Neonatal sepsis is a dangerous and potentially life-threatening infection. However, raising awareness that the symptoms warrant a swift hospital referral and treatment can help to reduce infant morbidity. Emily Kirkham, Dr Paul Heaton and Dr Siba Paul alert you to the key signs
What is neonatal sepsis?
Neonatal sepsis occurs when a serious infection affects infants within the first 28 days of life. It is a significant cause of mortality and morbidity in newborn babies and may be caused by bacteria or viruses. Neonatal infections due to bacteraemia, pneumonia and meningitis account for approximately 23.4% of neonatal deaths worldwide each year; half of these deaths occurring during the first week of life (Chan et al, 2013). Data available from a prospective multicentre surveillance of 12 English neonatal units showed that the incidence of all neonatal infections is eight per 1,000 live births, and the majority of these infections occurred in premature (<37 weeks) and low-birth weight neonates (<2.5 Kg) (Vergnano et al, 2011).
Neonatal sepsis is further categorised into early or late-onset sepsis. Early-onset neonatal sepsis manifests itself within 72 hours of birth and, in the UK, is usually caused by Group B streptococcal infection, typically presenting as meningitis, pneumonia or generalised as sepsis. Late-onset neonatal sepsis manifests between seven and 28 days of birth and has different causes, symptoms and outcomes – meningitis and bacteraemia being more common (Hanley, 2008). Viral infections acquired during birth or shortly afterwards can also have serious consequences. Herpes simplex virus (HSV) is one of the most serious viral causes of neonatal sepsis and encephalitis with an estimated incidence of one in every 3,200–10,000 live births (Demmler-Harrison, 2014). Community health professionals (including community midwives and health visitors) who have regular contact with infants in the neonatal period are suitably placed to identify or raise concerns about late onset neonatal sepsis and refer promptly to paediatric services for specialist management.
Why are neonates at increased risk?
Newborn infants are dependent on innate immune pathways and maternally-derived passive immunity to protect them from microbiological attack. They have not developed any acquired immunity since the intrauterine environment is considered to be effectively sterile. Babies born at term have acquired passive immunity from transfer of maternal antibodies, however those born before 30 weeks of gestational age have had reduced transfer of maternal antibodies and hence are more vulnerable to developing infections in the neonatal period (Crawford & Buttery, 2010). A neonate’s ability to generate an immune response is therefore initially limited but rapidly rises in the postnatal period on exposure to micro-organisms (Berardi et al, 2013).
Antenatal infections can trigger premature birth. Most infants who are born prematurely or with a low birth weight may need invasive procedures (including intravenous cannulas, peripherally inserted central catheters, endotracheal tubes) to provide life-supporting care and nutrition. These interventions can increase susceptibility to severe late-onset sepsis (Berardi et al, 2013). The physical and chemical barriers to infection in the human body are also deficient in the newborn. Skin and mucous membranes are more easily broken down in premature neonates allowing access to disease causing organisms (van den Hoogen et al, 2009).
What are the most common infections?
Neonatal sepsis can be caused by bacteria and viruses. Group B streptococcus (GBS) is a major perinatal pathogen and is the most common cause of neonatal bacterial sepsis identified in developed countries. It usually presents as sepsis, meningitis or pneumonia. The organism is commensal in the gastrointestinal tract and vagina, and is usually acquired by the infant intrapartum during vaginal deliveries or when there is prolonged rupture of membranes (McCartney, 2001). GBS infection is most commonly an early-onset infection causing shock and breathing difficulty in the infant. Late-onset GBS, although less common, accounts for up to 25% of cases, and is more likely to cause illness with fever, breathing difficulty, feeding problems and seizures. Late-onset GBS infection can occur any time from a week up to one month of life, and community health professionals are more likely to encounter these sick infants in their clinical practice. It may be complicated in 40–60% of cases by bacterial penetration of the blood-brain barrier to produce meningitis (Doran et al, 2002). Other bacteria responsible for neonatal bacterial sepsis include Escherichia coli, Listeria monocytogenes and Staphylococcus aureus (Klinger et al, 2009). Certain viral infections including HSV, enterovirus, adenovirus, varicella zoster, respiratory syncytial virus (RSV) may also manifest as early or late-onset sepsis (Manzoni et al, 2012; Kimberlin et al, 2013). Neonatal HSV infections are usually transmitted from maternal genital herpes (newly exposed or reactivation of HSV during pregnancy). Most transmissions occur during vaginal delivery although babies delivered by caesarean sections after prolonged rupture of membranes are also at increased risk (Paul, 2011; Kimberlin et al, 2013).
What are the risk factors?
Newborns can acquire early-onset neonatal infections vertically from endogenous bacteria in the mother’s reproductive tract that may not cause disease in the mother but can cause disease in the baby. Ascending infections from the mother to the foetus may occur before labour with transmission in utero or during labour if there is rupture of membranes with systemic infection occurring via the umbilical cord, respiratory tract or skin abrasions, and symptoms appear within six hours of birth (Chan et al, 2013). NICE guidelines (2012) entitled Antibiotics for Early-onset Neonatal Infection has mentioned a number of risk factors which will be useful for community health professionals to consider while reviewing a baby with suspected neonatal sepsis. These risk factors may also be relevant for lateonset neonatal sepsis.
Other risk factors
Other risk factors include maternal ethnicity (black and Hispanic mothers are at increased risk), endometriosis and frequent vaginal examinations during labour and delivery (Hanley, 2008). Obstetric procedures that damage the infant’s skin (eg, foetal scalp pH monitoring) can also increase the risk of infection (Allen & Robinson, 2014; Paul, 2011). Twin pregnancy is also known to be a predisposing factor for neonatal infections as there is likely to be increased maternal contact with the hospital. Premature twins are even more susceptible to concurrent infections (Doran et al, 2002).
The risk of HSV infection in the newborn is highest in infants born to mothers who have newly acquired asymptomatic genital infection near term (often the last-trimester). It is important to note that 85% of HSV infections are acquired intra-partum (Kimberlin et al, 2013).
Late-onset infection can be acquired from the mother but the environment can also play a significant role. Nosocomial transmission of neonatal infections through the hands of health care workers remains a significant concern, although this has significantly decreased following the ‘Clean Hands’ campaign. Late-onset sepsis is more common in preterm infants, particularly those with prolonged hospitalisation and/or intravenous catheters. Mothers and infants from low-income families are at increased risk of illness and may face more challenges in accessing high-quality care (Lawn et al, 2010). The infant is also at increased risk of acquiring respiratory viral infections from the environment, including from older siblings and other family members or close contacts early in life, including RSV with incidence peaking in winter months (Manzoni et al, 2012).
What are the signs and symptoms?
Community health professionals should educate parents to seek medical advice if their child is showing abnormal behaviour, is unusually floppy, has developed difficulties with feeding or not tolerating feeds, has an abnormal temperature preferably measure in the axilla (<36⁰C or >38⁰C), rapid breathing or a change in skin colour (NICE, 2012). Education about signs of sepsis may be especially relevant in infants from high-risk groups (see Table 1). Neonates often present with non-specific signs and symptoms making a clinical diagnosis of neonatal sepsis difficult, but an early referral is suggested if there are concerns (Qazi et al, 2009). Making an assessment Physical signs that may be picked up during assessment include abnormal heart rate, features of respiratory distress (fast breathing, in-drawing of chest wall muscles, pauses in breathing, nasal flaring, head bobbing, grunting) or jaundice within first 24 hours of birth, decreased activity level, signs of neonatal encephalopathy (drowsy, excessive irritability, poor feeding, seizures, abnormal level of consciousness) and seizures. Some of the babies may have needed cardio-pulmonary resuscitation at birth or mechanical ventilation and it is important to enquire about the condition after delivery. Other clinical features include oliguria (low urine output) persisting more than 24 hours after birth, altered glucose homeostasis (low or high blood sugar levels), metabolic acidosis, local signs of infection, diarrhoea and vomiting, hypothermia, lethargy and irritability (NICE, 2012). HSV infection generally manifests in three distinct ways. Herpetic infection with skin, eye and mucosa manifestations (SEM) are characterised by vesicular lesions on the skin, eye and mucosa but without any signs of systemic involvement, generally presenting in the first or second week of life. A suspicious rash such as this needs a viral and bacterial swab taken at the earliest opportunity to determine the nature of the lesion. Herpes infection of the central nervous system presents with decreased feeds, lethargy, raised anterior fontanelle, fever and seizures and has increased rates of mortality and morbidity. Disseminated neonatal herpes is the rarest presentation but is the most serious one. There is multi-organ involvement alongside clinical signs of sepsis (Kimberlin et al, 2013; Paul, 2011). Most neonatal rashes are benign and require reassurance. Vesicular rashes should also raise the suspicion of neonatal chickenpox infection. A previous maternal history of chicken pox should not be falsely reassuring as neonatal chickenpox can still occur following exposure to a case of chickenpox (Paul et al, 2013).
Early recognition is key
The outcome of infection in neonates is time-critical. Early recognition and referral to hospital is the key to effective treatment. A focused history (including enquiry about risk factors), physical examination and investigations are needed. The focused history may include an enquiry about antenatal infection, high vaginal swab results (maternal GBS), previous or active genital herpes, mode of delivery, gestational age at delivery and any previous child with confirmed GBS infection. Any baby with a suspected infection needs to be referred to hospital urgently. Following admission, a blood culture, blood test including full blood count and C-reactive protein (CRP) and lumbar puncture may be performed. This is part of a neonatal septic screen, which can also involve a chest x-ray (if there are signs of respiratory distress) and urinalysis. If HSV infection is suspected, vesicle fluid culture and/or polymerase chain reaction to detect HSV are needed. The blood culture, CRP and lumbar puncture should ideally be obtained before starting antibiotics in the baby. Although culturing for micro-organisms is the gold standard test for a definitive diagnosis of neonatal sepsis, this may not be possible (especially lumbar puncture) in very sick neonates. If there are symptoms and signs of infection, antimicrobial treatment should be started without delay (NICE, 2012). Improving identification of clinical signs and risk factors by community health professionals will facilitate earlier admission to hospital and is likely to result in a better prognosis (Chan et al, 2013). According to NICE guidelines (2012), intrapartum antibiotics should be offered to women who have had a previous baby with a previous confirmed GBS infection or who have GBS colonisation, bacteriuria or infection in current pregnancy, to reduce the risk of neonatal sepsis in the current pregnancy. Community midwives scan facilitate this by documenting the need for the intrapartum antibiotics in the antenatal notes.
Assessment and treatment in the hospital
When neonatal sepsis is suspected, treatment should begin immediately and involves both medical and supportive care. Medical care involves the use of intravenous antibiotics. Which empirical antibiotics to use depends on the clinical setting, but in general narrow-spectrum antibiotics effective against the most commonly encountered pathogens will be employed, such as benzyl penicillin and gentamicin (effective against GBS). The baby’s clinical condition should be repeatedly assessed during stay in the hospital and the antibiotics may be changed accordingly when results of the blood or cerebrospinal fluid culture are received (NICE, 2012). For confirmed viral infections, supportive care is essential; however, acyclovir (antiviral medicine) is used if HSV infection is suspected (Paul, 2011; Kimberlin et al, 2013). Alongside the antibiotic therapy, the baby should receive supportive care – oxygen, cardio-pulmonary support, intravenous nutrition and fluid resuscitation where necessary. An infant with temperature instability may need thermo-regulatory support (eg. nursing in an infant incubator or hot cot).
What is the prognosis?
In cases of untreated neonatal sepsis, the mortality can be as high as 50 to 100%. Lower birth weight and prematurity, respiratory distress, sepsis, meningitis or low white cell count are all associated with adverse outcomes (Hanley, 2008). Under-recognition of illness, delay in seeking care at the household/community level and lack of access to appropriately trained health workers and services to manage neonatal sepsis are all factors which may increase mortality (Qazi et al, 2009). Infection is a major cause of mortality during the first month of life, contributing to a significant number of neonatal deaths (Kermorvant-Duchemin et al, 2008). With early diagnosis and treatment, most term infants with neonatal sepsis are not likely to experience longterm health problems. However, if early signs (or risk factors) are missed, mortality/morbidity may increase. Residual neurologic damage is evident in up to 30% of neonates with bacterial meningitis. In preterm infants who have had sepsis, impaired neurodevelopment is a concern. Cognitive defects, cerebral palsy, hearing loss, nephrotoxicity and other neurodevelopmental disabilities can also occur (Stoll et al, 2004). Babies with major neonatal infections should have regular developmental screening and monitoring in the community; if any developmental delay is suspected they should be referred to the appropriate services. Community health professionals are best suited to provide appropriate support and information regarding disability living allowance. Breastfeeding is considered to be protective (by passive transfer of maternal antibodies and other elements of innate immunity) and should be encouraged.
How can community practitioners help?
The following useful strategies are provided for community practitioners dealing with infants presenting with neonatal sepsis. These have been derived from our experience in managing such children and from the available literature (Abdelrhim et al, 2014; Berardi et al, 2013; Kimberlin et al, 2013; Lawn et al, 2010; McCartney, 2001; NICE, 2012; Paul, 2011
● Community practitioners should increase their own and parental awareness of neonatal infection in order to encourage early diagnosis and treatment
● Antenatal care should be focused to ensure that appropriate steps are taken to minimise the risk of infection, and, when sepsis occurs, to identify and treat effectively at an early stage
● Health professionals should always follow infection control advice regarding hand washing and other practical measure to reduce the spread of pathogens to babies
● Parents should be encouraged to ensure that babies and all family members are fully immunised according to current guidelines and in a timely manner
● Practitioners should offer advice about smoking and the harmful effects it can have on both the unborn child and any other children in the home.