In subsequent sections of this report and as customarily done in discussions of the NCES data, the first three categories are subsumed under the heading “encephalopathies,” whereas severe or complicated convulsions are divided into the categories “febrile” and “other.” The NCES investigators deliberately cast a wide net in identifying case children. The implication of this is discussed in a subsequent section. For each case child there were two age-, sex-, and residence-matched control children. Immunization histories were collected from immunization records; other details came from interviews with parents or from hospital records. Immunization histories were available for 904 case children with diagnoses of encephalopathies or convulsions. Of those 904 children, 43 percent were in the encephalopathy group and 57 percent were in the convulsion group (approximately two thirds of the children in the convulsion group were “febrile” and one third were “other”). Thirty of these 904 case children had received DPT within 7 days of onset of the neurologic symptoms. The authors did not include cases with infantile spasms in the calculations regarding DPT on the basis of post-hoc analyses showing no association between infantile spasms and earlier DPT immunization. In comparison, 23 of 1,783 controls (matched by age, sex, and residence but who did not have an acute neurologic illness) had received DPT within 7 days of being the exact age of their matched case child at the time of onset of symptoms in the case child, yielding a relative risk (RR) estimate of 3.3 with a 95 percent confidence interval (CI) of 1.7 to 6.5.
The NCES study design has been critiqued many times in the literature (IOM, 1991). The focus of much of the criticism concerns potential sources of bias and error in case ascertainment, difficulties in determining the onset of illness, lack of control for potential confounding factors, and imprecise definitions of the clinical conditions (e.g., children whose encephalitis was possibly of infectious origin were not excluded from the study). The investigators and others have suggested that many of the biases would have led to an underestimate of the RR estimates, which would not undermine the overall conclusions (Fine and Chen, 1992; Miller et al., 1993). Other controlled studies investigating the relation between DPT and acute encephalopathy (Gale et al., 1990; Griffin et al., 1990; Walker et al., 1988) did not detect a statistically significant elevated RR for acute neurologic illness after DPT, but those studies lacked sufficient statistical power to detect any but a very large risk. The number of cases of encephalopathy in these studies was consistent with the attributable risks found in the NCES (IOM, 1991). Because of this consistency and despite the criticisms of the NCES, the IOM Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines concluded, “The evidence is consistent with a causal relation between DPT and acute encephalopathy” (IOM, 1991, p. 118). The committee further concluded that the range of excess risk of acute encephalopathy following DPT immunization is consistent with that estimated in the NCES: 0.0 to 10.5 per million immunizations. (See the 1991 IOM report for a full discussion of this issue.)