New data to inform clinical practice around preterm labour
Thursday 18 September 2008
For the first time clinicians will be provided with evidence on the long-term effects on children of using antibiotics in women at risk of giving birth early. The research consists of the seven-year follow up of a clinical trial, ORACLE, into the use of antibiotics in women presenting with signs of premature labour without obvious infection. The evidence obtained is crucial to ensuring women in these difficult circumstances receive the best clinical care for themselves and their babies. One in eight babies in the UK is born prematurely and prematurity is the leading cause of death in the first month after birth. The study, funded by the Medical Research Council and published in the Lancet, highlights the importance of conducting long-term follow-ups.
The follow-up of the children in the ORACLE Trial has confirmed that antibiotics should not be considered in cases of premature labour where the mother’s waters have not broken and there are no obvious signs of infection. At seven years, the study shows there are increased risks of functional impairment and cerebral palsy in these children, although the original trial had found no benefit or harm upon discharge from hospital.
The ORACLE Trial was the largest trial worldwide into premature labour and was set up to investigate whether giving antibiotics – which might tackle an underlying symptomless infection - to women presenting with signs of premature labour would improve outcomes for babies. The trial recruited two groups of women: those whose waters had broken, and those who showed signs of going into premature labour whose waters had not broken. The trial did not include pregnant women showing signs of infection as they should be treated with antibiotics. Untreated infections pose serious risks to both mother and baby.
Seven years ago, the ORACLE trial reported that the administration of the antibiotic erythromycin to women whose waters had broken prematurely yielded short-term benefits. These included delaying the onset of labour as well as reducing the need for assistance with breathing and the rate of infection in babies. The seven year follow-up study, designed to see whether better outcomes at birth made a difference to children’s health and development showed no benefit or harm in this group of children.
The follow-up study also shows that in the children of women whose waters had not broken there is an increase in parents’ reporting of impairment in their children, most of which is ‘mild’ - from poor eyesight, to experiencing difficulty walking around the block or struggling with day-to-day problem-solving. Parents also reported a small but statistically significant increase in the condition cerebral palsy (CP), a physical impairment that affects movement, in these children.
Sara Kenyon, from the University of Leicester who led the ORACLE Children Study, said: “Before the ORACLE Trial, there was some evidence of short-term benefits of antibiotics in premature labour, but we did not know what the long-term outcomes would be, which is why we conducted the follow-up. It’s thanks to each and every one of the mothers who were involved in the original trial and the seven year follow-up study that we now have the evidence to inform clinical practice. We could not have obtained these results with a smaller group of participants. The size of the study means that we were able to pick up such small differences in these outcomes.”
Sara Kenyon added: “It is unclear why the follow-up showed this unexpected increase in the number of cases of cerebral palsy in babies born to the group of women whose waters had not broken and not in the other group.”
Dr Catherine Elliott, Head of Clinical Research Support and Ethics at the Medical Research Council, said: “The ORACLE Children Study highlights the importance of conducting long-term follow-ups, especially in interventions in pregnancy and early life. The results were unexpected and the MRC is considering what further research could shed more light on these findings. We will be convening an expert group to look at what potential research avenues could be explored to understand what mechanisms may be involved.”
Phone: 0207 670 5139
press.office@headoffice.mrc.ac.uk
Notes:
- Kenyon, S, Pike, K, Jones DR, Brocklehurst, P, Marlow, N, Salt, A, Taylor, DJ. (2008) Childhood outcomes following prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial. Advance online publication, Lancet.
- S, Pike, K, Jones DR, Brocklehurst, P, Marlow, N, Salt, A, Taylor, DJ. (2008) Childhood outcomes following prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Advance online publication, Lancet.
- Original ORACLE Trial papers Lancet 2001; 357: 979-88 and 989-94.
- ORACLE stands for “Overview of the Role of Antibiotics in the Curtailment of Labour and Early delivery”
- For more information about the ORACLE Children Study please visit the study website: http://www.le.ac.uk/oraclechildren
- A leaflet designed for trial participants as well as Q&A documents are available from the MRC press office upon request.
- Everything possible has been done to contact all the mothers who took part in the original trial, which took place between 1994 and 2000, and who had asked to be kept informed of the results of the Children Study. A helpline has been set up for these families. Women who are pregnant and have any questions or concerns about these results can contact their GPs or NHS Direct who have been briefed about these results.
- Cerebral palsy (cp) is not a disease or an illness. It is the description of a physical impairment that affects movement. The movement problems vary from barely noticeable to extremely severe. No two people with cp are the same; it is as individual as people themselves.
- The trial recruited women from 161 centres across the world, 135 of which were in the UK. Other countries involved were Argentina, Australia, Belgium, Brazil, the Czech Republic, Hungary, Lithuania, Malaysia, Netherlands, Portugal, South Africa, Sri Lanka and United Arab Emirates. The vast majority of the recruitment was in the UK.
Ref: MRC/39/08
