Published: 28 April 2023
Infections are a main cause of maternal death
Most expectant women in the UK have a straightforward pregnancy and deliver their babies without complications. For around 8,000 women each year though, complications during birth or the immediate weeks afterwards can be life threatening. While fewer than 70 women die from pregnancy-related conditions each year, those who survive life-threatening complications, or “near-misses”, can be left with long-term health issues and trauma.
Understanding the causes and management of near-misses can help improve care for affected women and their families, but as few cases occur in any single healthcare setting or even region, they can be difficult to study. This was resolved with an award of nearly £2million from the NIHR Programme Grants for Applied Research to a group of researchers led by Marian Knight, Professor of Maternal and Child Population Health at the University of Oxford. With this funding, they created a national programme to investigate risk factors for maternal deaths and near-misses, as well as how those complications were managed.
Co-ordinated from the University of Oxford’s National Perinatal Epidemiology Unit (NPEU), which also receives NIHR Clinical Trials Unit funding*, and in collaboration with the UK Obstetric Surveillance System**, the team evaluated data from all 226 consultant-led maternity units. They studied six conditions that are commonly linked to severe complications and maternal deaths, including uterine rupture, placental growth problems and severe infection (sepsis). These findings were developed into evidence-based recommendations for clinical practice, published in the journal Programme Grants for Applied Research, to support improvements in the quality of care for women, their babies and families. The team also developed a publicly available resource for healthtalk.org about conditions that threaten women’s lives in childbirth and pregnancy, drawn from their research findings and women’s experiences.
Halving infection rates with a single antibiotic dose
Recognising that infections are one of the main causes of death among pregnant and recently pregnant women (7% in the UK and 11% globally), Professor Knight’s team focused on reducing rates of serious maternal sepsis. Unlike for caesarean births, no strong evidence or recommendations for antibiotic use existed for women undergoing operative vaginal births (assisted by forceps or a vacuum/suction cup), although up to 16% develop an infection.
To address this, the NIHR Health Technology Assessment Programme awarded the team £1.4 million to develop the randomised controlled ANODE (prophylactic ANtibiotics for the prevention of infection following Operative DElivery) study. The study, also led by the NPEU, recruited nearly 3,500 women from 27 obstetric hospital units across England and Wales to see whether a single dose of antibiotic after operative vaginal birth could reduce infections in the 6 weeks after giving birth. Following recruitment, which was supported by NIHR Clinical Research Network-funded midwives and NIHR Reproductive Health and Childbirth Champion research midwives, the women received either intravenous antibiotic or a dose of saline shortly after delivery.
The fantastic NIHR Reproductive Health and Childbirth research midwife network though the NIHR and the equivalent through the devolved nations means that we can run big trials like this across all sorts of hospitals, which means that our results are generalisable to many women.”
Professor Marian Knight
Published in The Lancet, their results showed that antibiotic use nearly halved the number of infections, with only 11% developing an infection in the antibiotic group compared with 19% in the saline group. In practice, this would prevent more than 7,000 women from developing infections each year in the UK. Other benefits included reduced post-natal pain, fewer wound breakdowns and fewer visits to health professionals. Overall, the NHS saved £52.60 per woman treated with antibiotics.
Driving changes in national and international maternity services
Informed by the significant reduction in infections reported by ANODE, the World Health Organization (WHO) updated its guideline on the prevention and treatment of maternal peripartum infections to recommend routine preventative antibiotics for women undergoing operative vaginal births.
The WHO recommendation means that women throughout the world who have an assisted birth can now benefit from this very simple preventive treatment. We know that infections are a major global cause of severe illness and even death after childbirth and yet are poorly recognised, so this recommendation has the potential to save many lives.
Professor Marian Knight
Dr Geeta Kumar, Consultant Obstetrician and Gynaecologist and Vice President of the Royal College of Obstetrics and Gynaecology (RCOG), commented: “This recommendation was added [to RCOG’s guidelines on assisted vaginal birth] to improve clinical practice and intends to benefit those who have had an assisted vaginal birth by helping to prevent maternal infection and any associated secondary outcomes and concerns.”
The research community also recognised the impact of the ANODE team’s work on women’s health by awarding their Lancet paper the 2020 BMJ Research Paper of the Year. A further analysis of the study’s results, published in 2022 in the American Journal of Obstetrics and Gynecology, also supported the single use of antibiotics for all women after operative vaginal birth, regardless of the type of perineal injury they experienced. Reflecting on ANODE’s contribution, Professor Knight noted: “Not only did we prevent infection but there was also an overall reduction of 17% in the number of doses of antibiotics because the infection had been prevented.” This reinforced how responsible prescribing of antibiotics can reduce their use and help limit the rise in antibiotic resistance.
*The National Perinatal Epidemiology Unit at the University of Oxford is funded by the NIHR and grants from other funding agencies and medical research charities.
**The UK Obstetric Surveillance System (UKOSS) was set up in 2005 by Professor Marian Knight and colleagues at the National Perinatal Epidemiology Unit, University of Oxford, to carry out studies of severe pregnancy complications in the UK.
The studies were funded by the NIHR Programme Grants for Applied Research and the NIHR Health Technology Assessment Programme.
More information about the studies are available on the NIHR’s Funding & Awards website.