Infants immunized in the afternoon who mount a temperature soon afterward sleep more over the next 24 hours than do those vaccinated early in the day and those whose temperatures don’t increase, according to a study published online Nov. 28 in Pediatrics.

While prophylactic acetaminophen did increase sleep time slightly, the association became nonsignificant in a multivariate analysis of the randomized controlled trial. The study suggests that suppressing the body’s natural immune response with an antipyretic agent may actually work against sleep, and even the level of immune response, Linda Franck, Ph.D., and her colleagues wrote (Pediatrics 2011 Nov. 28 [doi:10.1542/peds.2011-1712]).

"Temperature increase is considered a marker of immune response and is thought to be related to the release of endogenous pyrogens ... associated with increased T cell activity, enhanced antigen recognition, and immune response," wrote Dr. Franck and her colleagues at the University of California, San Francisco. "Therefore, longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

The investigators examined data from a completed study on sleep disruption in new mothers. The study included a component on prophylactic acetaminophen to reduce infant sleep disturbance after immunization.

For this portion of the study, the researchers had complete data on 70 infants who were randomized into two groups: a control group of standard care and an intervention group in which mothers used predosed acetaminophen 30 minutes before an immunization and every 4 hours afterward, for a total of five doses.

Each infant was fitted with an anklet actigraph that recorded 24 hours of motion data before and after immunization, from which sleep movement was extrapolated. Mothers also used sleep diaries to record infants’ sleep, and digital thermometers to record infants’ axillary temperatures each morning and evening over the 72-hour study period.

"Longer sleep duration and increased temperature after immunization may be indicators of the degree of antibody responses."

Mothers’ mean age was 27 years. The group comprised 31% Asian, 26% white, 23% Hispanic, 11% black, and 9% mixed or other race. Most mothers (90%) had finished high school, and 29% had completed college.

The infants’ mean age was almost 9 weeks and the mean birth weight was 3.4 kg. Most (80%) had received all recommended vaccines by the time of enrollment.

Despite the randomization, most infants in the study (80%) got acetaminophen either at the time of immunization or thereafter. However, the researchers noted, infants in the active group were more likely to have gotten the first dose at the time of immunization, and those in the control group were more likely to get it later for symptoms of fever or discomfort.

Those in the intervention group had significantly higher axillary temperatures in the 24 hours after immunization (mean of 0.23 centigrade higher), compared with their temperature prior to immunization. The results of a comparison of all three groups were not statistically significant.

Those in the intervention group also slept significantly longer than did those in the control group (average 69 minutes). "Most of the additional sleep was active, whereas quiet sleep time increased only slightly," Dr. Franck and her colleagues said.

They found a significant correlation between longer sleep and increased axillary temperature. There was also a significant association between additional sleep and the timing of the immunization; infants vaccinated after 1:30 p.m. slept more than did those immunized earlier in the day. Many of the latter slept less than they had in the prior 24 hours.

In a multivariate regression analysis, higher postimmunization axillary temperatures and afternoon immunizations were the only significant predictors of increased sleep over the next 24 hours; these accounted for 32.5% of the variance in postimmunization sleep time.

Although the researchers said the findings proved their hypotheses, they admitted that overall acetaminophen use might have affected the final analysis, noting that "71% in the usual-care group received acetaminophen and 20% received it prophylactically, which made it more difficult to detect group differences."

Only 14 infants in the study did not get the drug. Those 56 who did receive it had smaller increases in postimmunization sleep time regardless of when the drug was given. But because acetaminophen was not a significant factor in the final analysis, increased body temperature could be the main reason for the increased sleep, they said.

"Our findings are consistent [with other studies] and taken together, suggest that antipyretic agents should not be given prophylactically for infant immunization," to allow for natural body temperature increases, Dr. Franck and her colleagues said.

"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," they said.

The study was supported by the National Institutes of Health. None of the researchers had any relevant financial disclosures.

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