A child who experiences a serious medical event after a vaccine has a very low risk of having another serious event occur after the next vaccine, found a new study. Milder reactions, such as fevers, swelling, pain, sleepiness, decreased appetite, vomiting or persistent crying, re-occurred in 4% to 48% of those who experienced them the first time, depending on the event.
These re-occurring events “were generally less severe or equally severe compared with the initial episode,” wrote a group of Canadian researchers led by Joseline Guetsop Zafack, MD, MPH, of Laval University in Quebec, Canada.
The uneasiness that some parents may feel about taking their child in for recommended immunizations can morph into extreme anxiety if their child had a negative experience occur after a previous vaccine. Those parents may even want to stop vaccinating their child, concerned that something else, possibly worse, could occur after the next vaccination. This scenario creates a dilemma: how can doctors and parents ensure children are as protected as possible from vaccine-preventable diseases without putting a child at risk for injury from a vaccine?
“There are few experiences more challenging for a pediatrician than trying to convince a parent to continue vaccinating their child after they have witnessed a febrile seizure or a hypotonic hyporesponsive episode not long after a vaccination,” wrote Sean T. O’Leary, MD, MPH, of University of Colorado Denver and Children Hospital Colorado, and Yvonne A. Maldonado, MD, of Stanford University Department of Pediatrics, in an editorial accompanying the study. “Although studies have shown that these adverse events following immunization do not lead to adverse long-term consequences, this information is often not enough to convince these parents that the benefits of future vaccination outweigh potential risks.”
Difference Between Adverse Events and Side Effects
“Adverse events” differ from “side effects” or “vaccine reactions.” An adverse event is any medical event that occurs after someone receives a vaccine, but it may or may not be caused by the vaccine. A vaccine side effect and a vaccine reaction are basically the same thing — something that occurs after a person receives a vaccine that was directly, definitively caused by the vaccine.
All side effects/vaccine reactions are also adverse events, but not all adverse events are side effects or reactions. Many things may occur after a vaccination, immediately or within a few days or weeks, that are not related to the vaccine at all. They occur in the same time period but only because of coincidence, not because the vaccine and event are related.
This confusion is the source of a common misunderstanding about vaccine product labeling: Vaccine product inserts list all adverse events — everything that occurred after the vaccine was administered regardless of whether the vaccine caused it or not. This list is sometimes confused for being a list of side effects — medical events that are known to be caused by the vaccine — but adverse events only become side effects/vaccine reactions if evidence shows that the vaccine caused them. The FDA requires all adverse events to be listed, even if there’s not evidence the vaccine caused them, for the sake of transparency and as a reference for post-licensure safety research.
In this new study, the majority of adverse events included are ones that the vaccine was highly likely to have caused—likely side effects or vaccine reactions.
“Unsurprisingly, parents whose children have experienced a vaccine-related adverse event may be reticent to revaccinate their child when the next set of immunizations is due,” wrote O’Leary and Maldonado. “The question they want answered, of course, is, ‘Will it happen again?’”
To answer this question, the study researchers combed through three large databases of medical research — PubMed, Embase and Cochrane Library — to identify studies that looked at the vaccination experiences of children who previously had an adverse event occur after a vaccine. They included all studies written in English and French (some of the researchers are from Quebec) published before September 30, 2016.
The authors found 29 articles, including two randomized controlled trials and 27 observational studies (which cannot show causation). The studies compared medical events after vaccination for children who did and did not have a previous adverse events after immunization. The researchers also looked at the specific vaccines administered and how serious any adverse events were.
Most of the studies included only children, but three focused on adults and eight included both children and adults. The studies looked at allergic-like events, fever, extreme swelling of arms or legs, seizures, pain, pauses in breathing, decreased appetite, persistent crying, sleepiness, vomiting, and a couple other serious reactions.
Allergic-Like Events and Anaphylaxis
Allergic-like events had previously occurred in 594 children and adults in the studies. When they received another immunization, 5% of these individuals experienced another allergic-like event but did not experience anaphylaxis (a life-threatening allergic reaction). All occurrences were mild except one in which a girl developed hives and difficulty breathing after re-immunization with the measles-mumps-rubella. Her symptoms went away immediately with treatment.
Another 133 people in the studies had a history of anaphylaxis after a vaccine, but none experienced anaphylaxis or an allergic reaction after another vaccine (received in one dose or in three partial doses separated by an hour).
“None of the 727 patients with a history of allergic-like events or anaphylaxis in the included studies developed anaphylaxis after re-immunization,” the researchers wrote. “This finding supports the Joint Task Force on Practice Parameters 2012 practice guidelines, which state that patients who experienced an allergic-like event after immunization can be safely re-immunized when appropriate precautions are taken.”
However, they noted that patients with severe allergic-like events or positive skin tests often did not receive another immunization, and doctors followed different protocols with patients who did receive another vaccine. Therefore, people with a history of a severe allergic reaction after immunization should consult a specialist before receiving another.
Fevers and Seizures: Among children who had a fever after the DTaP vaccine, 21% had a fever after the second dose and 18% had a fever after the third dose—translating to a risk of fever about two to five times greater in those with a history of one. Fifty-two children in the studies had experienced a seizure after an earlier vaccine, but none experienced another seizure after a later vaccination.
Limb Swelling: Among 98 children who had experienced extensive limb swelling after the fourth dose of DTaP (diphtheria, tetanus, pertussis) vaccine, just over half (56%) experienced similar swelling after the fifth dose of DTaP or Tdap. Most of the children’s swelling went down within four days after vaccination, and all children had full recovered by the 19th day after immunization. The risk of swelling occurring again was about 1.5 times greater for a fifth dose of DTaP compared to Tdap. (Tdap, used in older children and adults, has a lower antigen load than DTaP.)
Non-Responsiveness or Blood Vessel Inflammation: The researchers also looked at a condition called Henoch-Schonlein purpura, an inflammation of small blood vessels in the skin, joints, kidneys and intestines that leads to bleeding and a rash. Only six children in the studies experienced this condition after a meningococcal B vaccination, and none had a repeat after additional doses.
The studies included 398 children who had previously experienced a hypotonic hyporesponsive episode after immunization. Only 0.3% (three children) had another episode after another immunization. During these episodes, sometimes called shock or collapse, children become non-responsive and appear pale and weak. They are initially feverish and cranky, and then within 12 hours after vaccination, they lose consciousness or awareness, breathe shallowly, may appear bluish and become pale or limp. These extremely rare events last from a few minutes up to three days, but evidence shows they have no long-term effects. The vaccine most likely to cause them, the DPT vaccine, is no longer used in the US.
Other effects: Vomiting recurred in 15% of children who previously had it, and 35% of children experienced sleepiness again after a previous episode. For those who experienced persistent crying or a decreased appetite after a previous vaccination, a quarter experienced that event again.
The authors noted that they did not have adequate data to draw firm conclusions about the safety of additional immunizations in people who experienced a serious adverse event after vaccination, but the data they have shows a very low risk of re-occurrence. Data on mild and moderate reactions show they can re-occur in up to half of patients, though often more mildly.
“This article reinforces what vaccinologists and pediatricians have known for many years: vaccines are incredibly safe,” wrote O’Leary and Maldonado. “Considering that the vaccines in the infant schedule are administered to millions of children each year, the list of known adverse events, even rare ones, is impressively short.”
Two researchers had links to pharmaceutical companies: One, Dr. De Serres, has received research grants from GlaxoSmithKline and Pfizer and has received travel reimbursement for attending a GSK advisory board meeting. Another researcher, Dr. Top, has received a research grant from GlaxoSmithKline and research support from Pfizer. None of the other authors had conflicts of interest.