Introduction

Sepsis is a major cause of maternal death and morbidity worldwide. In the 18th and 19th centuries, puerperal fever or childbed fever was the most common cause of maternal death, resulting in over 50% of maternal deaths in Europe. Today, sepsis still accounts for 15% of maternal deaths a year worldwide, despite advances in hygiene, antibiotic use and efficient healthcare systems. Puerperal sepsis causes at least 75,000 maternal deaths every year in low-income countries. A health disparity exists, with up to three times higher maternal death rates in low-income countries compared with high-income countries.

In the UK, the triennial Confidential Enquiries into Maternal Deaths reported Genital tract sepsis as the leading cause of direct maternal death. Between 2006 and 2008, 29 direct maternal deaths from sepsis were reported, reflecting an increase in mortality rate caused by sepsis from 0.85 (95% CI 0.54 to 1.35) per 100,000 maternities in 2003 and 2005 to 1.13 (95% CI 0.77 to 1.67) per 100,000 maternities between 2006 and 2008. The Netherlands has also reported an increase in maternal mortality from sepsis. A nationwide Dutch study reported an incidence of severe maternal morbidity from sepsis of 21 per 100,000 deliveries (78 out of 371,021), of which 79% of cases required admission to the intensive care unit.

Maternal deaths from sepsis are largely preventable. The 2006–2008 Confidential Enquiries into Maternal Deaths report commented on the lack of recognition of the signs of sepsis and lack of healthcare guidelines on its management. The Royal College of Obstetricians and Gynaecologists (RCOG) has since issued guidelines on bacterial sepsis in pregnancy and sepsis after pregnancy. This is timely and has a huge bearing on patient safety, clinical risk management, and clinical negligence. In this chapter, I discuss the risks of sepsis in pregnancy and highlight management options for eliminating and mitigating these risks.

Definition of sepsis in pregnancy

Understanding and tackling the challenge of sepsis in pregnancy is hampered by inconsistent terminology and numerous definitions. The various terms used include ‘puerperal sepsis’, ‘puerperal fever’, ‘puerperal infection’, ‘puerperal pyrexia’, ‘genital tract sepsis’, maternal sepsis’, ‘intrapartum septic pyrexia’, ‘intrapartum infection’, ‘maternal pyrexia’, ‘maternal fever’. Some of these terms focus attention on the puerperium, but sepsis could also pose a serious threat to maternal health in pregnancy and in labour.

The World Health Organisation (WHO) has a definition of puerperal sepsis and a more general definition of puerperal infections, with the intention of including infections not isolated to the genitourinary system ( Table 1 ). Puerperal sepsis is defined as ‘infection of the genital tract occurring at any time between the rupture of membranes or labour, and the 42nd day postpartum, of which two or more of the following are present: pelvic pain, fever 38.5 °C or more, abnormal vaginal discharge, abnormal smell of discharge, and delay in the rate of reduction of size of uterus (less than 2 cm a day during the first 8 days).’ According to the WHO, in addition to infections caused by sepsis, puerperal infections include all extra-genital infections and incidental infections and all infections specifically related to the birth process but not of the genitourinary system. These include infections of the genitourinary system related to labour, delivery and the puerperium; infections related to the uterus and its associated structures (endometritis); infections related to the urinary tract (e.g. breast abscess); and incidental infections (e.g. malaria and respiratory tract infections).

The International Classification of Diseases (ICD-10) defines sepsis as ‘systemic disease associated with presence and persistence of pathogenic micro-organisms or their toxins in the blood.’ In order to create homogeneity, the American College of Chest Physicians and Society of Critical Care Medicine created standard definitions of sepsis; however, this only applied to non-pregnant women. The definition described the systemic inflammatory response syndrome (SIRS), ‘an inflammatory process generated by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes.’ The clinical criteria for SIRS are listed in Table 1 . Sepsis was thereby defined as SIRS plus infection.

Severe sepsis is sepsis associated with organ dysfunction, hypoperfusion, or hypotension. Septic shock is defined as sepsis with arterial hypotension despite adequate fluid resuscitation. The American College of Chest Physicians and Society of Critical Care Medicine sepsis definitions have not been validated for pregnant women.

Definition of sepsis in pregnancy

Understanding and tackling the challenge of sepsis in pregnancy is hampered by inconsistent terminology and numerous definitions. The various terms used include ‘puerperal sepsis’, ‘puerperal fever’, ‘puerperal infection’, ‘puerperal pyrexia’, ‘genital tract sepsis’, maternal sepsis’, ‘intrapartum septic pyrexia’, ‘intrapartum infection’, ‘maternal pyrexia’, ‘maternal fever’. Some of these terms focus attention on the puerperium, but sepsis could also pose a serious threat to maternal health in pregnancy and in labour.

The World Health Organisation (WHO) has a definition of puerperal sepsis and a more general definition of puerperal infections, with the intention of including infections not isolated to the genitourinary system ( Table 1 ). Puerperal sepsis is defined as ‘infection of the genital tract occurring at any time between the rupture of membranes or labour, and the 42nd day postpartum, of which two or more of the following are present: pelvic pain, fever 38.5 °C or more, abnormal vaginal discharge, abnormal smell of discharge, and delay in the rate of reduction of size of uterus (less than 2 cm a day during the first 8 days).’ According to the WHO, in addition to infections caused by sepsis, puerperal infections include all extra-genital infections and incidental infections and all infections specifically related to the birth process but not of the genitourinary system. These include infections of the genitourinary system related to labour, delivery and the puerperium; infections related to the uterus and its associated structures (endometritis); infections related to the urinary tract (e.g. breast abscess); and incidental infections (e.g. malaria and respiratory tract infections).

The International Classification of Diseases (ICD-10) defines sepsis as ‘systemic disease associated with presence and persistence of pathogenic micro-organisms or their toxins in the blood.’ In order to create homogeneity, the American College of Chest Physicians and Society of Critical Care Medicine created standard definitions of sepsis; however, this only applied to non-pregnant women. The definition described the systemic inflammatory response syndrome (SIRS), ‘an inflammatory process generated by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes.’ The clinical criteria for SIRS are listed in Table 1 . Sepsis was thereby defined as SIRS plus infection.

Severe sepsis is sepsis associated with organ dysfunction, hypoperfusion, or hypotension. Septic shock is defined as sepsis with arterial hypotension despite adequate fluid resuscitation. The American College of Chest Physicians and Society of Critical Care Medicine sepsis definitions have not been validated for pregnant women.

Epidemiology of sepsis in pregnancy

The reported incidence of sepsis in pregnancy is likely to be inaccurate owing to under-reporting or erroneous classification. In the UK and the USA, contemporary data are lacking. Blanco et al. reported a prevalence of bacteraemia in US obstetric patients of 7.5 per 1000 obstetric admissions, and a rate of sepsis of 8–10% in that population.

Sepsis has an insidious onset, but progression can be rapturous with a sudden catastrophic circulatory collapse and mortality up to 50%. Septic shock in pregnancy has a reported incidence of 2.3 per 100,000 maternities. A study in the Netherlands found a case fatality rate of 7.7%. Other studies have reported rates of 12% overall maternal mortality in women admitted to the intensive care unit and 20–28% maternal mortality in those with septic shock. The UK Obstetric Surveillance system is currently carrying out a population-based case-control study to estimate the incidence of severe maternal sepsis and investigate risk factors, causes and outcomes.

Risk factors for sepsis in pregnancy

In the 2006–2008 Confidential Enquiries into Maternal Deaths, Lancefield classification Group A streptococcus (GAS) or Streptococcus pyogenes was a significant cause of maternal death. Obstetric interventions, obesity, maternal age over 35 years, artificial reproduction, and multiple pregnancies and low socioeconomic status are risk factors. The risk factors for maternal sepsis in pregnancy are shown in Table 2 .

Group A streptococcus

In the 2006–2008 the Confidential Enquiries into Maternal Deaths reported that 13 out of the 29 maternal deaths were caused by GAS. In a study on maternal mortality in the Netherlands, GAS accounted for 42.9% (9 out of 21) of direct maternal deaths from sepsis and 31.8% (14 out of 44) of cases of maternal morbidity from sepsis. The reported case fatality rate for GAS was 14.3%. About 5–30% of the populations are thought to be asymptomatic carriers. Spread occurs directly through contact with mucus or droplet or skin sores, or perineal contamination. Family members, in particular, young children or closed communities, facilitate spread. Group A streptococcus has a myriad of presentations, but commonly throat and respiratory tract infections. Rarely, scarlet fever, streptococcal toxic shock syndrome, and necrotising fasciitis.

Obesity

Obesity is a modern day global ‘epidemic’ and escalating public health issue. It is defined as ‘a condition of abnormal or excessive body fat accumulation to the extent that health may be impaired.’ Body mass index (BMI, kg/m ² ) reflects overweight if BMI is 25–29.9 kg/m ² , obese if BMI 30 kg/m ² or over, and morbidly obese if BMI 40 kg/m ² or over. Recent UK data suggest that 24% of women aged between 16 and 44 years are obese and 3% are morbidly obese. In the USA, one-third of women of reproductive age are obese. Obese women have a 3.5-fold increase in the rate of infection compared with women of an ideal BMI. Wound infections are common, and their rate increases with worsening obesity.

Caesarean section

In high-income countries, rates of caesarean section have increased and range from 14.3–42.7%. Non-medically indicated caesarean sections are also increasing. Caesarean section carries a five to 20-fold increased risk of infectious morbidity compared with vaginal birth. Wound infections, urinary tract infections, pyelonephritis, respiratory tract infections, and mastitis are common. Emergency caesarean section (OR 1.39 [95% CI] 1.11 to 1.75), prolonged rupture of membranes over 18 h (OR 3.13 [95% CI] 1.34 to 7.38), increased intrapartum vaginal examinations (e.g. over 7) (OR 1.9 [95% CI] 1.2–3.1), and absence of antibiotic prophylaxis (OR 2.63 [95% CI] 1.50 to 4.6) further increase risks.

Prelabour rupture of membranes and chorioamnionitis

Prelabour rupture of membranes (PROM) refers to rupture of the fetal membranes before the onset of labour. It is termed pre-term prelabour rupture of membranes (PPROM) if occurring before 37 weeks of gestation. It occurs in about 8–10% of pregnancies, and PPROM occurs in about 2% of pregnancies. Ruptured membranes are a significant risk factor for chorioamnionitis, an acute inflammation of the chorion and placenta.

Medical conditions

In the Confidential Enquiries into Maternal Deaths report, three black women (two with sickle cell disease and one with sickle cell trait) died after suffering spontaneous PPROM between 17 and 23 weeks of gestation. In sickle cell disease, autosplenectomy increases infection risk. In low and middle-income countries, significant infectious mortality from HIV/AIDS, tuberculosis, pneumonia, and meningitis occur.

Causes of sepsis in pregnancy

Sepsis presents throughout pregnancy and postpartum. In one study, 21.8% of cases occurred before 26 weeks gestation, 21.8% occurred after 26 weeks gestation, 10.3% were intrapartum, and 46.2% postpartum.

Respiratory tract infections

Respiratory tract infections can lead to acute respiratory distress syndrome in pregnancy. The estimated prevalence of antepartum pneumonia is similar to non-pregnant women at 0.78 to 2.7 per 1000. Pneumonia may be bacterial, viral and fungal. Influenza A and B and varicella are the most common pathogens in pneumonia in pregnancy. Acute varicella infection affects 0.5–0.7 in 1000 pregnancies.

Community-acquired pneumonia complicates 0.5 to 1.5 per 1000 pregnancies in the USA, and Streptococcus pneumoniae accounts for 15–20% of cases. Mycoplasma pneumoniae or Legionella species are reported. Pneumonia in pregnancy is associated with a higher rate of morbidity and mortality than among non-pregnant women. Medical co-morbidities exacerbate poor outcomes. Treatment with a beta-lactam antibiotic together with a macrolide cover typical and atypical organisms.

Consequences of maternal sepsis include septic shock, endotoxic shock, circulatory collapse, and fetal demise. The causes of sepsis in pregnancy are presented in Table 3 .

Table 3

Causes of sepsis in pregnancy.

Pregnancy-related infections

Chorioamnionitis

Endometritis

Wound infection

Perineal infection

Mastitis

Infection related to regional anaesthesia

General infections

Pharyngitis

Gastroenteritis

Respiratory tract infection and pneumonia

Hepatitis

Urinary tract infection

Pyelonephritis

Chicken pox

Sickle cell sepsis

Malaria

Human immunodeficiency virus

Appendicitis

Pancreatitis

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