Abstract
A CAUSAL ASSOCIATION BETWEEN MEASLES mumps–rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.
Cases of idiopathic thrombocytopenic purpura (ITP) occurring within a few weeks of measles–mumps–rubella (MMR) immunisation were first reported and clinically described by Scandinavian workers,1-3 although an association between thrombocytopenia and measles immunisation had been reported previously.4 A causal relation between MMR immunisation and thrombocytopenia was accepted in the 1994 Institute of Medicine Report, apparently on the grounds of biological plausibility.5 The first controlled study6found evidence of an increased risk of ITP with onset 15–35 days after immunisation, but was based on only four vaccine associated cases (that is, cases within this risk period). We report an extended study, using record linkage methods in two regions in England, conducted to refine the risk estimates, compare the clinical features of the vaccine and non-vaccine associated cases, and investigate whether children diagnosed with ITP prior to MMR immunisation were at increased risk of a vaccine associated recurrence.
Methods
All hospital admissions for children aged under 5 years in the South East Thames (between October 1991 and September 1994) and North East Thames regions (January 1991 to March 1994), with an ICD 9 discharge code 278.3 were identified from regionally held computerised hospital episode records. This information was linked to immunisation data held on the regional child health computer system. Case notes for children with a linked MMR immunisation record and an admission for ITP in the second year of life were reviewed.
The relative incidence (RI) of an admission for ITP in children aged 12–23 months within the risk period 0–42 days after MMR immunisation compared with the control period was calculated by Poisson regression conditional on the number of admissions for each child,7with inclusion of cases from the earlier study in five English districts.6 The control period was defined as that time before or after MMR immunisation not included in the risk period. Absolute risk of an admission for ITP was calculated by dividing the number of admissions in the risk period by the total number of COVER estimated8 doses of MMR vaccine given in the hospital catchment areas, adjusting for the proportion of cases which matched with MMR immunisation records.
Results
A total of 45 admissions for ITP were identified in 36 children aged 12 to 23 months in the two study regions, of whom 24 (67% of children and 69% of ITP admissions) had a linked immunisation record. Case notes were traced for all 24 children, three of whom were found not to have had an admission for ITP in the second year of life. One of these children had congenital thrombocytopenia and was admitted with vomiting. A second child had an earlier admission for ITP at 10 months of age but the admission in the second year of life was for an unrelated condition. The third child was admitted for diarrhoea and was found to have a low platelet count of uncertain origin. None of these three cases occurred within 42 days of MMR. After removal of these cases, there were 28 verified admissions for ITP in the second year of life in 21 children with MMR immunisation records. Of these, nine were admitted within 42 days of MMR; none of these nine children had a prior or subsequent admission for ITP in the second year of life. The remaining 19 admissions occurred in 12 children; readmissions occurred at intervals ranging from 15 days to five months. Table 1 shows clinical features of the vaccine associated and non-vaccine associated admissions. The vaccine associated cases tended to be milder with a shorter duration of stay and higher platelet counts. Non-vaccine associated cases showed a predominance of males.