Multiple antenatal steroid courses do not improve preterm birth outcomes and can decrease baby size

December 18, 2008

Multiple courses of antenatal corticosteroids, every 14 days, do not improve outcomes for premature babies are associated with a decreased baby weight, length, and head circumference at birth. Therefore this treatment schedule is not recommended. These are conclusions of the MACS study, reported in an Article in this week's edition of The Lancet, written by Dr Kellie E Murphy, Department of Obstetrics and Gynaecology Mount Sinai Hospital, Toronto, Canada and colleagues from the MACS Collaborative Group.

Research suggests that for women at risk of preterm birth, one course of antenatal corticosteroids reduces the risk of neonatal mortality, respiratory distress syndrome and intraventricular haemorrhage (bleeding in the ventricles of the brain). However, some women may not give birth for weeks after this first course of steroids, and basic science and clinical research suggests that the effects of this one course could diminish over time. Thus, multiple courses of corticosteroids every 7-14 days have been administered even before completion of randomised controlled trials. The authors therefore wanted to investigate the effects of antenatal steroids in a randomised controlled study.

The authors analysed 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids, and who continued to be at high-risk of pre-term birth. Of these, 937 were assigned to multiple courses of antenatal corticosteroids, and 921 to placebo, every 14 days until week 33 or delivery, whichever came first. The primary endpoint of the study was a composite of perinatal or neonatal death and a collection of other conditions including severe respiratory distress syndrome and intraventricular haemorrhage.

The researchers found that infants exposed to multiple courses of antenatal corticosteroids had similar levels of diseases and death compared with those exposed to placebo. Infants receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216g v 2330g), were shorter (44.5cm v 45.4 cm) and had a smaller head circumference (31.1cm v 31.7cm).

The authors conclude: "Overall, multiple courses of antenatal corticosteroids, given every 14 days, are associated with decreased growth in utero and no neonatal benefits compared with one course of antenatal corticosteroids. Therefore, in women who remain at increased risk of preterm birth after receiving an initial course of antenatal corticosteroids, multiple courses every 14 days are not recommended."

In an accompanying Comment, Professor John P Newnham, School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia, and Professor Karen Simmer, Neonatal Care Unit, King Edward and Princess Margaret Hospitals, Perth, WA, Australia, say: "Follow-up of the children in MACS will provide invaluable insights into the long-term consequences, if any, of multiple doses of antenatal corticosteroids. Particular attention should be paid to those areas in which other studies have suggested problems, including behaviour, growth, glucose tolerance, and blood pressure. In the meantime, the evidence suggests it is prudent for obstetricians not to prescribe repeat injections of antenatal corticosteroids. Single-course therapy is of considerable benefit, but we should be aware of the potential dangers of giving too much of a good thing."
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For Dr Kellie E Murphy, Department of Obstetrics and Gynaecology Mount Sinai Hospital, Toronto, Canada, please contact Melissa McDermott, Media Relations T) +1 416 586-4800 ext. 8306 E) kmurphy@mtsinai.on.ca / MMcDermott@mtsinai.on.ca

Professor John P Newnham, School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia, T) +61 432 025216 / +61 8 93401220 E) john.newnham@uwa.edu.au

Full Article and Comment: http://press.thelancet.com/antenatalsteroidsfinal.pdf

Lancet

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