Abstract: One randomised controlled trial (RCT) and two quasi-RCTs contributed data on 1779 women who had uncomplicated vaginal births, comparing different antibiotic regimens with placebo or no treatment. The included trials took place in the 1960s (one trial) and 1990s (two trials). The trials were conducted in France, the USA and Brazil. Antibiotics administered included: oral sulphamethoxypyridazine or chloramphenicol for three to five days, and intravenous amoxicillin and clavulanic acid in a single dose one hour after birth. We rated most of the domains for risk of bias as high risk, with the exception of reporting bias and other potential bias. The quality of evidence ranged from low to very low, based on the GRADE quality assessment, given very serious design limitations of the included studies, few events and wide confidence intervals (CIs) of effect estimates. We found a decrease in the risk of endometritis (RR 0.28, 95% CI 0.09 to 0.83, two trials, 1364 women,very low quality). However, one trial reported zero events for this outcome and we rate the evidence as very low quality. There was little or no difference between groups for the risk of urinary tract infection (RR 0.25, 95% CI 0.05 to 1.19, two trials, 1706 women,low quality), wound infection after episiotomy (reported as wound dehiscence in the included trials) (RR 0.78, 95% CI 0.31 to 1.96, two trials, 1364 women, very low quality) and length of maternal hospital stay in days (MD -0.15, 95% CI -0.31 to 0.01, one trial, 1291 women, very low quality). Cost of care in US dollar equivalent was 2½ times higher in the control group compared to the group receiving antibiotics prophylaxis (USD 3600: USD 9000, one trial, 1291 women). There were few or no differences between treated and control groups for adverse effects of antibiotics (skin rash) reported in one woman in each of the two trials (RR 3.03, 95% CI 0.32 to 28.95, two trials, 1706 women, very low quality). The incidence of severe maternal infectious morbidity, antimicrobial resistance or women's satisfaction with care were not addressed by any of the included studies. Routine administration of antibiotics may reduce the risk of endometritis after uncomplicated vaginal birth. The small number and nature of the trials limit the interpretation of the evidence for application in practice, particularly in settings where women may be at higher risk of developing endometritis. The use of antibiotics did not reduce the incidence of urinary tract infections, wound infection or the length of maternal hospital stay. Antibiotics are not a substitute for infection prevention and control measures around the time of childbirth and the postpartum period. The decision to routinely administer prophylactic antibiotics after normal vaginal births needs to be balanced by patient features, childbirth setting and provider experience, including considerations of the contribution of indiscriminate use of antibiotics to raising antimicrobial resistance. Well-designed and high-powered randomised controlled trials would help to evaluate the added value of routine antibiotic administration as a measure to prevent maternal infections after normal vaginal delivery.

Plain-language summary: The review assessed whether routine antibiotic treatment after uncomplicated vaginal birth, compared with either placebo or no antibiotics, prevents maternal infection. We searched for evidence in August 2017 in three databases. We identified three trials involving 1779 women. The quality of the evidence ranged from low to very low. Different antibiotics were administered in the three trials and for different lengths of time. The trials took place in the 1960s (one trial) and 1990s (two trials), and were carried out in France, the USA and Brazil. Routine antibiotic administration reduced the number of women with infection of the lining of the uterus (endometritis) (2 trials, 1364 women) by 70%. The use of antibiotics did not reduce the incidence of urinary tract infections (2 trials, 1706 women), wound infections after episiotomy (2 trials, 1364 women) or length of maternal hospital stay (1 trial, 1291 women). There were no differences between the groups for skin rash due to antibiotics, reported in one woman in each of the two trials (1706 women). The cost of care was higher in the group that did not receive antibiotic prophylaxis. The incidence of severe maternal infections and illness, antimicrobial resistance or women's satisfaction with care were not addressed. The small number of trials limits the interpretation of the evidence for routine use of antibiotics after normal vaginal births. The low incidence of endometritis in the studies suggests that a relatively large number of women may have to be treated to avoid a few case of infection. There needs to be a balance between women's needs, childbirth setting and provider experience (for example, with frequent vaginal examinations or interventions) and the public health threat of antibiotics resistance. Further research from well-designed randomised controlled trials would help to evaluate the added value of routinely giving women antibiotics after normal vaginal birth to prevent maternal infections.