Animal, epidemiological and limited human studies have reported that obesity increases susceptibility to both bacterial and viral infections. Obesity has now reached worldwide epidemic proportions with a recent study estimating that there are currently 2.1 billion obese adults in the world. The rates of sepsis in both the non-pregnant and pregnant population are also increasing. Obesity is an independent risk factor for both infection and sepsis in pregnancy. This review article addresses the epidemiology, immunological factors, infection sites, investigation, management, specific intrapartum care and postnatal care of the obese pregnant woman with infection.
Highlights
- •
We summarise the epidemiology of both obesity and sepsis in pregnancy.
- •
We summarise the immunological factors associated with both the pregnant and the obese state.
- •
We provide a summary of the surgical issues that should be taken into account when doing a caesarean section on the obese patient to prevent infection.
- •
We summarise best practice investigation and management for the septic obese patient.
- •
We give an overview of the specific infections that obese pregnant patients are susceptible to.
Introduction
The physiological immune system response to pregnancy is associated with immunogenic suppression with known susceptibility to certain pathogens and an increased incidence of site-specific infections . Animal, epidemiological and limited human studies have reported that obesity increases susceptibility to both bacterial and viral infections . In addition, obese pregnant patients are also thought to have an increased susceptibility to infection and sepsis due to a variety of other factors as discussed below.
The terms ‘overweight’ and ‘obesity’ are defined by the World Health Organization (WHO) as an abnormal or excessive fat accumulation that presents a risk to health. The international standard of measurement of obesity is calculated using body mass index (BMI). The BMI is calculated as body weight (kg) height (m) −2 .
The WHO classification of obesity is shown in Table 1 . The obese state is further sub-classified as shown in Table 2 .
| Body mass index | Classification |
|---|---|
| ≤18.5 | Underweight |
| 18.5–24.9 | Normal range |
| ≥25 | Overweight |
| ≥30 | Obese |
| Body mass index | Classification |
|---|---|
| 30–34.9 | Class1 |
| 35–39.9 | Class 2 |
| ≥40 | Class 3 |
Obesity has now reached worldwide epidemic proportions with a recent study estimating that there are currently 2.1 billion obese adults in the world . Obesity rates continue to increase. There is a high prevalence in the UK of maternal obesity with as many as one in 15 pregnancies with class 2 or class 3 obesity . The obesogenic environment and practices of the developed world in combination with genetic influences are to blame for this high prevalence of obesity.
The rates of sepsis in the non-pregnant and pregnant population are also increasing . As reported in the most recent Confidential Enquiry into Maternal and Child Health (CEMACH) report, it is now the most common cause of direct maternal deaths . This is the first time it has been ranked as the most common cause of death since this report was first established in 1952.
Obesity is an independent risk factor for both infection and sepsis in pregnancy. This chapter addresses the epidemiology, immunological factors, infection sites, investigation, management, specific intrapartum care and postnatal care of the obese pregnant woman with infection.
Epidemiology of obesity and sepsis
Obesity has been recognised as a global epidemic affecting both developed and developing countries. The rate of obesity has been increasing over the last 3 years. A comparison shows that 29.8% of women were overweight in 1980 . However, this figure had risen to 38% in 2013 .
In some countries, the prevalence of obesity even exceeds 50%. Since 2006, the incidence of adult obesity in developed countries has continued to increase. However, this rate has now slowed. In the UK, only 40.6% of women have a normal BMI, with 25.1% being classified as obese . The known associated risk factors for obesity are social deprivation, ethnic minorities, age >35 years, regional location and diabetes mellitus. The UK has one of the highest obesity rates in the world .
The prevalence of obesity in pregnancy is also increasing. It is now thought that approximately one in 20 pregnant women in the UK are obese . The CEMACE 2010 reported that 5% of pregnant women have a BMI >35, 2% >40 and 0.2% >50 . There is a continuous relationship between obesity, morbidity and mortality. Essentially, this means that the more obese a person is, the higher the morbidity associated with the condition.
Predicting future trends in obesity is difficult, but it is thought that rates are set to increase across all age groups throughout the world . WHO has issued a target to halt the rise in obesity by 2025. Globally, obesity in pregnancy causes significant ill health effects and poses a great economic burden.
The mortality rate from sepsis in pregnancy has doubled in the last two decades in the UK. The rate has also increased in other European countries . The 2003–2005 CEMACH report highlighted obesity as a risk factor for maternal death . Twenty-eight percent of all pregnant women whose deaths were included in this report were obese compared to a background population rate of 16–19%. Of those who died from sepsis, 33% were obese and 48% had a caesarean section (all of whom were obese).
The association between obesity and sepsis was not completely clear in the most recent 2005–2008 CEMACH report . Perhaps the recognition of obesity as a risk factor for sepsis has crept into practice since the 2005 report and has led to changes in clinical practice. In response to the 2003–2005 CEMACH report, the RCOG guideline on ‘Management of woman with Obesity in Pregnancy’ was issued in 2010 .
In the 2003–2005 CEMACH report, the substandard care of sepsis was identified in 71% of deaths . This figure was only marginally improved upon in the 2005–2008 CEMACH report where it was a considered to be a factor in 69% of women who died . Lessons learnt from these reports include ‘delay in consultant involvement’, ‘delay in prescribing and administering antibiotics’ and ‘failure to recognise the sick patient’.
There has since been a drive to improve training for all health professionals involved in obstetric care regarding the recognition and treatment of the acutely unwell septic patient. Clinical guidelines, care bundles and annually audited skills and drills sessions have been employed in the hope of improving care. The need for timely referral and the involvement of multidisciplinary care is paramount in the management of a septic patient. The key message of the 2006–2008 CEMACH report regarding sepsis was ‘ Be aware of sepsis – beware of sepsis ’ .
Epidemiology of obesity and sepsis
Obesity has been recognised as a global epidemic affecting both developed and developing countries. The rate of obesity has been increasing over the last 3 years. A comparison shows that 29.8% of women were overweight in 1980 . However, this figure had risen to 38% in 2013 .
In some countries, the prevalence of obesity even exceeds 50%. Since 2006, the incidence of adult obesity in developed countries has continued to increase. However, this rate has now slowed. In the UK, only 40.6% of women have a normal BMI, with 25.1% being classified as obese . The known associated risk factors for obesity are social deprivation, ethnic minorities, age >35 years, regional location and diabetes mellitus. The UK has one of the highest obesity rates in the world .
The prevalence of obesity in pregnancy is also increasing. It is now thought that approximately one in 20 pregnant women in the UK are obese . The CEMACE 2010 reported that 5% of pregnant women have a BMI >35, 2% >40 and 0.2% >50 . There is a continuous relationship between obesity, morbidity and mortality. Essentially, this means that the more obese a person is, the higher the morbidity associated with the condition.
Predicting future trends in obesity is difficult, but it is thought that rates are set to increase across all age groups throughout the world . WHO has issued a target to halt the rise in obesity by 2025. Globally, obesity in pregnancy causes significant ill health effects and poses a great economic burden.
The mortality rate from sepsis in pregnancy has doubled in the last two decades in the UK. The rate has also increased in other European countries . The 2003–2005 CEMACH report highlighted obesity as a risk factor for maternal death . Twenty-eight percent of all pregnant women whose deaths were included in this report were obese compared to a background population rate of 16–19%. Of those who died from sepsis, 33% were obese and 48% had a caesarean section (all of whom were obese).
The association between obesity and sepsis was not completely clear in the most recent 2005–2008 CEMACH report . Perhaps the recognition of obesity as a risk factor for sepsis has crept into practice since the 2005 report and has led to changes in clinical practice. In response to the 2003–2005 CEMACH report, the RCOG guideline on ‘Management of woman with Obesity in Pregnancy’ was issued in 2010 .
In the 2003–2005 CEMACH report, the substandard care of sepsis was identified in 71% of deaths . This figure was only marginally improved upon in the 2005–2008 CEMACH report where it was a considered to be a factor in 69% of women who died . Lessons learnt from these reports include ‘delay in consultant involvement’, ‘delay in prescribing and administering antibiotics’ and ‘failure to recognise the sick patient’.
There has since been a drive to improve training for all health professionals involved in obstetric care regarding the recognition and treatment of the acutely unwell septic patient. Clinical guidelines, care bundles and annually audited skills and drills sessions have been employed in the hope of improving care. The need for timely referral and the involvement of multidisciplinary care is paramount in the management of a septic patient. The key message of the 2006–2008 CEMACH report regarding sepsis was ‘ Be aware of sepsis – beware of sepsis ’ .
Immunology
Immunology of pregnancy
Pregnancy alters the maternal immune system to allow the genetically foreign foetus to develop without causing rejection in a variety of ways, none of which are fully understood.
T helper cells produce cytokines in response to infection to provoke other immune cells of the innate system, whilst cytotoxic T cells kill the pathogen directly. T helper cells can be divided based on the cytokines that they produce: type 1 T helper produce interferon, interleukin (IL) and tumour necrosis factor (TNF), which promote an antibody response, whilst type 2 T helper produce differing ILs, which stimulate a cell-mediated innate immune response. Type 1 T helper cell response predominately fights infectious agents; by contrast, a type 2 T helper cell response alone is insufficient to protect against the majority of infectious agents (excluding parasites).
In pregnancy, there is a shift of T helper cells from type 1 to type 2 . Therefore, the antibody-mediated immune response is suppressed, and this is compensated by an increased activation of the innate immune system. The innate system is less efficient in clearing viruses and bacteria than the specific antibody response. Hence, the pregnant state puts a woman at an increased risk of certain pathogens. Pregnant women are known to be more susceptible to some intracellular viruses, bacteria and parasites . Pregnancy also puts a woman at a risk of placental infection with Plasmodium and Listeria . Table 3 shows those infections that pregnant women are prone to and those pathogens that tend to have a more severe clinical course in pregnancy.
| Pathogens with an increased susceptibility in pregnancy | Malaria |
| Measles | |
| Toxoplasmosis | |
| Listeriosis | |
| Leprosy | |
| Pneumocystis carinii | |
| Pathogens resulting in an increased disease severity in pregnancy | Influenza |
| Varicella | |
| Psittacosis | |
| Viral haemorrhagic fevers (Ebola and Lassa) | |
Peripherally, there are decreased numbers of natural killer (NK) cells and their cytotoxicity is suppressed. There is increased activation of granulocytes and monocytes; that is, the innate system is activated. Peripherally, there is also an increased level of complement regulatory proteins and decreased complement activation .
A summary of other placental mechanisms for pregnancy-induced immunosuppression is shown in Table 4 .
| Foetal trophoblastic cells lack the vast majority of class 1a major histocompatibility complex (MHC) antigens to allow invasion of maternal decidua, and hence avoiding provocation of maternal rejection. |
| MHC Ib antigens (HLA-G and HLA-E) are expressed instead. These inhibit the migration of natural killer cells through placenta, influence T cell shift locally and protect the foetal trophoblasts. |
| ‘Apoptosis-inducing ligands’ in the placenta destroy activated maternal immune cells. |
| Specialised uterine natural killer cells that ignore semi-allogeneic foetal cells. |
| Selective placental transfer of only beneficial maternal IgG antibodies to the foetus. |
| Trophoblast inhibits cytotoxic T cells and produces cytokines that locally drives the shift towards type 2 T helper cells. |
| Natural killer (NK) cells, T cells, dendritic cells and macrophages migrate to the placenta decidua; this decreases the maternal peripheral availability of these cells. |
Immunology of obesity
Adipose tissue is known to have endocrine, steroidogenesis and immunological function. The full extent of dysregulation of the immune system in obesity is yet to be established but there is clear evidence, both in epidemiological research and in immunological animal models, that adipose tissue causes immunosuppression .
The mechanisms by which obesity may result in immunosuppression are as follows:
- •
Suppression of functionality of both CD4 T cells and CD8 T cells
- •
T cell diversity
- •
Impaired NK cells
- •
Decreased cytokine production
CD8 and NK cells cause endocytosis and apoptosis of infected cells, particularly for viral and intracellular infections. Lower levels of these may account for the increased susceptibility of pregnant obese women to severe illness or mortality from the H1N1 influenza epidemic seen in 2009–2010 .
In obese people, there are also higher levels of baseline inflammatory cytokines and monocytes. It is thought that this chronic inflammatory state may desensitise the response of the immune system to infection and subsequently diminish the ability to mount an acute cytokine response to an infection.
It is also hypothesised that an increased systemic inflammation and hence oxidative stress in obesity result in an increased proliferation of B cells at the expense of T cells. Progesterone and IL-10 are increased in adiposity and suppress the proliferation of T cells. Increased B cells levels should be protective against previously encountered pathogens, but obesity has been shown to change the memory T cell response causing individuals to be at a risk of repeat infections.
Adiponectin is one of the adipokines (a cell signalling protein released by adipose tissue). Its level is decreased in obesity. This has been shown to diminish NK cells number, cytotoxicity and their cytokine production. In obesity, there are also increased levels of TNF and ILs.
Leptin is another adipokine with receptors on T cells, which induce cytokine release. Leptin levels are increased in obesity. Leptin has a several functions in the immune system: signalling for cytokine production, phagocytosis, chemotaxis, reactive oxygen species generation, NK cells and differentiation of T cells. Individuals with a genetic leptin deficiency become morbidly obese and are immune deficient. Leptin-deficient individuals have low levels of CD4 T cells and impaired T cell proliferation and cytokine release. It is yet unknown how increased leptin levels in obesity cause immune deficiency, but it is hypothesised that it may be due to leptin resistance .
Specific infections
Obesity is an independent risk factor for maternal sepsis from a variety of sources including surgical site infection, endometritis, chorioamnionitis, skin and soft tissue infections, urinary tract infections, viral infections, periodontal and hospital-acquired infections .
Genital tract
Offensive, green or heavy vaginal discharge, preterm labour, foetal distress, offensive meconium-stained liquor, premature rupture of membranes and stillbirth can all be signs of a genital tract infection. A continuous cardiotocograph (CTG) should be used if the maternal temperature is >38 °C once or >37.5 °C twice as foetal distress can be a sign of chorioamnionitis and foetal infection. In the presence of a suspicious CTG, a normal foetal scalp blood sample in labour unfortunately does not exclude foetal infection. The early use of a foetal scalp electrode to ensure a good-quality CTG recording is beneficial in the obese patient. When a genital tract infection is suspected, microbiology swabs from the vagina, placenta and baby should all be taken for culture and determination of antibiotic sensitivity. If a caesarean section is performed, a bacteriological swab from the uterine cavity should also be sent. The placenta should also be sent to histopathology.
A higher incidence of preterm premature rupture of membranes (PPROM) has been reported in obese patients due to subclinical infection . A 10-day treatment with erythromycin antibiotic should be prescribed for PPROM and delivery considered. The neonatologists should be informed if there is suspicion of chorioamnionitis as the neonate may require neonatal intensive care unit (NICU) admission and benefit from antibiotic treatment. Mixed growth of organisms is common in chorioamnionitis.
The presence of a postnatal vaginal discharge, heavy lochia and/or delayed involution of the uterus may be symptoms of endometritis, which is typically associated with streptococcal and Gram-negative anaerobes. In the postnatal period, the perineum should be regularly inspected as a potential site of infection. Obese pregnant patients are at a significantly higher risk of endometritis. The incidence of endometritis in obstetric patients with a BMI >45 was found to be 26.8% .
Breast
Breast pain can be a symptom of breast abscess, necrotising fasciitis and toxic shock syndrome. The Royal College of Obstetricians and Gynaecologists (RCOG) highlights the need for patients with mastitis to be seen in hospital if there has been no response to first-line antibiotics within 48 h, if symptoms have recurred or if the patient has signs of sepsis . Breast infections are typically caused by staphylococcal, streptococcal or methicillin-resistant Staphylococcus aureus (MRSA) organisms.
Surgical site infections
The risk of a surgical site infection following a caesarean section in the general population is 10% but may be as high as 26.8% in patients with a BMI >45 . A recent multicentre study has reported that the pathogenicity for wound infections following a caesarean section was polymicrobial in up to 24% of cases . The most common pathogen observed was Staphylococcus aureus , anaerobes in 23.2%, MRSA in 17%, Enterobacteriaceae in 13.3% and streptococci in 7.4% of cases.
Wound exudate, pain and swelling are typical signs of a wound infection. It is unusual for a patient to require high dosages of opiate analgesia following an uncomplicated caesarean section or operative delivery. The requirement for high dosages of opiates may suggest an undiagnosed pathology. Therefore, those patients who need opiates for analgesia should be regularly reviewed by a consultant.
In early necrotising fasciitis, there can be no visible skin change if the infection is deep but there will be severe pain. The skin will eventually blister and undergo necrosis. A plastic surgeon should be contacted urgently if necrotising fasciitis is suspected as the patient may require a fasciotomy. A magnetic resonance imaging (MRI) scan is the imaging modality of choice for diagnosing deep soft tissue infections.
There should also be daily vigilance of all intravenous cannula, injection sites, invasive parenteral lines, drain sites and bed sores.
Infection at regional anaesthesia sites is fortunately very rare but should be considered in the septic patient. Neurosurgical input should be sought urgently if suspected. Such infections are usually caused by staphylococcal, streptococcal or Gram-negative rods. Resiting of epidural cannulas is more common in the obese patient, with rates as high as 42% of cases . Multiple attempts at resiting epidural cannulas during labour can predispose to an infection at these sites.
Hospital-acquired infections
Compared with the general population, obese patients are more susceptible to nosocomial infections . In the UK, there is an increased use of antibiotics in the obstetric population and, therefore, nosocomial infections such as MRSA, carbapenemase-producing Enterobacteriaceae (CPE) and Clostridium difficile may be a developing clinical problem in obstetric patients .
Screening for the colonisation of MRSA on hospital admission is not performed routinely for obstetric patients but is the case for many other clinical disciplines. MRSA refers to Staphylococcus aureus strains that have developed a resistance to β-lactam antibiotics such as penicillin, cephalosporins and carbapenems. MRSA infections are associated with mastitis, cellulitis, breast abscess, pelvic thrombophlebitis, pneumonia, wound infections, urinary tract infections and sepsis. The rates of MRSA have decreased in the general population but seem to be increasing in the obstetric population . Two percent of postnatal patients were found to be colonised with MRSA in the USA .
CPE are part of normal bowel flora. They commonly cause urinary tract infections, intra-abdominal infections and sepsis. In the UK, these are very rare causes of infection but are increasingly common in other European countries . Worryingly, such infections are highly resistant to most antibiotics. Screening for these infections should be carried out for any patient who has had a hospital stay abroad in the last 12 months. Screening is conducted via a rectal swab or faecal culture. Until the patient has been confirmed to be screen negative, they should ideally be isolated.
Clostridium difficile infections are associated with pronged, recurrent and multiple antimicrobial use, particularly the use of cefuroxime or clindamycin. In America, there has been an increase in the incidence and severity of Clostridium difficile infections both in the general population and in the pregnant population, doubling the rate of those diagnosed between 2000 and 2003 . This may be due to the emergence of a hyper-virulent strain, although this is hard to substantiate as stool culture (and molecular typing) is rarely done for Clostridium difficile . The diagnosis of a Clostridium difficile infection is typically made by detecting Clostridium difficile toxin and/or antigens.
Typical symptoms of Clostridium difficile infection are diarrhoea, abdominal distention, abdominal pain, vomiting and fever. It is treated with oral metronidazole or vancomycin. In the general population, it has a 30% mortality rate. In the case of a fit, young and healthy pregnant woman, it has been reported to cause foetal loss, intensive care unit (ICU) admission, colectomy, septic shock and death . Frequent use of hand hygiene and the avoidance of unnecessary antibiotic treatment are key preventive measures. Alcohol-based hand sanitisers do not eradicate Clostridium difficile spores.
Urinary tract
Urinary tract infections are commonly caused by Gram-negative bacteria. Gram-negative bacteria can produce extended spectrum β-lactamases, which make them resistant to many antibiotics. These are increasingly common and now affect approximately 12% of coliform infections .
Cough/shortness of breath
It is currently unclear if obese patients are at an increased risk of bacterial pneumonia. However, obese pregnant women are at an increased risk of viral pneumonia . Obese patients are more at a risk of pneumonia following aspiration during the administration of a general anaesthetic. Pneumonia is typically caused by a variety of organisms including Streptococcus pneumoniae , Staphylococcus aureus , Mycoplasma pneumoniae, Haemophilus influenzae and Chlamydia pneumoniae, but atypical organisms that can be difficult to Gram-stain such as Mycoplasma pneumoniae , Chlamydia pneumoniae and Legionella pneumoniae should be considered. A discussion with an infectious disease physician and microbiologist will help target the relevant investigations and treatment required.
Sore throat
A sore throat can be a symptom of a Streptococcus infection. Around 10% of patients with pharyngitis are infected with group A Streptococcus (GAS). If three out of four of the Centor criteria are present (fever, tonsillar exudate, cough or tender anterior cervical lymphadenopathy), then the patient should be treated for presumed GAS . Rates of GAS have been increasing over the last 10 years, and it is associated with severe morbidity and mortality. It was the cause of 13 out of 29 maternal deaths from sepsis in the 2006–2008 CEMACH report .
Of the UK population, 5–30% are asymptomatic carriers in the throat or on the skin. It is a very common source of infection in children and all the women who died of GAS had young children or had worked with them. GAS is associated with sepsis, streptococcal toxic shock syndrome and necrotising fasciitis. Increased rates of GAS infection are usually seen between the months of December and April.
All attending staff should use personal protective equipment, including fluid-repellent masks with visors. The patient should be nursed in a single room with en-suite facilities. If GAS is confirmed, the infection control team and neonatologists should be informed as the baby should receive antibiotic treatment and all household contacts should also be given prophylactic antibiotics. Household contacts and staff should be warned of possible symptoms of GAS infection. Asymptomatic GAS infection in pregnant women should be treated aggressively.
Rare infections
A thorough history and clinical examination is imperative in a septic patient. The intake of unpasteurised milk can be a source of gastrointestinal infection with S almonella , Campylobacter , or Listeria . Contact with birthing animals can be a source of Coxiella burnetii , which can cause pneumonia, hepatitis, endocarditis and placentitis, whilst contact with aborting sheep or infected birds can be a source of Chlamydia psittaci respiratory infection in humans.
The recreational use of intravenous drugs typically causes infections by staphylococcal, streptococcal and MRSA organisms. These patients are at a risk of septic seeding, which can cause endocarditis and septic pelvic thrombosis.
A widespread rash suggests toxic shock syndrome, which is also associated with conjunctival hyperaemia or suffusion. Toxic shock syndrome caused by Staphylococcus results in a generalised macular rash. However, 10% of these rashes will be caused by a streptococcal infection. Staphylococcal toxic shock syndrome causes high fevers of ≥39.9 °C, hypotension and multi-system involvement. The skin will desquamate 10–14 days after the initial infection, particularly the hands and feet .
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
