OBJECTIVE--To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. DESIGN--Follow up study of cases and matched controls. SETTING--Assessment of children at home and at school throughout Britain. SUBJECTS--Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES--Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. RESULTS--Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. CONCLUSIONS--Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.

Comments: Comment in: BMJ 1994 Jan 29;308(6924):343 PMID: 7504540, UI: 94072962 http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7504540&form=6&db=m&Dopt=b

The first 1000 cases notified to the National Childhood Encephalopathy Study were analysed. The diagnoses included encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye's syndrome. Eighty-eight of the children had had a recent infectious disease, including 19 with pertussis. Only 35 of the notified children (3.5%) had received pertussis antigen within seven days before becoming ill. Of 1955 control children matched for age, sex, and area of residence, 34 (1.7%) had been immunised with pertussis vaccine within the seven days before the date on which they became of the same age as the corresponding notified child. The relative risk of a notified child having had pertussis immunisation within that time interval was 2.4 (p less than 0.001). Of the 35 notified children, 32 had no previous neurological abnormality. A year later two had died, nine had developmental retardation, and 21 were normal. A significance association was shown between serious neurological illness and pertussis vaccine, though cases were few and most children recovered completely. PMID: 6786580, UI: 81209144 http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6786580&form=6&db=m&Dopt=b

The National Childhood Encephalopathy Study received reports on 1182 cases of serious acute neurological illnesses in children admitted to hospital in Britain. The frequency of risk factors in cases was compared with matched controls. A personal or family history of convulsions was found significantly more often in cases than in controls, but no such excess was found for a history of allergy. Case children were significantly more likely to have received diphtheria, tetanus and pertussis (DTP) vaccine within seven days before onset and to have a history of whooping cough during the month of onset. The risk of serious acute brain conditions after the disease was more than six times that of three doses of DTP. In addition, there is evidence that deaths attributed to whooping cough may seriously underestimate the number associated with pertussis infection. PMID: 3879684, UI: 86221304 http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3879684&form=6&db=m&Dopt=b