Safety of Benzathine Penicillin for Preventing Congenital Syphilis: A Systematic Review

Objective: To estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis. Methods: We searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95 % confidence intervals (95 % CI). We employed the DerSimonian and Laird random effects model in the meta-analyses. Results: From 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95 % CI: 0%–0.003 % I2 = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95 % CI: 0.073%–0.265 % I2 = 97%). The quality o