Progesterone treatment does not prevent early preterm birth in women pregnant with twins, despite showing promise in high-risk singleton pregnancies, finds an Article published Online first and in this week's issue of The Lancet.
Multiple pregnancies have a much greater risk of stillbirth and neonatal death. Indeed, premature birth is the major cause of death in multiple births and is known to lead to poor health and reduced achievement in school and adulthood, as well as placing extra financial costs on the health service. Previous trials have suggested that progesterone treatment might prevent preterm birth in high-risk singleton pregnancies, but whether progesterone treatment is effective in twin pregnancies is not known.
To investigate, Jane Norman and colleagues undertook the STOPPIT study (STudy Of Progesterone for the Prevention of Preterm birth In Twins), a randomised trial of 500 women with twin pregnancy recruited from nine UK National Health Service clinics specialised in caring for women with multiple pregnancy, between 2004 and 2008.
Starting at 24 weeks, women were randomised to receive daily vaginal progesterone gel (90mg) or placebo gel for 10 weeks. The authors also did a meta-analysis of published and unpublished data to examine the effectiveness of progesterone at preventing preterm delivery in twin pregnancies.
Overall, progesterone did not reduce the likelihood of delivery or intrauterine death (death of the fetus in utero) before 34 weeks of pregnancy in women with twin pregnancy. Findings showed that the proportion of women delivering or with an intrauterine death before 34 weeks of pregnancy was 24.7% in the progesterone treated group and 19.4% in the placebo group. The rate of adverse events did not differ between the two groups.
The meta-analysis confirmed that progesterone does not prevent early preterm birth in twin pregnancies.
The authors say: "Progestogens are not effective in women with twin pregnancy for prevention of preterm delivery." They conclude by calling for further investigation into the biological mechanism by which preterm delivery occurs which might explain the different outcome in twin and singleton pregnancy.
In an accompanying Comment, Lex Doyle from the University of Melbourne, Australia, cautions that just delaying preterm delivery will only be useful if it is also shown to have other long-term health benefits for the mother or fetus. He calls for funding of trials of perinatal interventions to include the long-term follow-up of survivors into childhood to establish the balance between long-term benefits and risks of progesterone to prevent preterm delivery of both singleton and multiple births.
Professor Jane Norman, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK. T) +44 (0)131 242 2694 or 07900 883 969 (Wednesday June 10 only) E) jane.norman@ed.ac.uk
Professorr Lex W Doyle, University of Melbourne, Victoria, Australia. T) +61 3 8345 3716 E) lwd@unimelb.edu.au
For full Article and Comment, see: http://press.thelancet.com/stoppit.pdf
Journal
The Lancet