Intervention Review

Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes

  1. Caroline A Crowther1,*,
  2. Christopher JD McKinlay2,
  3. Philippa Middleton1,
  4. Jane E Harding3

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 15 JUN 2011

Assessed as up-to-date: 18 APR 2011

DOI: 10.1002/14651858.CD003935.pub3


How to Cite

Crowther CA, McKinlay CJD, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database of Systematic Reviews 2011, Issue 6. Art. No.: CD003935. DOI: 10.1002/14651858.CD003935.pub3.

Author Information

  1. 1

    The University of Adelaide, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia

  2. 2

    University of Auckland, Liggins Institute, Auckland, New Zealand

  3. 3

    University of Auckland, Department of Paediatrics, Auckland, New Zealand

*Caroline A Crowther, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, 5006, Australia. caroline.crowther@adelaide.edu.au.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 15 JUN 2011

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト

Background

It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial.

Objectives

To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), searched reference lists of retrieved studies and contacted authors for further data.

Selection criteria

Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth.

Data collection and analysis

We assessed trial quality and extracted data independently.

Main results

We included 10 trials (more than 4730 women and 5650 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, numbers needed to treat (NNT) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNT 30, 95% CI 19 to 79).

Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) -75.79 g, 95% CI -117.63 to -33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.

At early childhood follow-up no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments.

Authors' conclusions

The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.

Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.    

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト

Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease

This review shows that a repeat dose of prenatal corticosteroids given to women who remain at risk of an early birth after an initial course of prenatal corticosteroids helps the baby's lungs and reduces serious health problems in the first few weeks of life.

Infants born preterm (before 37 weeks' gestation) are at risk of difficulty breathing and lung disease because their lungs are not fully developed. Woman at risk of preterm birth include those with ruptured membranes, antepartum haemorrhage, preterm labour, cervical incompetence, pre-eclampsia or multiple pregnancy. Preterm babies who survive the early weeks of life are also at risk of long-term neurological disabilities such as epilepsy and cerebral palsy. A single course of corticosteroids, given to women who may give birth early, helps develop the baby's lungs. This benefit does not last beyond seven days. This review of 10 randomised controlled trials, involving more than 4730 women who remained at risk of early birth more than seven days after an initial course of corticosteroids and 5650 babies between 23 and 34 weeks' gestation showed that repeat dose(s) of prenatal corticosteroids reduced the risk of the baby having breathing difficulties and serious health problems in the first few weeks of life. Some of the trials showed that the baby may be smaller at birth but not if adjusted for gestational age nor by the time of hospital discharge. In four trials that followed up the babies to early childhood, no long-term benefits or harms were seen at 18 months to two years' corrected age. Further research is needed on the long-term benefits and risks for the woman and baby, which should include later child health, growth and development.

Repeat prenatal corticosteroid treatment could increase the risk of infection and suppress pituitary-adrenal function for the mother and her baby. For the women, there was no increase in infectious morbidity of chorioamnionitis or puerperal sepsis, and the likelihood of a caesarean birth was unchanged.

Betamethasone was the only corticosteroid evaluated. It is uncertain whether the effects seen for betamethasone would be the same for dexamethasone.

 

アブストラクト

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト

早産リスクのある女性に対する新生児の健康アウトカムを改善するための出生前のステロイド薬反復投与

背景

出生前の副腎皮質ステロイド(以下、ステロイド)薬の反復投与が有益であるか否かは明らかになっていない。

目的

出生前のステロイド薬反復投与の有効性および安全性を評価すること。

検索戦略

Cochrane Pregnancy and Childbirth Group's Trials Register(2011年3月31日)を検索し、抽出した研究の文献リストを検索し、追加データについては著者に問い合わせた。

選択基準

7日以上前にステロイド薬の投与を1コース受けた女性で、依然早産のリスクがあると考えられる女性に関するランダム化比較試験(RCT)。

データ収集と分析

試験の質および抽出したデータを別々に評価した。

主な結果

バイアスのリスクが低度から中程度の10件の試験(女性4,730例および児5,650例超)を選択した。早産のリスクのある女性に対して出生前にステロイド薬を1コース実施後7日以降にステロイド薬を反復投与したとき、反復投与しなかったときと比較して、主要アウトカムである呼吸窮迫症候群[リスク比(RR)0.83、95%信頼区間(CI)0.75~0.91、8試験、児3,206例、治療必要数(NNT)17、95%CI 11~32]および児の重篤なアウトカム(RR 0.84、95% CI 0.75~0.94、7試験、児5,094例、NNT 30、95% CI 19~79)について児が発現するリスクが低下した。ステロイド薬の反復投与による治療は、出生時体重の平均値の低下と関連していた[平均差(MD)-75.79 g、95%CI -117.63~-33.96、9試験、乳児5,626例]。しかしながら、妊娠期間で出生時体重を補正したアウトカム(出生児体重のZ値、中央値および胎児発育遅延での出生時体重の倍数)は、治療群間で差が認められなかった。乳児期のフォローアップでは、出生前にステロイド薬を反復投与した乳児は未投与の乳児と比較して、主要アウトカム(総死亡数、何らかの障害もしくは重大な障害を伴わない生存、障害、または重篤なアウトカム)および副次アウトカムである成長評価について、統計学的な有意差は認められなかった。

著者の結論

出生後数週間における乳児の呼吸困難や重篤な健康問題が減少するという短期的な利益が認められるため、1回目のコース投与後7日以降に依然、早産のリスクのある女性については、出生前ステロイド薬の反復投与が支持される。これらの利益は出生時体重のわずかな低下を伴っていた。現在得られているエビデンスから、乳児期における利益もないが、有意な有害性もないことが改めて示唆される。

訳注

監  訳: 江藤 宏美,2011.11.1

実施組織: 厚生労働省委託事業によりMindsが実施した。

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