Case study: Preventative antibiotics halve the risk of infection in childbirth
Infections in childbirth and antibiotic use
Around ten percent* of maternal deaths in the UK are due to severe infection (sepsis). Medical intervention during delivery is known to increase the risk of infection. Infection rates after a caesarean birth without antibiotic prophylaxis (preventative antibiotics) are estimated at 20-25%, and up to 16% after an operative vaginal birth (involving forceps or vacuum extraction) - sometimes referred to as ‘assisted delivery’.
For every woman who dies from pregnancy-related infection, 70 more have severe infection and survive often with long-term health consequences.
While the use of antibiotics during birth by caesarean section is widely recommended, and there is strong evidence to support this, antibiotics have not been routinely recommended for women undergoing assisted delivery as there hasn’t been enough evidence that they reduce infection rates.
A 2017 Cochrane review identified just one single trial looking at antibiotic prophylaxis for assisted delivery in 393 women. It suggested that antibiotics have no effect on infection rates or length of hospital stay, but the quality of this evidence was low and more evidence was needed.
With funding from NIHR’s HTA Programme, and support through the NIHR Clinical Research Network (CRN), a team of researchers led by Professor Marian Knight from the National Perinatal Epidemiology Unit (NPEU), Nuffield Department of Population Health, University of Oxford, set out to investigate whether a single dose of antibiotic prevented maternal infection after operative vaginal birth.
The large trial included almost 3,500 women from across the UK, and was conducted at 27 hospital obstetric units in the UK between March 2016 and June 2018. Overall, 65% of births to women in the trial were by forceps and 35% by vacuum extraction. 1,719 women received amoxicillin/clavulanic acid, and 1,708 were given a placebo (saline). The antibiotic or placebo was administered about three hours after the women had given birth. The researchers found that women who received the antibiotic had a statistically significantly lower rate of confirmed or suspected infection than women given the placebo.
Unlike many previous observational studies of infections after operative vaginal birth which only followed women until they were discharged from hospital, in the ANODE trial, information on antibiotic prescription for presumed infection was collected from medical records both at the time of hospital discharge and by telephone interview six weeks after women gave birth.
The trial showed a clear benefit of a single dose of preventative prophylactic antibiotics, halving the risk of infection for women who have assisted vaginal births.
Six weeks after giving birth, rates of perineal infection, perineal pain, use of pain relief for perineal pain, need for additional perineal care and wound breakdown were statistically significantly lower in the group who received a single dose of antibiotics.
Study lead, Professor Marian Knight said "The trial showed a clear benefit of single dose prophylactic antibiotic after operative vaginal birth and both UK and World Health Organisation guidance should be changed to reflect this.’ She added “Almost one in five women experience an infective complication and our results show that this can be reduced by almost half with routine use of antibiotic prophylaxis at operative vaginal delivery. This equates to prevention of over 8,000 infections annually in the UK."
We also assessed the effect of using prophylaxis on overall antibiotic use. We found that for each additional 100 doses of antibiotic used in prophylaxis, 168 treatment doses will be saved, representing a 17% overall reduction in antibiotic use with a policy of universal prophylaxis.
The compelling evidence from the ANODE trial has led to guideline changes from the Royal College of Obstetricians and Gynaecologists (RCOG) - which now recommends a single prophylactic dose of intravenous antibiotic following assisted vaginal birth as a direct result of this research - and could prevent around 8,000 women having an infection across the UK.
“The trial showed such a reduction in infection and pain for women that many of the clinicians who helped recruit participants to the trial were really keen to implement the change in practice – even before the full results had been published, said Professor Knight.
"Because lots of centres were involved this meant that practice changed really quickly, and the guideline from the RCOG has helped this even more.”
Lead Health Economist, Associate Professor Oliver Rivero-Arias, said ‘The results of the ANODE trial also have implications for healthcare resources. Women who received amoxicillin or clavulanic acid prophylactically were statistically significantly less likely to report any GP, nurse or midwife home visits or hospital outpatient visits in relation to concerns about their wound healing compared to the placebo group. The total mean NHS costs per woman at six weeks after giving birth was estimated to be £52.60 less for women who received the single dose of antibiotic.’
The team also found that there was a reduction in the overall doses of antibiotics used in the first six weeks after delivery. Importantly, given recent concerns over sepsis in the UK, highlighted by organisations such as the UK Sepsis Trust, women receiving antibiotic prophylaxis had a 56% reduction in the risk of confirmed infection in the bloodstream compared to women receiving the placebo.
The NIHR Clinical Research Network (CRN) helped to recruit participants across 40 study sites across the UK, of which 27 recruited a combined total of over 3000 participants during the study.
Mr Nigel Simpson, NIHR CRN National Specialty Lead for Reproductive Health and Childbirth, said:
The NIHR CRN's presence in most maternity units allowed many women to participate in the study, further strengthening its relevance to national practice, and this practice is now incorporated in the most recent RCOG guidance.
The ANODE Trial was awarded BMJ UK Research Paper of the Year 2020. Watch an interview with Dr Fiona Godlee, Editor in Chief at The BMJ , who said "This is a great example of how high quality research evidence can have a real and positive impact on patient care and society as a whole, by preventing thousands of infections and reducing antibiotic use. Professor Knight and her team are worthy winners of this year’s award."
More research still needed
It is unclear whether prophylactic antibiotics administered orally would have the same preventative efficacy. Further analysis of the mechanism of action of a single dose of antibiotic is needed to investigate whether earlier administration, prenatal administration or repeated administration is likely to be more effective.
- For further information on this study, visit NIHR Funding & Awards.
- Read Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial, in The Lancet.
*Figures from the MBRRACE-UK Maternal Report 2019