from Devender Roberts and Stuart Dalziel, Presumably the original sheep studies were done with parenteral steroids, so perhaps the initial extrapolation to humans was intra- muscular use. We are not aware of evidence about the effects of Carol Preston ( Summary of response from Devender Roberts and Stuart Dalziel, Liabsuetrakul, September 2003 May2006) Contributors The results, and reviewer's conclusions, are that administering cor- Mark Selinger ticosteroids(24 mg betamethasone, or 24 mg dexamethasone) women who are expected to give birth at 28-34 weeks gestar Hutchon, May 2006 reduces neonatal morbidity and mortality. However, there is no Summary clarification of how this should be prescribed. Standard regimens There have been two recent reports(1, 2 )of 30-year fol are for 48 hours treat g either 12 mg betamethasone IM every 24 hours, or 6 mg dexamethsone IM every nours. But people recruited whilst in utero to Liggins 1972a.Both used in- data in this review show the maximum benefit for corticosteroids tention-to-treat analysis, as does this review. One of these report is after 24 hours of treatment (1)stated"that there were similar numbers of neonatal survivors with much the same perinatal morbidity in both treatment and I have some questions about how to maximise the benefit in clinical control groups". Clearly this means that Liggins 1972a showed no Practice. overall benefit in terms of survival or morbidity, which to me seem 1)For a woman in preterm labor who is being given tocolytic treatment to facilitate steroid administration, how long should Liggins 1972a forms a major part of this Cochrane review, yet the tocolytics be continued, 24 hours or 48 hours? data from the follow-up reports differ from those in the review This new evidence therefore raises questions about the validity of over 24 hours, for example 8 mg dexamethasone IM every 8 hours this version of the review, and its earlier published versions, for affect adrenal suppression and fetal growth like repeated doses? some of the other trials. The version published in Effective care in Pregnancy and Childbirth(3)contained 12 trials reporting the 3)Do we need a review comparing the benefits and adverse events effect of corticosteroids on early neonatal death(0-7 days). Some of between different regimens of prophylactic corticosteriods these 12 are in the analysis presented here of corticosteroids versus placebo for the outcome neonatal death(0-28 days). However, for (Summary of comments from Tippawan Liabsuetrakul, Septem- Liggins 1972a, Block 1977, Gamsu 1989, and Morales 1989the data remain unchanged between the two reviews. Does this Authors reply there were no deaths from 8-28 days? We now know this is not true for Liggins 1972a. There is also something peculiar about the These questions have all been addressed by sub-group analyses in randomisation in Schmidt 1984. Between appearing in Effective the updated Care in Pregnancy and Childbirth and inclusion in the Cochrane (Summary of response from Devender Roberts and Stuart Dalziel review 15 women were added to this study, all in the treatment May2006) group and with no change in the number of deaths Contributors I understand an update of the review is in preparation. However, since the early nineties it would have been considered unethical carry out a randomised trial of steroids versus placebo and so I do Selinger, December 2005 not expect any new trials to have become available since the last Cochrane review in 2002 (Summary of feedback from David Hutchon, May 2006.) Why do the corticosteroids need to be administered by inti cular injection? Is there any evidence that this is preferable References 1. Dalziel SR, Walker NK, Parag V, Mantell C, Rea H, Rodgers (Summary of comment from Mark Selinger, December 2005. A et al. Cardiovascular risk factors after exposure to antenatal be- tamethasone: 30-year follow-up of a randomised controlled trial Author's repl Lancet2005;365:1856-62 Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth(rev Copyright @2006 The Cochrane Collaboration. Published by John wiley& Sons, Ltd(Summary of responsefrom Devender Roberts and Stuart Dalziel, May 2006.) Contributors Carol Preston Liabsuetrakul, September 2003 Summary Theresults,and reviewer’sconclusions,arethatadministering cor￾ticosteroids (24 mg betamethasone, or 24 mg dexamethasone) to women who are expected to give birth at 28-34 weeks’ gestation reduces neonatal morbidity and mortality. However, there is no clarification of how this should be prescribed. Standard regimens are for 48 hours treatment, using either 12 mg betamethasone IM every 24 hours, or 6 mg dexamethsone IM every 12 hours. But data in this review show the maximum benefit for corticosteroids is after 24 hours of treatment. I havesome questionsabout howtomaximisethe benefitin clinical practice. 1) For a woman in preterm labor who is being given tocolytic treatment to facilitate steroid administration, how long should tocolytics be continued, 24 hours or 48 hours? 2) Would the benefit of steroids bethesamefora modified regimen over 24 hours, for example 8 mg dexamethasone IM every 8 hours for 3 doses, or 12 mg dexamethasone IM every 12 hours? Will this affect adrenal suppression and fetal growth like repeated doses? 3) Do we need a review comparing the benefits and adverseevents between different regimens of prophylactic corticosteriods? (Summary of comments from Tippawan Liabsuetrakul, Septem￾ber 2003.) Author’s reply These questions have all been addressed by sub-group analyses in the updated review. (Summary of responsefrom Devender Roberts and Stuart Dalziel, May 2006.) Contributors Tippawan Liabsuetrakul Selinger, December 2005 Summary Why do the corticosteroids need to be administered by intramus￾cular injection? Is there any evidence that this is preferable to oral administration? (Summary of comment from Mark Selinger, December 2005.) Author’s reply Presumably the original sheep studies were done with parenteral steroids, so perhaps the initial extrapolation to humans was intra￾muscular use. We are not aware of evidence about the effects of oral administration. (Summary of responsefrom Devender Robertsand Stuart Dalziel, May 2006.) Contributors Mark Selinger Hutchon, May 2006 Summary There have been two recent reports(1,2) of 30-year follow-up of people recruited whilst in utero to Liggins 1972a. Both used in￾tention-to-treat analysis, as does this review. One of these reports (1) stated “ that there were similar numbers of neonatal survivors with much the same perinatal morbidity in both treatment and control groups”. Clearly this means that Liggins 1972a showed no overall benefit in terms of survival or morbidity, which to meseem the most important end points. Liggins 1972a forms a major part of this Cochrane review, yet the data from the follow-up reports differ from those in the review. This new evidence therefore raises questions about the validity of the Cochrane meta-analysis. There are also discrepancies between this version of the review, and its earlier published versions, for some of the other trials. The version published in Effective care in Pregnancy and Childbirth (3) contained 12 trials reporting the effect ofcorticosteroids on early neonatal death (0-7 days). Some of these 12 arein theanalysis presented here of corticosteroids versus placebo for the outcome neonatal death (0-28 days). However, for Liggins 1972a, Block 1977, Gamsu 1989, and Morales 1989 the data remain unchanged between the two reviews. Does this mean there were no deaths from 8-28 days? We now know this is not truefor Liggins 1972a. Thereis also something peculiar about the randomisation in Schmidt 1984. Between appearing in Effective Care in Pregnancy and Childbirth and inclusion in the Cochrane review 15 women were added to this study, all in the treatment group and with no change in the number of deaths. I understand an update of the review is in preparation. However, since theearly nineties it would have been considered unethical to carry out a randomised trial of steroids versus placebo and so I do not expect any new trials to have become available since the last Cochrane review in 2002. (Summary of feedback from David Hutchon, May 2006.) References 1. Dalziel SR, Walker NK, Parag V, Mantell C, Rea HH, Rodgers A et al. Cardiovascular risk factors after exposure to antenatal be￾tamethasone: 30-year follow-up of a randomised controlled trial. Lancet 2005;365:1856-62. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth (Review) 15 Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd 第 109 页