Syphilis During Pregnancy

All women should be screened serologically for syphilis early in pregnancy (106). Most states mandate screening at the first prenatal visit for all women (441). In populations in which receipt of prenatal care is not optimal, RPR test screening and treatment (if the RPR test is reactive) should be performed at the time pregnancy is confirmed (442). Antepartum screening by nontreponemal antibody testing is typical, but treponemal antibody testing is being used in some settings. Pregnant women with reactive treponemal screening tests should have additional quantitative nontreponemal testing, because titers are essential for monitoring treatment response. For communities and populations in which the prevalence of syphilis is high and for women at high risk for infection, serologic testing should also be performed twice during the third trimester: once at 28–32 weeks’ gestation and again at delivery. Any woman who has a fetal death after 20 weeks’ gestation should be tested for syphilis. No mother or neonate should leave the hospital without maternal serologic status having been documented at least once during pregnancy, and if the mother is considered high risk, documented at delivery.

Diagnostic Considerations

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 appropriately for the stage of syphilis. In general, the risk for antepartum fetal infection or congenital syphilis at delivery is related to the stage of syphilis during pregnancy, with the highest risk occurring with the primary and secondary stage. Quantitative maternal nontreponemal titer, especially if >1:8, might be a marker of early infection and bacteremia. However, risk for fetal infection is still significant in pregnant women with late latent syphilis and low titers. Pregnant women with stable, serofast low antibody titers who have previously been treated for syphilis might not require additional treatment; however, rising or persistently high antibody titers might indicate reinfection or treatment failure, and treatment should be considered.

If a treponemal test (e.g., EIA or CIA) is used for antepartum syphilis screening, all positive EIA/CIA tests should be reflexed to a quantitative nontreponemal test (RPR or VDRL). If the nontreponemal test is negative, then the results are considered discrepant and a second treponemal test (TP-PA preferred) should be performed, preferably on the same specimen. If the second treponemal test is positive, current or past syphilis infection can be confirmed. For women with a history of adequately treated syphilis who do not have ongoing risk, no further treatment is necessary. Women without a history of treatment should be staged and treated accordingly with a recommended penicillin regimen. If the second treponemal test is negative, the positive EIA/CIA is more likely to represent a false-positive test result in low-risk women with no history of treated syphilis (400). If the woman is at low risk for syphilis, lacks signs or symptoms of primary syphilis, has a partner with no clinical or serologic evidence of syphilis, and is likely to follow up, repeat serologic testing within 4 weeks can be considered to determine whether the EIA/CIA remains positive or if the RPR/VDRL or the TP-PA becomes positive. If both the RPR and TP-PA remain negative, no further treatment is necessary. If follow-up is not possible, women without a history of treated syphilis should be treated according to the stage of syphilis.


Penicillin G is the only known effective antimicrobial for preventing maternal transmission to the fetus and treating fetal infection (443). Evidence is insufficient to determine optimal, recommended penicillin regimens (444).

Recommended Regimen
  • Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection.

Other Management Considerations

  • Some evidence suggests that additional therapy is beneficial for pregnant women. For women who have primary, secondary, or early latent syphilis, a second dose of benzathine penicillin 2.4 million units IM can be administered 1 week after the initial dose (445-447).
  • When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for congenital syphilis. However, 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 (448); cases accompanied by these signs 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 (449). 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. No data are available to suggest that corticosteroid treatment alters the risk for treatment-related complications in pregnancy.
  • Missed doses are not acceptable for pregnant women receiving therapy for late latent syphilis (423). Pregnant women who miss any dose of therapy must repeat the full course of therapy.
  • All women who have syphilis should be offered testing for HIV infection.


Coordinated prenatal care and treatment are vital. At a minimum, serologic titers should be repeated at 28–32 weeks’ gestation and at delivery. 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. 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, clinical signs of infection are present at delivery, or the maternal antibody titer at delivery is fourfold higher than the pretreatment titer.

Management of Sex Partners

See Syphilis, Management of Sex Partners.

Special Considerations

Penicillin Allergy

No proven alternatives to penicillin are available for treatment of syphilis during pregnancy. Pregnant women who have a history of penicillin allergy should be desensitized and treated with penicillin. Skin testing or oral graded penicillin dose challenge might be helpful in identifying women at risk for acute allergic reactions (see Management of Persons Who Have a History of Penicillin Allergy).

Tetracycline and doxycycline are contraindicated in the second and third trimester of pregnancy (317). Erythromycin and azithromycin should not be used, because neither reliably cures maternal infection or treats an infected fetus (444). Data are insufficient to recommend ceftriaxone for treatment of maternal infection and prevention of congenital syphilis.

HIV Infection

Placental inflammation from congenital infection might increase the risk for perinatal transmission of HIV. All women with HIV infection should be evaluated for syphilis and receive a penicillin regimen appropriate for the stage of infection. Data are insufficient to recommend any alternative regimens for pregnant women with HIV infection (see Syphilis Among Persons with HIV infection).