Adverse Events following 12 and 18 Month Vaccinations: a Population-Based, Self-Controlled Case Series Analysis

Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
PLoS ONE (Impact Factor: 3.23). 12/2011; 6(12):e27897. DOI: 10.1371/journal.pone.0027897
Source: PubMed


Live vaccines have distinct safety profiles, potentially causing systemic reactions one to 2 weeks after administration. In the province of Ontario, Canada, live MMR vaccine is currently recommended at age 12 months and 18 months.
Using the self-controlled case series design we examined 271,495 12 month vaccinations and 184,312 18 month vaccinations to examine the relative incidence of the composite endpoint of emergency room visits or hospital admissions in consecutive one day intervals following vaccination. These were compared to a control period 20 to 28 days later. In a post-hoc analysis we examined the reasons for emergency room visits and the average acuity score at presentation for children during the at-risk period following the 12 month vaccine.
Four to 12 days post 12 month vaccination, children had a 1.33 (1.29-1.38) increased relative incidence of the combined endpoint compared to the control period, or at least one event during the risk interval for every 168 children vaccinated. Ten to 12 days post 18 month vaccination, the relative incidence was 1.25 (95%, 1.17-1.33) which represented at least one excess event for every 730 children vaccinated. The primary reason for increased events was statistically significant elevations in emergency room visits following all vaccinations. There were non-significant increases in hospital admissions. There were an additional 20 febrile seizures for every 100,000 vaccinated at 12 months.
There are significantly elevated risks of primarily emergency room visits approximately one to two weeks following 12 and 18 month vaccination. Future studies should examine whether these events could be predicted or prevented.

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Available from: Jeffrey C Kwong, Oct 04, 2015
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    • "All study data were linked using unique, encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES). We identified vaccinations from the OHIP database using general vaccination billing codes and methods described previously [1] [2]. "
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    ABSTRACT: Objectives: To determine if birth month has an effect on the incidence of adverse events following the 2- and 12-month recommended vaccinations. Study design: Using health administrative databases, we conducted a population-based retrospective cohort study and employed a self-controlled case series analysis approach. We included children born in Ontario, Canada between April 1st 2002 and March 31st 2010 who received the diphtheria, tetanus, pertussis, inactivated poliovirus and Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine recommended at 2 months and/or the measles, mumps, and rubella vaccine recommended at 12 months. We calculated the relative incidence (RI) of hospitalizations and emergency room visits within a pre-specified risk period compared to a control period following vaccination. We measured the effect of birth month using relative incidence ratios (RIRs) to compare the RI for infants born in each month to that for the month having the lowest RI. Results: For the 2-month vaccination, we observed the lowest and highest RIs for infants born in October and April, respectively. The RIR (95% CI) for April compared to October was 2.06 (1.59-2.67, p<0.0001), consistent with a strong seasonal effect. For the 12-month vaccination, November births had the lowest RI, whereas August births had the highest. The RIR (95% CI) for August compared to November was 1.52 (1.30-1.77, p<0.0001). Conclusions: Our findings suggest a seasonal effect on susceptibility to adverse events following vaccination exists. Further study will be important to elucidate potential biological and/or behavioral explanations for the seasonal effect we observed.
    Vaccine 11/2014; 32(52). DOI:10.1016/j.vaccine.2014.09.059 · 3.62 Impact Factor
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    • "vaccine, an elevation in events was evident in the first 24 h [8]. We have also identified a significant elevation in incidence of hospital admissions or emergency room visits from days 4 to 12 post 12-month (MMR) vaccination compared to a control period (Relative Incidence (95% CI) = 1.33 (1.29 to 1.38) [10]. This risk period is consistent with the biologically expected period and previous studies and our estimate of febrile seizures was also consistent with previous estimates [11] [12] [13] [14]. "
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    ABSTRACT: Previous studies have suggested that a child's sex may be a predictor of vaccine reactions. We used a self-controlled case series design, an extension of retrospective cohort methodology which controls for fixed confounders using a conditional Poisson modeling approach. We compared a risk period immediately following vaccination to a control period farther removed from vaccination in each child and estimated the relative incidence of emergency room visits and/or hospital admissions following the 2-, 4-, 6-, and 12-month vaccinations to investigate the effect of sex on relative incidence. All infants born in Ontario, Canada between April 1, 2002 and March 31, 2009 were eligible for study inclusion. In analyses combining immunizations at 2, 4 and 6 months and examining these vaccinations separately, there was no significant relationship between the relative incidence of an event and sex of the child. At 12 months, we observed a significant effect of sex, with female sex being associated with a significantly higher relative incidence of events (P=0.0027). The relative incidence ratio (95% CI) comparing females to males following the 12-month vaccination was 1.08 (1.03 to 1.14), which translates to 192 excess events per 100,000 females vaccinated compared to the number of events that would have occurred in 100,000 males vaccinated. As the MMR vaccine is given at 12 months of age in Ontario, our findings suggest that girls may have an increased reactogenicity to the MMR vaccine which may be indicative of general sex differences in the responses to the measles virus.
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