We observed a RIR (95% CI) of 1.09 (1.03, 1.15) for females versus males, which is similar to the result of our non-restricted analysis (Table 3). We then further restricted the event definition to include Epigenetics Compound Library only specific types of adverse events

that would be expected following MMR vaccine. The four event types included, based on ICD-10 codes, were: fever, rash, febrile convulsions and viral enanthema [13] and [10]. The results of this restricted analysis showed a much larger RIR for females versus males of 1.23 (95% CI 0.99, 1.51) p = 0.06, which did not achieve nominal statistical significance due to the loss of events with the restricted event definition ( Table 4). Higher relative incidences in girls compared to CT99021 chemical structure boys were exhibited for each of the four event types, though none achieved nominal

statistical significance. We demonstrated that females had an increased risk of ER visits and/or hospitalizations during a specified ‘at risk’ period, immediately following the 12-month vaccination but not 2-, 4- and 6-month vaccinations. The increased risk associated with female sex translates to 192 excess events in females as compared to males, for every 100,000 infants vaccinated. As previously noted, the vaccine routinely administered at 12 months of age in Ontario during the entire period of study was MMR. A meningococcal disease (type C) vaccine was added to Ontario’s publicly-funded immunization schedule in September 2004. The time period

for increase in ER visits or hospitalizations following 12-month vaccination is consistent with the next known risk period following MMR vaccination [11], [13] and [18]. Our observations could either be explained by gender differences – the socially constructed distinction between the sexes, or by sex differences – the physiological differences between males and females. If gender differences accounted for our observation, one explanation would be that parents respond differently to similar adverse reactions between boys and girls, and are more likely to seek medical care for girls. Our analysis cannot find evidence to support or refute this hypothesis, although we may have expected lower acuity of presentation in girls if this were the case. In contrast, it is recognized in the medical literature that important physiological differences exist between males and females that govern their responses to infections and vaccines [19], [20], [21] and [22]. For example, estrogen can potentiate antibody responses to antigens, while both progesterone and androgens tend to have immunoregulatory or immunosuppressive actions [20], [22] and [23]. Sex differences in immune responses to measles vaccines have certainly been observed both in terms of immunogenicity [21] and [24] and short-term reactogenicity of both the live-attenuated rubella [1] and both high- and standard-titer measles vaccines [4], [25] and [26].