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

Crowther CA, Alfirevic Z, Han S, Haslam RR

Published Online:

January 20, 2010

Thyrotropin-releasing hormone (TRH) given with corticosteroids does not improve the benefit of steroids on the lungs of babies born too early, and may increase harm. Babies born very early are at risk of breathing difficulties (respiratory distress syndrome). TRH increases thyroid hormones in the baby and it has been thought that adding TRH to steroids for women giving birth early may increase the benefit on steroids on the baby's lungs. However, this review of 13 trials, involving over 4600 women, shows that TRH, given with steroids to women at risk of early birth, does not further reduce the breathing difficulties for the babies; and adverse effects were more common for both baby and mother.

Abstract (click to read)

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 strategy:

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.

This record should be cited as:

Crowther CA, Alfirevic Z, Han S, Haslam RR. Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD000019. DOI: 10.1002/14651858.CD000019.pub2

Assessed as up to date:

November 10, 2009

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Primary Review Group:

Pregnancy and Childbirth Group

Health topics:

Pregnancy & childbirth > Preterm labour > Fetal maturation/treatment

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

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

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