Marion Knight and colleagues conducted a national prospective case-control study in the UK from June 2011 through May 2012 to estimate the incidence, describe the causative organisms and sources of infection, and identify the risk factors for severe maternal sepsis.
Please see later in the article for the Editors' Summary
In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK.
Methods and Findings
A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%).
For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The rapid progression to severe sepsis highlights the importance of following the international Surviving Sepsis Campaign guideline of early administration of high-dose intravenous antibiotics within 1 h of admission to hospital for anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency.
Please see later in the article for the Editors' Summary
Every year, nearly 300,000 women worldwide die during pregnancy or labour, or shortly after. According to a recent World Health Organization estimate, sepsis (blood poisoning) is responsible for 10.7% of these maternal deaths. Sepsis is caused by an inappropriate immune response to an infection. Normally, when bacteria or other microbes enter the human body, the immune system efficiently destroys the invaders. In sepsis, the immune system goes into overdrive, and the chemicals it releases into the blood to combat infection trigger widespread inflammation. This inflammation leads to the formation of small blood clots and leaky blood vessels that block the flow of blood to the vital organs. In the most severe cases (septic shock), blood pressure falls to dangerously low levels, multiple organs fail, and the patient can die. Symptoms of sepsis include fever, rapid breathing, and a fast heart rate. Sepsis, which often progresses rapidly, can be treated in its early stages with antibiotics alone. People with severe sepsis need to be admitted to an intensive care unit, where their vital organs can be supported while the infection is treated.
Why Was This Study Done?
Deaths from maternal sepsis mainly occur in low- and middle-income countries, but the rate of such deaths is increasing in countries with advanced healthcare systems. In the UK, for example, the incidence (the number of cases) of fatal maternal sepsis has increased markedly over the past two decades, and although the absolute risk of maternal death from sepsis is low, increasing numbers of women are experiencing severe maternal sepsis. To avoid preventable maternal illness and death in the UK, it is essential that clinical management and infection control strategies for maternal sepsis are improved. Here, to learn more about the incidence of maternal sepsis, the causative organisms and sources of infection, and the risk factors for maternal sepsis in the UK, the researchers undertake a national case-control study of severe maternal sepsis. A case-control study compares the characteristics of individuals with and without a given disease.
What Did the Researchers Do and Find?
For this study, clinicians in all the UK obstetrician-led maternity units (obstetricians care for women throughout pregnancy, labour, and the post-labour period) sent information about every woman who developed severe sepsis between June 2011 and May 2012 (365 cases) and about two unaffected (control) women per case to the United Kingdom Obstetric Surveillance System (UKOSS). Using this information and data on the number of maternities in the UK during this 12-month period, the researchers calculated that the incidence of severe sepsis was 4.7 per 10,000 maternities. Seventy-one women with severe sepsis (19.5% of cases) developed septic shock, and five women (1.4% of cases) died. The most common source of sepsis (implicated in about a third of cases) was a genital tract infection. Statistical analyses identified several risk factors for severe maternal sepsis, including having a fever or taking antibiotics in the two weeks preceding sepsis and all types of operative delivery (including cesarean delivery). Importantly, although Escherichia coli was the most common causative organism in severe maternal sepsis (present in a fifth of cases), infection with group A streptococcus was strongly associated with progression to septic shock. Moreover, in half the women with a group A streptococcal infection, severe sepsis was diagnosed within two hours of the first signs of a systemic inflammatory response.
What Do These Findings Mean?
These findings show that for every death from maternal sepsis in the UK, about 50 women develop life-threatening severe sepsis, that the onset of severe sepsis is very rapid, and that women who have recently had an infection are at particularly high risk of developing maternal sepsis. Although some pregnant women who developed severe sepsis during the study period may not have been included in the study, these findings have important clinical implications for the management of maternal sepsis in the UK and elsewhere. The findings suggest that pregnant or recently pregnant women with an infection need closer attention than women who are not pregnant, and adequate follow-up to ensure eradication of the infection. The findings also highlight the importance of giving high-dose intravenous antibiotics to anyone with suspected sepsis within an hour of admission to hospital as recommended by the international Surviving Sepsis Campaign, an initiative that was developed to improve the management, diagnosis, and treatment of sepsis. Finally, these findings suggest that signs of severe sepsis, particularly in women with a confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency.
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001672.
The UK National Health Service Choices website has information about sepsis
The international Surviving Sepsis Campaign guidelines for the treatment of sepsis are available through the campaign's website
The Sepsis Alliance, a US not-for-profit organization, also provides information about sepsis for patients and their families (in English and Spanish), including information about maternal sepsis and several personal stories about maternal sepsis (see the stories of Alanna Basinger, Alisa Proctor, Sandy C, and Natalie Banathy)
The not-for profit UK Sepsis Trust is another useful source of information about sepsis that includes patient stories
MedlinePlus provides links to additional resources about sepsis (in English and Spanish)
UKOSS provides more information about its national case-control study on severe maternal sepsis in the UK