Single versus three doses of benzathine penicillin G for early syphilis in pregnancy: no added benefit in serological response or neonatal outcomes

Objectives To determine whether intensifying therapy with three weekly doses of benzathine penicillin G (BPG) improves maternal serological response in early syphilis during pregnancy compared with the standard single dose. Methods In this randomised, non-blinded, single-centre study, 23 pregnant women with secondary or early latent syphilis and no previous history of the disease were enrolled. Participants were assigned to receive either a single intramuscular 2.4 million International Units (MIU) dose of BPG (n=12) or 3 weekly intramuscular doses of 2.4 MIU (n=11). Venereal Disease Research Laboratory (VDRL) titres were measured at baseline, delivery and 2 months postpartum. Serological change (ΔVDRL) was defined as the number of twofold dilution decreases between baseline and follow-up. Neonates underwent clinical and serological evaluation at birth and were followed up to 6 months. Results Median gestational age at treatment initiation was 16.5 weeks in the single-dose group and 19 weeks in the three-dose group. Baseline median VDRL titres were 1:16 and 1:8, respectively. By delivery, 60.9% of women showed no change in VDRL titre, and only a minority achieved a ≥2-dilution decrease. Two months postpartum, further declines were observed but most women still did not reach a fourfold decline. There were no significant differences in VDRL titres between groups at delivery (median 1:8 in both, p=0.66) or 2 months postpartum (median 1:4 in both, p=1.0). ΔVDRL was not associated with gestational age at treatment or treatment-to-delivery interval. All neonates were clinically healthy, had VDRL titres equal to or lower than their mothers at delivery and achieved complete seroreversion of both treponemal and non-treponemal tests by 6 months. Conclusions This is the first randomised study evaluating intensified therapy for early syphilis in pregnancy. Three weekly BPG doses did not improve maternal serological response or neonatal outcomes compared with a single dose. These findings support current recommendations for single-dose therapy in early syphilis during pregnancy.