Syphilis management during pregnancy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]; Nate Michalak, B.A. Muhammad Saad, M.B.B.S.[3]

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## Overview

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All women should be screened serologically for syphilis early in pregnancy. If a treponemal screening test is seropositive, confirmatory nontreponemal tests should be performed. Late gestation serologic testing should also be performed in populations with high prevalence of syphilis. Penicillin is effective for preventing maternal transmission to the fetus and for treating fetal infection. When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for congenital syphilis, but this evaluation should not delay therapy. Placental inflammation from congenital infection might increase the risk for perinatal transmission of HIV.

## Management During Pregnancy

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* All women should be screened serologically for syphilis early in pregnancy.[1][2]

* Most states mandate screening at the first prenatal visit for all women;[3] antepartum screening by nontreponemal antibody testing is typical, but in some settings, treponemal antibody testing is being used.

* Pregnant women with reactive treponemal screening tests should have confirmatory testing with nontreponemal tests with titers to monitor treatment response.

* In populations in which use of prenatal care is not optimal, RPR test screening and treatment (if the RPR test is reactive) should be performed at the time that pregnancy is confirmed.

* For communities and populations in which the prevalence of syphilis is high and for patients at high risk, serologic testing should be performed twice during the third trimester (ideally at 28-32 weeks' gestation) and at delivery.

* Any woman who delivers a stillborn infant after 20 weeks' gestation should be tested for syphilis.

* No infant should leave the hospital without the maternal serologic status having been determined at least once during pregnancy.

### Diagnostic Considerations

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* Seropositive pregnant women should be considered infected unless an adequate treatment history is documented clearly in the medical records and sequential serologic antibody titers have declined.

* Serofast low antibody titers might not require treatment; however, persistent higher titer antibody tests might indicate reinfection, and treatment might be required.

### Treatment

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* Penicillin is effective for preventing maternal transmission to the fetus and for treating fetal infection.[4] [5]
* Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection as follows:[6]
* Primary, secondary, and early latent syphilis: BPG 2.4 million units intramuscularly once daily.
* Late latent or unknown duration: BPG administered as 3 doses of 2.4 million units intramuscularly, given at 1 week intervals.
* Neuro, ocular, and otic syphilis: Aqueous crystalline penicillin G, 18-24 million units daily given as 3-4 units intravenously every 4 hours.

### CDC Recommendations: Pregnancy

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#### Recommended Regimen

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* Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection.[7]

### Other Management Considerations

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* Some evidence suggests that additional therapy can be beneficial for pregnant women in some settings (e.g., a second dose of benzathine penicillin 2.4 million units IM administered 1 week after the initial dose for women who have primary, secondary, or early latent syphilis).[8]

* When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for congenital syphilis, but this evaluation should not delay therapy.

* Sonographic signs of fetal or placental syphilis (i.e., hepatomegaly, ascites, hydrops, fetal anemia, or a thickened placenta) indicate a greater risk for fetal treatment failure;[3] such cases should be managed in consultation with obstetric specialists. Evidence is insufficient to recommend specific regimens for these situations.

* Women treated for syphilis during the second half of pregnancy are at risk for premature labor and/or fetal distress if the treatment precipitates the Jarisch-Herxheimer reaction.[9] These women should be advised to seek obstetric attention after treatment if they notice any fever, contractions, or decrease in fetal movements.

* Stillbirth is a rare complication of treatment, but concern for this complication should not delay necessary treatment.

* Pregnant women taking treatment for late latent syphilis should not miss any dose, else she must repeat the whole course of therapy.[10]

* All patients who have syphilis should be offered testing for HIV infection.

### Special Consideration

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#### Pencillin Allergy

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* For treatment of syphilis during pregnancy, no proven alternatives to penicillin exist.

* Pregnant women who have a history of penicillin allergy should be desensitized and treated with penicillin.

* Oral step-wise penicillin dose challenge or skin testing may be helpful in identifying women at risk for acute allergic reactions.

* Tetracycline and doxycycline usually are not used during pregnancy. Erythromycin and azithromycin should not be used, because neither reliably cures maternal infection or treats an infected fetus.[5] Data are insufficient to recommend ceftriaxone for treatment of maternal infection and prevention of congenital syphilis.

#### HIV Infection

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* Placental inflammation from congenital infection might increase the risk for perinatal transmission of HIV.

* All HIV-infected women should be evaluated for syphilis and receive treatment as recommended.

* Data are insufficient to recommend a specific regimen for HIV-infected pregnant women.

### Follow Up

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* Coordinated prenatal care and treatment are vital.

* Serologic titers should be repeated at 28-32 weeks' gestation and at delivery as recommended for the disease stage. Providers should ensure that the clinical and antibody responses are appropriate for the patient's stage of disease, although most women will deliver before their serologic response to treatment can be assessed definitively.

* Inadequate maternal treatment is likely if delivery occurs within 30 days of therapy, if clinical signs of infection are present at delivery, or if the maternal antibody titer at delivery is fourfold higher than the pretreatment titer.

* Serologic titers can be checked monthly in women at high risk for reinfection or in geographic areas in which the prevalence of syphilis is high. [7]

## References

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1. ↑ https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/syphilis-infection-in-pregnancy-screening Accessed on september 27,2016
2. ↑ http://www.cdc.gov/std/tg2015/references.htm#424 Accessed on September 27, 2016
3. ↑ 3.0 3.1 Hollier LM, Harstad TW, Sanchez PJ, Twickler DM, Wendel GD (2001) Fetal syphilis: clinical and laboratory characteristics. Obstet Gynecol 97 (6):947-53. PMID: 11384701
4. ↑ Alexander JM, Sheffield JS, Sanchez PJ, Mayfield J, Wendel GD (1999) Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 93 (1):5-8. PMID: 9916946
5. ↑ 5.0 5.1 Walker GJ (2001) Antibiotics for syphilis diagnosed during pregnancy. Cochrane Database Syst Rev (3):CD001143. DOI:10.1002/14651858.CD001143 PMID: 11686978
6. ↑ Chevalier FJ, Bacon O, Johnson KA, Cohen SE (December 2025). "Syphilis: A Review". JAMA. 334 (21): 1927–1940. doi:10.1001/jama.2025.17362. PMID 41100079 Check `|pmid=` value (help).
7. ↑ 7.0 7.1 "Sexually Transmitted Diseases Treatment Guidelines, 2010". Retrieved 2012-12-19.
8. ↑ Wendel GD, Sheffield JS, Hollier LM, Hill JB, Ramsey PS, Sánchez PJ (2002) Treatment of syphilis in pregnancy and prevention of congenital syphilis. Clin Infect Dis 35 (Suppl 2):S200-9. DOI:10.1086/342108 PMID: 12353207
9. ↑ Klein VR, Cox SM, Mitchell MD, Wendel GD (1990) The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy. Obstet Gynecol 75 (3 Pt 1):375-80. PMID: 2304710
10. ↑ Nathan L, Bawdon RE, Sidawi JE, Stettler RW, McIntire DM, Wendel GD (1993). "Penicillin levels following the administration of benzathine penicillin G in pregnancy". Obstet Gynecol. 82 (3): 338–42. PMID 8355931.CS1 maint: Multiple names: authors list (link)

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