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Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

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Authors

Devender Roberts1, Julie Brown2, Nancy Medley2, Stuart R Dalziel3

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs


1Obstetrics Directorate, Liverpool Women's NHS Foundation Trust, Liverpool, UK [top]
2Liggins Institute, The University of Auckland, Auckland, New Zealand [top]
3Cochrane Pregnancy and Childbirth Group, Department of Women's and Children's Health, The University of Liverpool, Liverpool, UK [top]
3Children's Emergency Department, Starship Children's Health, Auckland, New Zealand [top]

Citation example: Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.pub3.

This is a Cochrane Pregnancy and Childbirth External Web Site Policy systematic review.

Below you will find the abstract. The full review will be posted here in the fall of 2017. To access the full review now, please go to the Cochrane Library External Web Site Policy.

Contact person

Devender Roberts

Obstetrics Directorate
Liverpool Women's NHS Foundation Trust
Crown Street
Liverpool
Merseyside
L8 7SS
UK

E-mail: devender.roberts@lwh.nhs.uk

Dates

Assessed as Up-to-date: 17 February 2016
Date of Search: 17 February 2016
Next Stage Expected: 18 February 2019
Protocol First Published: Issue 4, 2003
Review First Published: Issue 3, 2006
Last Citation Issue: Issue 3, 2017

What's new

Date / Event Description
17 February 2016
New citation: conclusions not changed

Nine new studies added for this update (Attawattanakul 2015; Balci 2010; Goodner 1979; Gyamfi-Bannerman 2016; Khazardoust 2012; Lopez 1989; Mansouri 2010; Porto 2011; Shanks 2010). The review now includes a total of 30 studies. The conclusions remain unchanged.

17 February 2016
Updated

Search updated. The methods updated and the analyses have been restructured. 'Summary of findings' table has been incorporated.

History

Date / Event Description
23 January 2013
Feedback incorporated

Feedback 8 received from Vincenzo Berghella.

30 April 2010
Amended

Search updated. Fourteen reports added to Studies awaiting classification.

25 June 2008
Feedback incorporated

Feedback from Vasiliy Vlassov added with a reply from the review author.

23 June 2008
Amended

Converted to new review format.

14 March 2007
Feedback incorporated

Feedback from David Hutchon added.

30 October 2005
Updated

The review substantially updates the Crowley 2006 review due to new Cochrane guidelines for inclusion and exclusion of studies and the need for the review to be standardised with the repeat courses of prenatal corticosteroids review. Six new trials have been included (Amorim 1999; Dexiprom 1999; Fekih 2002; Lewis 1996; Nelson 1985; Qublan 2001). Three studies that were included in the previous review have been excluded. The results are now presented as relative risks. Results from recent follow-up studies have been included. Individual participant data were available from the Liggins and Howie study and these were analysed completely by intention-to-treat analysis for the first time. These data contribute nearly a third of the data to the review. This represents an important development. The review also provides new information on corticosteroid use in the presence of rupture of membranes, hypertension syndromes, in multiple pregnancies and according to gestational age at first corticosteroid dose.

[top]

Abstract

Background

Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. While researching the effects of the steroid dexamethasone on premature parturition in fetal sheep in 1969, Liggins found that there was some inflation of the lungs of lambs born at gestations at which the lungs would be expected to be airless. Liggins and Howie published the first randomised controlled trial in humans in 1972 and many others followed.

Objectives

To assess the effects of administering a course of corticosteroids to the mother prior to anticipated preterm birth on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.

Search methods

We searched Cochrane Pregnancy and Childbirth's Trials Register (17 February 2016) and reference lists of retrieved studies.

Selection criteria

We considered all randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following spontaneous labour), regardless of other co-morbidity, for inclusion in this review. Most women in this review received a single course of steroids; however, nine of the included trials allowed for women to have weekly repeats.

Data collection and analysis

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.

Main results

This update includes 30 studies (7774 women and 8158 infants). Most studies are of low or unclear risk for most bias domains. An assessment of high risk usually meant a trial had potential for performance bias due to lack of blinding. Two trials had low risks of bias for all risk of bias domains.

Treatment with antenatal corticosteroids (compared with placebo or no treatment) is associated with a reduction in the most serious adverse outcomes related to prematurity, including: perinatal death (average risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.89; participants = 6729; studies = 15; Tau² = 0.05, I² = 34%; moderate-quality); neonatal death (RR 0.69, 95% CI 0.59 to 0.81; participants = 7188; studies = 22), RDS (average RR 0.66, 95% CI 0.56 to 0.77; participants = 7764; studies = 28; Tau² = 0.06, I² = 48%; moderate-quality); moderate/severe RDS (average RR 0.59, 95% CI 0.38 to 0.91; participants = 1686; studies = 6; Tau² = 0.14, I² = 52%); intraventricular haemorrhage (IVH) (average RR 0.55, 95% CI 0.40 to 0.76; participants = 6093; studies = 16; Tau² = 0.10, I² = 33%; moderate-quality), necrotising enterocolitis (RR 0.50, 95% CI 0.32 to 0.78; participants = 4702; studies = 10); need for mechanical ventilation (RR 0.68, 95% CI 0.56 to 0.84; participants = 1368; studies = 9); and systemic infections in the first 48 hours of life (RR 0.60, 95% CI 0.41 to 0.88; participants = 1753; studies = 8).

There was no obvious benefit for: chronic lung disease (average RR 0.86, 95% CI 0.42 to 1.79; participants = 818; studies = 6; Tau² = 0.38 I² = 65%); mean birthweight (g) (MD -18.47, 95% CI -40.83 to 3.90; participants = 6182; studies = 16; moderate-quality); death in childhood (RR 0.68, 95% CI 0.36 to 1.27; participants = 1010; studies = 4); neurodevelopment delay in childhood (RR 0.64, 95% CI 0.14 to 2.98; participants = 82; studies = 1); or death into adulthood (RR 1.00, 95% CI 0.56 to 1.81; participants = 988; studies = 1).

Treatment with antenatal corticosteroids does not increase the risk of chorioamnionitis (RR 0.83, 95% CI 0.66 to 1.06; participants = 5546; studies = 15; moderate-quality evidence) or endometritis (RR 1.20, 95% CI 0.87 to 1.63; participants = 4030; studies = 10; Tau² = 0.11, I² = 28%; moderate-quality). No increased risk in maternal death was observed. However, the data on maternal death is based on data from a single trial with two deaths; four other trials reporting maternal death had zero events (participants = 3392; studies = 5; moderate-quality).

There is no definitive evidence to suggest that antenatal corticosteroids work differently in any pre-specified subgroups (singleton versus multiple pregnancy; membrane status; presence of hypertension) or for different study protocols (type of corticosteroid; single course or weekly repeats).

GRADE outcomes were downgraded to moderate-quality. Downgrading decisions (for perinatal death, RDS, IVH, and mean birthweight) were due to limitations in study design or concerns regarding precision (chorioamnionitis, endometritis). Maternal death was downgraded for imprecision due to few events.

Authors' conclusions

Evidence from this update supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids could be considered routine for preterm delivery. It is important to note that most of the evidence comes from high income countries and hospital settings; therefore, the results may not be applicable to low-resource settings with high rates of infections.

There is little need for further trials of a single course of antenatal corticosteroids versus placebo in singleton pregnancies in higher income countries and hospital settings. However, data are sparse in lower income settings. There are also few data regarding risks and benefits of antenatal corticosteroids in multiple pregnancies and other high-risk obstetric groups. Further information is also required concerning the optimal dose-to-delivery interval, and the optimal corticosteroid to use.

We encourage authors of previous studies to provide further information, which may answer any remaining questions about the use of antenatal corticosteroids in such pregnancies without the need for further randomised controlled trials. Individual patient data meta-analysis from published trials is likely to answer some of the evidence gaps. Follow-up studies into childhood and adulthood, particularly in the late preterm gestation and repeat courses groups, are needed. We have not examined the possible harmful effects of antenatal corticosteroids in low-resource settings in this review. It would be particularly relevant to explore this finding in adequately powered prospective trials.


This review is published as a Cochrane review in The Cochrane Library, Issue 3, 2017 (see http://www.thecochranelibrary.com External Web Site Policy for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback. The Cochrane Library should be consulted for the most recent recent version of the review.