Is It Safer to Delay MMR Vaccination?

Most people follow the recommended schedule of childhood immunizations. They understand the importance of immunization, not only for their own children, but for their communities as well. Certainly, parents put varying degrees of thought into their decision. Some simply go along with whatever their pediatrician recommends, while others thoroughly research the vaccines their child will receive before accepting the science-based recommendations behind the current vaccination schedule. Whatever level of scrutiny they give to the issue, the majority immunize their children fully and on-schedule, barring valid medical reasons to the contrary.

Then there's the minority, the parents who either delay vaccines, spreading them out over a much greater timeframe than recommended by the Centers for Disease Control and Prevention and the American Academy of Pediatrics, the parents who only allow some vaccines, and those who eschew vaccines altogether. Some are strongly committed to the ideology that vaccines cause all manner of maladies, often becoming quite vocal about it. Their views stem from misunderstanding of the science, confusing correlation with causation, and distrust of large corporations and the government. Some parents have simply been misled by those anti-vaccine activists. The arguments resonate on an emotional level, despite being void of scientific validity. And finally there are those who delay or skip vaccines because they lack access or the resources to keep up. They cannot afford insurance to cover the vaccines. They may not be able to take the time off from work to take their children to the doctor's office. In short, through failures of the health care system, rather than any fear or distrust of vaccines, their children are under- or unimmunized.

Whatever the reasons, the decision to delay or avoid vaccinations carries certain risks. Most readily apparent is the increased risk of infection, contributing to outbreaks in regions of low vaccination. We need only look, for example, at recent measles outbreaks (Minnesota, New South Wales, Australia, Massachusetts, Indiana, North Carolina and New York, Pakistan and Wales, Texas) to see how lack of immunization increases the risks of infection and spread of disease. Not so obvious is that delaying some vaccines increases the risk of not being fully immunized.

And now there's another risk to add to the list, at least as regards measles vaccines.

Published in JAMA Pediatrics, Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children by Ali Rowhani-Rahbar, MD, et al., investigated whether the age at which a child received the MMR or MMRV affected the risk that they would have a high fever or suffer a seizure. We know that in the U.S. and England, about 0.1%-2.3% of children who contract measles suffer a febrile seizure, while the rates of febrile seizure following MMR and MMRV are ~0.03% (1 in 3,000 doses) and ~0.08% (1 in 1,250 doses), respectively. They occur most commonly between the ages of 6 months and 5 years, with a peak between 16 and 18 months of age. We also know that while febrile seizures can be scary, they are almost always harmless and of short duration, but there are some risks associated with them, so if we can reduce the risk of a febrile seizure, we should.

The study looked at 840,348 children who were 12 to 23 months of age when they received their first dose of a measles-containing vaccine between January 2001 and December 2011. All of the subjects were drawn from the Vaccine Safety Datalink, a collaborative effort between CDC and 9 managed care organizations (MCOs) in 8 states. The MCOs maintain electronic documentation of birth data, vaccinations and various medical outcomes (e.g., outpatient and inpatient visits, urgent care visits, etc.). It is a robust and very useful database that researchers can use to identify safety concerns, investigate questions (e.g., the safety of thimerosal-containing vaccines [spoiler: they're safe]), and so on.

Dr. Rowhani-Rahbar and his team divided the children into two groups: those who received a measles-containing vaccine at 12 to 15 months of age, per the recommended schedule, and those who received one between 16 and 23 months of age, representing a delayed schedule. They looked for fevers (defined according to ICD-9 code 780.6) and seizures (defined as ICD-9 codes 780.3 or 345) occurring within the 42 days following vaccination with MMRV (measles, mumps, rubella, varicella vaccine) or MMR vaccine with or without a separate varicella vaccine. Events occurring 7 to 10 days post-immunization were considered vaccine-related, with the remainder of the 42-day period used as a control.

They discovered some interesting findings. First, they confirmed that MMRV has a greater risk of febrile seizures than separating out MMR and varicella vaccines, as expected from previous VSD studies looking at the MMRV. No real surprise there. What was more intriguing was that age does appear to have an effect on the risk of suffering a fever or seizure following immunization with a measles-containing vaccine. Children who were vaccinated at 12-15 months of age had a lower risk of fever or seizure than children vaccinated at 16-23 months of age. In fact, Rowhani-Rahbar, et al., found that there were 4 more seizure cases per 10,000 doses among the older children compared to the kids who were vaccinated on-schedule.

The study did have some limitations, though. Because they relied on ICD-9 codes to define fever and seizures, there is potential for afebrile seizures to have skewed the data. However, 87% of seizures identified in the study were febrile seizures, so the authors suggest that it is unlikely that including afebrile seizures would account for the differences seen between the groups. They also did not track fever-inducing illnesses or concomitantly administered vaccines, but state that they "do not believe that such illnesses had preferentially occurred within the risk interval of interest as opposed to other periods following immunization".

This is a robust study that provides a better view of how delaying vaccination can affect the risk of adverse events. It's the type of study that helps to inform the review of the recommended vaccination schedule each year. When it comes to measles vaccination, leaving aside all of the other consequences of the disease, vaccination (whether on-time or delayed) lowers the risk of febrile seizures, because the vaccine helps protect against infection. And vaccinating on-schedule reduces the risk of febrile seizure even further.

The next time you hear someone claiming that delaying vaccines is safer, not only can you remind them that delaying vaccination increases the risk of infection, but now there's evidence that it can actually increase the risk of adverse events after getting the vaccine, compared to on-time immunization. Delaying increases the risks without adding any benefit.