METHODS

A total of 229 infants <3 months old presenting acutely unwell to a regional children's hospital accident and emergency (A&E) department from May 1999 to April 2000, identified by reviewing haematology department full blood count records, were selected for this retrospective study. Children who were seen as planned admissions, or who had a known chronic illnesses, were excluded. Of the total cohort of 229 children, 42 (18%; 31 boys and 11 girls) had a lymphopenia, defined as a total lymphocyte count below the 3rd centile for children of this age group (2.8 × 10⁹/l) (lymphopenic group).³ A gender matched and randomly selected sample of the cohort who were not lymphopenic were studied as the control group. Clinical and laboratory data were obtained from the medical records. Leucocyte counts were determined using routine flow cytometry of peripheral venous blood samples.

RESULTS

Gender and gestational age at birth of the two groups were not different. None of the children had a past medical history of recurrent infections or immunodeficiency, nor were they being treated with glucocorticoids. All but two were admitted to hospital, with a median (interquartile range) length of stay in hospital of 5 (3–7) days. The median absolute lymphocyte count of the lymphopenic group was 1.8 × 10⁹/l (range 0.05–2.78 × 10⁹/l); this was associated with a significantly lower total leucocyte count of 6.4 × 10⁹/l when compared with controls (lymphocyte count 6.3 × 10⁹/l; total leucocyte count 11.5 × 10⁹/l; p = 0.0001). The duration of lymphopenia was studied in 26 infants and lymphocyte count returned to normal in all: within two days in 19 (73%) and within one week in all but one case (96%). The median neutrophil counts of the two groups did not differ significantly.

More infants in the lymphopenic group than in the control group had clinical features of an acute infection (88% v 52%; p = 0.0001). Significantly more lymphopenic infants than controls had respiratory syncytical virus bronchiolitis (33% v 5%; OR 10, 95% CI 2 to 47; p = 0.004). Blood cultures were positive in seven of the lymphopenic infants compared with none of the controls (p = 0.006). Of the 25 children with non-infective causes, 11 (44%) had pyloric stenosis; five (20%) had other gastrointestinal problems.

Acute resuscitation in the A&E department was required by 29 (69%) of the lymphopenic group (fluid boluses in eight, immediate intubation and fluid boluses in 19, cardiopulmonary resuscitation in two), compared with only three (7%) of the control group (fluid boluses in two, intubation and fluids in one; p = 0.0001). Twenty six (62%) of the lymphopenic group required admission to the paediatric intensive care unit (PICU) compared with only one (2%) of the control group (p = 0.0001; table 1). None of the children in the study died and no patients in either group were diagnosed as having severe combined immunodeficiency. The association between lymphopenia and need for resuscitative measures on presentation of infants to the A&E department remained significant (OR 29, 95% CI 5 to 175; p = 0.0005), even when absolute leucocyte count, gender, age, degree of prematurity, and whether the underlying diagnosis was infective or non-infective were taken into account. A lower total leucocyte count, male gender, and younger age were other independent factors associated with a significantly increased risk of infants requiring active resuscitation (table 2).

DISCUSSION

In this study we have shown for the first time, that previously well infants presenting to a paediatric A&E department with an acute illness are more likely to require any active resuscitation if they are lymphopenic. A significant proportion (90%) of these lymphopenic patients required admission to a PICU. A number of confounding factors might be expected to influence the association between lymphopenia and the need for acute medical intervention. Males are thought to cope less well with illnesses than females, but the potential confounding effect of this factor was avoided by matching the study groups for gender. Possible confounding effects of age, gestational age at birth, and presenting diagnosis were excluded using multivariate analysis.⁴ Lymphopenia also appears to be associated with a poorer prognosis in non-infected as well as infected patients, in keeping with previous studies which have shown that up to 68% of adults in a surgical intensive care unit for management of acute trauma not associated with super added infection have significant lymphopenia.⁵ Further studies are required to determine whether lymphopenia in children requiring more active medical management is an epiphenomenon, or directly causes more severe disease.