Key:
0   <;1%
+   5–10%
++  10–25%
+++     25–55%
Note: The frequency of signs varies with disease severity and between Western and developing countries (see text) but these are the approximate frequencies derived from a literature search.

In developing countries, two systematic reviews concluded that in young infants under 60 days old brought to a health-care facility, the most valuable signs and symptoms of sepsis were feeding difficulty, convulsions, fever or hypothermia, change in level of activity, tachypnoea, severe chest in-drawing, grunting and cyanosis.8,9 Pallor and poor capillary return were also positively associated with sepsis. These data help community health-care workers decide about hospital referral of sick infants.

In Western countries, septic infants usually present earlier with less florid signs. In a large US study of very low birth-weight infants the positive predictive value for most clinical signs varied from 14% to 20%, while hypotension had a positive predictive value of 31% but only occurred in 5% of babies.1

A minority of septicaemic babies has a focal infection, for example, skin abscess or swollen joint, which will not only provide a strong diagnostic indicator but also a likely focus for biopsy and hence a microbiologic diagnosis.

Simple laboratory tests may yield clues to sepsis: 10% of very low birth-weight infants with sepsis had hypoglycaemia and 11% had metabolic acidosis (see Chapter 4).1

3.1 Fever or hypothermia

Rectal temperatures measured with a mercury thermometer are the traditional ‘gold standard’ for temperature measurement in newborns. In one study, axillary temperatures were consistently about 0.27°C (SD 0.20oC) lower than rectal temperatures,10 but another study using the same electronic device found significant differences between axillary and rectal temperatures.11 An infrared skin thermometer gave similar readings to a rectal mercury thermometer below 37oC, but concordance was only 74% for readings ≥37oC.12 Most of these studies study mainly afebrile infants, yet febrile infants are the major clinical concern.

The incidence of fever and hypothermia is gestation-dependent and also differs somewhat between early- and late-onset sepsis. Full-term infants are far more likely to respond to infection with fever than pre-term infants while pre-term infants are more likely to develop hypothermia. In a study of infants with early-onset GBS bacteraemia, 12% of full-term infants had fever at the time of admission compared with only 1% of pre-term infants, whereas the figures for hypothermia were 3% and 13%, respectively.3 Significantly, about 85% of both full-term and pre-term infants with GBS sepsis had normothermia on admission.3

In late-onset sepsis, the reported onset of fever is nearer 50%, while 10–15% of septic infants have hypothermia.1

3.2 Meconium

Meconium is usually sterile. There are two potential links between meconium and infection. Firstly, aspiration of thick meconium may cause airways obstruction and lung collapse, potentially complicated by bacterial pneumonia. There are no RCTs of antibiotics in meconium aspiration syndrome.16 Secondly, meconium-stained liquor, uncommon in pre-term labour, was described in early-onset Listeria monocytogenes neonatal infection and postulated as being specific to listeriosis.17,18 Subsequent studies show that meconium-stained liquor can occur with infection due to other organisms and is not common in Listeria infection.19,20 Obstetric studies have reported culturing Ureaplasma urealyticum, streptococci, Escherichia coli, Candida albicans and L. monocytogenes from amniotic fluid in association with meconium-stained liquor in pre-term labour.21,22 In a UK case-control study, early-onset infection was no more common in pre-term babies born after meconium-stained liquor than in controls.20

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