There may be a wrong time to vaccinate ELBW infants. The Healthy Vaccinee Effect

Ask any health care professional how our tinyest babies fare after an immunization and they will tell you “not well”.  In fact the belief is so pervasive that we go out of our way to find excuses to delay immunizations.  I have heard myself uttering such comments as “today is not a good day” or “let’s wait until there is greater respiratory stability” or simply “they are too sick”.  Perhaps this tendency develops because we are shaped by our past experiences and if we have had a baby get intubated who was on CPAP after an immunization, we subconsciously say to ourselves “that won’t happen again”.

By no means am I writing an anti-vaccination piece but rather exploring our behaviours and trying to come up with a means of changing them.  Adverse Events After Routine Immunization of ELBW Infants was published on this very topic this week and with nearly 14000 infants from 23 – 28 weeks included who received their first 2 month immunization, it certainly caught my attention!

The table indicates the risks of certain adverse events in the 3 days preceding the immunization to the 3 days afterwards. Table 2 What you will note is that the evaluations for sepsis increased 4X, Respiratory support and intubation almost 2X, with no difference in seizures.  It is important to note that the definitions for sepsis were based on two blood cultures being drawn rather than fever alone. Curiously with respect to sepsis there was an increase in the number of positive cultures as well from 2.1 to 3.8% in the evaluations that were done before and after.  It is worth pointing out though that I can find no analysis of those results to determine if they were statistically different so at most it is an “interesting” finding.

The figures below demonstrate the rate of the same adverse events before time zero and then afterwards for the same duration as in the table.
What you notice aside from the rise in adverse events is a sharp decline in the rate of adverse events just prior to the immunization and then a sharp rise after it is given. figure The steep decline just prior to immunization is known as the Healthy Vaccinee Effect. That is to say that we may see a higher rate of complications simply due to the fact that we wait for kids to be at their healthiest and when they have only had one or two days without apnea or are off their antibiotics that is when we choose to give the vaccine as we believe they can now “handle it”.  What we have created is a special sample of patients that actually does not reflect the whole population.  What I mean by this is that the response of all patients to their vaccines in this age group might be quite different with no increases in any adverse events if we paid no attention to our preconceived notions that the infant in our care is “too sick” to get their immunization.  When we only immunize those kids that are at their best, the likelihood of them deteriorating is higher than when they were “worse”.

We know from previous literature that ELBW infants have higher rates of apnea and need for respiratory support after their vaccines. If we gave them an immunization when they were on CPAP or a higher dose of caffeine would we notice the impact as much?  By waiting till they have weaned off CPAP or outgrown their dose of caffeine we are setting ourselves up for a setback.

Similarly perhaps the optimal time to give the vaccine is when they are actually on an antibiotic for a sepsis evaluation or have had a CRP for one reason or another in the preceding 24 hours.  Would a mild fever after the vaccine trigger the same response to do a septic workup or would you take comfort in knowing your patient was already on antibiotics or had no signs of inflammation prior to the vaccine?

In summary I question if I have had it all wrong.  I am not saying to give a vaccine to a patient who is on high frequency ventilation and inotropes due to septic shock but rather when they are recovering and off the inotropes but still ventilated what is the harm?  They are already intubated, and covered with antibiotics.  Seems to me to be the perfect conditions to prevent me from either escalating their respiratory support or doing a septic workup. They are already covered!

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3 thoughts on “There may be a wrong time to vaccinate ELBW infants. The Healthy Vaccinee Effect

  1. Do you know of any studies that have been done showing the safety of vaccinating babies within days/weeks of antibiotic use?

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    1. I can’t say that I do. I am not sure though how they would impact the vaccine response since a specific antigen is provided so even if the antibiotics had been used they would not likely be in sufficient levels to clear the bacterium. Add to this that several are viruses and the others mostly inactivated or part of a bacterium and there should be no effect but can’t say for Sure

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