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Later in the day immunizations linked to longer sleep next day

Franck L. Pediatrics. 2011;doi:10.1542/peds.2011-1712.

Immunizing a child later in the day — specifically after 1:30 p.m. — may lead to longer sleep durations the next day, according to research published online this week.

Linda Franck, RN, PhD, and colleagues of the department of family health care nursing at the University of California, San Francisco, School of Nursing, conducted a trial of 70 infants who were randomly assigned to acetaminophen before and after immunization or a control group that did not receive acetaminophen. The researchers monitored sleep by ankle actigraphy for 24 hours before and after the infants’ first immunization series.

There was a statistically significant difference in sleep in those infants who were immunized later in the day, according to Franck and colleagues, who also noted a similar trend for infants with higher temperatures. They said acetaminophen use was associated with more sleep during the following 24 hours, but to a lesser extent than the immunization timing or temperatures of the infants.

The researchers said some study limitations were found; specifically, that the infants were all term firstborn infants receiving their first vaccine series, and the small number of children who did not receive acetaminophen, both of which may limit generalizability.

“If further research confirms relationships between the time of day of vaccine administration, increased sleep and antibody responses, then our findings suggest that afternoon immunizations should be recommended to facilitate increased infant sleep in the 24 hours after immunization,” the researchers concluded.

Disclosure: The researchers reported no relevant financial disclosures.

Linda Franck and colleagues have provided us with some interesting data in this small pilot study of reactogenicity after first infant immunization. The devil is in the details. I highly recommend this study to all academic journal clubs.

Initially, the primary purpose (I think) of the RCT study was to compare whether prophylactic acetaminophen 30 minutes prior to immunization reduced sleep duration and fever in the first 24 hours after shots.

-Only 25 infants completed the study in the experimental group.

-But 20% of the total of 45 control group infants still received a prophylactic dose of acetaminophen, the same as the 25 infants in the “experimental” group; and 51% in the control group also received doses of acetaminophen post immunization.

-Using twice daily axillary temperature recordings in the first 24 hours after immunization, the temperature differences were minimal (0.22· to 0.29·C) between experimental and control patients, probably because acetaminophen after vaccination was actually received in 80% of ALL patients. This would likely obscure any possibility of seeing a reactogenicity/fever blunting with acetaminophen in the experimental group, as shown in the 2009 Prymula study in The Lancet of post-vaccination acetaminophen after each infant dose.

-Greater increases in sleep time were recorded in those who were immunized after 1:30 p.m. and in those whose axillary temperatures were greater than 36.85·C (a normal temperature, and no note of actual fevers greater than 38·C as used in Pyrmula’s study).

So what does all this mean? The authors hypothesize that the longer the sleep time in infants after vaccination, the more immunogenic the vaccine. But no antibody titers were ever obtained or recorded to show this phenomenon, as the authors disclosed. And this “poor sleep/poor immunogenicity” hypothesis was purely based on a study of 4 days of sleep deprivation in 11 young adults prior to receiving influenza vaccine, whose antibody levels were half those observed in nonsleep-deprived subjects.

Adult response to influenza vaccine, 11 subjects, and 4 days of prior sleep deprivation? I really see no correlation to this infant study.

Thus, suggesting any substantial changes in vaccination policy on the basis of speculation seems hardly prudent. Plus, immunizing well infants only at the busiest time of day in most pediatric offices (think sick children and the after school crunch) would be a logistical conundrum. My office scheduling to keep the masses happy is way too complicated already.

—Stan L. Block, MD

Infectious Diseases in Children Editorial Board

Disclosures: Dr. Block reports no relevant financial disclosures.

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