Level 3: Lacking direct evidence

Prophylactic acetaminophen, or paracetamol, has been advocated to reduce the frequency and severity of fever and other adverse reactions associated with pediatric immunization. Because fever is a natural part of the immune response, a new study investigated the effects of postvaccination prophylactic acetaminophen use on both fever reduction and antibody production (Lancet. 2009;374:1339-1350). A total of 459 healthy infants were randomized to acetaminophen prophylaxis vs. as-needed antipyretic treatment following immunization with pneumococcus, Hemophilus influenzae type b (Hib), diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and oral human rotavirus vaccines. Babies in the prophylactic group received three doses of acetaminophen within the first 24 hours after the primary vaccination; most of these children also received prophylaxis after a booster vaccination. Body temperature was monitored on a scheduled basis during the first four days whether the child exhibited symptoms or not.

Fever (temperature >38°C [100.4°F]) occurred after primary vaccination in 42% of children receiving acetaminophen vs. 66% in the control group (P <.05, NNT 5). Rates of fever after the booster vaccination were 36% with acetaminophen vs. 58% with control (P <.05, NNT 5). There were no significant differences in severe fever (>39.5°C [103.1°F]), which was rare in both groups. However, antibody titers were significantly lower in the prophylactic group compared with controls and remained lower even after the booster dose. Prophylactic acetaminophen use led to statistically significant reductions in the proportion of patients meeting prespecified measures of immune response for three of 10 pneumococcal subtypes and Hib but not for any of the other immunizations given. Clinicians may wish to advise parents about the potential trade-offs associated with prophylactic use of acetaminophen.