What is the recommended treatment for syphilis in pregnancy?

Treatment of Syphilis in Pregnancy

Benzathine penicillin G is the only acceptable treatment for syphilis in pregnancy, as it is the only proven therapy to prevent congenital syphilis and maternal-to-fetal transmission. 1, 2, 3

Treatment Regimens by Stage of Disease

Primary, Secondary, or Early Latent Syphilis

• Administer benzathine penicillin G 2.4 million units IM as a single dose, followed by a mandatory second dose of 2.4 million units IM exactly one week later. 1, 2
• The second dose is particularly critical for women in the third trimester or those with secondary syphilis, as single-dose therapy has been associated with treatment failure. 1, 3, 4
• Research from South Africa demonstrated that treponemicidal coverage of 3 weeks or less (essentially one injection) resulted in significantly worse outcomes including decreased birth weight (2,748 vs. 3,130 g), 8.5-fold increased risk of prematurity, and 20.5-fold increased perinatal mortality compared to longer coverage. 4

Late Latent or Latent Syphilis of Unknown Duration

• Administer benzathine penicillin G 7.2 million units total, given as three doses of 2.4 million units IM each, at weekly intervals (7 days apart). 1, 2, 3

Critical Management of Penicillin Allergy

There are no acceptable alternatives to penicillin for treating syphilis in pregnancy—pregnant women with penicillin allergy must undergo skin testing and desensitization, then be treated with penicillin. 1, 2, 3

Contraindicated Medications

• Never use tetracycline or doxycycline in pregnancy: these cause maternal hepatotoxicity and fetal bone/teeth staining. 1, 2, 3
• Never use erythromycin in pregnancy: it does not reliably cure fetal infection and will not prevent congenital syphilis. 1, 2, 3
• Note that doxycycline is FDA-approved for syphilis treatment in non-pregnant penicillin-allergic patients (100 mg PO twice daily for 2 weeks for early syphilis, 4 weeks for late syphilis), but this is absolutely contraindicated in pregnancy. 5

Monitoring During and After Treatment

Jarisch-Herxheimer Reaction Precautions

• Up to 44% of pregnant women experience Jarisch-Herxheimer reaction after treatment, which can cause contractions, fetal heart rate abnormalities, and even stillbirth in severely affected pregnancies. 6
• Administer the first dose of benzathine penicillin G in a labor and delivery unit with continuous fetal monitoring for at least 24 hours for all viable pregnancies, particularly those beyond 20 weeks gestation. 3, 6
• Instruct women to seek immediate obstetric attention if they notice contractions or decreased fetal movements within 24 hours of treatment. 3
• Subsequent weekly doses can be administered in an outpatient setting. 6

Serologic Follow-Up

• Repeat serologic titers in the third trimester and at delivery. 1, 2, 3
• Check titers monthly in women at high risk for reinfection or in areas with high syphilis prevalence to detect four-fold increases that may indicate reinfection or treatment failure. 1, 2, 3, 6
• The rate of maternal titer decline is not tied to pregnancy outcomes, so do not retreat based solely on slow decline. 6

Ultrasound Surveillance

• Perform pretreatment ultrasound in viable pregnancies when feasible, particularly after 20 weeks gestation. 1, 3, 6
• Sonographic signs of fetal syphilis include hepatomegaly, placentomegaly, ascites, hydrops fetalis, and elevated middle cerebral artery peak systolic velocity (indicating fetal anemia). 1, 6
• Pregnancies with ultrasound abnormalities are at higher risk of compromise during treatment and fetal treatment failure, requiring consultation with obstetric specialists. 3, 6

Screening Requirements

• Screen all pregnant women for syphilis at the first prenatal visit. 1, 2, 3, 7
• In high-risk populations or areas with high syphilis prevalence, perform additional screening at 28-32 weeks gestation and at delivery (three times total during pregnancy). 1, 2, 3, 7
• Test any woman who delivers a stillborn infant after 20 weeks gestation for syphilis. 1, 2
• No newborn should be discharged without documented maternal syphilis screening at least once during pregnancy. 1, 2, 3

Partner Management and HIV Testing

• Treat sexual partners exposed within 90 days of diagnosis presumptively, even if seronegative. 1, 2, 3
• Offer HIV testing to all patients with syphilis, as HIV-infected pregnant women may require more intensive treatment. 1, 2, 3

Critical Pitfalls to Avoid

• Do not delay treatment due to concerns about Jarisch-Herxheimer reaction causing stillbirth—untreated syphilis causes far greater fetal harm, with 40% pregnancy loss and another 40% resulting in congenital syphilis. 3, 8
• Do not use single-dose therapy for pregnant women, even for early syphilis—the second dose one week later is essential to ensure adequate treponemicidal coverage, especially when women may deliver before 4 weeks post-treatment. 1, 4
• Do not compare titers between different types of tests (traditional vs. reverse-sequence algorithms), as they are not directly comparable. 2
• Do not use non-penicillin regimens under any circumstances in pregnancy, as they do not prevent congenital syphilis. 2, 3