Centers for Disease Control and Prevention (CDC) mentioned in September 2025, that congenital syphilis cases increased for the 12^th consecutive year.¹ This information, in combination with periodic shortages of Bicillin LA², the primary treatment of syphilis in pregnancy, suggest it may not decrease soon.

Why is Congenital Syphilis an Issue?

Congenital syphilis is an issue because syphilis can be transmitted from the mother to the fetus.  It can result in still birth, preterm birth, low birthweight, and birth defects. Furthermore, in cases where the congenital syphilis goes untreated, the child can present with bone, teeth, eye and nervous system abnormalities, as well as hearing loss.³ Symptoms in infants include hematologic suppression (e.g., anemia, thrombocytopenia), liver and bone abnormalities, lesions, “snuffles”, seizures, as well as eye and nerve issues.^3,4

Recent Data and Impact of Maternal Treatment and Timing on Infant Outcomes

Estimates suggest that about 16% of infants born to mothers with syphilis will have congenital syphilis.⁵ Carlson and colleagues reported the outcomes of 1682 infants born to mothers who were positive for syphilis from 2018-2021 in pregnancy. Their data reinforced that still birth is less common among those who received guideline recommended therapy (e.g., one-three doses of penicillin G started at least 30 days prior to delivery with appropriate spacing) versus no therapy (1.4% vs 10%; p<0.001).⁶ Among those with live births, receipt of guideline-recommended therapy showed differences versus both other treatment (either not penicillin based, not correct number, or did not start with at least 30 days before birth) for low birth weight (10% guideline, 25% other, 30% no treatment; p=0.02 vs no treatment; <0.001 vs inadequate treatment), and NICU stay overall (27% guideline, 57% other, 67% no treatment; p< 0.001 for both comparisons), including those ≥ 34 weeks gestation (25% guideline, 54% other, 63% no treatment; p< 0.001 for both comparisons).⁶ Further another meta-analysis also confirmed that guideline recommended therapy was associated with decreased risk of congenital syphilis versus penicillin therapy begun within 30 days of delivery.⁷ This meta-analysis included one study that used aminopenicillin (e.g., ampicillin, amoxicillin), and this group had a high rate of congenital syphilis.⁷ There was no control group, but until there is more data, these reinforce the recommendations for penicillin as the only recommended therapy for pregnancy treatment of syphilis. ^4,8

Opportunity to Improve Congenital Syphilis Treatment

A recent study by Nlandu and colleagues published in March 2026 in the Pediatric Infectious Diseases Journal, suggests that many newborns are not receiving appropriate treatment.⁹ Specifically, even among those newborns meeting criteria for either proven or highly probably congenital syphilis, only about 67% received guideline recommended therapy with 10 days of penicillin G IV therapy.⁹ The others received either a single dose of benzathine penicillin G (14.5%), another non recommended treatment (3.9%), or no treatment at all (14.5%).⁹ As pharmacists, we are in a role to be able to help providers ensure that patients receive the optimal therapy to prevent and treat congenital syphilis.¹⁰

Recommended Treatment of Congenital Syphilis

Both the CDC and the American Academy of Pediatrics agree upon the general approach for the treatment of congenital syphilis.^4,8 Essentially, aqueous penicillin G administered IV at a dose of 50,000 units/kg/dose every 12 hours, then changed on day 8 of life to every 8 hours to complete 10 days of therapy, is recommended. Alternative therapy with procaine penicillin G intramuscularly at 50,000 units/kg/day IM can be used either for 10 days (proven, highly probable, or possible syphilis), or as a single dose for those with possible syphilis if clinicians think it is less likely and have reason to believe in reliable follow-up. ^4,8 Lastly, in cases when syphilis is less likely or unlikely, then either a single dose or close follow-up is recommended. ^4,8

References:

1. Centers for Disease Control and Prevention&nbsp. 2024 Annual Sexually Transmitted Infections Surveillance report. Accessed April 3, 2026. https://www.cdc.gov/sti-statistics/annual/index.html
2. Centers for Disease Control and Prevention. CDC NCHHSTP: Bicillin L-A Shortage. Accessed April 3, 2026. https://www.cdc.gov/nchhstp/director-letters/bicillin-update.html
3. Sandoval C. Syphilis Complicating Pregnancy and Congenital Syphilis. N Engl J Med. 2024;390(13):1251.
4. Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, Sawyer MH. Red Book: 2024-2027 Report of the Committee on Infectious Diseases. 33rd ed. American Academy of Pediatrics; 2024
5. Gomez GB, Kamb ML, Newman LM, et al. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis. Bull World Health Organ. 2013;91(3):217–226.
6. Carlson JM, Sancken CL, Nguyen K, et al. Birth Outcomes Among Women With Syphilis During Pregnancy in Six U.S. States, 2018-2021. Obstet Gynecol. 2025;146(1):121–128.
7. Gutiérrez-Tamayo AM, Mirama-Calderón LV, Vallejo-Ortega MT, Gaitán-Duarte HG. Effectiveness of treating gestational syphilis in the last trimester on the incidence of congenital syphilis: a systematic review and meta-analysis. Rev Colomb Obstet Ginecol. 2025;76(4):4268. doi: 10.18597/rcog.4268.
8. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187.
9. Nlandu MV, Lewis EL, Carlson JM, et al. Evaluations and Treatment Among Infants Exposed to Syphilis in Utero, Six U.S. States, 2018-2021. J Pediatric Infect Dis Soc. 2026;15(3):piag011. doi: 10.1093/jpids/piag011.
10. Barnes T, Girotto JE. The Role of Pediatric Pharmacists in the Prevention and Treatment of Congenital Syphilis. J Pediatr Pharmacol Ther. 2024;29(4):429–433.