Review: multiple doses of antenatal corticosteroids prevent preterm neonatal respiratory disease more than a single dose

ED FROM Crowther CA, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev 2007;(3):CD003935. Correspondence to: Dr C Crowther, University of Adelaide, Adelaide, South Australia, Australia; caroline.crowther@adelaide.edu.au Source of funding: Australian Department of Health and Aging. c Clinical impact ratings: Obstetrics 7/7; GP/FP/Obstetrics 6/7; Paediatrics 6/7; Paediatric neonatology 6/7 Repeat dose(s) of antenatal corticosteroids (ACSs) v placebo after the first dose to prevent neonatal morbidity in women still at risk of preterm delivery >7 days after a first dose* Weighted event rates Outcomes Number of trials (n) Repeat ACSs Placebo RRR (95% CI) NNT (CI) Respiratory distress syndrome 4 (2155) 26% 32% 18% (7 to 28) 18 (12 to 45) Severe lung disease 3 (2139) 10% 17% 40% (25 to 52) 15 (12 to 24) Serious infant morbidity{ 4 (2157) 18% 23% 21% (7 to 33) 22 (14 to 64) *Abbreviations defined in glossary; weighted event rates, RRR, NNT, and CI calculated from data in article using a fixed-effects model. {Composite outcome, variously defined. C O M M EN TA R Y T he advisability of repeat courses of ACSs for women at ongoing risk of preterm birth at ,34 weeks’ gestation has been queried since Liggins and Howie showed that ACSs provided survival and respiratory benefit over placebo. That trial, and subsequent RCTs and meta-analyses, supported the use of ACSs, but it was immediately clear that its benefits were time-limited. Why? Type II pneumocytes are irreversibly induced to produce surfactant by ACSs; however, ACSs are administered during a phase of exponential pulmonary growth and production of new, and presumably immature, alveoli. An initial wave of enthusiasm for repeat courses was tempered by concerns raised by animal and casecontrol studies about adverse effects on neurodevelopment and fetal growth. In this important meta-analysis, Crowther and Harding reviewed the findings of 5 recent, highquality, placebo controlled RCTs, all of which administered repeat courses of ACSs weekly. The primary findings were that treatment with repeat dose(s) of ACSs was associated with reductions in respiratory distress syndrome, severe lung disease, and serious infant morbidity. The direction of effect towards benefit was similar across RCTs. However, these benefits occurred at the expense of a mild reduction in fetal growth velocity and an increased risk of birth by caesarean section. The recently completed Multiple Courses of Antenatal Steroids for Preterm Birth Study (MACS), which randomised women to receive repeat doses of ACSs or placebo at 14-day intervals, was not included in the review. Preliminary results showed equivalent composite perinatal morbidity and mortality between groups and reduced fetal growth velocity in the repeat ACSs group. Accumulating paediatric follow-up from this and other trials will provide additional information for clinical decision-making. In the meantime, a pragmatic response to current evidence may be to reserve repeat doses of ACSs for women who have remained pregnant for .1 week but are now being considered for delivery in the next 2 days. Peter von Dadelszen, MBChB, DPhil University of British Columbia Vancouver, British Columbia, Canada 1. Liggins GC, Howie RN. Pediatrics 1972;50:515–25. 2. Murphy K, MACS Collaborative Group. Am J Obstet Gynecol 2007;197(Suppl 1):S2. Therapeutics EBM June 2008 Vol 13 No 3 81 on 17 July 2008 ebm.bmj.com Downloaded from

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