Transcript Slide 1

The ORACLE Children Study
Sara Kenyon University of Leicester
Peter Brocklehurst University of Oxford
Neil Marlow University College London
David Taylor University of Leicester
Rationale for ORACLE
• 1 in 8 babies in the UK are born prematurely.
• Being born prematurely is the leading cause of death in
the first month of life.
• The consequences of prematurity are a major public
health challenge with increased risk of disability and
those without disability having behavioural and
educational difficulties.
ORACLE Trial 1994 - 2000
• Previous research:
• Spontaneous premature labour with intact membranes
(SPL) or premature rupture of the membranes-broken
waters- (PROM) possibly due to underlying infection.
• Evidence suggested antibiotics may prevent or delay
labour and improve neonatal outcome.
• The women in the study had no obvious infection.
• Trial evaluated the antibiotics erythromycin and co-amoxiclav.
• Women randomly allocated to one of four arms using a
factorial design:
• Erythromycin
• Co-amoxiclav
• Erythromycin and co-amoxiclav
• Placebo pills
ORACLE Trial - results
• In women whose waters broke early:
• Erythromycin was beneficial for babies in the short-term:
• Prolonged pregnancy
• Babies had less infection, respiratory difficulties, and
abnormal brain scans
• Co-amoxiclav, while prolonging pregnancy, also increased
the risks of necrotising enterocolitis (NEC).
• No short-term effects were seen for babies born to women
showing signs of going into premature labour without broken
waters.
ORACLE Children Study
• UK follow up began in 2002.
• Original ORACLE trial participants asked to fill in
questionnaire about their child’s health and how they
were doing at school at age 7.
• 4148 children born to mothers with early broken
waters were eligible; 3171 (75%) returned a
questionnaire.
• 4221 children were born to mothers without early
broken waters were eligible; 3196 (71%) returned a
questionnaire.
ORACLE Children Study –
Results for women without broken waters
• As expected in a group of children like this, 40% of the
children born to mothers who showed signs of
premature labour have some kind of functioning
problem.
• In the group who received erythromycin (either with or
without co-amoxiclav) there were slightly more children
with a ‘functioning’ problem compared to those who did
not receive erythromycin.
• Functioning problems included very mild difficulties and
most of the functioning problems reported by parents
were classified as minor (e.g. wearing glasses, some
difficulty walking or struggling with day to day problem
solving).
ORACLE Children Study –
Results for women without broken waters
Functioning problems in children
100%
80%
60%
40%
20%
42%
38%
0%
Erythromycin
No erythromycin
ORACLE Children Study –
Results for women without broken waters
• Unexpected increase in numbers of children with cerebral
palsy in those who were given either antibiotic.
• Cerebral palsy is the description of a physical impairment
disorder that affects movement. The movement problems
vary from mild to extremely severe. Cerebral palsy is most
commonly the result of failure of a part of the brain to
develop, either before birth or in early childhood.
ORACLE Children Study –
Results for women without broken waters
Cerebral palsy in children
Cerebral palsy in children
100%
100%
90%
90%
80%
80%
70%
70%
60%
60%
50%
50%
40%
40%
30%
30%
20%
10%
3.30%
20%
1.70%
0%
10%
3.20%
1.90%
0%
Erythromycin
No erythromycin
Co-amoxiclav
No co-amoxyclav
The risk was clearest for mothers given both antibiotics: 35
(4.4%) of children had cerebral palsy compared with 12
(1.6%) for mothers receiving double placebo.
ORACLE Children Study –
Results for women without broken waters
• For mothers who had signs of premature labour
without broken waters, having antibiotics did not make
any difference to their child’s behaviour, most medical
conditions, or Key Stage 1 results.
• Being in the co-amoxiclav group did not make any
difference to children’s functioning.
ORACLE Children Study Results for women with broken waters.
• For mothers whose waters broke early, neither
erythromycin or co-amoxiclav made any clear
differences to child’s functioning, behaviour,
most medical conditions, or Key Stage 1
results.
Impact of ORACLE
• Erythromycin may have some short-term, but not longterm, benefits for children whose mothers have early
broken waters.
• Antibiotics should not be given to women who are
showing signs of going into premature labour but do not
have broken waters and do not have an obvious
infection.
• These findings do not mean that antibiotics are
unsafe for use in pregnancy. Where there is obvious
infection, antibiotics can be life-saving for both mother
and baby.
• These findings will make a difference to future
generations.
References
• 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.
• 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
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.