Objective: To estimate the incidence and risk of misoprostol-induced fever with different doses and routes when used for the prevention of postpartum hemorrhage.
Data sources: We searched MEDLINE, the Cochrane CENTRAL, and PubMed free-text terms "misoprostol AND third stage of labor," "misoprostol AND third stage of labour," "misoprostol AND postpartum hemorrhage," and "misoprostol AND postpartum haemorrhage." Randomized trials with at least one group randomized to misoprostol administered by any route to prevent postpartum hemorrhage were included.
Methods of study selection: Two hundred thirty-one studies were initially identified and 61 of them were assessed for eligibility. We excluded nonrandomized trials, studies without a control group, and trials that did not record the rate of fever. The date of last search was July 20, 2010. Data were extracted, tabulated, and analyzed with Reviewer Manager software.
Tabulation, integration, and results: We included 33 trials with 38,478 participants in the final analysis. The highest reported incidence of fever was in the sublingual route (15%) with lower rates with the oral (11.4%) and rectal (4%) routes. The overall risk ratio of fever with misoprostol in comparisons with placebo and other uterotonics was approximately 5. There was frequent heterogeneity, however, which could not be explained by study quality or publication date.
Conclusion: The incidence of fever with misoprostol is related to both its dosage and route with the highest incidences found in the high-dose sublingual routes. However, this is not the only influence on postnatal fever. There appear also to be other effects that could be genetic or cultural.