Sepsis is a leading cause of direct and indirect maternal death in the UK, and, globally, is estimated to cause almost 20,000 maternal deaths annually.1,2 In addition to very maternal death, an estimated 70 women have severe sepsis (requiring level 2 or 3 critical care) but survive.3 An increased risk of sepsis in association with caesarean section has been recognised for many years,4 and the National Institute for Health and Care Excellence (NICE)’s guidance recommends the use of prophylactic antibiotics at all caesarean births,5 based on substantial randomised controlled trial (RCT) evidence of clinical effectiveness.6 Three separate studies, conducted as part of a previous National Institute for Health Research (NIHR) Programme Grants for Applied Research programme, using both UK and US data, have documented an additional risk associated with operative vaginal birth (forceps or ventouse/vacuum extraction),3,7–9 particularly in relation to group A streptococcal infection, one of the most rapidly progressive causes of maternal infection.2,3 A Cochrane review,10 updated in 2017, identified only one small previous trial of prophylactic antibiotics following operative vaginal birth, including a total of 393 women, with a relative risk of 0.07 [95% confidence interval (CI) 0.00 to 1.21] for post-partum endometritis; given the small study size and extreme result, the authors suggested that further robust evidence is needed.
Further work suggests that the burden of localised infection following operative vaginal birth is also significant,11 with > 10% of women experiencing symptoms of perineal wound infection in the 3 weeks after giving birth. Women prioritising childbirth-related perineal trauma outcomes have rated ’fear of perineal infection’ as the most important outcome they are concerned about in the first few weeks after childbirth.12
Latest figures show that approximately 12% of women have an operative vaginal (forceps or ventouse) birth in England, representing a significant burden of potentially preventable morbidity.13 Current NICE guidelines for intrapartum care make no reference to prophylactic antibiotics following instrumental vaginal birth.14 The Royal College of Obstetricians and Gynaecologists (RCOG)’s guidance on operative vaginal delivery15 states that there are insufficient data to justify the use of prophylactic antibiotics in operative vaginal birth, referencing the Cochrane review10 identified above. Recognising the importance of antibiotic stewardship, the World Health Organization (WHO)’s recommendations on prevention and treatment of maternal peripartum infections explicitly state that routine antibiotic prophylaxis is not recommended for women undergoing operative vaginal birth, again citing a lack of evidence of benefit.16 The RCOG’s guidance on bacterial sepsis following pregnancy does not identify operative vaginal birth as a risk factor for post-partum infection;17 a lack of awareness of the associated risk may contribute to a delay in diagnosis. Evidence suggests that progression to severe sepsis following birth, particularly in association with group A streptococcal infection, can be very rapid.2,3 This emphasises the importance of urgent investigation of potential prophylactic measures.
Women with generalised and localised infection following operative vaginal birth incur additional health-care resources compared with those without infection. Although there are no studies quantifying these additional resources accurately, women with post-surgical infection after undergoing caesarean section follow a similar treatment pathway to women with localised infection after instrumental vaginal birth. Research has estimated that infection after caesarean section costs, annually, an additional £226 per patient compared with women with no post-surgical infection.18 These extra health-care costs are attributable to additional hospital length of stay, re-admissions and community care. Therefore, there remains the potential for a reduction in health-care costs if routine antibiotic prophylaxis prevents post-partum infection.
Presentations of the data from the NIHR programme studies3,7–9 at national meetings clearly showed that the natural response of the clinical community is to introduce prophylactic management with antibiotics, without clear evidence for the effectiveness of this approach following operative birth, because antibiotic prophylaxis been shown to be effective in reducing the risk of infection following caesarean birth.10 Giving antibiotic prophylaxis after operative vaginal birth has thus been introduced into local guidance unsupported by evidence. Although similar in some ways, there are clear differences between the wound sites and potential contaminating organisms at caesarean section and instrumental birth, so it cannot be assumed that single-dose prophylactic antibiotics will be equally effective in both circumstances. In addition, in the context of growing concerns about antibiotic resistance,19–21 it is vital that there is robust evidence behind any prophylactic use of antibiotics.
Recent recommendations suggest that antibiotic prophylaxis for caesarean section should be given prior to delivery. This trial specifically aimed to investigate the use of antibiotic prophylaxis after operative vaginal birth of the infant for the following reasons:
- The potential risks of in utero exposure to antibiotics are now widely recognised. The risk of necrotising enterocolitis22 and cerebral palsy23 is known to be increased among the children of women managed with antibiotics for suspected preterm labour. Maternal antibiotic use in late pregnancy has also been associated with an increased risk of asthma in early childhood24 and with very early-onset inflammatory bowel disease.25 Reports have identified differences in the infant microbiome with maternal antibiotic administration and the potential for long-term impacts on other disease states is a concern.26
- The major difference between the episiotomy wound and the caesarean section wound is the fact that there is ongoing contamination of the surgical field. Thus, with caesarean section, as soon as the operation is completed and a wound dressing applied, the major risk of infection is over. In contrast, an episiotomy wound is impossible to cover and, therefore, our rationale is to actually increase the length of time that there would be therapeutic levels of antibiotic from a single dose by giving it post delivery, to cover for ongoing contamination for as long as possible.
- There have been several cases of anaphylaxis relating to antibiotics given prophylactically for caesarean birth identified in a NIHR-funded study.27 Although the incidence is extremely low, this is of concern, particularly with antenatal administration, in which there is the potential for fetal compromise.
Twelve per cent of women in the UK undergo forceps or ventouse deliveries,13 which is an estimated 90,000 women annually. The conservatively estimated incidence of maternal infection following operative vaginal birth is 4%, based on the one previous trial,10 which results in an estimated 3600 women potentially having an infection after instrumental vaginal birth. Of these women, around 200 will be diagnosed with severe infection7 and up to four may die from their infection.28 There is, therefore, considerable scope for direct patient benefit from an effective preventative strategy. Other non-randomised studies suggest higher infection rates of up to 16%,29 which would correspondingly lead to an even greater potential benefit from a preventative therapy.
Objective
The objectives of this research were to investigate whether or not a single dose of prophylactic antibiotic following operative vaginal birth is clinically effective for preventing confirmed or presumed maternal infection and to investigate the associated impact on health-care costs.