History of Treated Syphilis Before Pregnancy and Risk of Congenital Syphilis

To evaluate the odds of congenital syphilis in neonates of mothers with a history of adequately treated prepregnancy syphilis compared with those with no prepregnancy history of syphilis.

We conducted a retrospective cohort study of deliveries within a large multihospital health care system in the southern United States from January 2015 to December 2023. Pregnant individuals were stratified based on whether there was a prepregnancy history of adequately treated syphilis infection. Propensity score full matching was performed, retaining all 382 patients with prior treated syphilis, with covariates including maternal age, neighborhood Area Deprivation Index, tobacco use, insurance payer, prenatal visits, and gestational age at delivery. The primary outcome was congenital syphilis as defined by Centers for Disease Control and Prevention case criteria; secondary outcomes included maternal syphilis infection during pregnancy and neonatal administration of a single intramuscular dose of penicillin-G.

Among 57,925 pregnancies, 382 patients (0.66%) had a history of adequately treated syphilis before pregnancy. Congenital syphilis occurred in 26 of 382 (6.8%) pregnancies in women with prior treated syphilis compared with 40 of 57,543 (0.1%) without (adjusted odds ratio [aOR] 19.61; 95% CI, 4.57-84.25). This is equivalent to 6,806 per 100,000 live births in those with a prior history compared with 70 per 100,000 live births in those with no prior history. Maternal syphilis reinfection occurred in 68 of 382 (17.8%) with prior treated syphilis compared with 258 of 57,543 (0.4%) without (aOR 11.92; 95% CI, 5.89-24.10).

A history of treated syphilis infection before pregnancy was associated with dramatically increased risks of congenital syphilis and maternal syphilis reinfection during pregnancy. These findings challenge assumptions about the protective effects of prior treatment and support enhanced surveillance strategies for this high-risk population.