search: January 1999.

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 neonatal mortality, neonatal morbidity, childhood development and maternal morbidity.

All assessments of trial eligibility, quality and data extractions were done by at least two authors independently.

Over 4500 women were recruited into the 11 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, chronic oxygen dependance, or improve fetal, neonatal or childhood outcome in any of the 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 infants needing ventilation (relative risk (RR) 1.16, 95% confidence interval (CI) 1.03-1.29), having a low Apgar score at five minutes (RR 1.80, 95% CI 1.14-1.92) and, for the one trial providing data, was associated with poorer outcomes at the 12 month follow up. Sensitivity analyses by trial quality, or subgroups with differing times from entry to delivery, or different dose regimens of TRH, did not change these findings.

On the basis of currently available evidence, prenatal TRH, in addition to corticosteroids, given to women at risk of very preterm birth cannot be recommended for clinical practice.