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History of Suspected Association with Pertussis Vaccines

Among the earliest case reports suggesting a possible link between infantile spasms and pertussis immunization are those of Baird and Borofsky (1957). They described 24 children who had hypsarrhythmia and infantile myoclonic seizures and whose development prior to the onset of spasms was apparently normal. Nine cases of infantile spasms were reported to have occurred between 1 and 5 days after DPT vaccination. Three of these nine children also had a history of perinatal complications that the authors thought might have been related to a risk of infantile spasms. The authors also stated, on the basis of a review of published EEG tracings, that hypsarrhythmia was present in two of the affected children described by Byers and Moll (1948). Since these early case reports, additional cases of infantile spasms in association with pertussis immunization have been described in the literature (Fukuyama et al., 1977; Millichap, 1987; Portoian-Shuhaiber and Al Rashied, 1986). The time intervals reported between vaccination and the onset of infantile spasms have been from minutes to weeks (Melchior, 1971).

Evidence from Studies in Humans

Case Reports and Case Series

One of the largest case series of infantile spasms following pertussis immunization was published by Millichap (1987). Six children ranging in age from 2 to 9 months were included. The time interval from immunization to the onset of spasms was from 6.5 hours to 5 days, and first seizures were reported to have occurred in conjunction with the first, second, or third doses of pertussis vaccine. Except for one case who had experienced myoclonic seizures since birth, no mention was made of the children having seizures prior to immunization. In reviewing the etiology and treatment of infantile spasms, Millichap (1987) listed the postulated mechanisms for pertussis-related seizures as (1) a direct neurotoxic effect, (2) an immediate immune reaction, (3) delayed cellular hypersensitivity reaction, and (4) vaccine-induced activation of a latent neurotropic virus infection.

In addition to the variability in age at the time of onset of spasms, associated vaccine dose, and time from immunization to the onset of spasms, there was no consistent pattern in the types of neurologic abnormalities reported in conjunction with infantile spasms. These included spastic diplegia, psychomotor retardation, hypotonic diplegia, and progressive neurologic deterioration. Not all children with infantile spasms have other neurologic or developmental problems, and when they do, diversity of expression of these associated neurologic conditions is typically reported (Lacy and Penry, 1976). This case series