In a world where "antibiotic resistance" has been a concern, not just among those opposed to medical science but by mainstream consensus, it may seem odd to discuss the benefits of preventative antibiotics, but a large randomized trial indicates that the World Health Organisation and other national organizations should change antibiotic guidelines, at least for assisted childbirth.

In 2016, an estimated 19,500 women died because of pregnancy-related infections globally. Even in high-income settings, infections account for 1 in 20 maternal deaths, and as many as 1 in 8 in the USA. For every woman who dies from pregnancy-related infection, another 70 women develop a severe infection and survive often with long-term health consequences.

Giving a single dose of preventative antibiotics to all women after childbirth involving forceps or vacuum extraction could prevent almost half of maternal infections including sepsis—equivalent to over 7,000 maternal infections every year in the UK, and around 5,000 in the USA. Around 1 in 8 women in the UK have an assisted vaginal birth (104,000 women annually), this compares to around 1 in 25 in the USA, and less than 1 in 100 in some low-income countries. Infection rates after assisted vaginal birth without antibiotic prophylaxis are around 16% worldwide, and up to 25% after Cesarean section. Despite that, WHO antibiotic guidelines and other guidance from organizations in the UK, North America, and Australasia, do not recommend antibiotic prophylaxis for assisted childbirth.

A randomized trial involving 3,420 women from 27 obstetric units, published in The Lancet, found that for every additional 100 doses of antibiotic given prophylactically, 168 doses could be avoided due to fewer post-delivery infections—meaning that a policy of universal prophylaxis after birth could help to reduce antibiotic use by 17%.

A recent Cochrane review of 95 trials showed that giving antibiotics before caesarean section reduced wound infection, endometritis, and serious maternal infection by 60–70%, and the use of antibiotics during Cesarean section is widely recommended. In contrast, evidence on the use of prophylactic antibiotics in assisted vaginal birth is limited to a small trial of 393 women. 

The study

Between March 2016 and June 2018, women were randomly assigned to receive intravenous amoxicillin and clavulanic acid (1,715 women) or placebo (saline; 1,705) within 6 hours of operative vaginal delivery. The researchers also assessed the effect of using prophylaxis on overall antibiotic use. Suspected or confirmed maternal infection within 6 weeks of giving birth was identified by a new prescription for antibiotics, confirmed systemic infection on culture, or endometritis.

Overall, around two-thirds of babies were delivered by forceps and about a third by vacuum extraction. Data were missing for 195 (6%) of women who were not included in primary outcome analyses. Results suggested that women who received a single dose of antibiotics had significantly fewer suspected or confirmed infections than women given placebo (180/1,619; 11% vs 306/1,606; 19%).

Importantly, women receiving antibiotic prophylaxis were also much less likely to have confirmed culture-proven sepsis compared to those receiving placebo (56% reduction – 11/1,619; 0.6% vs 25/1,606; 1.5%).

Rates of perineal wound infection or breakdown (burst stiches), perineal pain, use of pain relief for perineal pain, and need for additional perineal care were also substantially lower in the group who received antibiotics compared to the placebo group. Additionally, women who received antibiotics were much less likely to report any GP, nurse, or midwife home visits, or hospital outpatient visits due to their wound healing compared to the placebo group (table 3).

The researchers estimate that the total average NHS costs 6 weeks after birth were £52.60 less per women in those who received the single dose of antibiotic compared to women given placebo (£102.50 vs £155.10; appendix table S8).

One woman in the placebo group reported a skin rash and two women in the antibiotic group reported other allergic reactions, one of which was reported as a serious adverse. Two other serious adverse events were reported, neither was considered related to the treatment.

Commenting on the implications of the findings in a linked Comment, Dr Vincenzo Berghella from Thomas Jefferson University, USA, says the ANODE study is “practice changing” and writes: “Even if one conservatively estimates 2% of babies are born by operative vaginal delivery globally, about 2,700,000 of the world’s 135 million annual births are operative vaginal deliveries. Up to 16% of these births can be associated with infection without antibiotics prophylaxis, representing about 432,000 annual infections associated with operative vaginal delivery worldwide…Clinical guidelines should be updated to reflect the new recommendation of giving a single dose of intravenous amoxicillin and clavulanic acid within 6 h after operative vaginal delivery, in particular to women who also have an episiotomy.”