Study provides more evidence for safety of immunization schedule
Sean T.O’Leary, M.D., M.P.H., FAAP and Yvonne A.Maldonado, M.D., FAAP
A study published today in the Journal of the American Medical Association (JAMA) offers more reassuring evidence for the safety of the childhood immunization schedule.
Glanz and colleagues from the Vaccine Safety Datalink (VSD) conducted a nested case-control
study of nearly half a million children to determine if exposure to multiple vaccines
in early childhood was associated with an increased risk for infections that weren’t
targeted by the vaccines (nontargeted infections). The VSD, funded by the Centers
for Disease Control and Prevention, conducts large epidemiological studies of vaccine
safety using electronic health record databases.
Investigators identified about 50,000 nontargeted infections treated in emergency
departments and inpatient settings from 2003-’13 in the study population. Then, they
selected a random sample of 385 children who had nontargeted infections from ages
2-4 years. Upon chart review, 193 were confirmed as cases of nontargeted infections.
Each case was matched with four control children having the same mean age, sex and
distribution of chronic diseases.
Investigators calculated the total number of proteins and polysaccharides in each
vaccine received by cases and controls from birth through age 23 months, which they
termed the “mean cumulative antigen exposure.” Then, they calculated the risk of nontargeted
infections between 2 and 4 years old.
Results showed no statistically significant difference in the cumulative antigen exposure
of cases and controls (240.6 for cases and 242.9 for controls).
“In an integrated health plan setting, cumulative vaccine antigen exposure through
the first 23 months of life was not associated with an increased risk of emergency
department and inpatient visits for infectious diseases not targeted by vaccines over
the next 24 months,” the authors concluded.
The background for this study goes back to 2002, when the Institute of Medicine (now
the National Academy of Medicine) called for studies examining whether vaccines could
have an effect on nontargeted infections. There are some data, primarily from the
developing world, for this possibility.
Several studies have shown that children who receive a measles-containing vaccine
are significantly less likely to die from infections other than measles than children
who had not received the vaccine, suggesting the vaccine has a positive impact on
the immune system. A few studies, however, show that whole cell pertussis vaccine
— which has not been used in the U.S. since the 1990s — could increase mortality from
diseases other than pertussis if given after Bacillus Calmette-Guérin vaccine, although
this has yet to be confirmed.
In addition, a 2012 Institute of Medicine report called for more research into the
safety of the childhood vaccination schedule in general. While the safety of individual
vaccines and vaccines given in specific combinations had been studied in great detail
through pre- and post-licensure studies, few studies had examined the schedule as
a whole. The overall childhood immunization schedule also had evolved from eight routine
vaccinations in 1994 to 14 in 2010. Furthermore, some parents were concerned that
the increasing number of vaccines weakened children’s immune systems, although the
biologic plausibility for this premise is weak.
Thus, VSD investigators embarked on this study to answer the question of nontargeted
It is difficult to overstate the value of the VSD to the U.S. immunization program.
Since its creation in 1990, its purpose has been to study vaccine safety and strengthen
public confidence in vaccines. The present study is yet another example of how the
VSD successfully monitors vaccine safety.
However, studies continuing to demonstrate the safety of childhood vaccines have not
translated into increased public confidence. Indeed, despite the work of the VSD,
rates of vaccine refusal and vaccine delay have increased over time. It is clear that
providing factual information to parents is not enough. Engaging health care providers
and public health messaging regarding vaccine effectiveness and safety also are paramount
in promoting the positive impact of vaccines on child health.